Background. While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pan-creatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. Methods. A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narra-tive synthesis was performed. Results. The searches yielded 1016 publications. After assessing 203 full texts and additional sources, 80 studies were included. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacteria resistance and fungal infec-tions, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN not always require microbiological samples, as clinical suspicion or CT signs can suffice. Early di-agnosis and treatment may be improved by using biomarkers such as procalcitonin and novel mi-crobiological methods; (3) When indicated, early initiation of antibiotics of IPN is a key determinant in reducing mortality; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN manage-ment; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Conclusions. Early antibiotic therapy is essential for the treatment of IPN, but prophylactic anti-biotics are not recommended in AP. High-quality RCTs are required to better understand the role of antibiotics and antifungals in AP management.

Perioperative acute pain management in pediatric patients is essential to reduce complications. Adenoidectomy-Tonsillectomy are surgical procedures requiring pain control, and risk minimization for postoperative bleeding, nausea, and vomiting. Despite their known secondary effects, the use of opioid analgesics remains preponderant in pediatric perioperative management. We present an updated review on perioperative pain management in children and describe the development and implementation of a multimodal analgesia protocol aimed to improve patients’ pain management while consistently reducing opioids use. Information from relevant articles was summarized, then compared to our clinical needs. Learnings were used to create and implement a multimodal analgesia protocol to be used in patients 3-9 years-old undergoing adenoidectomy/tonsillectomy. Analgesic strategies have emerged to reduce or avoid the use of opioids. Among these strategies, combining different non-opioid analgesics (Ibuprofen, Paracetamol, Metamizole) has been shown to be an effective and safe pharmacological strategy when implemented as part of postoperative multimodal analgesia protocols. Significant evidence associating the use of NSAIDs with a bigger risk of postoperative bleeding does not exist. Multimodal and preventive analgesia has shown to provide significantly more effective analgesia than some opioid regimens. Ibuprofen offers highly effective analgesia for postoperative pain, particularly when combined with acetaminophen.

Pain diagnosis remains a challenging task due to its subjective nature, the variability in pain expression among individuals, and the difficult assessment of the underlying biopsychosocial factors. In this complex scenario, artificial intelligence (AI) can offer the potential to enhance diagnostic accuracy, predict treatment outcomes, and personalize pain management strategies. This review aims at dissecting the current literature on computer-aided diagnosis methods. It also discusses how AI-driven diagnostic methods can be integrated into multimodal models that combine various data sources, such as facial expression analysis, neuroimaging, and physiological signals, with advanced AI techniques. Despite the significant advancements in AI technology, its widespread adoption in clinical settings faces crucial challenges. Ethical considerations related to patient privacy, biases, and lack of reliability and generalizability are the main issues. Furthermore, there is a need for high-quality real-word validation as well as the development of standardized protocols and policy rules to guide the implementation of these technologies in diverse clinical settings.

Petit vert (scientific name: Brassica oleracea var. gemmifera DC. × Brassica oleracea var. acephala DC.) is a new variety of vegetable created by crossbreeding kale and brussels sprouts (Brassica oleracea species). The present study aimed to identify biologically active compounds in extracts of the outer leaves of Petit vert by purification and to examine their biological activities. Dried and powdered outer leaves of Petit vert were extracted, fractionated, and purified to isolate active compounds. Nuclear magnetic resonance and mass spectrometries were performed to elucidate the structures of five compounds (1‒5). The compounds isolated from Petit vert leaves were glycosides that contained kaempferol, quercetin (flavonol), or sinapinic acid (phenylpropanoid).　Glucose uptake in cultured C2C12 murine myoblasts in the absence of insulin was significantly increased by these compounds, kaempferol, sinapic acid, and ferulic acid, while that in the presence of insulin was also significantly increased by compounds 3 and 4, kaempferol, and sinapic acid. The present study reports for the first time the isolation of five compounds containing sinapic acid from the outer leaves of Petit vert and their stimulation of glucose uptake in cultured C2C12 murine myoblasts. The results obtained herein suggest the potential of these compounds to effectively attenuate hyperglycemia and maintain muscle strength by promoting glucose metabolism in muscle cells.

Rapid microscopic analysis of tissue is an essential diagnostic tool in oncological surgery. The gold standard for intraoperative histological tissue evaluation are frozen sections. However, frozen sections are prone to a variety of artefacts and require skilled staff and specialized lab equipment. A potential method for rapid intraoperative tissue evaluation that does not require fixation, freezing nor sectioning of the tissue, is ex vivo fluorescence confocal microscopy (FCM). The visualization of the structurally important extracellular matrix (ECM) in conventional ex vivo FCM lags behind the standards of conventional histology. The objective of this study was to find a stain that will improve the depiction of the ECM to resemble FFPE H&E sections as closely as possible.

Novel ZNF proteins such as ZNF671 that are located on chromosome 19q13 are known to be hypermethylated at a high frequency in HNSCC as well as in other epithelial solid tumors. Their function is largely unknown. Here, we show that ZNF671 is epigenetically silenced in HNSCC primary tumors compared to matched adjacent normal tissue. Moreover, low expression of ZNF671 is significantly associated with decreased survival in HNSCC patients. Over-expression of ZNF671 in UM-SCC-1 oral cancer cells resulted in a significant reduction in tumor cell mobility and invasion compared to the empty-vector control cells. Transcriptomic analysis showed that ZNF671 re-expression resulted in a significant decrease in the expression of a major oncogenic long non-coding RNA LINC00665. Together, these results suggest that epigenetic silencing of ZNF671 may activate multiple oncogenic signaling pathways via the resulting up-regulation of LINC00665.

Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes have not been thoroughly explored. Objectives: The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD). Methods: In our retrospective analysis we included 240 patients treated between 1993 and 2013, and divided them into 3 groups according to the therapy administered prior to matched related or matched unrelated donor allo-HCT (imatinib group n=41, dasatinib/nilotinib group n=28, TKI naïve group n=171). Results: Both the cumulative incidence of aGvHD (p=0.044) and cGvHD (p<0.001) in individuals receiving second generation TKIs (2G-TKIs) prior to allo-HCT compared to patients receiving no TKIs or imatinib (IMA) (40.7% vs 61.4% vs 70.7%, p=0.044; 25.0% vs 76.4% vs 51.2%, p<0.001, respectively). In case of the 2G-TKI cohort, the number of low-grade aGvHD and cGvHD was significantly lower compared to the IMA and TKI-naïve groups (p=0.018, p=0.004; p<0.001 versus TKI-naïve, respectively). In terms of 3-year overall survival (OS) there were no important variations between TKI-naïve, IMA and 2G-TKI (55% vs 49.9% vs 69.6%, p=0.740). Conclusions: The results of our study suggest that TKI treatment prior to allo-HCT may have protective impact on immune-mediated outcomes.

Objectives: The goal of this pilot study was to validate and introduce a new AI tool (algorithm), providing and comparing (1) the periodontal/peri-implant diagnosis between professional (specialist) and automated tool, (2) risk assessment and prognostication with the algorithm, and (3) establish cut-off limits for clinically significant disease with a new score system (GF-PeDRA score). Methods: All patients were evaluated by two evaluators, and in case of any divergence, the case was revisited and discussed until clarification and definition. The validation sample constituted 221 patients. The AI tool (GF-PeDRA©) had eighteen parameters to be assessed, involving systemic and local predictors, achieving an octadecagon (an eighteen-sided polygon). The parameters were: (1) The highest probing depth (PD); (2) Number of interproximal sites with bone loss; (3) The highest clinical attachment loss (CAL); (4) Maximum radiographic bone loss (RBL); (5) Bleeding on probing (% BoP); (6) Bone loss pattern; (7) Tooth loss including periodontally hopeless teeth planned for extraction; (8) Evidence of progression over five years; (9) Need for complex rehabilitation; (10) Patient’s age; (11) CAL and biofilm accumulation; (12) Smoking; (13) Diabetes; (14) Extension and distribution of the disease; (15) Peri-implant disease; (16) Other systemic conditions (other than diabetes); (17) Furcation involvement; and (18) Necrotizing lesion. A new score system (GF-PeDRA© score) based on the percentual of the octadecagon area is obtained; if the area was ≥0% to ≤9%, the prognosis is good; ≥10% and ≤ 24%, it is fair; ≥25% and ≤37%, poor; ≥38% and ≤49%, it is questionable; and between ≥50% to ≤100%, the prognosis is hopeless. Results: 221 patients were enrolled, with a mean age of 46.73. 5301 teeth were examined. 187 non-smokers (84.62%) and 34 smokers (15.38%) were included. 193 (87.33%) patients did not have diabetes, whereas 28 (12.67%) had. Comparing the diagnosis between both evaluators, k=0.83; all disagreed cases were re-discussed, and a final decision/diagnosis was reached. After this, the diagnosis found was contrasted with the diagnosis achieved by GF-PeDRA© and a perfect agreement was observed, 100% (k=1.0). 28 patients were diagnosed as periodontally healthy, 55 with plaque-induced gingivitis, and 138 with periodontitis. Only one case of molar/incisor pattern was observed. No peri-implant disease or necrotizing condition was found. The mean CAL found was 3.19 mm; 25 patients (11.31%) had a furcation involvement. The mean percentual of BoP found was 28.67% (median = 19%; maximum: 100%; minimum: 100%); and the mean PD was 5.31 mm. The mean of the new GF-PeDRA© score (ranging from 0% to 100%) was 28.64%, with a median of 32.2% (minimum: 0.6% and maximum: 64.1%). Then, analyzing the GF-PeDRA© score of 221 patients enrolled, 48 (21.73%) were sorted as a Good prognosis for periodontal treatment, 43 (19.45%) had a Fair prognosis, 43 (19.45%) had a Poor prognosis, 68 (30.77%) had a Questionable prognosis, and 19 (8.60%) had a Hopeless prognosis. Conclusion: The new AI tool (GF-PeDRA©) was validated and proved to be extremely helpful in diagnosing and providing risk assessment and prognosis.

Nasal polyposis is defined by a Th2-driven chronic inflammation of the nose and sinus with polyps visible in the nasal fossae. It is a prevalent disease with a significant impact on the HRQL. Allergy, allergic rhinitis, asthma, and aspirin intolerance are frequently associated. The management is individual. The first line of treatment is a long-term treatment with intranasal corticosteroids. Oral corticosteroids should be used with caution. When the medical treatment fails the patient is eligible for sinus surgery. In case of symptomatic recurrence after both medical treatment and ethmoidectomy, biologics are nowadays a very promising treatment effective on all the respiratory tract. Dupilumab seems in the literature the molecule of choice. However, besides the international guidelines published by EPOS and Euforea, the molecule prescribed depends also on the availability of it in each country and the criteria edited by the health authorities to get reimbursement. Long treatment is mandatory. Traditional medical treatment is necessary as a complement to biologics.

Background: The Advanced Lung Cancer Inflammation Index (ALI) is a novel, comprehensive index that integrates inflammation and nutritional status, incorporating parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). Unlike traditional inflammation biomarkers, this study aims to evaluate the prognosis of IPF patients by considering both inflammation and nutritional status. Method: A total of 102 patients with IPF were included in the study. Clinical data were obtained from the patients’ medical records. NLR and ALI score were calculated based on data collected at the initiation of antifibrotic treatment using the following formula: Neut/Lym and albumin × BMI / NLR. Results: IPF subject subgroups in terms of ALI based on gender–age–physiology (GAP) stages (1,2,3), FVC (median split, <70% vs ≥70%), DLCO (<51% vs ≥51%), 6-Minute Walk Test (6MWT) (<350 vs ≥350) and CCI (≤1 vs >1). ALI showed significant difference depending on the categories of GAP stage, FVC, DLCO, and 6MWT but these differences were not observed based on the charlson comorbidity index (CCI) categories (sırasıyla p=0.000, p=0.000, p=0.000, p=0.001, p=0.233). Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the sensitivity and specificity of ALI, albumin, NLR, and BMI in determining the mortality risk in IPF patients. ALI demonstrated a sensitivity of 63.6% and a specificity of 98.9% at a threshold of 11.2 (AUC = 0.945, 95% CI 0.892–0.998, p < 0.000). Conclusion: We determined that ALI levels are significantly associated with disease severity and mortality in patients with IPF.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Cleft lip and palate are the most common congenital craniofacial anomalies. The etiology of this condition is unclear. The overall incidence of cleft lip and palate is 1/700. Prenatal diagnosis of cleft lip by 3D ultrasound is possible in more than 70% of cases, while it is less effective for cleft palate. There are several classifications of cleft lip and palate that were proposed over the years, however, only few have found clinical application, with none of them generally accepted as most effective and understandable. Allori et al. presented classification of a cleft lip and palate which is comprehensive and uniform, and it can precisely define the vast majority of the clefts, thus enabling easier communication between the health workers during their everyday practice. In this paper, we compared the accuracy of preoperative diagnoses compared to intraoperative diagnoses according to Kernahan and Stark classification from 1958, and these diagnoses were converted according to the Allori et al. classification of cleft lip and palate. Classification of cleft lip and palate presented by Allori et al. is clear, easy to understand, and it can be successful tool in studying the epidemiology of clefts.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

This study investigates the diversity and evolution of research topics within the dental sciences from 1994 to 2023 using topic modeling and Shannon's entropy as a measure of research diversity. We analyzed a dataset of 412036 scientific articles across six dental disciplines: Orthodontics, Pros-thodontics, Periodontics, Implant Dentistry, Oral Surgery, and Restorative Dentistry. This research relies on BERTopic to identify distinct topics within each field. The study revealed significant shifts in research focus over time, with some disciplines exhibiting robust growth in article numbers such as Periodontics and Prosthodontics. The application of Shannon's entropy revealed an increasing diversification of research efforts in disciplines such as Restorative Dentistry, while others, like Prosthodontics, in spite of their size and their high number of research topics, maintain a more specialized research focus. Taken together, our findings describe the dynamic nature of dental re-search and highlight the balance shifts in research focus across several key areas of Dentistry.

Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than pancreatic ductal adenocarcinoma. We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022. Patient information was extracted from our institutional database with the approval of Institutional Review Board. We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, 1 had borderline resectable disease, and 1 had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (1 patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases which had BostonGene tests was found to have NTRK1 fusion. RNA and TME analysis by BostonGene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74 and MMP1 and higher CDH6 compared with PDAC.

Background: The Fat-Augmented Latissimus Dorsi (FALD) flap is an autologous flap that combines Latissimus Dorsi (LD) flap with immediate autologous fat transfer (AFT) in order to improve breast reconstruction (BR) volume. In recent years, our team has described the ergonomic FALD flap, an evolution of this technique which helps to achieve a complete BR in a single surgical step. In this long-term study, we analyze morphological variations of the breast after ergonomic FALD flap reconstruction compared to the traditional transverse FALD flap technique. Methods: Between December 2020 and September 2022 we prospectively enroll patients undergoing BR using FALD flap into 2 groups: Group A included ergonomic FALD flap, while Group B included traditional FALD flap. The primary endpoint of the study was to compare the two groups in terms of breast projection (BP), breast width (BW) and breast height (BH), while the second endpoint concerned the analysis of the aesthetic outcomes. Results: 32 FALD flaps (23 patients) were performed for the Group-A and 31 FALD flaps (25 patients) for Group-B. There were no significant differences regarding demographic variables. After propensity score weighting analysis, Group-A showed a statistically significant better breast projection (p<0.0001) compared to Group-B. (6.05 vs 5.60). Final aesthetic analyses showed to be superior in Group-A concerning breast shape (p=0.001) and global score evaluation (p=0.004). Conclusion: The ergonomic FALD flap offers better long-term aesthetic outcomes for autologous BR with higher breast projection compared to the traditional transverse FALD flap.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

Ovarian torsion (OT) is a rare gynaecological emergency that requires a prompt diagnosis for optimal patient management. To determine whether there were any biomarkers suitable for the non-invasive detection of OT, two independent reviewers performed systematic searches of five literature databases following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Full-texts of 24 selected articles were assessed for risk of bias and quality assurance using a modified Newcastle-Ottawa Scale (NOS).  15 articles described studies on animals and all described serum biomarkers comparing results between OT versus a sham operation, a control group or readings before and after OT. Ischaemia modified albumin (IMA), serum D-dimer (s-DD), heat shock protein-70 (hsp-70), Pentraxin-3 (PTX-3) and c-reactive protein (CRP) showed the most promise, each with p-values for the difference between groups achieving ≤0.001. In studies of humans, the biomarkers ranged from 16.4-92.3% sensitivity and 77-100% specificity. The most promising biomarkers for the early prediction of OT in patients included s-DD, interleukin-6 (IL-6), IMA and tumour necrosis factor-alpha (TNF-. IL-6 had the highest sensitivity of any biomarker identified in this review and was raised in all 13 patients with proven OT, with values of ≥10.2pg/ml, indicative of a 16 times higher risk of having OT. Signal peptide, CUB domain and EGF like domain containing 1 (SCUBE1) had a high specificity at 93.3%, second only to s-DD and a positive likelihood ratio (LR)&gt;10. IMA was the only other biomarker that also had a positive LR&gt;10, making it a promising diagnostic biomarker. The studies identified by this systematic literature review each analysed small patient groups but IMA, DD and SCUBE1 nevertheless showed promise as serum biomarkers with a pooled LR&gt;10. However, further well-designed studies are needed to identify and evaluate individual markers, or diagnostic panels to help clinicians manage this important, organ-threatening condition.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Introduction After the first use of infliximab in Crohn’s disease in 1995, the wide scale introduction of anti-tumour necrosis factor alfa (anti-TNF alfa) medications revolutionized the treatment of inflammatory bowel diseases (IBD’s). During the last two decades an increased number of molecules with multiple mechanisms of action were approved for the treatment of IBD with substantial increase of the costs of related to therapy. The increasing costs and access to therapy became a concern of payers and regulators but also for healthcare professionals. Biosimilars are biologic medical products that are highly structurally identical to their reference products and without any clinically meaningful differences in immunogenicity, safety or effectiveness. The introduction of biosimilars was seen as a way to provide a lower-cost alternative to the originator anti-TNF molecules and hence to increase treatment access and availability for patients. Material and methods This an observational, prospective study conducted in two IBD centers in Bucharest. The study included 53 patients, 27 male(M) and 26 female(F), diagnosed with UC or BC according to standard clinical,endoscopic, radiological, histological criteria that were non medically switched to a biosimilar. All patients completed at least the induction treatment with the originator adalimumab and they were clinically stable. After switch they received one of the market available biosimilars of Adalimumab(Hukyndra, Imraldi or Hyrimoz). For each patient, the following data were collected: age, sex, BC or UC diagnosis, previous and current therapy, clinical evolution, endoscopic scores as well as several biological markers. Aim The primary objective was the maintenance of clinical remission at twelve months after switching the original Adalimumab treatment to the biosimilar Adalimumab. The secondary objectives were to evaluate the presence of adverse effects and the treatment persistence at one year. Results In our population, there were 42 patients with Crohn's disease and 11 with ulcerative colitis who switched from the originator adalimumab to a biosimilar Adalimumab. The average age was 44,07 years old for patients with BC and 51,72 years old for patients with UC. No significant differences were found in terms of CF and CRP levels at 6 and 12 months after changing the originator biologic treatment to a biosimilar. Only one patient required changing the biological treatment, following the clinical and biological loss of response. The main adverse effect reported by patients was pain at the injection site. Of the 53 patients, only 2 patients reported pain at the injection site, but this was considered not significant because the patients had a BMI below 20 and they also reported the same symptom when administering the originator. One patient reported experiencing abdominal pain and rectal bleeding immediately after switch, but no recurrence was observed clinically and endoscopically. Conclusion: This observational study is the first carried out in Romania that shows that the after the non-medical switch, biosimilars of Adalimumab were as efficient as the originator Adalimumab in the clinical practice of patients with IBD. These results support that conclusion that the large-scale use of biosimilars does not significantly affect the effectiveness of the therapy and the safety of the patient.

Background/Objectives: Lung cancer remains a global health concern, with substantial variation in patient survival. Despite advances in detection and treatment, the genetic basis for the divergent outcomes is not understood. We investigated germline polymorphisms that modulate overall survival in 1,464 surgically resected lung adenocarcinoma patients. Methods: A multivariable Cox proportional hazard model was used to assess the association of more than 7 million polymorphisms with overall survival at the 60-month follow-up, considering age, sex, pathological stage, decade of surgery and principal components as covariates. Genes in which variants were identified were studied in silico to investigate functional roles. Results: Six germline variants passed the genome-wide significance threshold. These single nucleotide polymorphisms mapped to non-coding (intronic) regions on chromosomes 2, 3, and 5. The minor alleles of rs13000315, rs151212827, and rs190923216 (chr. 2, 3 and 5, respectively) were found to be independent negative prognostic factors. All six variants have been reported to regulate the expression of nine genes, seven of which are protein-coding, in different tissues. Survival-associated variants on chromosomes 2 and 3 were already reported to regulate the expression of NT5DC2 and NAGK, with high expression associated with the minor alleles. High NT5DC2 and NAGK expression in lung adenocarcinoma tissue were already shown to correlate with poor overall survival. Conclusions: This study highlights a potential regulatory role of the identified polymorphisms in influencing outcome and suggests a mechanistic link between these variants, gene expression regulation, and lung adenocarcinoma prognosis. Validation and functional studies are warranted to elucidate the mechanisms underlying these associations.

Aim: The purpose of this study is to evaluate the remineralization potential of primary teeth enamel after being exposed to different laser diode therapy. Methods: Ninety-six vestibular primary teeth enamel samples were divided into eight groups (n=12) with varying treatments: control (G1), CPP-ACP-fluoride varnish (G2), diode lasers at 980 nm (G3), 808 nm (G4), 450 nm (G5), 980 nm + CPP-ACP-fluoride varnish (G6), 808 nm + CPP-ACP-fluoride varnish (G7), and 450 nm + CPP-ACP-fluoride varnish (G8). Each sample was assessed using DIAGNOdent® at baseline, post-treatment, and post-pH cycle re-mineralization. SEM imaging was performed before and after treatment and following the pH cycle. Results: The results indicated that the 980 nm and 808 nm diode lasers, both alone and in combination with CPP-ACP-fluoride varnish, either maintained or increased the calcium (Ca) weight percentage (Wt%) in the enamel. The 980 nm diode laser combined with CPP-ACP-fluoride varnish (G6) showed a significant increase in Ca Wt%, suggesting a strong remineralization effect. Similarly, the 808 nm diode laser alone (G4) also promoted a substantial increase in Ca Wt%. In contrast, the 450 nm diode laser, whether applied alone or in combination with CPP-ACP-fluoride varnish, resulted in a lower Ca Wt% and an increase in phosphorus (P) Wt%. Most groups, except for the CPP-ACP-fluoride varnish alone (G2), demonstrated an increase in P Wt%, indicating a complex interaction between laser therapy and enamel remineralization. Conclusions: The combined use of laser therapy with CPP-ACP-fluoride varnish significantly enhanced the remineralization of temporary teeth enamel. The 980 nm diode laser + CPP-ACP-fluoride varnish showed the most pronounced improvement in remineralization, while the 808 nm diode laser alone also effectively increased calcium solubility. These findings suggest that higher wavelength diode lasers, particularly when combined with remineralizing agents, can effectively enhance the mineral content of primary teeth and promote enamel remineralization.

Onychomycosis is a common fungal nail infection for which new antibiotics are needed to overcome antifungal resistance and other limitations of conventional treatments. This study reports the development of antifungal nail lacquers containing oregano essential oil (OEO), rosemary essential oil (REO), and/or biogenic silver nanoparticles (bioAgNP). The formulations (F) were tested against dermatophytes by agar diffusion, ex vivo nail infection, and scanning electron microscopy techniques. They were evaluated pharmacotechnically and by FTIR-PAS to access permeation across the nail plate. F-OEO and F-OEO/Ag were promising for the final nail lacquer formulation, they permeated through the nail plate and showed antifungal efficacy against dermatophytes-contaminated nails after 5 days of treatment. The treated nails had decreased hyphae and spores compared to untreated control; the hyphae were atypically flattened which indicates loss of cytoplasmic content due to damage to cytoplasmic membrane. Formulations were stable after centrifugation and thermal stress, maintaining organoleptic and physicochemical characteristics. F-OEO and F-OEO/Ag had pH compatible with the nail, and drying time (59-90 s) within the reference for nail lacquer. For the first time, OEO and bioAgNP were incorporated in a nail lacquer, resulting in a natural and nanotechnological antifungal product for onychomycosis that may combat microbial resistance.

Recent data has shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. Liquid biopsy’s monitoring for biomarkers of head and neck cancer, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regula-tory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to en-tail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA-FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic sig-naling in Treg subsets. Therefore, in this study, by using conventional and imaging flow cytome-try, we monitored STAT5 signaling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and disease course during follow-up of 37 patients with CLL. aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was character-ized by more frequent episodes of severe infections during follow-up, suggesting that aTreg frac-tion could represent a possible marker of severe disease course with infectious complications. Augmented homeostatic STAT5 signaling could support aTreg expansion, as higher pSTAT5 lev-els were significantly corelated with increased aTreg frequency among CD4+FOXP3+ T cells during follow-up of patients on therapy as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

Lung involvement in rheumatic diseases is a major determinant of patient morbidity and mortality; however, its diagnosis depends on the detection methods used. We compared the incidence of pulmonary involvement in newly diagnosed treatment-naive patients with rheumatic diseases, as assessed by pulmonary function tests (PFTs) and chest high-resolution computed tomography (HRCT). This retrospective study reviewed the symptoms, spirometry results, and HRCT scans of 22 newly diagnosed, treatment-naïve patients and age-matched controls from the University General Hospital “Attikon”, Athens, Greece, between January 2021 and December 2023. Correlations between clinical findings and spirometry parameters were tested. HRCT scans revealed lung abnormalities in all patients, including peribronchial wall thickening (61.5%), ground glass opacities (59.1%), parenchymal bands (54.5%), air-trapping (50%), reticular patterns (45.5%), bronchiectatic changes (40.9%), and parenchymal opacities (31.8%). PFTs, performed in 17/22 (77.3%) patients, revealed definite pathology in 5 patients (restrictive: N=4; obstructive: N=1). No association was found between spirometric indices and clinical parameters. The results indicate a higher prevalence of abnormal chest CT than of PFT abnormalities, suggesting that HRCT is more sensitive in detecting early lung involvement in pediatric patients with rheumatic disease and should be considered in the routine evaluation of these patients.

Simple Summary (148 words) There is increasing evidence, that cannabinoids may play an important and dual role in tumour therapy. On one hand, they are cytotoxic against cancer cells with a low toxicity against normal, healthy tissues, and on the other, they may reduce typical side effects of chemotherapy. Publications on the main motive for use of cannabis (cannabinoids) by cancer patients show that patients' expectations exceed scientific facts. This article briefly describes results of combinations of cannabinoids with standard antineoplastic drugs on tumours and on side effects of tumour therapy. Although observations are still limited to animal studies with very few experiences in patients, preliminary data suggest that adjuvant cannabinoids may improve the survival of glioblastoma and perhaps of patients with other tumours. Benefits have also been reported about chemotherapy-induced nausea and vomiting, chemotherapy-induced peripheral neuropathic pain, loss of appetite and anxiety. Although results are promising, much more research is necessary. Abstract (192 words) Cancer, one of the leading causes of death worldwide, is on the rise. The high toxicity of conventional chemotherapy, often applied as drug cocktails, and resistance development limits the use of anti-neoplastic drugs and reduces the quality of life. With an easier access, a growing number of patients are using cannabis (cannabinoids) for alleviation of their symptoms, and in the hope of improving survival. This narrative article summarizes results observed with combinations of phytocannabinoids and standard chemotherapeutic agents in animal tumour models and in patients. Preliminary data suggest that standard antineoplastic agents combined with cannabinoids exert increased anti-cancer actions, reduce resistance development and improve survival. Respective experiences in patients are still scarce and concern small numbers with glioblastoma, and pancreatic carcinoma. Further benefits of combinations with cannabinoids have also been reported for chemotherapy-induced nausea and vomiting, loss of appetite (dronabinol), chemotherapy-induced peripheral neuropathic pain and anxiety (cannabidiol). In addition, phytocannabinoids, in particular cannabidiol, may play a role in the protection of organs such as heart, lung or kidney against chemotherapy-induced toxicity. Although results are promising, much more research is needed to determine whether positive experiences of adjuvant cannabinoids outweigh eventual risks.

Background: Surgical complications are devastating both for patients and treating surgeons. When these complications occur after bariatric procedures, due to specific characteristics of this population, management, although multidisciplinary should always be led by a surgical team. Methods: We present major complications treated at our general surgery service over a seven -year period. Case series: we present 5 cases that were treated at our service after a bariatric procedure was performed. Two patients were operated at another country and one of them at another service. Three of patients showed perforation and leak related complications. One patient died due to refeeding syndrome complications after revisional surgery. Conclusions: Optimal preoperative evaluations and surgical planning are mandatory for any type of surgery including bariatric procedures, attempting to adequate and well-established surgical techniques extensively described in medical literature is associated with better outcomes. Also is our understanding that easy channels of communication between patients and treating surgeons could avoid delay in detecting and treating life-threatening conditions.

Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods and Results: 91 consecutive ATTR-CM patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU)=42] prior to, and insurance [n(IA)=49] after regulatory approval. Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p= 0.92) was similar between groups. Timely access (after tafamidis approval) reduced time-from-first-presentation-to-diagnosis from median 6.2 (IQR: 1.3-28.9) to 2.4 (0.7-21.7) months, and from-first-presentation-to-therapy from 24.4 (10.7-46.8) to 11.8 (6.4-32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S’-velocity 10.0±2.2 to 9.2±2.2cm/s; p=0.018; TAPSE 17.3±4.7 to 15.7±3.9mm, p=0.008), it remained unchanged in IA patients (S’-velocity 9.6±2.6 to 9.4±2.3cm/s; p=0.83; TAPSE 15.6±4.2 to 16.3±3.1mm, p=0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction of annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p<0.001) and improved MACE-free survival (HR=0.51; 95%CI: 0.26-1.00; p=0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR=0.424; 95%CI:0.22-0.81; p=0.004), and reduced HFH (HR=0.40; 95%CI:0.19-0.81); p=0.011) and all-cause mortality (HR=0.29; 95%CI:0.11-0.74); p=0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events.

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth; autoimmune diseases with circulating antibodies are often clinically expressed transiently in newborns due to the crossover of the specific IgG through the placenta during pregnancy. The offspring can inherit maternal genetic anomalies, but clinical expression usually becomes patent later in life. If prenatal medical history is not available or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. In this article, we present three cases of pregnant women, without any known pathology before or during pregnancy, who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The neonates’ complications were considered initially as consequences of prematurity or infection, but later investigations revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. In all cases, mothers were asymptomatic and unaware of their subclinical disease. Preemies’ diagnosis has contributed to the identification of their mothers’ pathology and adequate treatment was prescribed with favourable short- and long-term outcomes. In one of the cases (myasthenia gravis) both mother and child had associated infectious diseases in the perinatal period that complicated the clinical picture and created problems of diagnosis. This article intends to emphasize the paramount importance of prenatal care, for both mother and newborn. Repeated medical visits and investigations throughout the pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiate among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of mother towards the infant, proving that inter-speciality collaboration can work bi-directionally.

Background: We investigated the significance of the para-aortic node (PALN) and other regional node metastases (RLN), reflecting malignant histological findings or poor patient prognosis, in patients with biliary duct cancers (BDC) and pancreatic carcinomas (PC) who underwent radical resections at two institutes. Methods: Conventional clinicopathological factors, including metastasis to the PALN and RLN, and surgical outcomes or long-term prognosis in 181 PC and 116 BDC patients between 1994 and 2022 were examined. Results: In patients with PC, cancer metastasis was observed in the RLN and PALN in 54% and 9% of patients, respectively. In patients with BDC, cancer metastasis was observed in the RLN and PALN in 39% and 9% of patients, respectively. Disease-free survival (DFS) and overall survival (OS) in patients with BDC and PALN metastasis were significantly lower than those without PALN metastasis; however, several patients survived over three years. Multivariate analysis revealed that, in patients with BDC, PALN metastasis was an independently related factor of OS, and RLN was an independently related factor for DFS, respectively (p

The present study aimed to undertake a detailed investigation of pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in smart city Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis on the basis of history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded an increase in incidences among dogs less than one year of age (41%), males (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), summer months (55%) and dogs housed on pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their life. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin with an increase in the levels of globulin, AST, ALT, BUN, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Pro-teinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus.

Background: The new therapeutic modality incorporating countermeasure against the most plausible environmental factor in inflammatory bowel disease, i.e., a plant-based diet, showed far better outcomes than current standards in inflammatory bowel disease. Infliximab is widely used for induction and subsequent scheduled maintenance therapy in patients with inflammatory bowel disease. However, the efficacy of infliximab diminishes over time. Objectives: To investigate the durability of scheduled infliximab maintenance therapy incorporating plant-based diet in inflammatory bowel disease. Methods: This was a prospective single-group trial at tertiary hospitals. Infliximab maintenance therapy was indicated in patients with severe or unresponsive to conventional therapy. Infliximab (5 mg/kg body weight) was infused every 8 weeks on an inpatient basis, and plant-based diet, a lacto-ovo-vegetarian diet, was served three or four times during hospitalization. Durability was assessed using the Kaplan-Meier method. Results: Twenty-four patients (16 with Crohn’s disease, eight with ulcerative colitis) were included: median age 27.5 years old, disease duration 53.5 months, and concomitant use of immunosuppressant 21%. Intensification of infliximab was employed in 46% of patients. There was no significant difference in durability rates between Crohn’s disease and ulcerative colitis. Durability rates were 87% at both 5 and 10 years. Plant-based diet score in the median follow-up period of 9.3 years, which indicates adherence to the plant-based diet, was significantly higher than the baseline score. Conclusions: Infliximab maintenance therapy incorporating plant-based diet yielded a high durability rate of 87% at 5 years in patients with Inflammatory bowel disease.

Major depressive disorder (MDD) is a prevalent mental health condition with substantial social and economic consequences. This study focuses on the interplay between genetic and environmen-tal factors in MDD, with particular emphasis on epigenetic mechanisms such as stochastic epige-netic mutations (SEMs), epigenetic age acceleration, and epigenetic drift. We conducted a meta-analysis of DNA methylation patterns across six datasets (n=1125 MDD cases, 398 controls in whole blood; n=95 MDD cases, 96 controls in brain tissues) from the Gene Expression Omnibus. The analysis did not reveal significant global methylation differences between MDD cases and controls. However, a brain-specific probe (cg25801113) near the SHF gene consistently exhibited hypomethylation, suggesting its potential relevance to MDD. SEMs were assessed, revealing a dis-tinct burden at the gene level in MDD cases, though no significant findings emerged for epigenetic age acceleration, indicating it may not play a central role in MDD. The study also identified rare epivariations in specific genes unique to MDD cases. In blood tissue, 51 genes were associated with these unique epivariations, while 1 gene was highlighted in the brain tissue. These results un-derscore the importance of exploring rare epivariations in understanding the molecular mecha-nisms underlying MDD and offer potential targets for further investigation.

Canine parvovirus (CPV) infection is a widespread ailment among young dogs globally, characterized by high morbidity, mortality, and significant infectivity. Due to its grim prognosis, it is often likened to canine "cancer" with a medium-term mortality rate of 46.43% and late-stage mortality reaching up to 100%.Current treatment modalities primarily encompass fluid therapy, antiemetics, antimicrobial medications, pain relievers, and enteral nutrition. However, the absence of specific internationally recognized medications necessitates substantial care expenses. This review aims to elucidate recent advancements in pharmacological interventions for mitigating CPV infection symptoms, underscoring the potential of novel pharmaceutical technologies in veterinary medicine to enhance clinical outcomes for afflicted animals and their caregivers，lay a theoretical foundation for the development of specific drugs.

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors, metastatic sites, and assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Introduction: Peripheral neuropathies are very common and occur due to multiple causes including diabetes, tuberculosis, vasculitis, thyroid disorders, immune mediated diseases, vitamin B12 deficiency and drugs. Drug induced peripheral neuropathy (DIPN) is potentially irreversible, resulting in sensory deficits and paraesthesia. DIPN due to anti-tubercular drugs is common and can be implicated on linezolid, cycloserine and isoniazid.Case: 40-year-old female, diabetic with MDR-TB presented with severe, sharp, burning pain in her lower limbs. The patient was on all longer acting ATT drug regimen and was suspected with drug induced peripheral neuropathy. Conclusion: Linezolid, is used in treatment of tuberculosis and one of the major side effects includes peripheral neuropathy which is usually quite severe, presenting predominantly with sensory symptoms. Cessation of linezolid and neuropathic pain medications reduced the pain of patient from VCPS 8-10 to 1-2. Treatment of DIPN can be challenging as adverse drug reactions while treating tuberculosis should be kept in mind. It also warrants earliest treatment by identification of the drug in disguise and timely discontinuation of the drug.

Background: Malnutrition screening in hospitalized children is essential, and the STAMP is a val-idated tool for this purpose. The study aimed to modify STAMP for a Saudi context and assess the sensitivity and specificity of both the original and modified tools. Method: A cross-sectional study was conducted among 307 hospitalized children, where both the original and Saudi-modified STAMP were applied. Anthropometric measurements were also recorded, and statistical analysis was used to assess the tools' validity. Results: The Saudi-modified STAMP identified a higher percentage of children at high risk of malnutrition compared to the original STAMP (91.6% vs. 62.9%). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and agreement of the Saudi-modified STAMP compared to the original were 94.3%, 13.2%, 64.8%, 57.7%, 0.654, and 0.089, respectively. Conclusion: The Saudi-modified STAMP showed excellent sensitivity and varied negative predictive value, indicating its potential effectiveness in screening for malnutrition among hospitalized children compared to the original STAMP and using an-thropometric measurements as references.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by progressive motor and non-motor symptoms. Traditional treatments primarily manage symptoms rather than address the disease's root causes, highlighting the need for novel therapeutic approaches. Natural phytochemicals, particularly phenolic compounds, have shown potential due to their neuroprotective effects. Antiaris africana is commonly used in traditional African medicines to treat several illnesses including neurodegenerative disorders. However, its neuroprotective mechanism remains elusive. This study aimed to employ network pharmacology-based prediction to identify key targets and pathways through which A. africana exerts its effects on PD. Targets associated with Parkinsonism were identified and analyzed for interaction with compounds from A. africana. Protein-protein interaction (PPI) networks were constructed, and key hub genes were identified using Cytoscape. Functional enrichment analysis highlighted significant pathways involved in PD. Molecular docking was performed to evaluate the binding affinities of the compounds to PD-related targets. Our results reveal that compounds such as caffeic acid, chlorogenic acid, catechin, ellagic acid, epigallocatechin, gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and rutin interact with key proteins implicated in PD, including APP, EGFR, CASP3, ESR1, AKT1, and MAPK8. Notably, rutin exhibited strong binding affinity for EGFR, and chlorogenic acid showed potential in modulating the APP pathway. These findings suggest that phenolic compounds in A. africana may exert neuroprotective effects through multiple molecular mechanisms, offering potential therapeutic strategies for PD. This study underscores the importance of integrating molecular docking and network pharmacology to elucidate the therapeutic potential of natural compounds in complex diseases like Parkinson's disease

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

A Clinical Prognostic Index (CPI) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child-Pugh Score (CPS) (p=0.002), serum albumin (p=0.039) and presence of extrahepatic disease (p=0.012) were significant predictors of early death on multivariable analysis and were included in the CPI (total score 0 to 5). Median survival was 23.8, 9.1, 4.5 and 2.6 months for patients with 0, 1-2, 3 and 4-5 points, respectively. In the HCC dataset, CPS (p&lt;0.001) and gross tumor volume (p=0.013) were predictive of early death. In the metastatic dataset, serum albumin (p&lt;0.001) and primary disease site (p=0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, 0.80 respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.

The current study investigated the neuroprotective effects of rutin hydrate (RH) in an Alzheimer’s disease (AD)-like learning and memory impairments rat model. Since AD is an age-related degenerative brain disorder characterized by a progressive worsening in cognitive function and memory, RH may be a potential drug for the treatment of AD-like memory loss, and this work is aimed to evaluate whether RH has neuroprotective effects in memory deficits induced by scopolamine (SCO). In our study, RH demonstrated beneficial effects as a neuroprotector in the brain and improved learning, memory, and synaptic plasticity in a rat. Rats were administered RH (100 mg/kg) and SCO (1.5mg/kg), and performed behavioral tests such as Morris water navigation test, Y-maze test, and passive avoidance test to evaluate the ability of learning and memory. In accordance with these findings, RH behaviorally attenuated SCO-induced shortening of step-through latency in the PA test, increased the percent of alternation in the Y-maze, and increased the time spent in the target zone in the MWN. Moreover, the neuroprotective effect of RH on learning and memory was investigated through the long-term potential on organotypic hippocampal slice cultures. RH increased the total activity of field excitatory postsynaptic potential (fEPSP) following theta burst stimulation and attenuated SCO-induced blockade of fEPSP. This approach could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD. SCO treatment decreased the levels of BDNF/TrkB/ERK/CREB/Bcl2 and increased the Bax protein level in rat hippocampus. RH ameliorated the expression of these proteins by attenuating SCO-induced up or downregulation in the hippocampus. Based on these findings, the results highlight the molecular and cellular mechanisms through which RH is proposed to exert its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders.

BACKGROUNDBrain death in most countries requires supplementation of clinical diagnosis with ancillary tests such as EEG, cerebral angiography, or radionuclide imaging. Transcranial Doppler sonography (TCD) is one such non-invasive, real-time, bedside test that sidesteps the logistic hurdles associated with some of the tests mentioned above. OBJECTIVETo substantiate the utility of TCD as a reliable ancillary test to diagnose brain death with more certainty and reliability.METHODOLOGYMeta-analysis was performed with the use of statistical and analytical software to obtain data and estimate Sensitivity, Specificity, positive predictive value(PPV), diagnostic odds ratio (DOR), and relative risk with 95 percent confidence intervals to examine critical clinical outcomes(CI).RESULTSInitial dataset of 31 studies of which 16 studies, with a total of 1317 patients was used considering the reliability of the data. The pooled sensitivity and specificity of TCD were 0.91 (95% CI range: 0.89-0.93) and 0.99 (95% CI range: 0.97-0.99) respectively. The summary of the ROC curve showed an area under the curve of 0.9750 and an overall diagnostic odds ratio (DOR) was 323.26 with the Younden Index being 0.9. Summary of Fagan plot analysis of all studies showed a prior probability of 63% (1.7); a Positive Likelihood Ratio of 56, a post-test probability of 99% (96); a Negative likelihood ratio of 0.09, and a post-test probability of 13% (0.2).CONCLUSIONOur study emphasizes that clinical diagnosis is sufficiently adequate to declare a patient cerebrally dead. However, for ambiguous cases, TCD is a practical and fast method showing close correspondence to angiography and is superior to other bedside tests like EEG.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C&gt;T, not yet reported, and c.838C&gt;T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Introduction. Pituitary adenomas constitute the second most frequent neoplasm of the central nervous system and despite the often-indolent behavior of these tumors, patients affected by pituitary adenomas show higher morbidity and mortality rates. Surgery offers good results in terms of symptoms and disease control: the aim of this study was to evaluate how the neurosurgical treatment for the removal of a pituitary adenoma through a trans-sphenoidal approach can modify the patient's hormonal panel and its influence on the overall clinical outcome. Materials and methods. Between January 2018 and September 2021, 69 patients who underwent surgery for pituitary adenoma operated via the trans-sphenoidal approach were enrolled in the study. Clinical and laboratory data included pre- and post-operative hormonal status, assessed before surgery and within the following 48 hours. Results. Remission of endocrinological values outside physiological ranges and resolution of symptoms were considered as favorable outcome. Surgical treatment was statistically significant as factor to normalize the following hormones: ACTH (p = 0.014), TSH (p &lt; 0.0001), fT3 (p &lt; 0.0001), fT4 (p &lt; 0.0001), FSH (p &lt; 0.0001), LH (p = 0.001), testosterone (p = 0.001), prolactin (p &lt; 0.0001), confirming previous literature findings. Furthermore, the association between surgery and resolution of pre-operative visual disturbances was statistically significant (p &lt; 0.0001). Overall, 59% of patients experienced complete or partial remission of the pre-operative endocrinological abnormalities and in 76% their initial symptoms improved. Conclusions. This study confirms, in our experience, the excellent risk-benefit ratio supporting the use of trans-sphenoidal endoscopic surgery as an effective therapeutic approach for the removal of pituitary adenomas with improvement in the post-operative hormonal and clinical status.

Background: Good reduction of the articular surface and restoration of the congruent joint space are crucial for promoting positive outcomes in ankle fracture treatment. A good understanding of the mechanism of ankle fractures is indispensable to achieve these goals. Unfortunately, until now, the mechanism has still not been fully elucidated, particularly regarding the posterior malleolar fractures (PMFs). This study aims to provide insight into the mechanism of PMFs, thereby grasping the key to proceeding with PMFs reduction and fixation. Methods: An FE model of a normal ankle in tiptoe posture with 9 collateral ligaments was constructed from CT images. On the model, lateral malleolar fractures were made below, through, and above the syndesmosis; the medial malleolus was broken at its base; and ligaments were suppressed to simulate ligament rupture. A force of 1000 Newtons was applied on the talus head along talus axis. The posterior malleolar fragment (PMF) displacement, whether the talus impacts the posterior malleolus, and the initial mechanism displacing the PMF, were recorded. Results: A total of 15 tests were conducted. The tests, 'all collateral ligaments rupture', 'LMFB', 'LMFC+AITFL rupture', 'ATFL+CFL+PTFL rupture', 'ATTL+PTTL+TCL rupture', 'MMF', and 'MMF+AITFL rupture', presented significant PMF displacement. In tests 'MMF' and 'ATTL+PTTL+TCL rupture', the talus hit the medial edge of the PMF; but in tests 'ATFL+CFL+PTFL rupture' and 'all collateral ligaments rupture', the talus impacted the center part of the PMF. Except tests 'all collateral ligaments rupture' and 'ATFL+CFL+PTFL rupture', where PMF displacement was initially caused by talus impact, the other tests demonstrated PMF displaced following PITFL drag. Conclusions: This research discovered that rotation is the initial and major mechanism causing PMF displacement. The subsequent impact of the talus on the posterior malleolus may be the reason for large/blocky PMF. The talus impacting the posterior malleolus is always combined with talus rotation. Without the medial ankle structure being broken, big/blocky PMF may not occur. These findings suggest that, in clinical practice, reconstructing both the medial and lateral ankle structures is critical for achieving ankle stability, and this procedure even takes precedence over posterior malleolar fracture fixation itself.

Background: Lower limb length discrepancy (LLD) in children and adolescents, often due to congenital or acquired conditions, is treated to achieve limb equality and alignment, optimizing function and minimizing cosmetic concerns for an active adulthood. This study evaluated the Health-Related Quality of Life (HRQoL) and physical functioning of adults who underwent unilateral limb lengthening with circular external fixators (EFs) in childhood. Methods: Fifty patients treated at a median age of 14.9 years completed the Short Form 36 (SF-36) and Stanmore Limb Reconstruction Score (SLRS) questionnaires in adulthood, with a median follow-up of 8.9 years. Results: Among the 50 patients, 38 underwent a single limb lengthening (21 tibia, 12 femur, 5 both), while 12 required multiple cycles. The median residual LLD was 0.4 cm, with 12 patients (24%) having over 2 cm. Complications occurred in 67% of procedures, mainly due to prolonged healing. Physical and mental health scores were significantly lower than normative data. The mean Physical Component Summary was 52.2 ± 7.2 (p = 0.20). The mean Mental Component Summary was 43.9 ± 8.6 (p = 0.001), notably lower in congenital LLD cases. Many SLRS items (Pain, Social, Physical Function, Work, and Emotions) strongly correlated with SF-36 items. Conclusions: The study highlights the challenges in treating LLD, emphasizing the significant mental health impact, especially in congenital cases, and the necessity for comprehensive long-term care strategies. These findings suggest that future therapeutic strategies should focus on both physical and psychological outcomes to improve overall recovery in LLD treatment.

Reactive oxygen species (ROS) are produced during cellular metabolism and in response to environmental stress. While low levels of ROS play essential physiological roles, excess ROS can damage cellular components, leading to cell death or transformation. ROS can also regulate protein interactions in cancer cells, thereby affecting processes such as cell growth, migration, and angiogenesis. Dysregulated interactions occur via various mechanisms, including amino acid modifications, conformational changes, and alterations in complex stability. Understanding ROS-mediated changes in protein interactions is crucial for targeted cancer therapies. In this review, we examine the role that ROS mechanisms in regulating pathways through protein-protein interactions.

Background: The chin tuck maneuver has been suggested to increase suprahyoid muscle activation, but a method to measure the strength of the chin tuck maneuver has not been established. We developed a method to measure the strength of the chin tuck maneuver (chin tuck strength) and examined the reliability and validity of chin tuck strength measurement in community-dwelling older adults. Subjects and Methods: The participants were 233 older adults aged ≥65 years without dysphagia or physical disability. Chin tuck strength was measured twice consecutively using the developed device, and reproducibility was analyzed using intraclass correlation coefficients (ICCs). In addition, maximum tongue pressure, oral diadochokinesis, grip strength, knee extension strength, and the timed up and go test (TUGT) were measured as indices of swallowing-related muscle function and appendicular muscle function. The associations of chin tuck strength with swallowing-related muscle function and appendicular muscle function were analyzed statistically. Results: The ICCs for chin tuck strength were 0.82 (95% confidence interval [CI]: 0.73-0.88) in males and 0.87 (95%CI: 0.70-0.93) in females. Chin tuck strength was significantly associated with maximum tongue pressure, grip strength, knee extension strength, and TUGT. Conclusions: This study suggests that chin tuck strength is a reliable and valid assessment of swallowing-related muscle strength.

The current research is focused on the discovery and optimization of an effective cosmetic carrier of alpha-bisabolol as a first step in the development of a cosmetic product with cleansing and antimicrobial action for facial skin hygiene. A micellar solution of Poloxamer 407 was selected as a cosmetic base because of the good washing ability, easy application, and high tolerability of this polymeric surfactant. The solubilization capacity of a 5% micellar solution with respect to α-bisabolol was investigated by applying varying solubilization techniques and increasing concentrations of the oily active substance. The test samples were subjected to an accelerated physical stability test, viscosimetry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), foamability test, and antimicrobial screening. In the course of research, the advantage of the film-hydration method over direct solubilization was demonstrated by the narrower size distribution and smaller hydrodynamic size of the micellar nano-carriers (ranging from 29.02-116.5 nm) and the respective higher physical stability of the dispersions. The optimized composition was found to possess a suitable for application on large skin areas viscosity in the temperature range from 20°C to 40°C (3.4-2.3 mPa.s). Preservation of the washing capacity of the micellar solution in the presence of solubilized α-bisabolol was established. The active composition demonstrated inhibitory activity against Staphylococcus aureus and Escherichia coli, and fungicidal activity against Candida albicans. The study concludes that the optimal concentration of α-bisabolol to be solubilized in a 5% Poloxamer 407 micellar solution by the film-hydration technique is 1% considering the desirable physical endurance and antimicrobial activity.

Thoracic aortic and arterial aneurysms are cardiovascular conditions associated with life-threatening endpoints including dissection and rupture. The genetic basis underlying the development these disease states is an evolving field, and the reporting of variants associated with aneurysms in patients are essential for advancing screening and diagnostic tools. Among all patients in our program who underwent clinical genetic screening (N=145) for arterial aneurysm and dissection disorders, we identified three patients with single nucleotide variants in the TNXB gene. This gene has known roles in collagen fibrillogenesis and classic Ehlers Danlos Syndrome. This is one of the first reports to associate this gene with aortopathy/arteriopathy and advances the literature relating extracellular matrix genes to arterial aneurysm development.

Introduction: The Fontan procedure, a palliative surgery for univentricular heart physiology, of-ten reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Methods: Fontan patients aged 8-30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions, with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results: The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and per cent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min, but did not reach statistical significance (p = 0.05). Most haemodynamic and ventila-tory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains (p < 0.001). High adherence (85-93%), no adverse events, and reduced NT-proBNP levels supported the program's safety. Conclusion: This study's findings have im-portant implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ven-tricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained ben-efits.

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. Back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA recovered at 20 weeks. SDH staining was lower in CKD than control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time.

Background: Parity and vaginal delivery may contribute to female urinary incontinence prev-alence. The aim of this study was to evaluate the impact of parity and type of child delivery on pelvic floor muscle strength (PFMS). Material and Methods: 140 healthy women were prospectively evaluated and distributed into 4 groups: G1 (n=34) 30-40 years old; G2 (n=38) 41-50; G3 (n=35) 51-60 and G4 (n=33) over 60. De-mographic data, and body mass index (BMI) were obtained using a clinical questionnaire. Sub-jective PFMS assessments were performed using transvaginal digital palpation (TDP), and ob-jective evaluation was obtained using a portable perineometer. Results: BMI was significantly higher in G4 compared to G1. There was a positive linear rela-tionship between age and BMI. The number of pregnancies was higher in G4 compared to G2 and vaginal delivery was more frequent in G4 compared to G1 and G3. There was no statistical correlation among different groups in PFMS assessed either by TDP and perineometer. Like-wise, we did not observe any negative linear relationship between PFMS and parity or number of vaginal deliveries. Conclusion: Our data demonstrates that both the number of pregnancies and of vaginal deliv-eries had no impact on PFMS in continent women.

Background/Objectives: The use of post-operative drains in gynaecologic oncology procedures is controversial with evidence both supporting and questioning their efficacy. Proponents argue that such drains help detect complications early, reduce abscess formation, and also alleviate post-operative pain. On the other hand, drains are associated with increased risks of incisional hernia, infection, prolonged hospitalization, and postoperative pain. Methods: We conducted a research in the PubMed database and supplemented it with a manual search to retrieve addition-al papers eligible for inclusion. Results: Their use is not always found to improve outcomes, no-tably in surgeries such as a radical hysterectomy with pelvic lymphadenectomy, where they may actually enhance lymphocyst formation and other complications. In cytoreductive surgery for ovarian cancer, negative pressure wound therapy showed some potential benefits, but evidence remained inconclusive due to limited studies. The international guidelines presented in this re-view, suggest avoiding the routine use of drains and promote early removal when their use is necessary. Conclusions: This review aims to present an update on the current knowledge re-garding the role of drainage in gynaecologic oncology and while further good-quality research is required, particularly in high-risk surgical procedures, numerous prospective trials have exten-sively addressed the topic, trying to provide clear suggestions.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

Histamine (HA), a biogenic monoamine, exerts its pleiotropic effects through four H1R–H4R histamine receptors, which are also expressed in brain tissue. Together with the projections of HA-producing neurons located within the tuberomammillary nucleus (TMN), which innervate most areas of the brain, they constitute the histaminergic system. Thus, while remaining a mediator of the inflammatory reaction and immune system function, HA also acts as a neurotransmitter and a modulator of other neurotransmitter systems in the central nervous system (CNS). Although the detailed causes are still not fully understood, neuroinflammation seems to play a crucial role in the etiopathogenesis of both neurodevelopmental and neurodegenerative (neuropsychiatric) diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD) and Parkinson's disease (PD). Given the increasing prevalence/diagnosis of these disorders and their socioeconomic impact, the need to develop effective forms of therapy has focused researchers' attention on the brain's histaminergic activity and other related signaling pathways. This review presents the current state of knowledge concerning the involvement of HA and the histaminergic system within the CNS in the development of neurodevelopmental and neurodegenerative disorders.

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. In the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, inducing antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS by autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

Background/Objectives: RAS is associated with coronary artery disease (CAD), exacerbation of arterial hypertension and progression to heart failure, but remains frequently unrecognised in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data of patients undergoing CAG due to suspected or stable CAD that received a bilateral renal artery angiography; Results: A total of 31 studies with 31,689 patients were included (mean age 63.2±8.7 years, 20.9% were female). Overall, 13.4% (95%CI 10.5-16.7%) of patients undergoing coronary angiography had significant RAS, with 6.5% (95% CI 4.5-8.9%) and 3.7% (95%CI 2.5-5.2%) having severe and bilateral RAS. The mean weighted proportion of patients with 3-vessel coronary disease (3VD) was 25.1 (95%CI 19.6-30.9%) while 4.2% (95%CI 2.6-6.2%) had leftmain (LM) coronary disease. Patients with RAS compared to those without RAS were significantly older (mean difference - MD 4.2 years, (95%CI 3.8-4.6). The relative risk of RAS was greater for the female sex (risk ratio, 95%CI; RR 1.3, 1.03-1.57), presence of diabetes (RR 1.2, 1.10-1.36), arterial hypertension (RR 1.3, 1.21-1.46), dyslipidemia (RR 1.1, 1.06-1.14), peripheral artery disease-PAD (RR 2.1, 1.40-3.16), chronic kidney disease-CKD (RR 2.6, 2.04-3.37), 3VD (RR 1.6, 1.30-1.87), and LM disease (RR 1.8, 1.28-2.47). Smoking had a neutral effect on the risk of RAS occurrence (RR 1.0, 0.94-1.06); Conclusions: RAS is common in patients undergoing coronary angiography. CKD, PAD, older age, and severe CAD were among the strongest predictors for the presence of significant RAS.

Background: Multisensory integration (MSI) avoids cognitive overload, and the traditional all-or-nothing perspective for dysfunctional MSI in schizophrenia has been increasingly challenged. This study aimed to systematically review and meta-analyze extant evidence on audiovisual MSI in schizophrenia. Methods: We searched Web of Science, PubMed, PsycINFO and PsycARTICLES databases from inception until April 16^th, 2024. Studies using appropriate audiovisual integration tasks to compare either behavioral or neural responses between schizophrenia individuals and healthy controls were included. Primary outcome measures included between-group differences (Hedge’s g) and symptomatic correlations (Fisher’s z) in three components of audiovisual integration tasks, including audiovisual processing, adaptation and integration. The multilevel random-effects models were used to address statistical dependency. Results: In total, 209 between-group and 116 correlational effect sizes were synthesized from 46 studies, representing 1,108 non-overlapped schizophrenia participants and 1,084 healthy controls. The overall dysfunctional audiovisual MSI in schizophrenia (g = -0.50, [95% CI, -0.64 to -0.37]) was primarily ascribed to the impaired audiovisual processing (g = -0.53, [95% CI, -0.71 to -0.35]) and adaptation (g = -0.71, [95% CI, -0.99 to -0.42]), rather than integration itself (g = -0.23, [95% CI, -0.56 to 0.11]). Pooled correlational effect size was extremely small (z = 0.16, [95% CI, 0.03 to 0.30]). Conclusions: Individuals with schizophrenia show dysfunctional multisensory processing and adaptation, but preserve a less impaired multisensory integration ability. Our findings provide implications for clinical interventions, as the relatively preserved audiovisual integration ability may serve as a possible avenue for cognitive training programs.

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods:  Twenty-three children (16 male and 7 female, mean age 5.9 years [range 1.3 to 12.2 years]) with ALL, treated at the Division of Hematology, Oncology and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from January 1, 2015 to December 31, 2020, were included in the study Results: One hundred and four infectious episodes (IEs) were reported (average 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%) and 10 mixed isolates (9.6%), while in 37 IEs (35.6%) pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. Modification of the first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, identification of risk factors, rapid empirical use of antibiotics in febrile neutropenia, and timely modification of antimicrobial therapy play a key role in reducing infection-related morbidity and mortality in children with ALL.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

According to current knowledge, although the beneficial effects of regular exercise training are well recognized, there are conflicting data regarding its relation with the occurrence of atrial fibrillation (AF) in competitive athletes. The aim of this literature review was to demonstrate a comprehensive report of incidence, pathophysiology and management of AF in elite athletes. The frequency of AF to be 2 to 10 times greater in high intensity endurance athletes compared to sedentary individuals. A U-shaped relationship between male elite athletes and AF has been observed, while the type and the dose of physical activity seems to play a major role in AF development. Male gender, increasing age, endurance sports, and time of training are associated with AF, thereby confirming a likely association between athleticism and AF. Pathophysiology of AF still remains unclear but, there are suggested theories that include complex mechanisms such as alterations of autonomic tone, left atrial enlargement and fibrosis, electrical remodeling, and increased inflammation. Elite athletes with AF require a comprehensive clinical evaluation and risk factor optimization, similar to that for nonathletes. Although anticoagulation and rate or rhythm control are corner stones for AF management, however, there are still no specific guidelines for elite athletes.

Background: Three-dimensional gait analysis plays a crucial role in the rehabilitation assessment of post-stroke hemiplegic patients. However, the data generated from such analysis is often complex and difficult to interpret in clinical practice, requiring extensive time and complicated procedures. The Gait Deviation Index (GDI) serves as a simplified metric for quantifying the severity of pathological gait. Although isokinetic dynamometry is widely employed in muscle function assessment and rehabilitation, its application in gait analysis remains underexplored. Objective: This study aims to investigate the use of isokinetic muscle strength data obtained from the Biodex system, combined with machine learning techniques, to predict the GDI in hemiplegic patients. Methods: A cohort of 150 post-stroke hemiplegic patients was evaluated. The peak torque, peak torque/body weight, maximum work of repeated actions, coefficient of variation, average power, total work, acceleration time, deceleration time, range of motion, and average peak torque for both flexor and extensor muscles on the affected side were measured at three angular velocities (60°/s, 90°/s, and 120°/s) using the Biodex System 4 Pro. GDI was calculated using data from a Vicon three-dimensional motion capture system. The study employed four machine learning models—Lasso regression, random forest (RF), support vector regression (SVR), and BP neural networks—to model and validate the data. Model performance was evaluated using mean squared error (MSE), the coefficient of determination (R²), and mean absolute error (MAE). SHapley Additive exPlanations (SHAP) analysis was used to enhance model interpretability. Results: The RF model outperformed others in predicting GDI, with an MSE of 16.18, an R² of 0.89, and an MAE of 2.99. In contrast, the Lasso regression model yielded an MSE of 22.29, an R² of 0.85, and an MAE of 3.71. The SVR model had an MSE of 31.58, an R² of 0.82, and an MAE of 7.68, while the BP neural network exhibited the poorest performance with an MSE of 50.38, an R² of 0.79, and an MAE of 9.59. SHAP analysis identified the maximum work of repeated actions of the extensor muscles at 60°/s and 120°/s as the most critical features for predicting GDI, underscoring the importance of muscle strength metrics at varying speeds in rehabilitation assessments. Conclusion: This study highlights the potential of machine learning techniques in analyzing complex clinical data. The developed GDI prediction model, based on isokinetic dynamometry data, offers a novel, streamlined, and effective tool for assessing rehabilitation progress in post-stroke hemiplegic patients, with promising implications for broader clinical application.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

Traditional Chinese medicine requires decoction and consumption, which is time-consuming and labor-intensive. Scientific Chinese medicine (SCM), on the other hand, uses concentrated granules that can be taken with hot water, making it widely welcomed. With the widespread adoption of SCM, the packaging technology has started to receive attention. Whether it is manpower allocation, operation time, or the uniformity and residue of the medicine powder, these factors can become bottlenecks in the process. A traditional SCM pharmacy machine is purely mechanically hardwired. This paper proposes SCMtalk, an Internet of Things (IoT)-based SCM mechanism designed to enhance the efficiency and accuracy of SCM medicine packets generation. We show how SCMtalk develops IoT hardware and software modules for medicine selection, mixing, dispensing, packaging, and cleaning. We also explain how the mechanical IoT hardware is integrated with the corresponding software module to become an individual IoT device. These IoT devices can be transparently replaced, allowing us to easily upgrade the individual components of the SCM packet generation through the IoT concept. Finally, we address quality control issues by leveraging IoT. One contribution of this paper is to introduce an interesting SCM application to IoT experts and to demonstrate how we collaborated with pharmacists and mechanical experts to use a powerful IoT platform to create a smart pharmacy.

Venous and arterial thromboembolism (VTE/ATE) often coexist with onco-hematologic diagnosis. The study aimed to assess the time relationship between the diagnosis of VTE/ATE and blood cancers. The second aim was to identify VTE/ATE risk factors related to the type of hematology disease and cardiac history. 1283 patients underwent cardio-oncology evaluation at the Institute of Hematology and Transfusion Medicine in Warsaw from March 2021 through March 2023 (2 years), and 101 (7.8%) cases were identified with VTE/ATE. ATE compared to VTE significantly more often occurred before the diagnosis and treatment of hematologic malignancy: 33/47 (70.2%) vs. 15/54 (27.8%), p<0.0001. The risk of a VTE episode is exceptionally high in the first months after the diagnosis of an onco-hematological disease. The higher frequency of VTE was associated with acute myeloid leukemia (17 cases/270 patients/6.30%/p = 0.055), acute lymphocytic leukemia (7 cases/76 patients/9.21%/p = 0.025) and chronic myeloproliferative disease (7 cases/48 patients/14.58%/p=0.0003). Only the risk of VTE was significantly increased before (OR=6.79; 95%CI: 1.85-24.95; p=0.004) and after diagnosis of myeloproliferative disease (OR=3.12; 95%CI: 1.06-9.16; p=0.04). ATEs occur more often than VTE before a diagnosis of blood cancer. The risk of VTE is exceptionally high before and after diagnosis of chronic myeloproliferative disease.

Background/Objectives: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection se-verity. However, this topic has not been studied in detail. We therefore investigated mortality risk post-acute COVID-19 in the CRIT-COV-U cohort. Methods: We could retrieve survival data from 651 patients and also assess the association between urinary peptides and future death. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched non-infected controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomics datasets. Results: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than non-infected controls, particularly evident in younger individuals (&lt;65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease, but also beyond, for a period of about one year. In our study we were further able to identify 201 Urinary peptides linked to mortality, and integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. Conclusions: Our findings underscore the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. Our data also suggest that mortality should be considered as one possible symptom or conse-quence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.

Lung cancer remains the most common cancer worldwide with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means to early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis. Methods: In the course of stool testing in a large-scale testing of 2,922 patients at increased risk of CRC we were able to ascertain 112 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for p87 with anti-adenoma antibody (Adnab-9) reactivity by ELISA and western blot. Survival data were obtained where available. Results: Of 112 cancers, approximately 27.6% were squamous (SSC), 17.9% were adenocarcinoma, 8% small, 6.25% large cell and 3.57% were designated non-small cell cancer (NSCLC), 0.89% indeterminate, 0.89% lepidic spread (1), 3.57% had metastasis and in 31.25% data was unavailable. 49.1% of the lung cancer patients had fecal Adnab-9 testing. Overall, 60% had positive testing compared to 38%, which was significant (OR2.19[1/06-4.53];p=0.045). Cancers with higher lethality were less likely to test positive (approximately, 8.5% each for both small and large cell lung cancers), and higher, 56% with SCC and 25% for adenocarcinoma. 0% NSCLC). In the larger groups overall survival was worse in those testing positive: 474 testing positive versus 844 days in SCC and 54 testing positive versus 749 days in adenocarcinoma patients. Most importantly, the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer. In excluded cases where cancer in the lung was believed to be metastatic,83.3% of cancers were positive. Conclusions: At a projected real-world sensitivity of 0.60 and specificity of 0.60 and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (87.5%) and those with worse prognosis amongst the more common, favorable phenotypes thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer also detected by the test should be identified by the follow-up imaging studies and therefore would not be considered to be a major pitfall.

Sensory processing challenges are crucial yet often neglected aspects in the care of children with neurodevelopmental disorders and genetic conditions. They represent a key area of interest in neuroscience, as they significantly impact children's daily functioning and quality of life. This observational study examines the characteristics of these challenges in a group of 614 children, aged 3 to 14 years and 11 months, divided into three groups: 183 with neurodevelopmental disorders (Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, developmental delays, learning disorders), 89 with genetic conditions (22q11.2 Deletion Syndrome, Williams Syndrome, Pseudohypoparathyroidism), and 342 controls. Sensory processing was assessed using the Sensory Profile 2 (SP2). Results indicated that children with neurodevelopmental disorders and genetic conditions exhibited significant sensory processing difficulties compared to controls. The SP2 identified sensory challenges across different sensory systems, with varying configurations depending on the diagnosis. Children with neurodevelopmental disorders and genetic conditions show marked sensory processing challenges impacting daily lives and well-being. These findings highlight the importance of early identification and tailored evidence-based interventions to address these specific sensory processing issues. Further research should explore the long-term impact of these interventions in these different populations and their integration into broader therapeutic programs.

Minimum Inhibitory Concentration (MIC) measures the lowest concentration of antibiotic that inhibits in-vitro growth of microorganisms. Canine pyometra is a frequently occurring reproductive disorder where reliable antibiotics along with surgical excision of uterus predicts better prognosis. Scarce literature is available to facilitate proper antibiotic selection to avoid septicemia in clinical cases. The present study was conducted to determine sensitivity and potency of selected antibacterials based on MIC values against bacterial isolates obtained from Canine Pyometra in Kathmandu district, Nepal by Agar Dilution method. Isolates obtained from 63 intra-uterine samples after ovariohysterectomy were Enterococcus spp (n=41), Klebsiella spp. (n=7), Staphylococcus spp. (n=11) and Streptococcus spp. (n=4). Enrofloxacin and Amikacin were found highly sensitive (0% resistance) with a null hypothesis of resistance to all bacterial isolates and were significantly more potent than other antibacterials tested (p<0.05; Kruskal-Wallis test) based on lower MIC ranks. Similarly, ceftriaxone was found to be least potent and was highly resistant to Enterococcus spp. (75.61%) and completely resistant to other bacterial species tested (100%). Comparative results on sensitivity and potency in the study revealed Enrofloxacin and Amikacin to be better antibacterial of choice in pyometra innervation in in-vitro setting. Further clinical trials considering other equally important variables along with MIC should be conducted to predict actual clinical efficacy of antibacterials during therapeutic management of canine pyometra in Nepal.

Background The operator's ability in performing carotid stenting (CAS) has improved clinical outcomes. However, more than 3% of patients need to be treated again after CAS. Most of the cases requiring further intervention are affected by hyperplasia. The recommended procedure is the DEBalloon. On the other hand, the literature reports a small number of carotid neoatherosclerosis cases and is recommended to be treated using elective Micronet-covered stent. Discriminating between the two types of in-stent-restenosis ISR (hyperplasia or neoatherosclerosis) is critical for a positive outcome.Case summary We describe a case in which a patient treated with carotid stenting 8 years before, was diagnosed with ISR. Due to the development of neurological symptoms and progressive increases in Peak Systolic Velocity (PSV) eight years following carotid stenting, a DEBalloon was used in a carotid in-stent-restenosis (ISR) standard procedure. About ten minutes after the procedure, the patient developed hemiplegia consistent with the treated carotid territory. The implantation of a MicroNet-covered stent excluded the thrombus and reverted symptoms with a normal MR control at 24 h. Conclusion This case illustrates that when in-stent stenosis evolves years after the stent implantation, neoatherosclerosis should be assessed, and a MicroNet-covered stent should be considered.

The elderly population is particularly susceptible to myocardial damage caused by heat stress (HS). With the continuous increase in global temperatures, this poses an undeniable challenge to human health. This study aimed to investigate the therapeutic effect of Shikimic Acid (SA) in treating HS-induced myocardial damage through network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments. Network pharmacology analysis revealed that SA alleviates the inflammatory response in the heart muscle associated with HS by targeting 60 disease-related targets, such as TP53, TNF, and IL-6. The tumor proteoglycan, the PI3K-Akt signaling pathway, and hepatitis B were identified as the primary therapeutic pathways. Molecular docking and MD simulation results confirmed that SA can stably bind to both TNF (-6.642 kcal/mol) and IL-6 (-7.261 kcal/mol), and the complexes of Shikimic Acid-IL-6 and Shikimic Acid-TNF did not undergo significant changes within 100 ns. In addition, the in vitro experiment showed that 250 μM SA significantly increased the survival rate of HL-1 cells exposed to 43°C for 2 h by 71.1% and promoted the proliferation of HL-1 cells by 30.7%. Overall, these findings provide substantial evidence for the therapeutic potential of SA in HS-induced myocardial damage.

Objectives: The global quotient of psychological development, along with the motor skills, coordination, speech, and social behavior scores, was analyzed in children born prematurely with varying degrees of intracranial hemorrhage (grades I–IV), considering the unilaterality or bilaterality and dimensions of the left and right lateral ventricles. Materials and Methods: The study included 120 children divided into four groups based on gestational age: Group 1 (25–29 6/7 weeks), Group 2 (30–32 6/7 weeks), Group 3 (33–34 6/7 weeks), and Group 4 (35–37 weeks). The maximum dimensions of the right and left lateral ventricles were recorded via ultrasound. At 3 years of age, psychomotor development was assessed using the Brunet–Lezine scale. Statistical analysis was performed using appropriate modules in the SPSS 23.0 for Windows software package, along with Pearson’s ꭓ2 test and analysis of variance (ANOVA). Results: Differences in the global development quotient (QR) between the groups were statistically significant (p &lt; 0.01). In Group 1, a larger dimension of the left lateral ventricle was associated with a decrease in motor skills, while in Group 2, a larger dimension of the right ventricle resulted in a significant decrease in coordination. In Group 3, all observed variables—that is, motor skills, coordination, speech, and social behavior—showed minimal values with a wider right ventricle, but without statistical significance. In Group 4, a significantly lower speech score was recorded with the dilation of the left lateral ventricle. Conclusions: The sizes of the left and right lateral ventricles after the resorption of intracranial hemorrhage affect the values (scores) obtained using the Brunet–Lezine scale in children at the age of 3 years.

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients’ quality of life. The disease is caused by genetic irregularities affected by the epigenetic and environmental factors. Some of these factors may include the seasonal changes, such as solar radiation, air pollution and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis.

Background: In high-risk breast cancer patients with skin infiltration the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential standard bolus’ inadequate dose distribution due to air gaps between the bolus and the skin. In this pilot study, we introduced in clinical practice the use of a personalized 3D printed bolus filled with ultrasound transmission gel. Methods: Seven patients undergoing radiotherapy after mastectomy were selected. 3D printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and subsequently on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control was assessed. Results: Overall, for the clinical cases the percentage median difference between measured and calculated doses was -2.7% (-7.0%÷4.9%). Median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. Conclusions: Personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus’ consistency providing an accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study and further investigations are needed.

Background/Objectives: Advancements in surgical stapling devices play a crucial role in improving outcomes for bariatric procedures. This study evaluates the performance and safety of a new endoscopic stapler (EnDrive®BelugaTM) regarding perioperative results across multiple bariatric surgery types. Methods: A retrospective analysis was conducted on 112 patients who underwent bariatric procedures using the Beluga stapler at two centres in the UAE and Kenya over 6-month period (June-December 2023). Procedures included laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (LRYGB), mini gastric bypass (OAGB-MGB), and revisions. Perioperative outcomes, complications, and haemoglobin changes were assessed. Results: The cohort included 29 males and 83 females, with a mean age of 32.8 years and preoperative BMI of 41.1 kg/m². Procedures performed were 88 primary LSG, three primary LRYGB, 12 primary OAGB-MGB, and nine revision surgeries. No conversions, deaths, bleeding, or leaks occurred. Minor complications were observed in 4 patients. One patient required reoperation for intestinal obstruction. The mean hospital stay was 1.5 days. Haemoglobin levels showed minimal change from preoperative (12.8 g/dL) to postoperative day 1 (12.3 g/dL). Conclusions: The new Beluga endoscopic stapler demonstrated safe and effective performance across various bariatric procedures, with low complication rates and minimal blood loss. Its enhanced articulation capabilities may offer advantages in specific cases. Further studies are warranted to compare long-term outcomes with established stapling devices.

Objectives: Imaging exams are requested in intensive care units as a diagnostic, evaluation, and clinical monitoring method. While Chest Computed Tomography is the gold standard, Chest X-ray is the exam usually performed in routine care. Lung ultrasound has been gaining ground as it is a reliable exam performed at the bedside without exposure to radiation and at a low cost. This study aimed to evaluate the accuracy of bedside lung ultrasounds performed by pediatric intensivists as a diagnostic method. Methods: A prospective, diagnostic test-type study comparing bedside lung ultrasound performed by a pediatric intensivist with the evaluation of chest X-ray and lung ultrasound performed by a radiologist. Result: 48 patients on mechanical ventilation, aged from 1 month to 14 years, were analyzed, corresponding to 95 chest X-ray exams and 95 lung ultrasound exams. The Kappa agreement coefficients between the pediatric intensivist and the radiologist, both analyzing the lung ultrasound, were: normal report (1.0), atelectasis (1.0), pneumothorax (1.0), consolidation (0.97), pleural effusion (0.95), and pulmonary edema (0.90). Sensitivity, specificity, and accuracy of lung ultrasound were, respectively, normal report (50%; 91.8%; 82.1%), consolidation (88.3%; 57.1%; 76.8%), atelectasis (11.1%; 90.7%; 83.2%), edema (0; 70.2%; 70.5%), pneumothorax (83.3%; 94.4%; 93.7%), and pleural effusion (71.4%; 73%; 72.6%). Conclusion: The pediatric intensivist was skilled in examining and diagnosing lung injuries. Lung ultrasound showed good sensitivity, specificity, and accuracy when the pediatric intensivist performed when diagnosing consolidation, pleural effusion, and pneumothorax. Furthermore, lung ultrasound demonstrated better accuracy in evaluating pulmonary edema when compared with chest X-ray.

This study investigates the collapse of the medial longitudinal arch (MLA) as a risk factor for medial tibial stress syndrome (MTSS), hypothesizing that overuse of extrinsic foot muscles to prevent MLA collapse can lead to disability. Twenty healthy adults (39 feet) with a foot posture index score below 6 and no recent lower extremity orthopedic history participated. Ultrasonog-raphy measured foot muscle cross-sectional areas, while three-dimensional motion analysis us-ing VICON assessed foot kinematics during gait, focusing on navicular height at initial contact (ICNH) and dynamic navicular drop (DND) during the stance phase. Hierarchical cluster analy-sis based on ICNH and DND compared muscle cross-sectional areas between clusters using ANOVA or Kruskal–Wallis test. The analysis indicated that ICNH was lower in clusters 1 and 3 than in cluster 2, and DND was smaller in clusters 1 and 2 than in cluster 3. Although there was no significant difference in muscle cross-sectional area between the clusters, the flexor hallucis longus tended to be thicker in cluster 1 than in cluster 3 (p = 0.051). The findings suggest that the flexor hallucis longus may help prevent MLA compression during loading, indicating that over-use of extrinsic foot muscles may contribute to MTSS development.

Astragalus plants belong to the legume family and have obvious rhizosphere effect. The northwestern area of Yunnan China is the main distribution region of Astragalus plants with high application value, but low recognition and resource reserves. The aim of this research is to explore the species diversity of cultivable rhizosphere fungi derived from A. acaulis, A. forrestii, and A. ernestii growing in special high-cold environment of northwest Yunnan, and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fungus Aspergillus calidoustus AA12 from A. acaulis fermentation substance showed a broad antibacterial spectrum and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species of A. calidoustus, including a sesterterpine 6-epi-ophiobolin G (1), two sesquiterpenes penicisochroman A (2), pergillin (3) and 7-methyl-2-(1-methylethylethlidene)-furo[3,2-H]isoquinoline-3-one (4), and three polyketides trypacidin (5), 1,2-seco-trypacidin (6) and questin (7). Compound 1 exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL, and prominent inhibitory effect on the biofilm of Streptococcus agalactiae at MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizosphere fungi Astragalus-derived in special high-cold environment and further increased the library of fungi available for natural anti-infectious products screening.

Potentially, traditional medicine is used to manage multidrug resistance (MDR) bacterial infections. This study determined the antioxidant and antibacterial activities of Thymus schimperi (Ts), Rhamnus prinoides (Rp) and Justicia schimperiana (Js) from Addis Ababa against MDR-Uropathogenic Bacteria. Hydromethanolic extracts were prepared. Quantitative determination of phytochemicals and DPPH, ABTS and FRAP assays for antioxidant activities were carried out. In vitro, antibacterial activity and minimum inhibitory concentration (MIC) were performed. Ts had the highest total phenolic (TPC), flavonoid (TFC) and proanthocyanidin content. GC-MS analyses identified 14 bioactive-compounds: in Ts extract, with hexanedioic acid, bis(2-ethylhexyl) ester, thymol, and o-cymen-5-ol being the most predominant, respectively; in Rp extract (6 compounds; hexanedioic acid, bis(2-ethylhexyl) ester, β-D-glucopyranoside, methyl and desulphosinigrin respectively); and in Js extract (5 bioactive-compounds: hexanedioic acid, mono (2-ethylhexyl) ester, debrisoquine, and 8,11,14-heptadecatrienoate, methyl ester) being predominant, respectively. The extracts' TPC showed a strong negative correlation with the DPPH assay (r= -0.999; p=0.023), while its TFC correlated significantly with the ABTS assay (r=0.999; p= 0.032). Ts showed the highest antibacterial activity against clinical isolates of Escherichia coli and Klebsiella pneumoniae ESBL at 1000 mg/mL, and TS had the lowest MIC (4 mg/mL) among evaluated extracts against E. coli (ATCC25922). In conclusion, Ts and Rp showed activity against patient-isolated MDR-uropathogenic E. coli and K. pneumoniae ESBL.

Prevalence estimates of Parkinson’s disease (PD) – the fastest growing neurodegenerative disease – are underestimated due to issues surrounding diagnostic accuracy, symptomatic undiagnosed cases, suboptimal prodromal monitoring, and limited screening access. Remotely monitored wearable devices and sensors provide precise, objective, and frequent measures of motor and non-motor symptoms. Here, we used consumer-grade wearable device and sensor data from the WATCH-PD study to develop a PD screening tool aimed at eliminating gaps between patient symptoms and diagnosis. Early-stage PD (n=82) and age-matched comparison (n=50) participants completed a multidomain assessment battery during a one-year longitudinal multicenter study. Using disease- and behavior-relevant feature engineering and multivariate machine learning modeling of early-stage PD status, we developed a highly accurate (92.3%), sensitive (90.0%), and specific (100%) Random Forest classification model (AUC=0.92) that performed well across environmental contexts. These findings provide robust support for further exploring consumer-grade wearable devices and sensors for global population-wide PD screening and surveillance.

Background/Objectives: This literature review, on occasion of the reported case report, explores the complex interplay between gabapentin (GBP), a gamma-aminobutyric acid (GABA) analog, and the hypothalamic-pituitary-adrenal (HPA) axis in patients undergoing major surgical procedures. It specifically investigates the potential impact of GBP on cortisol levels, stress responses, and infection risk, illustrated by a detailed clinical case. Methods: This review combines a comprehensive literature search with a case report of a 17-year-old male with osteosarcoma who experienced transient adrenal insufficiency and infections while receiving GBP. The case is analyzed in the context of existing literature on GBP and the HPA axis. Results: The findings highlight the intricate relationship between GBP use, adrenal insufficiency, and infection susceptibility. It underscores the need for further research and clinical vigilance when prescribing GBP to patients with underlying medical conditions, particularly in the context of major surgical procedures. The review underscores the need for further research and clinical vigilance when prescribing GBP, particularly in perioperative settings. Conclusions: GBP’s effects on the HPA axis and immune responses are complex and multifaceted. Clinicians should exercise caution when prescribing GBP, especially for patients with underlying conditions undergoing major surgery. Further research is needed to elucidate the mechanisms of GBP's influence on cortisol levels and stress responses.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

Ischemic stroke is a leading cause of mortality worldwide, and intravenous thrombo-lysis, while improving functional outcomes, still leaves a significant mortality rate. This study aimed to investigate the clinical and pathological data of thrombolysed stroke patients who subsequently died and underwent autopsy, focusing on hemorrhagic transformation (HT). Over a 10-year period, 1426 acute ischemic stroke patients re-ceived thrombolysis at our center, with an in-hospital mortality rate of 11.7%. Autop-sies were performed on 98 of the 167 deceased patients. HT was found in 47% of these cases, only less than half occurring within a day of thrombolysis. Significant inde-pendent predictors of HT included higher lactate dehydrogenase (LD) levels and higher INR values at admission. HT directly caused death in 30% of cases, often through herniation, while other complications (pulmonary embolism, pneumonia) were also common. These findings underscore the importance of postmortem investi-gations to accurately determine the incidence of HT and contributing factors. Our data indicate that in the vast majority of HT cases, the role of contributing factors other than rt-PA may be important. Of the routinely assessed clinical and laboratory parameters at admission only LD and INR were found to be independent predictors of HT in the autopsied studied cohort.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The al-tered tumor microenvironment after tuberculosis infection appears to contribute to cancer pro-gression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of select exosomal microRNAs. TPE-derived exosome treatment en-hanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell inva-sion. Exosome-mediated transfer of select microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phos-phorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p sup-pressed the promotion of lung cancer by TPE derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TBE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

Background: Chronic kidney disease (CKD) is a significant cardiovascular (CV) risk factor, with dialysis-dependent CKD (DD-CKD) patients facing high mortality rates. Hypercholesterolemia is another crucial CV risk factor, typically managed with lipid-lowering therapy, though its efficacy in DD-CKD remains uncertain. Evidence shows mixed results regarding the benefits of statins in these patients. Citrate-based dialysates are known to reduce inflammatory biomarkers compared to acetate-based ones, potentially impacting lipid profiles and immune responses. This study aimed to determine the effects of citrate versus acetate dialysate on lipid profiles and immunophenotypes in DD-CKD patients. Methods: This unicentric, cross-over, prospective study included 21 hemodialysis patients (10 males, 11 females, average age 62.25 years). Each patient underwent 24 dialysis sessions (12 with each dialysate) and acted as their own control. Lipid profiles, immunological parameters, and nutritional and inflammatory markers were measured before the last session with each dialysate. Results: Compared to acetate dialysate (AD), citrate dialysate (CD) resulted in significantly higher LDL (75.71 vs. 67.05 mg/dL, p=0.042) and HDL (51.19 vs. 47.14 mg/dL, p=0.013), and lower TG (97.86 vs. 110.38 mg/dL, p=0.046). CD also led to higher NK cells (19.24 vs. 16.95%, p=0.035), higher complement C3 levels (115.14 vs. 107.81 mg/dL, p=0.009) and lower CD3+ CD8+ and CD16+56+ lymphocytes. Finally, total lymphocytes were lower with AD than with CD. We found no difference in predialysis nutritional nor inflammatory parameters (IL-6 and hs-CRP) except for ESR, which was higher when subjects used CD than AD. Conclusion: There are significant differences in lipid and immunophenotypic profiles that should increase the CV risk of patients who use CD. However, numerous studies have shown no differences, or even a benefit in mortality in certain HD subpopulations that use CD. Further studies are needed to understand if the observed changes may be counterbalanced by other mechanisms potentially provided by citrate (e.g., reducing vascular calcification).

The antimicrobial resistance to clinically approved antibiotics is rapidly increasing worldwide. Staphylococcus aureus is a critical contributor to deaths associated with antibiotic resistance. In this regard, the search for natural compounds is quite active, that alone or in combination with other agents can be effective as new antibacterial agents. The antibacterial activity of essential oils has presented an increasing interest during the last years and was effective even on multidrug-resistant strains. The present study aims to investigate the interaction effects of oregano essential oil (OEO) with some conventional antibiotics against Staphylococcus aureus tested by agar methods. For this purpose, we selected S. aureus ATCC 29213 and five clinical isolates representative of the species. The essential oil was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). The analysis of the Oregano essential oil revealed the main component to be carvacrol (81,20%). Concentration 2.5% (v/v) OEO was combined with drugs proposed by EUCAST, 2024, specifically penicillin, cefoxitin, erythromycin, gentamycin and tetracycline. The research results showed that the combination of OEO with penicillin, cefoxitin, erythromycin, and tetracycline enhanced the antimicrobial activity of the antibiotics against S. aureus in almost all cases. The area of suppression remained identical (but not smaller) in the unaffected cases. When comparing the effects of the GEN-OEO combination and GEN against most S. aureus strains, a decrease in antimicrobial activity was reported by the diffusion agar method.

Metal-reinforced polymethyl-methacrylate (PMMA) is considered the gold standard material for immediate loading on dental implants. However, mechanical problems under loading cycles can occur, such as fractures. To overcome these drawbacks, a novel polymer-based material has been proposed. The aim of the present in vitro comparative research is to validate a novel composite polymer developed to replace metal-reinforced PMMA interim restoration due to its advantages of good mechanical proprieties, easier manufacturing, and handling. Ten interim restorations were CAD/CAM designed and fabricated (five in the composite "ONLY" group, and five in the metal-reinforced PMMA group). All the samples were screwed into the prototype models, simulating a complete edentulous mandible rehabilitated with six straight implants. Outcome measures were breakpoint (load, N) and displacement (mm) thought a static, compression test and material behavior under dynamic cyclic test method (fatigue test). A total of twenty samples were tested. Ten samples were used for each test (10 for static and 10 for dynamic), five samples were used in each group (test and control). All the specimens completed the mechanical tests, as planned. There was no statistically significant difference between groups for all, breakpoint, displacement and fatigue tests. Breakpoint in the test group was 1953.19 ± 543.73 N, while, it was 2031.10 ± 716.68 N in the control group, with no statistically significant difference (P=0.775). The displacement was 1.89 ± 0.34 mm in the test group and 1.98 ± 0.75 mm in the control group, again, with no statistically significant difference (P=0.763). Under dynamic cyclic test method, in the control group the mean load was 2504.6 ± 972.15 N, while, in the test group the mean load was 3382 ± 578.5 N. The difference between group was 877.4 ± 579.3 N (p value=0.121). With the limitation of this in vitro study, the novel composite polymer can be used to immediately load dental implants. Further clinical researches are needed to confirm this preliminary results.

Gastroesophageal cancers, are among the most prevalent cancers globally and represent the third leading cause of cancer-related mortality worldwide. Surgical resection remains the primary curative approach for localized and locally advanced stages, but its effectiveness is limited for locally advanced diseases, evidenced by a low 5-year survival rate of around 25%. High relapse rates post-surgery, particularly in western populations, necessitate the use of neoadjuvant, adjuvant, or perioperative strategies involving chemotherapy and radiation to improve surgical outcomes. Neoadjuvant chemoradiation therapy has demonstrated a significant improvement in overall survival. Recent advances have identified several target genes and pathways involved in the pathogenesis and progression of these cancers, leading to the development of targeted drugs, including immunotherapy, anti-HER-2 antibodies, and anti-VEGFR antibodies. These targeted therapies are emerging as promising interventions for better patient outcomes and personalized treatment approaches and therefore could eventually evolve into a novel therapeutic regimen for gastroesophageal cancer.

Antiviral therapy such as Oseltamivir has been recommended for hospitalized children with suspected and confirmed influenza for almost 20 years. The therapy is officially authorized for newborns two weeks of age or older, however, questions about its safety and effectiveness still surround it. Our goal was to assess the epidemiological features of two consecutive seasonal in-fluenza cases in children following the COVID-19 pandemic and also to observe the clinical ef-fectiveness and tolerability of oseltamivir in hospitalized children who were not vaccinated against influenza and who had different influenza subtypes, including A (H1N1), A (H3N2), and influenza B, and to identify specific comorbidities associated with influenza in children. We performed an observational study on 1300 children, enrolled between 1st October 2022 and 30th May 2023 and 1st October 2023-4th of May 2024, to the IX Pediatric Infectious Diseases Clinical Section of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș". During the 2022-2023 influenza sea-son, 791 pediatric patients tested positive for influenza and received Oseltamivir. Of these, 89% (704/791) had influenza A, with 86.4% subtypes A(H1N1) and 13.6% of cases had A(H3N2), and influ-enza B 11%(87/791) pediatric patients. Of the total group, 59% were male, and the median age was 2,4 years (1.02-9.28). For the 2023-2024 influenza season, 509 pediatric patients tested positive for influen-za, 56.9% were male gender and were treated with Oseltamivir. 81.6 % had Influenza A, and 18.4% had influenza B. Treatment with neuraminidase inhibitors like Oseltamivir, 2mg/kg/dose twice daily for 5 days, was well tolerated by the children, and we recorded no deaths. The duration of fever hospitaliza-tion after the Oseltamivir administration was significantly longer for patients with A(H1N1) infection than A(H3N2), during both seasons. We identified more complications in the 2022-2023 season and a decreasing number of Influenza B for the 2023-2024 season. Among children with comorbidities, the most common were asthma, gastrointestinal disorders, and metabolic and endocrine diseases. In terms of effectiveness, oseltamivir significantly reduced the intensity of influenza symptoms, thus reducing the number of days of hospitalization (p=0.001) as well as post-infection complications (p=0.005) in both groups. Oseltamivir was less effective in Influenza A (H1N1) than A(H3N2), (p=0.0035). In this study, we evaluated the clinical effectiveness of oseltamivir therapy for all influenza types/subtypes in children, and the length of hospitalization. We identified comorbidities associated with prolonged dura-tion of hospitalisation. Influenza vaccination should be the main tool in the prevention of influenza and its complications in children, especially with comorbidities.

The potassium-chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation leading to a depolarizing activity of GABA and glycine. Downregulation of this cotransporter occurs in neurological disorders characterized by hyperexcitability, such as epilepsy, neuropathic pain and spasticity. KCC2 is also downregulated after axotomy. If muscle reinnervation is allowed, KCC2 levels recover in motoneurons. Therefore, we argued that target-derived neurotrophic factors might be involved in the regulation of KCC2 expression. For this purpose, we performed the axotomy of extraocular motoneurons by monocular enucleation of adult rats, and a pellet containing either VEGF or BDNF was chronically implanted in the orbit. Double confocal immunofluorescence of ChAT and KCC2 was carried out in brainstem sections. Axotomy led to a KCC2 decrease in the neuropil and soma of extraocular motoneurons, peaking at 15 days post-lesion, with the exception of abducens motoneuron somata. VEGF administration prevented the axotomy-induced KCC2 downregulation. By contrast, BDNF either maintained or reduced KCC2 levels following axotomy suggesting BDNF is involved in the axotomy-induced KCC2 downregulation in extraocular motoneurons. The finding that VEGF prevents KCC2 decrease opens new possibilities for the treatment of neurological disorders coursing with neuronal hyperactivity due to KCC2 downregulation.

Aspergillosis is a fungal disease caused by the inhalation of fungal spores of the genus Aspergillus spp. This fungus mainly affects the lungs but can spread and infect the maxillofacial region through the bloodstream. The disease has nonspecific clinical manifestations, which hinders early diagnosis. Even though the Polymerase Chain Reaction (PCR) technique holds promising potential to aid in diagnosing aspergillosis, anatomopathological analysis services have not yet routinely adopted the method. Therefore, the present study aims to evaluate the applicability and standardize the techniques of preparation of biological samples and PCR for the detection of the species Aspergillus niger, Aspergillus fumigatus and Aspergillus flavus. Six samples of formalin-fixed, paraffin-embedded tissue (FFPE), with histopathological diagnosis suggestive of aspergillosis, were investigated by PCR. Five of the six samples evaluated were positive for the fungus Aspergillus spp, 2/5 of which were co-infected by A. fumigatus and A. flavus species, and the others were positive for A. flavus species. The findings of this study suggest that PCR may be an auxiliary method in diagnosing aspergillosis. However, the expansion of the sample size and the evaluation of PCR in comparison with other diagnostic tests for aspergillosis is essential to determine the accuracy of the method.

Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable brain-tumor-barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, ¹²⁵I, allowed clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy of targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

Thyroidectomy has been post-operatively managed by hormone replacement therapy in order to satisfy the reference ranges of thyroid stimulating hormone (TSH) and thyroxine (T4) levels. While medication and standardized reference ranges have proven to be effective, many patients continue to report unintentional weight gain despite adequate amounts of treatment and levels of TSH and T4. Physicians, over the years, have become complacent to these “normal” ranges, and have ignored the metabolic consequences that are affecting thyroidectomy patients. This paper aims to redefine the approach to post-thyroidectomy clinical care by: challenging the current standardized hormonal range values, exploring the gaps in thyroid hormone conversion, investigating the metabolic pathways of T3, considering the influence of inflammatory markers, and proposing the future for patient-centered management.

Technology-based approaches for upper limb (UL) motor rehabilitation after stroke are designed mostly for severely affected patients to increase their recovery chances. However, the available randomised controlled trials (RCTs) focused on efficacy of technology-based interventions often include patients with a wide range of motor impairment. This scoping review aims at overviewing the actual severity of stroke patients enrolled in RCTs which claim to specifically address UL severe motor impairment. The literature search was conducted on Scopus and PubMed databases and included articles from 2008 to May 2024, specifically RCTs investigating the impact of technology-based interventions on UL motor functional recovery after stroke. Forty-eight studies were selected. They showed that upon patients’ enrolment the values of the UL Fugl-Meyer Assessment and Action Research Arm Test covered the whole range of both scales, thus revealing the non-selective inclusion of severe impaired patients. Heterogeneity in terms of numerosity, characteristics of enrolled patients, trial design, implementation, and reporting were present across studies. No clear difference in the severity of the included patients according to the intervention type was found. Patient stratification upon enrolment is crucial to best direct resources to those patients who will benefit the most from a given technology-assisted approach (personalised rehabilitation).

Background/Objectives: Boscia senegalensis (BS) Pers.) Lam. Ex Poir (Capparaceae), is an important local famine food plant in Africa and widely exploited by healers for its seeds in Sahelian region to reduce hyperglycaemia. Purpose: We studied the efficacy of commercial dosage form of BS namely Boscisucrophage (BSP) on type 2 diabetes (T2DM) patients with Oral antihyperglycemic drugs resistant. Study Design: Clinical benefits of BSP, were evaluated in multicentre cohort observational study on naïve patients (43) or diabetic patients resistant of oral antidiabetic drugs (289). All patients received capsules of the fixed dose containing 350 mg of BSP twice daily for 12 weeks and overactive control on vein blood sugar, glycosylated haemoglobin (HbA1c), urine glucose excretion (UGE), aspartate aminotransferase, alanine aminotransferase, creatinine, and clinical examination of functional symptoms. Results: In clinical study, BSP induced the reduction of glycaemia, HbA1c, and increase UGE, with removal of side effects functional symptoms of T2DM. Conclusions: In clinical studies, our findings lend support to use of BSP to reduce glycaemia, and HbA1c in T2DM patients with Oral antihyperglycemic drugs resistant without over adverse effects. BSP supressed clinical examination of functional symptoms.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.