Vaccination against HPV significantly reduced the incidence of HPV-related le-sions worldwide. Considering the increasingly younger age of patients in the gynaecological office and the resulting earlier sexual initiation and potentially contact with the HPV virus, doctors need to have tools to verify the diagnosis. Nowadays, women plan motherhood later, so it is necessary to consider whether sexual treatment in the form of, among others, LEEP-conization may increase the risk of premature birth or difficulty dilating the cervix during labour.For this reason, to avoid overtreatment of LSIL changes, methylation testing may be considered. In patients with histopathologically confirmed HSIL during biopsy and ultimately a lower diagnosis - i.e., LSIL or no signs of atypia - methylation turned out to be a useful tool. We performed Pap-smear, HPV genotyping, punch biopsy, LEEP-conization (if needed) and methylation test in 108 women admitted to the District Public Hospital in Poland. Women with a negative methylation test result were significantly more likely to be ultimately diagnosed with LSIL (p=0.013). This means that in 85.7% of patients with HSIL, major cervical surgery could have been avoided if methylation was negative. Methylation testing, as well as dual-staining and diagnostics detecting mRNA transcripts of highly oncogenic types of HPV, might be used in future in the diagnosis of pre-cancerous conditions, mainly of the cervix, and in HPV-dependent cervical cancer screening. The methylation test may also be used in the diagnosis and identification of lesions within the cervical canal, including those located deep within the frontal crypts, not visible even during a professional colposcopic evaluation of the cervix, as well as within the crypts of the palatine tonsils - in diagnostics of head and neck diseases.

This study evaluated metabolites and lipid composition in the calf muscles of Type 2 Diabetes Mellitus (T2DM) patients and age-matched healthy controls using multi-dimensional MR Spectroscopic Imaging. We also explored the association between muscle metabolites, lipids, and intra-abdominal fat in T2DM. Participants included 12 T2DM patients (60.3 ± 8.6 years), 9 age-matched healthy controls (AMHC) (60.9 ± 7.8 years), and 10 young healthy controls (YHC) (28.3 ± 1.8 years). We acquired 2D MR spectra of calf muscles using an enhanced accelerated 5D echo-planar correlated spectroscopic imaging (EP-COSI) technique, and abdominal MRI with breath-hold 6-point Dixon sequence. In YHC, choline levels were lower in the gastrocnemius (GAS) and soleus (SOL) muscles but higher in the tibialis anterior (TA) compared to AMHC. YHC also showed higher unsaturation index (U.I.) of extramyocellular lipids (EMCL) in TA, intramyocellular lipids (IMCL) in GAS, carnosine in SOL, and taurine and creatine in TA. T2DM patients exhibited higher choline in TA and myo-inositol in SOL than AMHC, while Triglyceride fats (TGFR2) in TA was lower. Correlation analysis indicated associations between IMCL U.I. and various metabolites in muscles with liver, pancreas, and abdominal fat estimates in T2DM. These findings may elucidate the impact of dysfunctional adipose tissues in T2DM.

Aim: This study aims to analyze the collaborative structure of Intestinal Behçet’s Disease (IBD) research by examining co-authorship networks in publications indexed in the Web of Science (WoS) Core Collection from 2000 to 2023. The goal is to identify key researchers, institutions, and collaboration patterns that have shaped the field over the past two decades. Method: This study utilized network analysis techniques to evaluate 484 publications related to IBD research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: From 2000 to 2009, the co-authorship network was highly fragmented with a low network density of 0.0114 and 84 distinct components, indicating limited collaboration. Key contributors during this period included Kim, Won Ho, and Cheon, Jae Hee (South Korea), who played central roles in connecting disparate research clusters. In the following decade (2010-2019), network density decreased slightly to 0.0086, and the number of components increased to 113, reflecting continued fragmentation despite growing research output. However, from 2020 to 2023, network density increased to 0.0171, and the number of components decreased to 73, indicating a trend towards greater integration and collaboration. Notable researchers in this period included Emmi, Giacomo (Italy), and Hatemi, Gulen (Turkey), who emerged as central figures, highlighting a shift in research leadership from Asia to Europe..Conclusion: The co-authorship network analysis of IBD research reveals an evolving collaborative landscape with increasing network density and decreasing fragmentation over time, particularly in the most recent period. From 2000 to 2019, Japanese and Korean researchers were prominent contributors, highlighting the significance of Asia in the global research arena. However, since 2020, researchers from Italy and Turkey have gained significant international prominence, suggesting a shift in the research focus from Asia to Europe. This transition may be attributed to changes in the incidence rates of IBD, where rapid increases were observed in Asian countries like Japan, Korea, and China until 2020, followed by stabilization or decline, while incidence rates have been increasing in European countries such as Italy and Turkey. These findings underscore the importance of expanding international collaborations to enhance the understanding of IBD. Fostering global partnerships could further advance the field, promoting more integrated and innovative research efforts, and addressing the shifting dynamics of IBD prevalence across regions.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

(1) Background: This retrospective cohort study aimed to investigate the cephalometric evaluation of facial height ratio (FHR) and growth patterns. (2) Methods: We assessed facial height ratios, Y-axis to SN angle, and growth patterns in 94 participants from Timis county using digital cephalograms. Participants were categorized based on Angle’s classification. Cephalograms were digitally traced and analyzed using WebCeph imaging software. Statistical analysis was conducted using Python version 3.11.9. (3) Results: Significant correlations were observed between FHR and craniofacial development, particularly regarding hypodivergent growth patterns. In a sample of 94, molar classes showed varying patterns: Class I—33.3% hyperdivergent, 61.5% normodivergent, 33.3% hypodivergent. Class II—50% hyperdivergent, 30.8% normodivergent, 52% hypodivergent. Class III—16.7% hyperdivergent, 7.7% normodivergent, 14.7% hypodivergent. Y-axis to SN angle values were within normal limits across groups (Group I: 65.0 (IQR: 61.2-69.0), Group II: 65.0 (IQR: 62.0-69.0), Group III: 67.0 (IQR: 59.7- 69.0). A strong negative correlation was found between Y-axis to SN angle and Jarabak’s ratio (r = -0.72, p < 0.001), highlighting the need for holistic assessment methods in orthodontic practice. (4) Conclusion: Patients from Timis county predominantly exhibit a hypodivergent growth pattern across all malocclusion types. Understanding these patterns is essential for comprehensive orthodontic treatment planning. Further research is needed to explore the implications of these findings on treatment outcomes and patient care.

Introduction. The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESA), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed at evaluating the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients. Methods. This mul-ti-center, retrospective cohort study evaluated adult hemodialysis patients within the European Fresenius Medical Care NephroCare network from 2014 to 2019. Patients treated according to ACM recommendations were compared to those from centers without ACM. Data on demographics, comorbidities, and dialysis treatment were used to compute a propensity score estimating the like-lihood of receiving ACM-guided care. The primary endpoint was hospitalizations during follow-up; the secondary endpoint was survival. A 1:1 propensity score-matched design was used to minimize confounding bias. Results. A total of 20,209 eligible patients were considered (reference group: 17,101; ACM adherent group: 3,108). Before matching, the mean age was 65.3±14.5 years, with 59.2% men. Propensity score matching resulted in two groups of 1,950 patients each. Matched ACM adherent and non-ACM patients showed negligible differences in baseline characteristics. Hospi-talization rates were lower in the ACM group both before matching (71.3 vs. 82.6 per 100 per-son-years, p<0.001) and after matching (74.3 vs. 86.7 per 100 person-years, p<0.001). During fol-low-up, 385 patients died, showing no significant survival benefit for ACM-guided care (hazard ratio = 0.93; p=0.51). Conclusions: ACM-guided anemia management was associated with a sig-nificant reduction in hospitalization risk among hemodialysis patients. These results further support the utility of ACM as a decision support tool enhancing anemia management in clinical practice.

The recent growth of wearable medical device technology in the form of fitness trackers, smart watches, smartphone apps, and patient monitoring systems has created people-generated health data (PGHD) that may benefit medical science with large amounts of continuous real-world data. The prevalence of these devices speaks to their broad popularity and user-friendliness and may lead us one day to a more fully “connected healthcare system.” Meanwhile, data security, confidentiality, and privacy issues have emerged in these hackable systems. Despite the promise of anonymized data, data can sometimes be re-identified, but even without that step, data breaches may reveal information (name, address, date of birth, social security number, and so on) sufficient for identity theft. Clinicians are often asked about the utility and value of wearable devices or monitors, but most are unaware that data from these systems may be transmitted, stored, and even sold without the user’s specific knowledge. Despite the confidentiality of medical information, cybersecurity surrounding wearables and monitors remains relatively lax, making them comparatively easy targets for cyber-villains. It is also important that efforts be taken to make PGHD more secure, since medical data may have great value to telehealth applications and AI-physician assistants. Clinicians should take an active role in informing patients about both risks and benefits of wearables and similar devices.

Due to their close anatomical and spatial relationships with left renal hilum, both superior mesenteric artery and celiac trunk injuries continue to be reported during left radical nephrectomy, either through an open, laparoscopic or robotic approach. The aim of this review, 50 years after the first reported cases, is to highlight anatomical and pathophysiological basis, risk factors, as well as diagnostic and therapeutic strategies for dealing with these injuries.

Cirrhosis is a critical global health issue, responsible for 2.4% of deaths worldwide in 2019. The Global Burden of Disease Study reported a near doubling of decompensated cirrhosis cases from 1990 to 2017. In the U.S., cirrhosis is the 12th leading cause of death and often requires hospitali-zation and procedural interventions for severe complications such as hepatocellular carcinoma, ascites, hepatic encephalopathy, and variceal bleeding. This study aims to identify racial, ethnic, and socioeconomic disparities in receiving critical interventions among U.S. patients with de-compensated cirrhosis during 2020-2021. We conducted a retrospective cross-sectional analysis using 2020-2021 National Inpatient Sample data of adult patients (≥18 years) with cirrhosis-related and cirrhosis complication-related ICD-10 codes and who underwent procedures for cirrhosis-related indications such as esophagogastroduodenoscopy (EGD) for variceal hemor-rhage, transjugular intrahepatic portosystemic shunt (TIPS) for variceal hemorrhage or refractory ascites, hemodialysis for acute kidney failure or hepatorenal syndrome, and liver transplantation We collected data on patient baseline clinicodemographic and procedural outcomes. Statistical analyses included multivariable logistic regression to assess for associations with outcomes. There were significant disparities in procedure utilization: White and Hispanic patients more likely than Black patients to receive EGD and TIPS, while Black and Hispanic patients had higher odds of receiving hemodialysis. Insurance type also influenced access, with Private/HMO insurance holders having higher odds of undergoing procedures. These findings underscore the need for targeted interventions to address healthcare inequities.

As an extraordinarily diverse group of bacteria, lactobacilli are now placed in several genera which names still contain “lactobacillus” in their core. Despite the names, this group of the lactic acid bacteria comprises microorganisms which are very important for our life especially in early development of the human microbiota and immune system. The interactions of the lactobacilli with elements of the mucosal immunity leads to its shaping and development, which is recognized as a potential driving force in the evolution of the human immune system. Although most of the evidence supporting the idea of the leading role of lactobacilli in housekeeping of the human health derives from articles on probiotics aiming to elucidate mechanisms of their functional activities and studies on mucosal immunity on germ-free mice, it is justifiable to extend observations on properties of the individual probiotic Lactobacillus related to health benefits onto other strains sharing common characteristic of the species. In this review, we will discuss acquisition, presence and functions of lactobacilli in different human microbiota throughout the whole life including those arising in amnion and their interactions with mucosal and immune cells. Examples of immune system modulation by probiotic lactobacilli due to competition for available nutrients in the colon, colonization site interference, and competition for binding sites on gut epithelial cells, production of bacteriocin, lowering of colonic pH, and nonspecific stimulation of the immune system will be shown.

Background/Objectives: This study aimed to evaluate compliance and accuracy in comparison with traditional PD diaries for tracking motor symptoms using a new smartphone application (My Parkinson’s) and paper diary strategies. Parkinson's disease (PD) is a neurodegenerative disorder with progressive motor symptoms. Treatment becomes more challenging as PD progresses, motor complications in the form of wearing-off phenomenon and levodopa-induced dyskinesia develop. Traditional paper diaries and clinical scales used to evaluate patients may be inadequate in assessing whether the patient is “on” or “off,” resulting in less-than-ideal treatment changes. Methods: A randomized crossover design was utilized to examine 22 advanced PD patients who underwent symptomatic assessment with both diaries during two separate 24-hour periods seven days apart. The compliance and accuracy of data were assessed by comparing diary entries with the clinical examination notes and WhatsApp queries. Latterly, patients' diary preferences were also evaluated.; Results: The digital diary had significantly better compliance and accuracy than the paper diaries, with substantial/almost perfect levels of agreement (κ = 0·615 to 0·818) between logged symptoms and clinical examination notes. 65% of patients preferred the digital diary for follow-ups, and there was no significant difference in ease of use compared to paper diaries. Conclusions: Digital diaries are helpful in the clinical management of PD patients as they minimize recall bias and reduce data errors in appropriately selected patients. Our study suggests a broader adoption of digital health technologies in PD management. Still, additional research is necessary to improve the tools and assess long-term patient outcomes.

Multidrug-resistant-tuberculosis (MDR-TB) patients are treated with a standardised, short, WHO-regimen, which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the Kv11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics on other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on the sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) activity of CMs, using the rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25 - 5 mg/L). Thereafter Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Both antibiotics demonstrated dose-response inhibition of the Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and lastly CFZ. Neither antibiotic, individually or in combination, demonstrated cytotoxicity under the experimental conditions used. The inhibitory effects of CFZ and BDQ individually and in combination, on the activity of the Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.

Background:The association between ABO and Rh blood groups and diseases is an intriguing topic that continues to be studied. However, how mandibular symmetry may vary by blood group has not been investigated. This study explored the relationship between these blood groups and mandibular condyle and ramal asymmetries in the Turkish adult population. Methods:The study included 149 adult patients (67 males and 82 females) without systemic diseases or temporomandibular disorder complaints. Asymmetry was assessed in panoramic radiographic images using a formula developed in a previous study. The chi-square and Kruskal-Wallis tests were used to analyze differences among ABO groups while the Mann-Whitney U test was used for Rh groups. Results:There were no statistically significant differences among the ABO blood groups, nor the Rh groups, in terms of sex, Rh factor, and age distribution. However, a comparison of the ABO and Rh blood groups revealed that condylar asymmetries were significantly more common in the AB group. Conclusions:These results suggest that mandibular asymmetry may be associated with the ABO blood group. These findings may guide future research to gain a deeper understanding of the relationship between mandibular asymmetry and blood groups.

Introduction: The aim of this study is to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. Material and Methods: Prospective case-control study. Data collection period was between May 2020-2022. 80 tracheostomies on patients with long intubation were performed and the resected tracheal ring was examined by standard microscopy. 40 consecutive tracheotomies in COVID-19 patients and 40 in patients without COVID-19 disease were carried out. Results: The mean age was 68.18 years in the COVID group and 56.1 years in the NO COVID group. The male/female ratio was 32/8 versus 29/11 respectively. No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented vasculitis (2,5%) and one case thrombotic microangiopathy (1,2%), all cases in the COVID group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2=0.779) no significant indices for measuring association (Rho= 0.1316) and no significant risk indices (RR = 1.8, OR=2.032, PAR= 44%). Conclusion: There is no evidence of increased risk of histopathological findings of the resected tracheal ring in patients with long intubation and COVID-19 disease.

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The Canine Distemper Virus (CDV) frequently affects the nervous system with demyelinating leukoenceph-alitis, the most common neurological manifestation. The disease has been linked to multiple sclerosis (MS) in humans due to the similar clinical presentation and pathophysiological mecha-nisms. In MS, visual evoked potentials (VEP) have been identified as a reliable marker for disease progression, enabling early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and Electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results revealed a bilateral increase in the latency of N1, P1, N2, P2 and N3 waves of the VEP, without any alterations in their amplitudes. No significant differences were observed in the ERG, between both groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neu-rological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease.

Background:Tourette syndrome (TS) is a characterized by motor and vocal tics, often accompanied by obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBM) present a promising avenue for future therapeutic intervention owing to their interaction with the endocannabinoid system, potentially mitigating tics and associated symptoms. Unlike conventional treatments such as antipsychotics, CBM exhibits improved tolerability and reduced side effects. While the available evidence is still limited, ongoing research underscores the potential of CBM to enhance the quality of life for patients, establishing it as a pivotal area for future therapeutic advancements in TS. Aim: In our systematic review and meta-analysis, we aim to assess the effectiveness of cannabis-based medicine (CBM) in the treatment of Tourette Syndrome. Methods: We searched in electronic databases (PubMed, Google Scholar, Science Direct, Cochrane Collaboration Database of Randomized Trials) was performed to identify cohort studies and randomized controlled trials (RCTs) up to 18th June 2024. Data extraction focused on baseline characteristics of the included studies and efficacy outcomes, including scores on the Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). We conducted the meta-analysis using Review Manager version 5.4. software. We compared the measurements before and after CBM intake using mean difference (MD) and 95% confidence interval (CI). Result: In total, 1105 articles were identified for screening, with eight studies included in the systematic review and seven in the meta-analysis. These studies involved 306 adult patients with TS treated with cannabis. YGTSS revealed a significant reduction in total scores (MD = -13.29, 95% CI [-21.67 to -4.91], P = 0.002) and PUTS revealed a significant decrease in scores (MD = -4.09, 95% CI [-7.24 to -0.93], P = 0.01). Conclusion: The research emphasizes the potential of cannabis-based medication in alleviating tics and premonitory urges associated with Tourette syndrome. While the initial results are promising, they are based on limited-scale studies. It is imperative to conduct larger, placebo-controlled trials encompassing diverse demographic groups to substantiate the effectiveness, ensure safety, and optimize dosages for long-term therapeutic advantages.

Plastic surgery is a diverse speciality, relevant to non-plastic doctors, as plastic surgeons frequently collaborate with other specialities and its’ basic principles are transferable across multiple specialities. Foundation year (FY) doctors are the most junior doctors in the workforce and may need to apply plastic surgery knowledge and principles during their clinical duties. Despite this, formal plastic surgery education for junior doctors is limited, resulting in an educational gap. This study gains insight into the perceived confidence, knowledge gaps, skills, educational activities and needs related to plastic surgery. This qualitative study uses phenomenology through semi-structured individual interviews with 8 FY doctors. Data was analysed using reflexive thematic analysis. This study revealed that plastic surgery features diversely in the work life of FYs, who often manage patients with a lack of knowledge and confidence, influencing patient care and FY wellbeing. FYs primarily acquire knowledge and confidence through experiential learning and individual initiative. A need for curriculum improvements was expressed. FYs are an essential part of the workforce who exhibited educational gaps and a lack of confidence in plastic surgery knowledge. We suggest improved integration of plastic surgery into the FY curriculum for improved FY knowledge and patient care.

Introduction: Migraine is a highly disabling neurological condition with substantial variability in its clinical presentation. This study aimed to explore the influence of familial transmission of comorbid medical conditions on the phenotype of chronic and episodic migraine. Methods: A total of 500 patients who presented to a private tertiary headache clinic were categorized into episodic and chronic migraine groups based on the International Classification of Headache Disorders-3 criteria. Data on demographics, clinical symptoms, and familial medical history were collected. Statistical analysis included chi-square and independent sample t-tests to evaluate the impact of familial comorbidities on migraine phenotypes. Results: Of the participants, 63% were diagnosed with episodic migraine and 37% with chronic migraine. Significant findings included higher rates of medication overuse (63.31%) and allodynia (58.82%) in patients with chronic migraine. Notably, patients with a maternal history of hypercholesterolemia showed a higher prevalence of chronic migraine (78.6%), whereas those with both parents affected tended to have episodic migraine. Educational levels are inversely correlated with the prevalence of chronic migraine, suggesting a socioeconomic influence on migraine chronification. Discussion: This study highlights significant associations between familial health conditions and migraine phenotypes. The findings suggest that the maternal transmission of comorbidities, particularly hypercholesterolemia, may influence the development of chronic migraine. These results underscore the importance of considering familial medical history in the management and understanding of migraine.

Background: Magnetic Resonance Imaging (MRI) is essential in pediatric diagnostics; however, the need for effective sedation due to children’s inability to remain still presents a challenge. Oral Chloral Hydrate (OCH) is commonly used for its efficacy and safety, but there is a lack of detailed exploration of the median induction time, the period from administration to effective sedation. This study aimed to evaluate the efficacy of OCH and identify the determinants of the median induction time for pediatric MRI procedural sedation.Methods: This retrospective study evaluated oral chloral hydrate (50-100 mg/kg) for pediatric MRI sedation using records from the Imam Abdulrahman Bin Faisal Hospital (2018-2022). Pediatric patients (1–8 years) were assessed for sedation efficacy, with exclusion criteria for allergies or incomplete data. Time-to-event analysis (Kaplan–Meier and Cox regression) was used to identify factors influencing sedation induction time. The data included age, weight, dose, and outcomes. The analysis highlighted the key predictors of sedation success and optimized procedural sedation protocols.Results: The study included 183 pediatric patients with a median age of 30 months and a median chloral hydrate dose of 66 mg. Sedation success was 85.79%, with younger age and shorter induction times being significantly associated with success (p<0.001). Kaplan-Meier analysis showed no significant difference in induction times between the neurological and non-neurological groups (p=0.64). Cox regression identified longer MRI duration and multiple doses as significant factors influencing the timing of sedation (p=0.050, p=0.008). Bootstrap analysis confirmed a robust median induction time of 30 minutes.Conclusions: Oral chloral hydrate achieved 85.79% success in pediatric MRI sedation, with younger and lighter patients having better outcomes. The median sleep induction time was 30 minutes, and extending sedation to 60 minutes further improved the success rate.

Asthma is a chronic respiratory disease characterized by hyperreactivity in the airways, which can lead to significant lung damage if not properly managed. While placebos—medications with no active therapeutic ingredients—are sometimes used in clinical trials to gauge the effectiveness of asthma treatments, their long-term use raises concerns. Placebos work primarily through psychological mechanisms by enhancing patients’ expectations of treatment. However, prolonged reliance on placebo treatment in asthma could potentially mask symptoms, delay proper management, and lead to undetected lung damage or other adverse effects. This study explores the potential risks and consequences associated with long-term placebo use in asthma management.

Diuretic resistance is a servomechanism involving superoxide that results from the use of escalating doses of diuretics in the treatment of heart failure. Without intervention this may lead to increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been proposed to explain the benefits of both these drug classes but this paper is the first to explain and propose superoxide induced diuretic resistance as a therapeutic target for the treatment of heart failure.

Background/Objectives: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study provides an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). Methods: We retrospectively evaluated patients who underwent combined ablation and resection in a HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. Clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. Results: A total of 23 patients were enrolled in this study. Twenty patients underwent unilateral procedures, and the other three patients underwent bilateral procedures. Ablations were performed before lung resection in 22 patients; only one patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14076 μGym2. The median hospital postoperative length of stay was 2 days. Conclusion: The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in a HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.

Canine distemper virus (CDV) poses a substantial threat to diverse carnivores, leading to sys-temic and often fatal diseases. Accurate and prompt diagnosis is paramount for effective man-agement and curbing further transmission. This study evaluates the diagnostic efficacy of drop-let digital PCR (ddPCR) in comparison to conventional reverse transcription (RT-PCR) and quantitative reverse transcription real-time PCR (RT-qPCR). Seventy-six clinical samples were collected from dogs with CDV symptoms diagnosed by specialized veterinarians, and sixteen samples from asymptomatic individuals. Conventional PCR, quantitative real-time PCR, and ddPCR were deployed, and their diagnostic capabilities were meticulously assessed. DdPCR ex-hibited heightened analytical sensitivity, reaching a detection limit of 3 copies/μL, whereas RT-qPCR had a detection limit of 86 copies/μL. The comparative analysis between clinical diagnosis and molecular techniques, including RT-PCR and RT-qPCR, demonstrated low concordance, with Kappa coefficients of 0.268 and 0.324, respectively. In contrast, ddPCR, showed a moderate concordance, with a Kappa coefficient of 0.477. Sensitivity was 42.39% for RT-PCR, 57.89% for RT-qPCR and 72.37% for ddPCR, with 100% of specificity for all methods. This study under-scores ddPCR's superior sensitivity and concordance with clinical CDV diagnosis, even at low viral concentrations, suggesting it as a promising alternative for CDV diagnosis.

SOCS2, an E3 ubiquitin ligase, regulates the JAK/STAT signaling pathway, essential for cytokine signaling and immune responses. Its dysregulation contributes to cardiovascular diseases (CVDs) by promoting abnormal cell growth, inflammation, and resistance to cell death. This study aimed to elucidate the molecular mechanisms underlying the interactions between Lumbricus-derived proteins and peptides and SOCS2, with a focus on identifying potential therapeutic candidates for CVDs. Utilizing a multifaceted approach, advanced computational methodologies, including 3D structure modeling, protein-protein docking, 100 ns molecular dynamics (MD) simulations, and MM/PBSA calculations, were employed to assess the binding affinities and functional implications of Lumbricus-derived proteins on SOCS2 activity. The findings revealed that certain proteins, such as Lumbricin, Chemoattractive glycoprotein ES20, and Lumbrokinase-7T1, exhibited similar activities to standard antagonists in modulating SOCS2 activity. Furthermore, MM/PBSA calculations were employed to assess the binding free energies of these proteins with SOCS2. Specifically, Lumbricin exhibited an average ΔGbinding of -59.25 kcal/mol, Chemoattractive glycoprotein ES20 showed -55.02 kcal/mol, and Lumbrokinase-7T1 displayed -69.28 kcal/mol. These values suggest strong binding affinities between these proteins and SOCS2, reinforcing their potential therapeutic efficacy in cardiovascular diseases. Further in vitro and animal studies are recommended to validate these findings and explore broader applications of Lumbricus-derived proteins.

Introduction Meningioma is the second most common primary intracranial tumor of the central nervous system. in Sudan, meningioma is the most common primary brain tumor, among Sudanese patients, Surgical total excision of meningioma offers a better survival, however, Chemotherapy has largely been unsuccessful for meningioma treatment, and therefore, refractory and recurrence meningioma treated with palliative surgery and radiotherapy. Monosomy of chromosome 22 is the utmost common genetic alteration among meningioma and many genes were investigated and described in the development of this tumor of which , NF2 hSNF5/INI1gene, P53. In addition to this, Molecular signal pathways in meningioma, and that contribute to the survival, proliferation, self-renewal, and differentiation properties of normal stem cells which are abnormally activated and nominated as cancerous stem cell (CSCs). Objectives 1/ To identify the possible pathway of candidate genes in both setting and whole genes hypothesis free approach 2/ To assess the presence of mutations in candidate genes among histological subtypes of meningioma in Sudan. Material and methods This is a prospective cross-sectional study done at the National Center of Neurological Sciences (NCNS) Khartoum, from 2018 to 2021. The study included all cerebral tumors that were radio- logically diagnosed preoperatively as meningioma. Ethical approval was taken from Institute of Endemic disease, Khartoum University, and written consent was obtained Three DNA extracts were randomly selected from 20 meningioma tissue samples and processed for WES. All genes harboring exonic and splice site variations stratified into SNVs and INDELs sets were prepared. The 1000G online database was used to explore novel mutations per 3 samples. SIFT and PolyPhen-2 programs were used to predict possible impact of amino acids substitution. To address meticulous genes interaction and particular centrality, all shared genes within the class INDEL and SNVs were used as input on Network Analysis to predict protein- protein interaction and functional gene ontology. Finally, shared mutations within genes of centrality were detected via Sanger sequencing and mutations were correlated between histological sub-types and recurrenceThree non meningioma brain tumor used as control. Results WES analysis revealed high number for mutational signature within 2 classes (INDEL and SNVs) per 3 samples, the findings of 1000 genome online database showed number of novel mutations; 5618 in fibrous , 6032 in meningothelial while in recurrent fibrous sample 5930. Network analysis of shared genes per each class (INDEL, SNVs), showed UBC is the most protein of remarkable degree centrality over thousand of genes. Whereas, all shared genes per 3 samples within the 2 classes (INDEL and SNVs) revealed Akt1 with the highest degree of centrality and betweenness. Akt1 rs17846829was detected in 20% of the samples, while CD44 stemness gene revealed mutation A>G (rs9666607) in all meningioma samples (100%), this mutation was associated with 60% of the recurrence. Conclusions Nevertheless, the present study, highlight how such complex molecular processes might contribute to tumorogenesis, in attempt to shed light over thousands of genes and multifaceted network analysis rather than a solitary gene which is challenging question.

Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP). There is little information about dose tapering and sustained remission after discontinuation in ITP. In this retrospective, multicenter study we evaluated efficacy and safety of fostamatinib in adult patients with ITP before, during and after tapering/discontinuation (T/D). T/D was performed in subjects who achieved complete platelet response (CR) with progressive, conditional dose reduction dose every 4 weeks. Sixty-one patients were included at 14 reference centers between October 2021 and May 2023. In subjects that completed T/D (n=9), median time from treatment initiation to response was 21 days (IQR:7.5-42), time to CR 28 days (IQR:28-42), time to start tapering 116 days (IQR: 42-140), duration of tapering 112.5 days (IQR 94.5-191). Median platelet count at tapering was 232×10⁹/L (IQR 152-345×10⁹/L) and at discontinuation 190×10⁹/L (IQR 142.5-316.5×10⁹/L). With a median follow-up since discontinuation of 263 days (IQR: 247-313 days), only two patients have relapsed (at 63 and 73 days. Fostamatinib was restarted, achieving a new CR. Platelet counts higher than 100x10⁹/L at week 12 was the only positive predictive factors for successful tapering and discontinuation.

Peri-implant infective diseases seem to be the most common cause for the late dental implant failure. Therefore, peri-implant microbiota has been intensively studied in modern implantology. Many studies showed a presence of extremely varied microflora in cases of peri-implant infective diseases. The main scope of this observational single-blind study was to analyze the presence of some microbial species in a group of patients with clinical signs of peri-implant mucositis compared to two other groups (patients treated with dental implants but without any clinical signs of peri-implant inflammation and patients treated with no dental implants). The identification of microorganisms was followed by an antibiogram in order to find their sensitivity to various antibiotics. The results showed a microbiota not necessarily specific for each situation (peri-implant infective diseases, healthy tissues around dental implants and healthy natural teeth and gums) with species like Candida albicans, Neisseria mucosa, Prevotella, Staphylococcus aureus, Streptococcus and others. Peri-implant infective diseases presented more bacterial species than other conditions.

Background: Synovial sarcoma is a rare soft tissue tumor that constitutes 5-10% of all soft tissue sarcomas. Early diagnosis and risk stratification are essential for effective management. This study leverages machine learning models to improve the risk stratification of mortality in synovial sar-coma patients. Methods: This retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to analyze patients diagnosed with synovial sarcoma between 2004 and 2015, as well as a validation cohort diagnosed from 2018 onward. The dataset encompassed demographic data, clinical characteristics, staging, treatment modalities, and outcomes. Four ma-chine learning models—support vector classifier (SVC), k-nearest neighbors (KNN), Gaussian naive Bayes, and gradient boosting—were trained and evaluated. Model performance was assessed using sensitivity, specificity, AUC-ROC, and Brier score. SHAP analysis was performed to determine the most influential features impacting model predictions. The top-performing model was validated using the 2018+ cohort. Results: The study included a total of 762 patients, with an average age of 39.4 years. The support vector classifier (SVC) outperformed the other models, achieving an AUC-ROC of 0.8153 (95% CI: 0.7578 to 0.8677) and a Brier score of 0.1715. Upon external validation with the 2018+ cohort, the SVC model yielded an AUC-ROC of 0.8179 (95% CI: 0.7632 to 0.8666). Key prognostic factors identified through SHAP analysis included tumor size, patient age, presence of metastasis, tumor differentiation, and cancer stage. Conclusion: Machine learning models can be used to stratify the risk of death in synovial sarcoma patients effectively, with the support vector classifier showing the most promise.

Endemic in over 45 countries globally, recent reports of locally acquired melioidosis in novel geographical areas, such as Southern US, have highlighted the expanding geographical range of Burkholderia pseudomallei. Climate change and severe weather events have been linked to an increase in cases of melioidosis, which follows environmental exposure to the bacterium. Healthcare professionals should be aware of the possibility of the disease, with its diverse and often delayed presentations, even in areas not previously known to have risk. Over 200 cases of travel-associated melioidosis have been reported in the literature, highlighting the need to consider this disease in non-endemic areas, as diagnostic delays of up to 18 months have been identified. The review updates the global epidemiology of melioidosis focusing on new geographical areas where cases have been diagnosed and imported cases, unusual clinical presentations and co-infections, and less frequent modes of transmission (laboratory exposures and the risk of acquisition due to imported infected animals and contaminated products).

Breast cancer remains a significant health concern worldwide, necessitating early detection and treatment. The rapid appearance or a change in the shape of skin lesion on the breast or just of the nipple-areola complex(NAC), especially if it is unilateral needs to be evaluated. Several primary or secondary tumours such as inflammatory skin lesions can affect this body area. Ultrasound, mammography, or magnetic resonance imaging (MRI) are the most used non-invasive diagnostic techniques for breast cancer, but in recent years reflectance confocal microscopy (RCM) and optical coherence tomography have emerged as additional tools to diagnose cases characterized by cutaneous changes.The introduction of new techniques such as reflectance confocal microscopy (RCM), may open new perspectives in the non-invasive diagnosis of mammary paget disease (MPD). RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time. It is non-invasive, painless and repeatable, making it a valuable tool in the early diagnosis and monitoring of skin diseases. We describe an atypical clinical presentation of mammary paget disease early diagnosed by reflectance confocal microscopy evaluation.

Background/Objectives: Parental internalizing issues, particularly maternal mental health, can significantly influence adolescents' mental health by altering parenting behaviors and roles. This study aims to explore how parental rejection, a dimension of both maternal and paternal behavior, moderates the relationship between parental depression, anxiety, and stress with adolescents' mental health and quality of life. We hypothesized that parental rejection would have a significant moderating effect on these relationships; Methods: This cross-sectional, non-interventional study involved 206 parents (138 mothers) of adolescents aged 12-18 years from the general population. Participants were recruited online via convenience sampling and completed the Depression Anxiety Stress Scale (DASS), the Parental Acceptance-Rejection Questionnaire, the KIDSCREEN-27 to evaluate adolescents' quality of life, and the Strengths and Difficulties Questionnaire to assess adolescents' mental health; Results: Parental rejection was found to moderate the relationship between maternal anxiety and adolescents' quality of life, as well as between maternal anxiety and adolescents' mental health problems. Paternal rejection moderated the relationship between paternal stress and adolescents' mental health. However, parental rejection did not moderate the relationship between parental depression and adolescents' quality of life or mental health; Conclusions: These findings emphasize the significant role of maternal rejection in the association between maternal mental health, particularly anxiety, and adolescents' mental health outcomes. Paternal rejection also showed some moderating effects, though to a lesser extent. These results underscore the importance of considering both maternal and paternal influences in adolescent mental health and quality of life. Further research is necessary to fully understand the gender-specific dynamics of these relationships.

Background: miRNA-122 has been reported to be a useful tool for monitoring ACR after LT. IL-28B SNP rs8099917 genotype is known to contribute to the control of HCV infection. We sought to investigate the relationship between IL-28B SNP rs8099917 genotype and miRNA-122 expression and immune mechanism of ACR after LT using hepatitis C antibody calibration. Patients and Methods: A total of 45 patients with chronic hepatitis C received LDLT. IL-28B SNP rs8099917 genotyping was used to divide TT and GT groups. The relative expression levels of miRNA-122 were calculated by quantitative PCR as 2[(Ct of miR-122) (Ct of U6)] normalized to a reference gene and compared to a control sample, and the anti-HCV titers before and after LT were tracked to observe the relationship with ACR. Results: In the genotype of rs8099917, TT was significantly more associated with higher serum miRNA-122 levels than GT (p = 0.029). The ACR was significantly higher in genotype TT than in GT (p = 0.002). TT was significantly associated with low levels of pre-LT anti-HCV compared with GT (p = 0.022). Multivariate analysis with 95% confidence intervals showed a significant association between rs8099917 genotype TT, lower pre-LT and higher post-LT anti-HCV and ACR. Conclusion: Based on our current data, IL-28B SNP rs8099917 genotype TT may express higher miRNA-122 and correlate with lower Pre-LT and higher Post-LT anti-HCV titers, and may correlate to the pathogenesis of ACR after LT.

Nanoparticle carriers can selectively deliver the drug cargo to tumor cells, thus having the ability to pre-vent early drug release, reduce non-specific cell binding, and prolong in vivo drug retention. We con-structed paclitaxel (PTX)-loaded lipid-shell mesoporous silica nanoparticles (LMSNs) for targeted an-ti-cancer drug delivery. The physical properties of PTX-LMSNs were analyzed by scanning electron mi-croscopy (SEM) and transmission electron microscopy (TEM). The drug loading (DL%) and entrapment efficiency (EE%) of PTX-LMSNs were measured by high performance liquid chromatography (HPLC). In vitro drug release test, in vivo imaging, tissue distribution and pharmacokinetics of PTX-LMSNs were also evaluated. The SEM examination showed that MSNs were sphere, whereas TEM showed that they were rich in fine pores. The uniform core-shell structure of PTX-LMSNs was also verified by TEM. The DL capacity of PTX-LMSN was as high as 21.75%, and PTX was released from the nanoparticles in vitro in a pH-dependent manner. The cumulative amount of free PTX increased at lower pH, which is conducive to selective drug release from LMSNs in the acidic tumor tissues. In vivo imaging showed prolonged reten-tion of PTX-LMSNs, which is beneficial to their therapeutic efficacy. In addition, PTX-LMSNs were primarily concentrated in the liver. Pharmacokinetic experiments showed that the half-life of PTX-LMSNs was 23.21% longer and 79.24% higher than that of Taxol. Together, LMSNs are a highly promising antineoplastic drug carrier system.

Abstract: Background/Objectives: Schizophrenia (SZ) is a severe psychiatric disorder characterized by a complex interplay of genetic, developmental, and environmental factors that significantly increase the risk of suicidal ideation (SI) and suicide attempts (SAs). This systematic review synthesizes current research on the developmental predictors of SI in individuals with SZ, aiming to delineate the multifactorial etiology of suicide within this population. Methods: A comprehensive search across Medline, PsycINFO, and EMBASE databases identified 23 eligible studies, emphasizing the varied methodological approaches and the global distribution of research efforts. Results: These studies demonstrate a robust association between early life adversities, particularly childhood trauma such as physical neglect, emotional abuse, and sexual abuse, and the increased prevalence of SI and SAs in SZ. This review also highlights the significant genetic factors associated with development of suicidality in SZ, suggesting that polymorphisms in inflammation-related genes and neurodevelopmental abnormalities may influence susceptibility to SI. Notably, family history of psychiatric conditions may exacerbate the risk of SI through both hereditary and environmental mechanisms. Environmental factors, including socioeconomic status and social support, are also implicated, underscoring the role of broader socio-environmental conditions influencing outcomes. Conclusions: This review supports the integration of biopsychosocial models in understanding SI in SZ, advocating for interventions addressing the complex interplay of risk factors and the need for longitudinal studies to elucidate the dynamic interactions between risk factors over time. This comprehensive understanding is crucial for developing targeted preventative strategies and enhancing the clinical management of SZ, aiming to reduce suicidality in this vulnerable population.

Background/aims: Prior research identified a significant association between heart disease and metabolic dysfunction-associated liver steatohepatitis (MASLD), but the mechanisms are unclear. This study aims to search predictive biomarkers for grade I left ventricular diastolic dysfunction (LVDD), an early stage of heart failure (HF), in type 2 diabetes mellitus (T2DM) patients. Methods: This single-center, prospective observational study screened 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: The study analyzed 50 patients (mean age 58±11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean BMI 34.4±5.9 kg/m2), and a mean HbA1c of 7.9±1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate to severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, ɑ2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s`, E wave, E/e`, E/A, medium E`, and septal e` (p&lt; 0.05 for all). ɑ2-macroglobulin &gt; 1.92 g/L (AUROC= 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score &gt; 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusion: HF is a multifaceted disorder associated with multisystem organ damage, including nonalcoholic MASLD. Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as ɑ2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

Background/Objectives: Patient positioning during surgery can influence intra- and postoperative complications. Therefore, we assessed the impact of the sitting and park-bench positions on anesthetic parameters and complications in neurosurgical patients. Methods & Patients: For this retrospective study, 314 adults who underwent neurosurgical procedures for posterior fossa pathologies were divided into two groups: sitting (n=231) and park bench (n=83). The following data were collected, monitored, recorded and compared: age, sex, tumor type, surgical approach, cardiovascular and respiratory complications, and postoperative surgical complications. The association of hypotension with position was further investigated through multivariate logistic regression models by adjusting for CO2 decrease, desaturation and documented gas embolism. Results: The average age was significantly lower in the sitting group (55 years, interquartile range (IQR)=43-63; female proportion=59.74%) than in the park-bench group (62 years, IQR=45-74; female proportion=57.83%) (p<0.001). Cerebellopontine angle tumors were detected in 37.23% of the patients who underwent operation in the sitting position and in 7.26% who underwent operation on in the park-bench position (p<0.001). Patients in the sitting position had significantly greater anesthetic complication (91.77% vs. 71.08%, p<0.001), hypotension (61.9% vs. 16.87%),and >2-mmHg CO2 decrease (35.06% vs. 15.66%, p<0.001) incidences. Hypoxemia and death occurred more frequently in the park-bench group (8.43% vs. 1.73% and 6.03% vs. 1.3%, respectively). Conclusions: Compared with the park-bench position, the sitting position was associated with a greater specific anesthetic complication incidence and lower postoperative mortality rate, indicating a need for careful risk‒benefit assessment when selecting each individual patient’s surgical position.

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected, and a range of clinical factors data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and ICU admission were found directly associated with a higher mortality risk (OR 6.9 and 3.2, respectively). The clinical predictors of mortality were need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminaemia, dementia, cancer, elevated CPK and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat and cough diminished risk of death (OR 0.5, 0.2 and 0.1 respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain and elevated LDH (OR 371.0, 3.6 and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity and elevated GGT (OR between 1.7 and 5.2), whilst prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.

Post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, Covid-19) sequalae’s, immune and RNA based treatments are associated with the development of micro-stones and chronic kidney disease (CKD). In addition, circulating cytokines cocktail and viral envelope spike protein (SP) instigates CKD. During epigenetic regulation, Covid-19 methyltransferase (MT) methylates the DNA/RNA/Proteins/Histones and generates homocysteine (Hcy). Although cysteine promotes the growth and aggregation of calcium oxalate crystals in normal undiluted human urine. However, during elevated levels of Hcy (i.e., hyperhomocysteinemia, HHcy) due in part to the impaired transsulfuration (i.e., mitochondrial sulfur metabolism) pathways, homocysteine is the only sulfur-denoting non-protein amino acid may promote crystals. HHcy is associated with severity of Covid-19 infection and pneumonia post Covid-19. It is unclear however whether the HHcy facilitates homocysteine crystals. Although an E. coli strain degrades tricarboxylic acid (TCA, citric acid), and disrupts mitochondrial TCA cycle, to dicarboxylic acid (DCA, oxalic acid), DCA also promotes calcium oxalate crystals and may contributes to kidney stones, it is unclear whether gut-dysbiosis by Covid-19 infection contributes to kidney stones. There is robust succinylation of enzymes in TCA cycle which causes dysfunctional mitochondrial bioenergetics during Covid-19 infection. In this regards interaction between SIRT5 and mitochondrial transsulfuration during Covid-19 infection attenuates TCA cycle. Interestingly, the mitochondrial bioenergetics though sulfur metabolism participate in TCA cycle and epigenetic acetylation/succinylation, therefore, Covid-19 infection transition acute kidney injury (AKI) to CKD by defective mitochondria sulfur metabolism (transsulfuration) pathways, forming uricemia micro stones.

This research presents an ensemble model developed to enhance the safety of bedridden patients in healthcare settings. The model utilizes a unique dataset capturing six typical movements performed by patients laying in bed, such as rolling over, falling off the bed, etc. The aim is to automate the classification of these movements, thereby enabling real-time monitoring of patients without the constant presence of hospital personnel in the room, a common practice in current healthcare settings. The dataset is preprocessed and balanced using the Synthetic Minority Over-sampling Technique, and then split into training and test sets for model training and evaluation. Three different models are explored: a Decision Tree Regressor, a Gradient Boosting Regressor, and a Bagging Regressor. The Bagging Regressor is an ensemble model that utilizes the Decision Tree Regressor as its base regressor. Each model’s performance is evaluated using accuracy, R2 score, and Mean Squared Error on both the training and test sets. The ensemble model demonstrates promising results, indicating the potential of machine learning to improve patient safety in healthcare settings. The study also employs K-Fold cross-validation and learning curves to validate the robustness of the ensemble model. This research contributes to the growing body of knowledge on the application of machine learning in healthcare and opens up new avenues for improving patient safety through real-time monitoring and classification of patient movements.

It is generally assumed that spirochetemia does not take place at the early localized stage of Lyme disease. This misassumption is due to the lack of sensitive and specific methods for detection. This paper reports that separation of the platelet-rich plasma immediately after venous blood collection to prevent the spirochetes from invading the lymphocytes in the test tube is crucial in molecular detection of a single Borrelia burgdorferi cell spun down in platelet pellets. In 2023, we tested the venous blood specimens of 145 people residing in Lyme disease-endemic areas in the United States. In 98 of them, who were suspected of having early localized Lyme disease irrespective of the absence or presence of a skin lesion, we found 33 specimens (33.7%) positive for B. burgdorferi, including 17 positive for FlaB gene only, 15 positive for both FlaB gene and 16S rRNA gene, and 1 positive for 16S rRNA gene only. Eight (17.0%) of the 47 asymptomatic resident controls were positive for FlaB PCR only. FlaB is a more sensitive chromosomal target than the 16S rRNA gene for the detection of 1-3 B. burgdorferi cells in 1 mL of platelet-rich plasma due to spirochetes gaining or retaining FlaB paralogs at the early localized stage of Lyme disease.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

Diagnosis of encephalitis is a challenging problem due to the heterogeneity of clinical presentations and the myriad of aetiology. The objective was to determine the aetiology, clinical features, laboratory parameters, radiological findings and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. Methods: A prospective analytic study was conducted at Neuromedical Ward of Yangon General Hospital during March to August 2023. 81 AES cases were enrolled and cerebrospinal fluids (CSF) samples were collected. Qiastat ME Panelwas used to detect viral, bacterial and fungal pathogens. Results: 17 out of 81 (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 encephalitis cases, the exact infectious and immune aetiologies were identified in 31/64 (48.4%); 26/31 cases (83.9%) were infectious causes and 5/31 patients (16.1%) were immune encephalitis. Among the infection causes, six Herpes Simplex Virus-1, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis, three Haemophilus influenzae, two Streptococcus pneumoniae, one Streptococcus pyogenes, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with meningoencephalitis), two Cryptococcus neoformans infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis and Aspergillus were identified. One case was dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (P<0.05). 6.45% (2/31) of encephalitis patients with identified causes and 12.12% (4/33) of those without organism identified had bad outcome. Conclusions: Herpes encephalitis and tuberculous meningoencepalitis were the commonest. This study highlighted that molecular testing with multidisciplinary approach is required to ensure the right treatment on time.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

Background/Objectives: Phenylketonuria is a hereditary metabolic disorder characterized by a deficiency of phenylalanine hydroxylase. Main treatment for PKU is a phenylalanine-restricted diet. Exclusion of protein rich natural foods and inclusion of low-Phe substitutes may give rise to an imbalanced diet increasing the risk of overweight and obesity in PKU is a cause of concern. We aimed to evaluate the body composition and nutritional biochemical biomarkers in adult PKU patients who are on Phe-restricted and essential amino acids supplemented nutrition therapy and to investigate the relationships, between these parameters and patient gender, adherence to dietary therapy and disease type defined as mild or classic PKU. Methods: The study group comprised 37 PKU patients and 26 healthy siblings as controls. The participants were assessed based on an analysis of anthropometric parameters, body composition and biochemical test results. Results: PKU patients do not have a higher incidence of overweight and obesity than healthy controls, and the proportion of energy derived from carbohydrates in their diets was below the recommended level, and the total energy intake was below the recommended daily allowance. It was remarkable that patients with a treatment adherence ratio of &lt;50% displayed a higher prevalence of overweight and abdominal obesity in comparison to those with a more favorable treatment adherence ratio. Conclusions: In view of the growing prevalence of overweight in the general population, PKU patients should be kept under close long-term follow-up. Particularly in the group with low treatment compliance, more caution should be paid in terms of adverse outcomes.

For a number of reasons, a curative treatment for most chronic diseases is still unrealized [2–4] and the incidence of many chronic diseases is rapidly increasing [5–9]. A new model is offered as a solution; that being the individualized diagnosis of homeostasis, leading to the correction of epimutations. Homeostasis diagnosis and epimutation correction, HDEC. Individuals with chronic diseases are increasingly being defined by their epimutation signatures [10,11]. Modern innovations in toxicogenomic studies are also becoming more accurate in their ability to identify the unique epigenetic signature of each toxin [12–14]. Hormesis studies (over 5,000) [15] suggest a universal principle, that a small dose is always a stimulant [16–18].These three facts present an opportunity; a method to diagnose and reverse chronic disease tendencies. This new model requires a paradigm shift in our understanding of disease origins: that dysfunctions in homeostasis [19,20] are the primary and deepest level of chronic disease causation. This is the level where the diagnosis needs to be made and where the corrections need to take place [21].

Objective: The main purpose of this meta-analysis was to assess the efficacy and safety of Oncolytic Viruses (OVs) in glioma therapy. Methods: We searched the literature in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was evaluated by sensitivity analysis and publication bias. Results: We identified 21 studies with 440 patients in this meta-analysis. In the single-arm analysis, the results showed that the 1-year OS rate was 47% (95% CI: 34%-61%, I2 = 75%) and the 2-year OS rate was 14% (95% CI: 10%-20%, I2 = 0%). The median OS was 12.48 months (95% CI: 10.71-14.25, I2 = 96%). The 1-year PFS rate was 13% (95% CI: 5%-24%, I2 = 0%), with the median PFS being 4.01 months (95% CI: 2.99-45.03, I2 = 96%). The pooled estimate of ORR was 7% (95% CI: 3%-12%, I2 = 23%). Funnel plots for median PFS were asymmetric with Egger’s test P < 0.01 indicating publication exists. The incidence of OVs-related AEs was 49% (95% CI: 20%-79%, I2 = 95%), and AEs > grade 3 was 8% (95% CI: 3%-16%, I2 = 62%). Conclusion: This meta-analysis indicated that OVs therapy was relatively safe but did not significantly extend survival in patients with gliomas.

This narrative review provides an in-depth analysis of attachment during adolescence, empha-sizing how early attachment experiences shape emotional, social, and psychological development. Drawing from the foundational work of Bowlby and Ainsworth, it revisits attachment theories and explores how the attachment system evolves as adolescents seek greater autonomy while maintaining bonds with caregivers. The review discusses the prevalence and developmental con-sequences of attachment-related disorders, such as reactive attachment disorder and disinhibited social engagement disorder, particularly in relation to adverse caregiving environments. Key themes include the intergenerational transmission of attachment, where parental reflective func-tioning and early caregiving behaviors influence attachment security across generations. The evolving role of fathers, peer relationships, and romantic bonds in adolescence are explored as significant factors shaping attachment patterns during this developmental period. Methodologi-cal considerations highlight the value of qualitative approaches, including interviews and obser-vational methods, for capturing the complexity of adolescent attachment dynamics. Additionally, the review addresses the processes that contribute to both continuity and change in attachment classifications over time, emphasizing the impact of life events, parental behaviors, and develop-mental transitions. The implications of attachment for developmental psychopathology, particu-larly in relation to emotional regulation and psychosocial functioning, are discussed. Finally, the review calls for further interdisciplinary research to deepen understanding of attachment mecha-nisms, using advanced technologies and culturally sensitive approaches to improve mental health and developmental outcomes across the lifespan.

Crigler-Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in two forms: CNS type 1 (CNS1), the more severe form with a complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients re-sponding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risks of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interven-tions.

Introduction: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients is limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL compared to MM patients (p=0.001), while post-vaccination IgG levels significantly increased in both CLL (p<0.0001) and MM (p<0.0001) patients. In actively treated CLL patients, the pre-vaccination IgG levels were significantly lower than in not actively treated patients (p=0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p=0.013). AEs were reported in 49.4% after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusion: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

The effects of toxic air in the form of air pollution are known to harm women’s health. New data has shown that air pollution has effects on maternal anemia. Yet the effects of particulate matter 2.5 (PM_2.5) on hemoglobin among reproductive maternal (15-49 years) has been understudied. In this population-based study, we study the region-specific associations between prevalence of hemoglobin among reproductive women and PM_2.5 in 43 countries of Africa from 2000-2019. Using generalized linear regression models, we found that after adjusting for key covariates, PM_2.5 had a slight negative association with hemoglobin among reproductive women. Other studies are needed in other low-income settings to expand our findings.

Endometrial cancer (EC) poses a significant global health challenge, with increasing prevalence in 26 of 43 countries and over 13,000 deaths projected in the United States by 2024. This rise correlates with aging populations, the obesity epidemic, and changing reproductive patterns, including delayed childbearing. Despite the early diagnosis in 67% of cases, approximately 30% of cases present with regional or distant spread, leading to nearly 20% mortality rates. Unlike many cancers, EC mortality rates are escalating, outpacing therapeutic advancements until recently. One of the reasons for this was the lack of effective therapeutic options for advanced disease until recently. The introduction of immunotherapy has marked a turning point in EC treatment, particularly benefiting patients with defects in mismatch repair proteins (dMMRs). However, dMMR status alone does not ensure a favorable response, underscoring the need for precise patient selection. This review explores the pivotal role of mismatch repair proteins in EC, emphasizing their heterogeneity, the challenges in their assessment, and their potential as predictive biomarkers.

The chronic high fat dysbiosis diet (HFD) instigates cardiac remodeling, dysfunction and chronic heart failure (CHF). The therapeutic approaches focusing oxidative stress, inflammation and hyperlipidemia have not yielded significant positive clinical outcomes. Recent studies report that although mitochondrial ATP citrate lyase (ACLY) supports cardiac function, however, decreases more in human HFpEF than HFrEF. Interestingly, the ACLY synthesizes lipids and creates hyperlipidemia. Epigenetically, ACLY acetylates histone. The mechanism(s) are unknown. One hypothesis is that the HFD induces epigenetic folate 1-carbon metabolism (FOCM), heperhomocysteinemia (HHcy, a cause of abrogation of sleep-time dipping in blood pressure and hypertension) and heart failure. Interestingly, the probiotics utilizes the fat/lipids post-biotically, and increases the mitochondrial bioenergetics and attenuates the HFD induced heart failure. We suggest a novel and paradigm-shift epigenetic mitochondrial sulfur transsulfuration pathways that selectively target HFD-induced CHF. The HFD via transport and metabolomic pathways instigates cardiac remodeling and dyfunction. Previous studies from our laboratory, using a single cell analysis, revealed increase in transporter (SLC25A) of s-adenosine-methionine (SAM) during elevated levels of homocysteine (Hcy, i.e., hyperhomocysteinemia, HHcy), a consequence of impaired epigenetic recycling of Hcy back to methionine by increase in FOCM methylation of H3K4, K9, H4K20 and gene writer (DNMT) and decrease in eraser (TET/FTO). The Hcy transported to mitochondria by SLC7A for clearance via sulfur metabolomic transsulfuration by 3-mercaptopyruvate sulfur transferase (3MST). Interestingly, the HHcy decreases ATP, OCR, H₂S, PGC1α, TFAM, and increase in fission/fusion ratio, causing mitochondria dysfunction. We suggest that gut dysbiosis by HFD disrupts rhythmic epigenetic memory via FOCM and increase in DNMT1 and creates HHcy, leading to decrease mitochondrial transsulfuration and bioenergetics. The treatment with a probiotic, lactobacillus will eat the fat/lipids post-biotically and bi-directionally will produce folic acid and lactone-ketone body that will mitigate the HFD-induced mitochondrial remodeling and heart failure.

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator capable of promoting wound healing and regenerative functions of mesenchymal stem cells (MSCs), en-dothelial cells, and macrophages. The third-degree (3o) burn healing and regenerative functions of MSCs are also enhanced by ACgel1, an arginine and chitosan-based protein-mimic hybrid hy-drogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporates PreM1 and MVFs into ACgel1 via optimal design and fabrication is capable of delivering PreM1 to 3o burn wounds at least up to 7 days post-burn (dpb), and of scaffolding and delivering MVFs, which promoted 3o burn the healing in mice, including vascularization and collagen formation. The re-epithelization and closure of 3o burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s) while PreM1-MVFs-ACgel1 was most effective. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of the 3o burns. These PreM1- and/or MVFs- functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapies for overcoming the drawbacks of current skin grafting or substituting for treating severe deep burns.

Background: Retinal hemorrhages are an important ophthalmic diagnostic sign of underlying systemic vascular disorder. Capsaicin is a bioactive component of chili peppers used in most countries. Capsaicin crosses the blood–brain barrier in an efficient manner. Human exposure to capsaicinoids through diet is frequent and often substantial. Presumed lack of capsaicin toxicity in diet does not preclude rare adverse effects related to actions on the central neural system. Particularly on the retina, due to the reasons outlined in this case report. Methods: A case of a 34-year-old man, who reported sudden blurring of vision and micropsia in his left eye following ingestion of a considerable amount of red pepper. Results: The case study suggests that acute or chronic consumption of substantial amounts of hot red pepper in individuals with high reactivity towards TRPV1 agonists and/or higher expression of TRPV1 receptors in retinal ganglion cells causes retinal neovascularization. Conclusion: Acute consumption of red pepper may harm vision. This hypothesis can be easily evaluated retrospectively in larger sets of data.

This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis entourage effects was conducted using the PRISMA model. Two research questions conducted the review: (1) What are the Physiological Effects of Terpenes and Terpenoids found in Cannabis? (2) What are the proven Entourage Effects of Terpenes in Cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases, using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity, however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa-prevalent monoterpenes and their triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically, however, in combination with CBD did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxing; linalool as sleep aid, exhaustion relief and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection, borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm these constituents' individual and combined effects.

Results: This case series study included 20 PD participants with STN-DBS, with a mean age of 61.2±10.1 years. There were no differences in equilibrium scores of SOT conditions between 60, 130, and 180 Hz frequencies (p&gt; 0.05), except the SOT6 score (p= 0.003), where 60 Hz showed better equilibrium performance in SOT6, indicating an advantage in postural control when visual and somatosensory cues are disturbed, and vestibular cues are not.

Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the presence of atherosclerosis in patients aged 18 to 55 years. Methods: A cross-sectional study was conducted involving 89 participants divided into two groups: 62 patients with documented atherosclerosis (main group) and 27 healthy controls without significant atherosclerosis. Comprehensive data—including demographic information, medication use, imaging results, laboratory parameters, and calculated inflammatory indices (SIRI, SII, AISI, NLR, PLR, MLR)—were collected. Statistical analyses included correlation assessments, group comparisons using the Mann-Whitney U test, logistic regression modeling, feature importance analysis with Random Forest and Gradient Boosting classifiers, receiver operating characteristic (ROC) curves, and K-means clustering. Results: Significant differences were observed between the main and control groups. Patients with atherosclerosis exhibited elevated inflammatory indices (SIRI, NLR, MLR, SII) and lipid profile abnormalities (higher TC and LDL-C, lower HDL-C). Lp(a) and ANGPTL3 levels were significantly higher in the main group (p < 0.001 and p < 0.01, respectively). Logistic regression identified SIRI and ANGPTL3 as significant predictors of atherosclerosis, with the model demonstrating high accuracy (77%) and sensitivity (93%). Feature importance analysis confirmed the significance of SIRI and ANGPTL3, alongside traditional lipid biomarkers, in predicting disease presence. ROC analysis showed excellent model performance (AUC > 0.80). Clustering analysis revealed two distinct patient subgroups characterized by predominant inflammatory profiles or lipid metabolism disturbances. Conclusions: Systemic inflammation and lipid abnormalities play significant roles in early atherosclerosis among young adults. Elevated SIRI and ANGPTL3 levels are potent predictors of disease presence. The integration of inflammatory indices and lipid biomarkers into predictive models enhances risk stratification and supports personalized medicine approaches. Further research with larger cohorts is warranted to validate these findings and inform targeted prevention and intervention strategies.

The incidence of venous thromboembolism is estimated at around 3% of cancer patients. However, a majority of incidental pulmonary embolism (iPE) can be overlooked by radiologists in asymptomatic patients, performing CT scans for disease surveillance, which may significantly impact the patient's health and management. Routine imaging in oncology is usually reviewed with delayed hours after the acquisition of images. Nevertheless, the advent of AI in radiology could reduce the risk of diagnostic delay of iPE by an optimal triage immediately at the acquisition console. This study aimed to determine the accuracy rate of an AI algorithm (CIN A-iPE) in detecting iPE and the duration until the management of cancer patients in our center in addition to describing the characteristics of patients with a confirmed pulmonary embolism (PE). MATERIALS AND METHODS This is a retrospective analysis of the role of Avicenna's CE-certified and FDA-cleared CINA-iPE algorithm in oncology patients treated at Gustave Roussy Cancer Campus. The results obtained from the AI algorithm were compared with the attending radiologist's report and analyzed by both a radiology resident and a senior radiologist. In case of any discordant results, the reason for this discrepancy was further investigated. The duration between the exact time of the CT scan and analysis was assessed as well as the duration from the result’s reporting and the start of active management. RESULTS Out of 3047 patients, 104 alerts were detected for iPE (prevalence of 1.3%) while 2942 had negative findings. 36 of the 104 patients had confirmed PE while 68 alerts were false positives. Only one patient reported as negative by the AI tool was deemed to have a PE by the radiologist. The sensitivity and specificity of the AI model were 97.3% and 97.74% while the PPV and NPV were 34.62% and 99.97% respectively. Most causes of FP were artifacts (22 cases, 32.3%) and lymph nodes (11 cases, 16.2%). Seven patients experienced delayed diagnosis, requiring them to return to the ER for treatment after being sent home following their scan. The remaining patients received prompt care immediately after their testing with a mean delay time of 8.13 hours. CONCLUSION The addition of an AI system for the detection of unsuspected PEs on chest CT scans in routine oncology care demonstrated a promising efficacy in comparison to human performance. Despite a low prevalence, the sensitivity and specificity of the AI tool reached 97.3% and 97.7% respectively with detection of all the reported clinical PEs except one single case. This study describes the potential synergy between AI and radiologists for an optimal diagnosis of iPE in routine clinical cancer care.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

Homeostasis and its interaction with gene expression in the development and maintenance of living systems is discussed in order to formulate a new method to diagnose and treat diseases on this causative level. This includes an inquiry into the unsolved homeostasis problems of: location (where in the cell are calculations performed?), communication (what language used?), identity (set of plans/hierarchy of set points?) and computational (mechanisms used to make necessary adjustments?). As these functions require the processing of vast amounts of information which is communicated at every level of organization including the mechanisms of epigenetics, different computer models are discussed, with examples for each; analog, digital and the possibility of quantum biological. Each one allows certain properties and cell functions to emerge. The difference between functional homeostasis and dysfunctional homeostasis is discussed with strategies to indirectly study dysfunctional homeostasis in terms of epigenetic signatures. Hormesis is discussed as a mechanism to reverse the epimutations, leading to a method of treatment for almost any chronic disease. These topics are discussed as being a whole interconnected system.

Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) in a variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.

Background: Bacterial/fungal coinfections (BFC) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections on ICU admission. Methods: Secondary analysis of two prospective multicenter cohort studies with confirmed influenza A(H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). Performance was assessed by area under the ROC curve (AUC) and out-of-bag (OOB) for MLR and RF, respectively. Results: Of the 8,902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall predictive models showed modest performance with AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA and shock were factors associated with BFC in most models. Conclusion: Machine learning models for predicting respiratory BFC in patients with pandemic viruses are not able to predict adequately. However, the presence of factors such as advanced age, elevated procalcitonin or CPR and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU.

The SARS-CoV-2 virus (COVID-19) has led to an initiative to develop safe and effective vaccines for public health safety. In December 2020, the United States Food and Drug Administration (FDA) administered an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine. Other vaccines from Johnson & Johnson, Moderna, and AstraZeneca shortly followed. This paper aims to examine the EUA process for COVID-19 vaccine approvals, including the requirements for the safety and efficacy of data, along with the role of the FDA and EMA in the approval process. Further, public concerns about vaccine approvals, including issues on the approval process's safety, efficacy, and speed, were also discussed. Using qualitative analysis of the extracted studies, trends and insights into the factors influencing public acceptance of COVID-19 vaccines, such as vaccine hesitancy and misinformation, were discussed. Overall, a transparent and rigorous regulatory process for vaccine approval is critical for education efforts between policymakers, vaccine developers, and the public to address concerns for increased population vaccine uptake.

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, an HMC dye, impedes the proliferation of breast cancer cells, even without light. However, the mechanism by which IR-783 exerts its antiproliferative effects remains unclear. We aimed to determine the efficacy of PDT using IR-783 liposomes. A heptamethine cyanine (HMC) dye excited by long-wavelength infrared light and with high tissue permeability was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with tongue and breast cancers. IR-783 liposomes similarly inhibited cell proliferation in lung cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor, but also to the improvement of airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers.

For dental implant treatment to be successful, esthetics, functionality, and cleanability are all required of the superstructure, the final prosthesis. Screw fixation and cementation have been the conventional methods of choice for the crown prosthesis of implants, but these individual methods cannot fulfill all the requirements. As a solution to this problem, we have devised a new implant superstructure restoration method (inlay covering esthetic technique) using computer-aided design / computer-aided manufacturing inlays. This involves the placement of an inlay covering the access hole in a highly translucent partially stabilized zirconia crown. This technique expands the indications for implant treatment and improves the oral quality of life of patients.

This literature review focusses on diagnostics of Equine Asthma (EA), possible influencing factors on diagnostic techniques and latest developments in diagnosing horses during EA remission or in case of subclinical disease. Routine EA diagnostics include clinical examination of the respiratory system including percussion and auscultation, clinical pathology including white blood cells and arterial blood gas analysis, bronchoscopy to evaluate the amount and viscosity of respiratory secretion, bronchoalveolar lavage and cytology of tracheal aspirates (TA) and bronchoalveolar lavage fluid (BALF). Grading of EA severity and inflammatory subtype is based on BALF cy-tology, while TA cytology helps to rule out previous bacterial infections. Different factors have an impact on the airways regarding structure of the epithelium, cytology and inflammatory markers possibly influencing the diagnosis of EA. Short-term exercise increases the total cell count and inflammatory mediators in BALF of men, asymptomatic horses and other species. Further factors involve cold or chlorinated air, long-term training effects and the co-incidence of further respir-atory disease, in particular exercise-induced pulmonary hemorrhage. As BALF cytology may be unremarkable during EA remission and low-grade disease, exercise and other factors stressing the bronchial epithelium may help to diagnose these patients.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

Objectives: We aim to evaluate technical and clinical outcomes with E-nside stent-graft for thoraco-abdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PAAA) endovascular treatment at our University Hospital Center. Methods: Retrospective analysis of patients electively treated by inner branched EVAR (iBEVAR) between 05/2021 and 03/2023. Demographics, procedural and clinical data were analyzed. Technical success and clinical outcomes, such as access-site related complications were reported. Perioperative and early mortality rate, freedom from aortic reintervention, Target vessels (TVs) patency and endoleak rate were evaluated during the follow-up. Technical aspects (external iliac artery diameter, iliac tortuosity, extent of aortic coverage) were retrospectively analyzed. Results: Twenty-two patients included (age 75.9±5.5; 72.7% male). Aneurism extent was Craw-ford I=4 (18.2%), III=8 (36.4%), IV=5 (22.7%), V=1 (4.5%) and PAAA=4 (18.2%). Mean aortic di-ameter was 63.5±9.9mm. The technical success 95.5% (assisted primary success 100%). The clini-cal success 86.4%. Perioperative and early freedom from all-cause mortality rate 90.9% and 90%, respectively. No case of inter-stage aortic-related mortality reported, as no permanent/temporary spinal cord ischemia (SCI). Seventy-eight out of 81 patent TVs were incorporated through a bridging stent (96.3%). TV success 95.1%. Mean external iliac artery (EIA) diameter 7.5±1.1mm. Twelve patients (six women, 100%) were considered outside the instructions for use (IFU) due to narrow iliac arteries. One access-site related complication reported. Conclusions: Our experience confirms that E-nside has promising technical and clinical success rates, as low reintervention rate, but requires a great sacrifice of healthy aorta and adequate iliac arteries that still represent a limitation, especially among women. Mid- to long-term studies and prospective registries are mandatory to evaluate long-term efficacy and safety, as a comparison between E-nside and other alternative off-the-shelf solution.

Beginning in 2022, the Mpox outbreak, formerly known as monkeypox, has since spread to more than 100 countries and is now a global public health concern. This disease, caused by the Mpox virus, is usually mild, and most infected individuals recover within a few weeks without treatment. However, severe cases have been seen especially in children, pregnant women, or immunocompromised individuals. Antiviral medications such as brincidofovir, tecovirimat, and cidofovir were recently approved for Mpox; but these drugs are expensive and not easily obtainable. Therefore, identifying effective and low-cost drugs against Mpox and testing these through clinical trials remains a priority for global health. Drug repurposing is a well-known strategy for redeploying existing licensed drugs for newer indications, allowing for the shortest possible transition from bench to bedside. Recent in silico studies have determined the efficacy of minocycline, oleanolic acid, ursolic acid, and glycyrrhizinic acid against Mpox virus. Notably, oleanolic acid, ursolic acid, and glycyrrhizinic acid are some of the components of Japanese Kampo medicines, which are low-cost medicines prescribed daily in Japan. Thus, minocycline and Japanese Kampo medicines could potentially be used to treat Mpox.

Honey is a natural product that, thanks to its composition, particularly the high sugar content, is highly appreciated as an energy nourishment. In addition to sugars, it contains many other substances (carbohydrates, free amino acids, enzymatic proteins, organic acids, polyphenols) from which the therapeutic properties of honey arise: hydrating and osmotic activity, antimicrobial action, antioxidant and anti-inflammatory power. The present work aims to deepen the activity of skin protection exerted by honey, as a synergic result of its multiple therapeutic effects.Moreover, the study want to find possible correlations between biological properties and chemical-physical traits of honey. To carry out this research, five varieties of citrus honey, one of acacia honey, one of chestnut honey and, finally, one of multifloral honey were used. The honeys were first characterized by chemical-physical analysis (determination of water content, sugars, amino acids, polyphenols) and then subjected to qualitative melissopalynological analysis. Tests were also carried out to evaluate both their antioxidant power and the effect on collagenase, an enzyme involved in the degradation of collagen present in the extracellular matrix and, therefore, in the processes of skin aging. Finally, they were used in in vitro experiments to assess their action in stimulating cell viability and proliferation on human keratinocytes.

Aim: This study aims to analyze the collaborative networks and identify key players in autoimmune pancreatitis (AIP) research from 2000 to 2023. Using data from the Web of Science (WoS) Core Collection, I assess the structure and evolution of co-authorship networks to understand collaboration trends and influential researchers in the field.Method: I conducted a network analysis of co-authorship patterns in AIP research using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The analysis included macro-level indicators: network density, clustering coefficient, components, and average distance, as well as micro-level indicators: degree centrality, closeness centrality, and betweenness centrality. These metrics were used to evaluate the connectivity, clustering, and key nodes within the network across three distinct periods: 2000-2009, 2010-2019, and 2020-2023.Result: The analysis revealed that the co-authorship network in AIP research evolved from a fragmented structure with limited collaboration in the early 2000s to a more interconnected but still dispersed network in recent years. Despite an increase in network density and a decrease in the number of disconnected components over time, the overall structure remains highly clustered, with many researchers operating within isolated groups. Key figures, such as Kazuichi Okazaki, Terumi Kamisawa, and Shigeyuki Kawa from Japan, consistently ranked high in centrality measures, highlighting their significant influence and leadership in the field. The findings suggest that while local collaborations are strong, broader international connections are still developing.Conclusion: This study provides a comprehensive overview of the collaborative landscape in AIP research, identifying central researchers and highlighting persistent fragmentation within the network. The prominent role of Japanese researchers in shaping the field underscores the importance of fostering greater international collaboration to bridge gaps between research clusters. Enhancing global partnerships could lead to more integrated and impactful research outcomes, ultimately advancing the understanding and management of autoimmune pancreatitis.

Anxiety-based cognitive distortions pertaining to somatic perception (ABCD-SP) - primarily catastrophizing, fear avoidance and kinesiophobia- have been repeatedly linked to worsening chronic, non-cancer pain (CNCP) outcomes of increased disability, amplified pain, ineffective opioid use, and opioid misuse. Several studies have suggested that treating ABCD-SP can improve pain outcomes, yet identification and targeting of ABCD-SP is not part of the standard medical pain assessment and treatment plan. Utilizing a narrative review of proposed mechanisms, published patient perspectives, and study correlates connecting these cognitive distortions with CNCP outcomes, a better practice approach to the delivery of standard medical CNCP care can be deduced and formulated into a Belief and Behavior Action Plan (BBAP) for medical clinicians treating CNCP to implement into initial and maintenance care planning. These recommendations require relatively few resources to implement and have the potential to disseminate more effective CNCP treatment on a large scale now, and into the new frontier of cognitive computing within medicine.

The peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated stea-tohepatitis (MASH) and fibrosis in mouse models, by signaling via the kisspeptin 1 receptor (KISS1R). However, whether kisspeptin impacts fibrogenesis in the human liver is not known. We investigated the impact of a potent kisspeptin analog (KPA) on fibrogenesis using human precision cut liver slices (hPCLS) from fibrotic livers from male patients, in human hepatic stellate cells (HSCs), LX-2 and in primary mouse HSCs. In hPCLS, 48 h and 72 h of KPA (3 nM, 100 nM) treatment decreased collagen secretion, and lowered expression of fibrogenic and inflammatory markers. Immunohistochemical studies revealed that KISS1R is expressed and localized to HSCs in MASH/fibrotic livers. In HSCs, KPA treatment reduced transforming growth factor beta (TGFb)-induced expression of fibrogenic and inflammatory markers, in addition to decreasing TGFb induced collagen secretion, cell migration, proliferation and colony formation. Mechanistically, KISS1R signaling downregulated TGFb signaling by decreasing SMAD2/3 phosphorylation, via activation of protein-phosphatases PP2A, that dehosphorylates SMAD 2/3. This study revealed for the first time that kisspeptin reverses human hepatic fibrogenesis thus identifying it as a new therapeutic target to treat hepatic fibrosis.

Background: Obesity and Type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity plays a key role in these diseases through biological mechanisms. This study examined the effect of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.

To date, the percentage composition of the lung microbiome in bronchopulmonary cancer has not been summarized. Existing studies on identifying the lung microbiome in bronchopulmonary cancer through 16S rRNA sequencing have shown variable results regarding the abundance of bacterial taxa. Objectives: To identify the predominant bacteria in the lung microbiome of bronchopulmonary cancer from samples collected through bronchoalveolar lavage and to assess their potential role in the diagnosis of bronchopulmonary cancers. Data Sources: A systematic review of English articles using MEDLINE, Embase, and Web of Science. Search terms included lung microbiome, lung cancer, bronchoalveolar lavage. Study Selection: Randomized clinical trials that investigated the lung microbiome in bronchopulmonary cancer with samples collected via bronchoalveolar lavage. Data Extraction: Independent extraction of articles using predefined data fields, including study quality indicators. Data Synthesis: Nine studies met the inclusion criteria, focusing on those that utilized a percentage expression of the microbiome at the phylum or genus level. There was noted heterogeneity between studies, both in terms of phylum and genus, with a relatively constant percentage of the Firmicutes phylum and the genera Streptococcus and Veillonella being mentioned. Significant differences were also observed regarding the inclusion criteria for study participants, the method of sample collection, and data processing. Conclusions: To date, there is no consistent percentage pattern at the phylum or genus level in bronchopulmonary cancer, with the predominance of a phylum or genus varying across different patient cohorts, resulting in non-overlapping outcomes.

Background: Mitral regurgitation (MR) is a common valvular disorder linked to high morbidity and mortality. For patients unsuitable for surgery, transcatheter mitral edge-to-edge repair (TEER) with the MitraClip® G4 system offers an alternative. This study aims to evaluate procedural, echocardiographic, functional, and quality of life (QoL) outcomes in patients who underwent TEER with the MitraClip® G4 system, along with possible predictors of New York Heart Associa-tion (NYHA) class I at 30 days and 1 year. Methods: Patients with moderate-to-severe (3+) or se-vere (4+) degenerative MR (DMR) or functional MR (FMR), classified as NYHA class III or IV, who underwent TEER with the MitraClip® G4 system at our center between January 2021 and De-cember 2023 were included. Results: A total of 83 patients [71% FMR, 66% male, median (IQR) age 70 (11) years] underwent TEER, with 100% procedural success. MR ≤2+ was achieved in 100% and 98% of patients at 30 days and 1 year, respectively. NYHA class I or II was achieved in 100% and 96.8% of patients at 30 days and 1 year, respectively. The Kansas City Cardiomyopathy Ques-tionnaire (KCCQ) score improved from 51±20 at baseline to 69±15 at 30 days (p< 0.001) and 70.5±15 at 1 year (p< 0.001). Lower baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) pre-dicted achieving NYHA class I at 30 days (HR: 0.63, 95% CI: 0.41–0.95, p = 0.030), while lower Eu-ropean System for Cardiac Operative Risk Evaluation II (EuroSCORE II) and NT-proBNP pre-dicted it at 1 year [(HR: 0.50, 95% CI: 0.28–0.89, p = 0.019), (HR: 0.67, 95% CI: 0.44–0.99, p = 0.049), respectively]. Conclusions: The MitraClip® G4 system provides significant improvements in MR severity, functional class, and QoL. Lower NT-proBNP and EuroSCORE II were strong predictors of achieving optimal functional status (NYHA class I).

GRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, namely serum, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a scarcity of data linking both intracellular and extracellular GRP78/Bip to the disease activity and progression of RA within the realm of rheumatology. This study was undertaken to investigate the differential expression of intracellular and extracellular GRP78/Bip in serum, SF, and synovium, and to determine their association with disease activity and progression in patients with RA. Patients with RA, osteoarthritis (OA), and traumatic meniscal injury (TMI) without radiographic OA were consecutively recruited for the study at our hospital. Among the patients with RA, six different subgroups were established based on their disease activity and progression. Disease activity was measured using the DAS28 criterion, while disease progression was evaluated using the Steinbrocker classification grade. This study conducted a comprehensive analysis of the differential expressions of GRP78/Bip in multiple sample types, including serum, SF, and synovium, with the specific emphasis on their associations with disease activity and progression in RA. The expression levels of GRP78/Bip, TNF-α, and IL-10 were significantly elevated in serum, SF, and synovium of patients with RA when compared to both the CON and iCON groups(P<0.05). During the status of disease activity, serum and synovium exhibited increased levels of GRP78/Bip, TNF-α, and IL-10 compared to periods of disease remission (P<0.05). However, in SF, the levels of GRP78/Bip and IL-10 were reduced, while TNF-α levels were elevated during disease activity status as opposed to the remission status (P<0.05). In serum and synovium of patients with RA, positive correlations were observed between the levels of GRP78/Bip expression and the stages of disease progression, along with TNF-α and IL-10 levels. Additionally, in SF, positive correlations were identified between the expression levels of GRP78/Bip and the concentrations of TNF-α and IL-10; conversely, a negative correlation was noted between GRP78/Bip expression and stages of disease progression. The differential expressions of GRP78/Bip in serum, SF, and synovium indicated that the potential role and function of GRP78/Bip might vary depending on its location within the specific biological fluids and tissues. The presence of intracellular and extracellular GRP78/Bip was associated with disease activity and progression of RA, 2 suggesting the involvement of GRP78/Bip in the pathogenesis and development of this debilitating autoimmune disorder, as well as its potential as a biomarker for monitoring disease activity and progression.

Background: The acute hemodynamic response to isometric exercise in hypertensive patients ischemic heart disease (IHD) has been poorly investigated. The aim of this study was to assess acute changes on left ventricular myocardial work (MW) during isometric bilateral knee extension in patients with IHD. Methods. Twenty stable hypertensive patients with IHD and ten healthy, age-matched controls (HC) were enrolled. All subjects performed an isometric knee extension exercise, at 30% of their maximal voluntary contraction. The effort was maintained for three minutes or until exhaustion. At baseline, at peak exercise and after 10 minutes of recovery, echocardiography evaluation was perforned, blood pressure (BP) and heart rate (HR) were measurement. Results. The exercise was well tolerated by all subjects. At peak exercise: systolic BP in the IHD was significantly higher than HC (37.6± 7.2 vs 8.4±2.3 mmHg; p = 0.002). HC group had a greater increase in HR than IHD (19.7±6.2 vs 8.4±2.2 bpm; p = 0.009). E/E’ ratio increased in IHD and was unchanged in control. Global work index increased significantly in IHD compared to HC (+15% vs +3%; p 0.026). Global constructive work increased significantly in IHD compared to HC (+29.8% vs +7.4 respectively, p 0.031). Global waste work increased by 92.3% in IHD and was unchanged in HC. Global work efficiency decreased in IHD (-18%) while was unchanged in HC (between-groups p 0.019). Stroke volume decreased in IHD. and was unchanged in HC. Cardiac output was unchanged in IHD while it increased in HC. Conclusion: In patients with hypertension and underlying IHD, an acute isometric load caused a great increase in systolic BP and LV filling pressure. It follows a mostly ineffective increase of MW that fails to maintain stroke volume.

Background: anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are clinically effective in preventing migraine attacks, photophobia, and migraine aura associated with headaches. However, no study has yet investigated the effectiveness of CGRP mAbs in preventing migraine aura without headache. Case report: A female patient of 49 years old has a long history (since age 10) of photosensitivity and typical migraine aura without headache. The symptoms slightly responded to oral medication but did not completely resolve. Just one day after the administration of galcanezumab, her photo-hypersensitivity and migraine aura had completely resolved. Consequently, the administration of the oral migraine preventive medication was discontinued. Monthly galcanezumab at the dose of 120 mg has been continuously given and she did not experience any aura or headache so far. Conclusions: CGRP mAbs is considered an effective treatment method in preventing migraine aura without headache. Although CGRP mAbs do not penetrate the blood-brain barrier, trigeminal nerve stabilization with CGRP mAb can prevent cortical spreading depression.

Background: Rod fracture (RF) is the most common cause of revision in adult spinal deformity (ASD) surgery, and various treatment strategies for preventing RF are reported in literature. This retrospective study involving 139 ASD patients (aged ≥65 years and a minimum 2-year follow-up) who underwent long-segment fixation from T10 to sacrum with pedicle subtraction osteotomy (PSO), analyzed long-term results, including radiographical parameters and the incidence of recurrent RF (re-RF), to determine the most effective revision method for preventing RF. Methods: Patients were classified into three groups according to the revision method performed for RF; simple rod replacement (SR group, n=17), lateral lumbar interbody fusion around PSO site (LLIF group, n=8), and accessory rod integration (AR group, n=22). Baseline characteristics, radiographical and clinical parameters were analyzed. Results: RF occurred in 47 patients (34%) at an average of 28 months following primary deformity correction. Re-RF occurred in six patients (13%) at an average of 37 months. Re-RF occurred most commonly in SR group (p=.048). Every re-RF in SR group occurred at the PSO site, none occurred in LLIF group, and one in AR group occurred near L4–5. After both primary deformity correction and revision surgery, spinopelvic parameters had shown favorable results and clinical outcomes had improved in all three groups, without significant intergroup differences. Conclusions: Accessory rod integration or additional LLIF around the PSO site seems to provide greater strength and stability to the previously fused segments than simple rod replacement, which demonstrates the need for additional support in revision surgery for RF after PSO.

The resurgence of mpox, particularly in regions where the virus was previously non-endemic, has reignited interest in the cross-protective potential of smallpox antibodies. Given the genetic similarity between the mpox virus and variola virus (the causative agent of smallpox), antibodies generated against smallpox may offer a degree of protection against mpox. This study investigates the presence of smallpox and mpox antibodies in human immunoglobulin preparations containing IgG against both mpox virus and vaccinia virus using ELISA techniques. The implications of these findings for post-exposure prophylaxis (PEP) are discussed in light of the recent mpox outbreaks in Africa, as reported by the World Health Organization (WHO). Current data suggest that smallpox vaccination, even decades after eradication, may confer substantial protection against mpox, thereby serving as a critical tool in managing emerging outbreaks. Further the presence of mpox antibodies in immunoglobulin preparations was also significant. These findings strongly suggest the potential use of intravenous immunoglobulins preparation as possible therapeutic strategy. Particularly it also underscores the need for further research into the development of targeted post-exposure prophylaxis strategies that leverage the cross-reactivity of orthopoxvirus antibodies.

Background Hepatic resection offers promising outcomes for patients with hepatocellular carcinoma (HCC) but can be constrained by factors like patient suitability. Continuous advancements in laparoscopic and robotic technologies have made minimally invasive hepatectomies (MIH) viable alternatives to open hepatectomies with benefits in recovery and complications. Materials and Methods We completed a retrospective review on 138 HCC patients at the Hume-Lee Transplant Center that underwent OH or MIH between 2010 and 2020. Univariate and multivariate analyses were completed on demographic, clinical, and tumor-specific data were collected to assess the impact of these variables on overall and disease-free survival at 1-, 3-, and 5-years. Preoperative metrics like length of hospital stay (LOS) and operation duration were also evaluated. Results Of the 109 OH and 29 MIH patients, MIH patients demonstrated shorter LOS and operative times. However, overall survival (OS) and disease-free survival (DFS) were similar between groups, with no significant variations in 1-, 3-, and 5-year survival rates. Ages > 60 years and lack of preoperative transcatheter arterial chemoembolization (TACE) were significant predictors of inferior OS and DFS in multivariate analyses. Conclusions MIH is an efficient substitute to OH with comparable survival even in older patients. The reduced LOS and operation time enhances its feasibility, and older patients previously denied for curative resection may qualify for MIH. Preoperative TACE also enhances survival outcomes, emphasizing its general role in managing resectable HCCs. Both robotic and laparoscopic hepatectomies offer acceptable short- and long-term clinical outcomes, highlighting MIH as the standard choice for HCC patients.

COPD is a "heterogeneous lung condition characterized by chronic respiratory symptoms. It is a leading cause of death and illness and is associated with a substantial economic burden worldwide. Furthermore, it is marked by frequent exacerbations, which significantly contribute to morbidity and mortality, as well as the overall burden. These exacerbations are frequently triggered by bacterial infections.So far, the most commonly implicated Bacteria are Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.The advent of culture-independent techniques, such as next-generation sequencing techniques (NGS), allows us to characterise the lung microbiome in different disease states.

No consensus exists on whether acute aerobic exercise alters the glomerular filtration rate in older adults. Objective: To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Methods: Eighteen healthy, sedentary older adults (12 men and eight women) voluntarily participated in the study. The participants underwent three standardized aerobic exercise tests (100%, 80%, and 60% of the maximal heart rate) on a bicycle ergometer. Blood samples were collected to determine cholesterol, triacylglycerol, glucose, serum creatinine (Cr), Cystatin C (CysC) concentrations, and eGFR. Results: eGFR and serum concentrations of Cr and CysC were not modified at any exercise intensity. There was a negative correlation between blood total cholesterol vs. eGFR (R= -0.512, R= -0.582, R= -0.531; p &lt;0.05) at rest, 60%, and 100% of the maximal heart rate, respectively. Besides, a negative correlation existed between age vs. eGFR at 60% of the maximal heart rate (R= -0.516; p &lt;0.05). Conclusion: Short-time aerobic exercise of low, moderate, and vigorous intensity did not significantly affect eGFR and is considered safe for kidney function in healthy, sedentary older adults.

Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointes-tinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation and metabolic processes was con-ducted. Clinical implications of chemerin on gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion and progression. Conclusions: Chemerin could repre-sent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observa-tional studies should validate its clinical applications and investigate the efficacy of chemerin in-hibitors as potential therapeutic targets.

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for optimization of their use with combination or consolidation strategies, which necessitates prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in current knowledge and suggest that insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients.

There have been multiple technological advancements that promise to gradually enable devices to measure and record signals with high resolution and accuracy in the domain of Brain Computer Interfaces (BCI). Multi-modal BCIs have been able to gain significant traction given the potential to enhance signal processing by integrating different recording modalities. In this review, we explore the integration of multiple neuroimaging and neurophysiological modalities including Electroencephalography (EEG), Magnetoencephalography (MEG), Functional Magnetic Resonance Imaging (fMRI), Electrocorticography (ECoG), and Single-Unit Activity (SUA). This multimodal approach leverages the high temporal resolution of EEG and MEG with the spatial precision of fMRI, the invasive yet precise nature of ECoG, and the single-neuron specificity provided by SUA. The paper highlights the advantages of integrating multiple modalities, such as increased accuracy and reliability, and discusses the challenges and limitations of multimodal integration. Furthermore, we explain the data acquisition approaches for each of these modalities. We also demonstrate various software programs that help in extracting, cleaning, and refining the data. We conclude this paper with discussion on the available literature highlighting recent advances, challenges, and future directions for each of these modalities.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analyzing the amplitude of the first block (100 sweeps), and to evaluate habituation by measuring the amplitude response decrement after 6 blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEPs parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication off. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli.

Aim: This study aims to analyze the structure of the co-authorship network in Budd-Chiari syndrome (BCS) research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 2,877 publications related to BCS research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The results revealed a highly fragmented network structure in the early years (2000-2009), characterized by low network density (0.0017) and a large number of disconnected components (533). Key researchers such as Aurelie Plessier and Dominique Valla emerged as central figures in terms of degree and closeness centrality. In the 2010-2019 period, the network showed slight improvements, with density decreasing to 0.0016 but an increase in the number of components to 645, indicating persistent fragmentation. From 2020 to 2023, the network demonstrated increased cohesiveness with a density of 0.0032 and a reduction in components to 376. Influential researchers in the final period included Virginia Hernandez-Gea and Valerie Paradis, who played pivotal roles in connecting disparate research clusters.Conclusion: The co-authorship network analysis of BCS research over the past two decades highlights a gradual yet incomplete evolution towards greater collaboration and integration among researchers. While the network's cohesiveness has improved, significant fragmentation remains, suggesting that further efforts are needed to enhance global and interdisciplinary collaboration. Addressing these challenges is crucial for fostering a more connected and productive research community that can advance the understanding and management of BCS.

Introduction: Transesophageal echocardiography (TEE) is a vital diagnostic tool in clinical prac-tice, particularly in transcatheter interventions where it aids in both pre-operative planning and intra-operative guidance. Traditional TEE probes often require general anesthesia due to patient discomfort. However, the development of miniaturized TEE probes presents a promising alter-native, enabling routine examinations and interventions with minimal sedation. This study evaluates the feasibility of performing a complete 2D/4D TEE protocol with the new 4D-mini-TEE probe in echocardiography departments and its application in transcatheter interventions. Methods: This prospective, observational study included 30 consecutive patients from two high-volume European hospitals (Interbalkan Medical Center, Thessaloniki, Greece, and Rennes University, France) undergoing TEE or transcatheter interventions. The new 4D-mini-TEE 9VT-D probe (GE Healthcare) was utilized. The quality of the images and the tolerance of the probe were assessed in the Cath lab during interventions and in the echocardiography department during routine TEE examinations. Results: Direct comparison of the 4D-mini-TEE probe with the standard 6VT-D probe, confirmed the excellent image quality of this new pediatric probe. Most of the patients required minimal sedation or local oropharyngeal anesthesia, with satisfactory tolerance reported. Most of the transcatheter procedures did not require general anesthesia and intubation, resulting in shorter procedural time. Both 2D and 4D imaging modalities offered adequate intra-operative guidance for transcatheter procedures. Conclusions: The 4D-mini-TEE probe delivers exceptional imaging capabilities for routine ex-aminations and transcatheter interventions without needing sedation. Its use reduces esophageal trauma and the need for general anesthesia, enhancing patient comfort and safety.

The purpose of the study is to analyse and to identify specific structural characteristics of melanocytic nevi, to youth pacients. Using the optical microscope, could be possible a proper describtion related melanocytic nevi. In this study play a significant role, different factors, such as genetic, epigenetic, microbiomic and proteomic factors. Future directions refers to preventive and prophylactic methods. Disease diagnostic and management directions are also important key points.

One-third of approximately 10 million deaths due to sepsis in a year are due to acute lung injury, and there is no effective treatment yet. Due to its high phenol content, Punica granatum L. bark extract exhibits high antioxidant activity. Amifostine is a free radical scavenger that converts into active thiol in tissues. This study aimed to investigate the antioxidative and anti-inflammatory effects of 2 different doses of PG peel extract and amifostine in sepsis-related acute lung injury. Fifty rats were randomly allocated into 5 groups. Group 1 served as the control group with no sepsis. The remaining groups 2-5 served as the cecal-ligation-puncture (CLP) groups. Group 3 was administered 200 mg/kg amifostine intraperitoneally (ip) 15 minutes before sepsis induction. Groups 4 and 5 received, respectively, 250 mg/kg and 500 mg/kg PG peel extract by oral gavage 9 days before and 30 minutes after the CLP procedure, with a total of 10 doses. MMP-2 and MMP-9 were investigated by immunohistochemical methods. MMP-2 and MMP-9 concentrations significantly increased in the sepsis group compared to the other 4 groups. This study provides evidence that Amifostine and Punica granatum pericarp benefit lung tissue in a rat model of sepsis induced by cecal-ligation puncture.

The objective of this study was to compare single-needle arthrocentesis with the conventional two-needle arthrocentesis, as well as, additional intracapsular injection of hyaluronic acid or platelet rich fibrin. 96 patients with established osteoarthritis (OA) (n= 48) or with internal de-arrangement (DD) (n= 48) were assigned for single-needle arthrocentesis with distension of the joint or conventional two-needle arthrocentesis with or without intracapsular injection of the medication (hyaluronic acid- HA or platelet-rich plasma- PRP) performed every month in the period of 6 months. The maximum mouth opening and pain as measured by the visual analog scale (VAS) were compared. Each group exhibited significant improvement: decrease of pain and in-creased mouth opening. Single- puncture technique provided similar pain reduction as two needle approach but provided significantly better results in maximum mouth opening. Reduction of pain was similar when comparing between the OA and DD cohorts, however patients with disc dis-placement reached significantly better mouth opening than OA. Intracapsular application of medication contributed to significant decrease of pain in both HA and PRP groups, with plate-let-rich fibrin being significantly superior in terms of mouth opening increase over HA.

Background: We explored the potential value of serum MUC5AC (sMUC5AC) as a biomarker to guide perioperative management of early-stage pancreatic ductal adenocarcinoma (PDA) patients receiving neoadjuvant therapy (NAT). Methods: We performed enzyme-linked immunoassays using a human MUC5AC kit (NBP2-76703) in serum samples obtained from The Ohio State University biorepository (between January 2010 and June 2021). Univariate (UV) and multivariate (MV) Cox regression models were used to quantify progression-free survival (PFS); clinical and pathological variables were adjusted in the MV models. UV logistic regression analysis was utilized to examine the association of sMUC5AC with pathological features and survival. 2 Results: Overall, 23 samples (19 FOLFIRINOX, 3 gemcitabine/nab-paclitaxel, 1 FOLFOX) were available for analysis. The median age was 66 years, and 52% were females. sMUC5AC was associated with a) treatment response, margin status, and residual disease (R0 vs. R1/R2) (all P<0.05); b) PFS on both UV (hazard ratio (HR) of 1.4, 95% confidence interval (CI) of 1.07 to 1.82, P=0.01) and MV (HR of 49.2, 95% CI, 4.4 to 1008.3, P=0.002) analyses; and c) PFS in pre-surgery models along with carbohydrate antigen 19-9 (CA19-9) measured on the same day alone (HR of 1.47, 95% CI, 1.06 to 1.93, p=0.04), with CA19-9 on the same day, and NAT regimen (HR of 1.44, 95% CI, 1.12 to 1.93, p=0.01), and with CA19-9 on the same day, NAT regimen, and CA19-9 at diagnosis (HR of 1.52, 95% CI, 1.1 to 2.09, p=0.007). Conclusion: sMUC5AC shows promise to helping to predict outcomes in our preliminary study. Larger prospective studies should validate these findings.

Emerging risk factors for childhood (<5 years) anemia cases in low-income countries have not been limited to COVID-19 and the spread of infectious diseases, hidden hunger, and other economic factors. Yet the effects of climatic factors, such as ambient temperatures, on child anemia have been in its infancy. In this population-based study, we study the region-specific associations between child anemia and ambient temperatures in 43 countries of Africa from 2000-2019. Using generalized linear regression models, we found that after adjusting for key covariates, the risk that temperatures pose on child anemia varies across the four African regions (Western, Eastern, Central, and Southern). This suggests that ambient temperatures have varying effects on child anemia by region. Other studies are needed in other low-income settings to expand our findings.

There are currently no effective screening measures to detect early or occult tubo-ovarian cancers resulting in late-stage detection and high mortality. This work explores whether an optical imaging catheter can detect early-stage tubo-ovarian cancers or precursor lesions where they originate in the fallopian tubes. This device collects co-registered optical coherence tomography (OCT) and autofluorescence imaging (AFI). OCT provides three-dimensional assessment of underlying tissue structures; autofluorescence imaging provides functional contrast of endogenous fluorophores. Ex vivo fallopian tubes (n=28; n=7 cancer) are imaged; we present methods for the calculation of and analyze eleven imaging biomarkers related to fluorescence, optical attenuation, and OCT texture for their potential to detect tubo-ovarian cancers and other lesions of interest. We visualize folded plicae, vessel-like structures, tissue layering, hemosiderin deposits, and regions of fibrotic change. High grade serous ovarian carcinoma appears as reduced autofluorescence paired with homogenous OCT and reduced mean optical attenuation. Specimens containing a cancerous lesion demonstrate significant increase in median autofluorescence intensity and decrease in entropy compared specimens with no lesion. Non-cancerous specimens demonstrate an increase in optical attenuation in the fimbriae when compared to the isthmus or ampulla. We conclude that this approach shows promise and merits further investigation of diagnostic potential.

Various measures have been attempted to prevent infectious diseases in calves, such as envi-ronmental improvement and vaccine administration. Probiotics are commonly used to im-prove the body condition of newborn calves and prevent disease. In our previous research, Lactiplantibacillus plantarum RGU-LP1 (LP1) inhibited the expression of inflammatory cyto-kines in PBMC from cows fed LP1. In this study, we evaluated the effect of LP1 on calf growth and disease control. Methods: Twenty-six one-week-old Holstein bull calves were divided into two groups (13 each), LP1 group (LP1 treated) and CN group (no LP1 fed), and tested as follows. The LP1 group was fed lyophilised LP1 (10⁹ CFU/head/day) in milk replacer for 40 days. The CN group was fed the same diet only. Calves were followed for 63 days. During this period, the weight and treatment times of the calves were recorded. Faeces and blood were collected from each calf during this period. Faeces were examined for gut microbiota, and blood for immune assay and cytokine gene expression. The LP1-treated group showed a de-crease in disease incidence and an increase in body mass compared to controls. Results: The average treatment cost during the observation period was significantly reduced compared to the CN group. The expression of TGFβ and IL10, inhibitory cytokines of inflammation, was sig-nificantly increased. The simultaneous expression of this set of inhibitory molecules resulted in low serum IL1β levels during the growth period. Conclusions: The Th1-type cytokine IFNγ was also significantly increased in LP1-treated calves. By reducing the number of disease treatment times and increasing body weight, LP1 is effective in preventing infectious diseases in calves. In addition, the increase in IFNγ by LP1 indicates improved Th1-type immunity in calves. These results show that LP1 has effects on the regulated inflammatory response and growth of calves.

Background: In response to the COVID-19 pandemic, the European Association of Urology (EAU) Guidelines defined priority groups to guide the prioritization of surgery for urological malignancies. The objective of this study was to evaluate the impact of the COVID-19 prioritization recommendations on tumor pathological characteristics in a real-world setting at our academic referral Institution. Methods: We compared baseline and pathological tumor features of all patients with urological malignancies treated during the pandemic period (2020-2021) versus in the post-pandemic period (2022-2023). Our institution adhered to the International recommendations and prioritized those cases defined as “high-risk”. Results: Data of 9196 patients treated for urological malignancies were reviewed and grouped according to period of surgery (4401 in the pandemic vs 4785 in non-pandemic period). The overall number of surgical procedures was comparable for all diseases except for the number of radical prostatectomy (1117 vs 1405; p=0.03) and partial nephrectomy (609 vs 759; p=0.02) which were significantly lower in the pandemic period. Regarding tumors’ pathological features, none of the recorded variable was found to differ according to period of surgery, including disease stage, tumor grading, presence of necrosis, lymphovascular invasion, histological variants. Conclusion: A correct policy of prioritization of oncological pathologies during emergency periods and a centralization of oncological cases in reference centers reduces the possible risk of worsening cancer disease features related to the reorganization of healthcare resources.

Cervical cancer is 4th the most common cancer in women worldwide. Due to the prevalence of HPV in the population (80-90%), the scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, ISH assays that use automated signal-detecting methods in ormalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. To evaluate automatic signal detection of in situ hybridization (ISH) assay for detecting human papillomavirus (HPV) DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Our findings showed significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = -7961.82 CI95 [-17230.00; -199.21], p = 0.005. Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is ​​the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.