Infection-related cardiovascular diseases (CVDs) represent a significant health challenge, necessitating novel therapeutic strategies targeting key receptors involved in inflammation and infection. Antimicrobial peptides (AMPs) offer a promising approach, potentially disrupting pathogenic processes. This study aimed to investigate the efficacy of AMPs as therapeutic agents by examining their interactions with critical CVD-related receptors. A comprehensive computational approach was utilized to assess the interactions between AMPs and receptors associated with CVDs. Molecular docking studies were conducted to evaluate AMP binding to target receptors: ACE2, CRP, MMP9, NLRP3, and TLR4. The top-performing AMPs were further analyzed through 100 ns molecular dynamics (MD) simulations, and their binding affinities were quantified using MM/PBSA calculations. The analysis revealed that Tachystatin, Pleurocidin, and Subtilisin A exhibit strong binding affinities to key CVD-related receptors, including ACE2, CRP, and MMP9. These AMPs demonstrated the potential for disrupting receptor-peptide interactions critical to infection and inflammation. MD simulations confirmed the stability of AMP-receptor complexes, with MM/PBSA calculations showing significant binding energies. Future directions include conducting in vitro and in vivo studies to validate the therapeutic efficacy and safety of these AMPs in clinical settings.

Control of oxidation/antioxidation homeostasis is important for cellular protective functions, and disruption of the antioxidation balance by exogenous and endogenous ligands can lead to profound pathological consequences of cancerous commitment within cells. Although cancers are sensitive to antioxidation drugs, these drugs are sometimes associated with problems including tumor resistance or dose-limiting toxicity in host animals and patients. These problems are often caused by the imbalance between the levels of oxidative stress induced reactive oxygen species (ROS) and the redox efficacy of antioxidants. Increased ROS levels, because of abnormal function, including metabolic abnormality and signaling aberrations, can promote tumorigenesis and the progression of malignancy, which are generated by genome mutations and activation of pro-oncogene signaling. This hypothesis is supported by various experiments to show that the balance of oxidative stress and redox control is important for cancer therapy. Although many antioxidant drugs exhibit therapeutic potential, there is a heterogeneity of antioxidation functions, including cell growth, cell survival, invasion abilities, and tumor formation, as well as the expression of marker genes including tumor suppressor proteins, cell cycle regulators, nuclear factor erythroid 2-related factor 2, and Jun dimerization protein 2; and their effectiveness in cancer remains unproven. Here, we summarize the rationale for the use of antioxidative drugs in preclinical and clinical antioxidant therapy of cancer, and recent advances in this area using cancer cells and their organoids, including the targeting of ROS homeostasis.

Purpose of review: In this review, we discuss the importance of digital health equity and how social determinants of health (and intersectionality with race, ethnicity, and gender) affect cardiovascular health-related outcomes in digital health trials. We propose strategies to improve digital health equity as we move to a digitally-connected world for healthcare applications and beyond.Recent findings: Digital health has immense promise to improve population health by reaching individuals in their homes, at their preferred times. However, initial data demonstrate decreased patient engagement and worse cardiovascular outcomes for racial and ethnic minorities, leading to unequal uptake of digital health technologies. In addition, while women generally have higher uptake of technology, they are less likely to be referred by clinicians for digital health interventions. We highlight several exemplar trials and analyze their methodology for replication in future digital health research.Summary: The promise of digital health equity has not been reached due to exclusionary practices. Specific focus must be placed on societal/governmental policies that enable digital inclusion, particularly of racial and ethnic minority populations and women, to ensure that the expansion of digital health technologies does not exacerbate existing health disparities.

Aim: This study aims to analyze the structure and impact of research collaborations in colonoscopy from 2000 to 2023 by examining co-authorship networks. The goal is to understand the evolution of these networks, identify key contributors, and assess how collaborative relationships influence the field. Method: I conducted a comprehensive network analysis of co-authorship patterns using data from the Web of Science (WoS) Core Collection database. The analysis included 41,213 articles related to colonoscopy published between 2000 and 2023. Using Python (Version 3.10.5) and PyCharm (Software Version 2022.1.3), we evaluated the networks through macro-level indicators (network density, clustering coefficient, number of components, average distance) and micro-level indicators (degree centrality, closeness centrality, betweenness centrality).Result: The analysis revealed a network with increasing but still fragmented collaboration over the years. The network density showed low proportions of realized connections relative to potential ones, with a high clustering coefficient indicating tight-knit groups when collaborations occurred. The number of components remained high, reflecting a fragmented structure. Prominent researchers such as Hassan, Cesare (Italy) and Dekker, Evelien (Netherlands) consistently emerged as central figures across different periods, demonstrating significant roles in facilitating connections between various research clusters.Conclusion: The study highlights a growing but fragmented collaborative landscape in colonoscopy research. Key researchers have played central roles in connecting different parts of the network, yet there remains substantial room for further integration. Strengthening collaborations across isolated groups could enhance the cohesiveness and impact of research in this field.

Background - Compared to the da Vinci platform, there is limited experience with the Hugo RAS platform for colorectal surgery in Europe. This difference is especially notable when considering a single complex procedure, such as total colectomy. Aim - To demonstrate the feasibility and safety of using the Hugo RAS for assisted total colectomy. Clinical case- Female patient: eighteen-year-old with Familial Adenomatous Polyposis (FAP). Her IBM was 19. She underwent a total colectomy with ileorectal anastomosis using the Hugo RAS platform. The procedure took 230 minutes and had no complications. The postoperative period was uneventful. She was discharged from the hospital on the third postoperative day. Conclusion - The Hugo RAS platform is one of the emergent minimally invasive robotic platforms that can be used even in total colectomy if the proper patient selection is made. The placement choice of arms and trocars was crucial to obtain a similar operative time of the single laparoscopic approach. The certification of Hugo’s new instruments, such as energy devices and staplers, will make this platform even more competitive.

Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in pre-term and is still associated with increased mortality and morbidity. The great interest lies in iden-tifying early biomarkers that can predict the development of BPD. Objectives: This pilot study explores the potential of e-nose for early identification of BPD risk in premature infants by analyzing volatile organic compounds (VOCs) in the exhaled breath con-densate (EBC). Materials and Methods: Fourteen mechanically ventilated very preterm infants were included in the study. Clinical parameters and EBC were collected within the first 24 hours of life. The dis-criminative ability of breath-prints between preterms who did and did not develop BPD was in-vestigated by pattern recognition, machine learning algorithm, and standard statistical methods. Results: We found that e-nose probes can significantly predict the outcome of “no-BPD” vs “BPD”. Specifically, a subset of probes (S18, S24, S14, and S6) were found to be significantly predictive, with an AUC of 0.87, 0.89, 0.82, 0.8 and p=0.019, 0.009, 0.043, 0.047, respectively. Conclusion: The E-nose is an easy-to-use, handheld, non-invasive electronic device that quickly samples breath. Our preliminary study has shown that it has the potential for early prediction of BPD in preterms.

The expression of the oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, making necessary to discover novel com-pounds. The present work aims to characterize the chemopreventive properties of cucurbitacin D , a compound with a broad range of anticancer effectsin relation to the ZNF217 expression. Different cucurbitacins were isolated from the Vietnamese plant Elaeocarpus hainanensis. The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematology cancer to study their effects on viability, apoptosis, cell cycle and on the expression of ZNF217. Cucurbitacin D reduced the number of acute myeloid leukemia cells by increasing apoptosis and blocking cell cycle progression. It also significantly decreased ZNF217 expression but only in the OCI-AML3 Nucleophosmin-mutated cell line, but not in other hematologic cancers. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but not to apoptosis as established by the silencing of the same gene. The obtained results suggest Cucurbitacin D as a promising molecule to target the mutated Nu-cleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in depth investigatiion of its specificity.

Medical laboratories are perhaps the largest measurement industry in the world. The metrology terminology is relevant for effective and efficient communication, particularly where metrology activities are carried out by operators with different metrology skills. WASPaLM and SIPMeL have had some opportunities to propose changes to the documents in preparation to CLSI and ISO in order to harmonise the terminology with the Metrology Vocabulary (VIM). Many proposals have been accepted. Here we summarise some particularly critical points for metrological terms. The main terms discussed are: Measuring, measuring range, examination, pre-examination, post-examination, manufacturer, measuring instrument, quantitative, qualitative, semi-quantitative, processing, easurement error, maximum permissible error of measurement, total error of measurement, monitoring, variability, performance, reliability, influence, interference, selectivity, sensitivity, detection limit, reliability, pomparability, compatibility, control material. Despite all efforts to coordinate terminologies, it is inevitable that overlapping and inconsistent terminologies will continue to be used because documents and policies are produced in different contexts. In some ISO and CLSI documents, phenomena of magnetic attraction towards common words (such as “analysis” and derivatives), without any consideration of the true metrological meaning, are noted. The ISO and CLSI working groups show, alongside moments of openness, phenomena of true self-referential conservatism.

Background: Surgery for Chiari I malformation (CMI) is indicated when typical clinic-radiological features (syringomyelia, exertional headaches, sleep apnea syndrome, tetraparesis) are present. Sometimes patients have atypical complaints suggestive of otolaryngological (ENT) involvement, and it is sometimes difficult for the neurosurgeon to determine if these complaints are related to the CMI. Our aim was to describe postural control pattern in children with CMI using Computerized Dynamic Posturography. To our knowledge, this is the first study addressing postural instability in paediatric CMI patients. Methods: twenty-eight children aged 6 to 17 years with both radiologically confirmed CMI and clinical ENT complaints were included. Children were separated into 2 groups: operated and non-operated patients, basing on neurosurgical indication. Epidemiologic and posturographic results (CDP - Equitest®) were compared between both groups, as well as pre and post operatively in the group 2. Results: in Group 2 patients, significant improvement of global SOT was found after intervention. When the three sensorial aspects of postural control calculated by the system were independently assessed, the greatest improvement was in the vestibular ratio. We also observed an altered CoG pattern (“lateral deviation”) in the Group 2 patients, which significantly differed from Group 1. Lateral deviation was significantly reduced postoperatively in Group 2 patients. A correspondence between preoperative MRI and side of lateralisation on posturography was found in 4 children, but this cannot be regarded as significant due to the low number of patients. Conclusions: postural control seems to improve after surgery for CMI in children, mostly due to improvement in vestibular function. There is a correspondence between the side of lateral deviation and the side of greatest tonsillar descent on MRI and perioperatively. Further studies are needed to support these results and to confirm utility of CDP in CMI patients.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Background and Objectives: Most of the research of the BRCA1 inactivation is focused on monoallelic germline alterations and loss of heterozygosity in tumour. The aim of this study was to identify characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its impact to the event-free breast cancer survival prognosis. Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signalling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed. Results: Kaplan-Meier analysis showed tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation is favourable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusion: In this study we identified transcriptomic profile of differentially expressed genes TPSD1, FABP4, CARTPT and MMP9 as indicative for homologous recombination impaired tumours with tendency for better therapy results.

Poland suffered an epidemic of louse-borne typhus from 1916-1923, with 400,000 cases and more than 130,000 deaths. The causative factors were depressed economic conditions and a refugee crisis that engulfed Poland after World War I. The recognition of the epidemic in 1919 stimulated the creation of the League of Red Cross Societies (LRCS). However, the LCRS had limited resources and the Poles requested help from other governments and the League of Nations (LoN). The United States sent the American-Polish Relief Expedition to conduct delousing. However, the Polish-Soviet War of 1920 disrupted typhus control and exacerbated the refugee situation. The LoN belatedly organized an underfunded Epidemic Commission. The LCRS sent a research team that did ground-breaking work on the pathology of typhus. Into 1921, the epidemic continued, driven by refugees from typhus-stricken Russia. By 1924, typhus cases were finally approaching pre-World War I levels. Multiple factors lead to the amelioration of the epidemic. The repatriation of prisoners of war and displaced civilians had concluded by 1923. Also, there had been a steady influx of sanitary, food, economic, and medical aid from various organizations into Poland since 1919. Administratively, within Poland, the anti-typhus campaign was also conducted more effectively by the Extraordinary Epidemic Commissariat.

The use of natural health products (NHP) is constantly increasing worldwide. Among the most NHP consumed are the resins of Commiphora myrrha (C. myrrha) tree. Consumption of C. myrrha may result in herb-drug interactions that can lead to serious health consequences. This study aims to determine the herb-drug interactions based on the induction of drug-metabolizing enzyme cytochrome P-450 (CYP) 2C9 by a non-toxic boiled aqueous extract of C. myrrha and to unveil the potential involvement of xenobiotic-sensing nuclear receptors such as Pregnane X Receptor (PXR), a well-known CYP 2C9 transcription factor. Tested at low concentrations (0.01-10 g/mL) devoid of anti-proliferative effects, boiled C. myrrha resin aqueous extract upregulated CYP 2C9 gene and protein expressions in a dose-dependent manner, reaching a mean expression level exceeding 3.0-fold change in Hep G2 cells, compared with the basal level expressed in untreated cells. Furthermore, chemical analysis using mass spectrometry and computational molecular docking using in silico studies revealed that few C. myrrha resin-derived metabolites are strongly bound to PXR. In particular, the identified metabolite named diayangambin exhibited a predicted molecular docking score close to that of a native PXR ligand. The use of the nuclear receptor binding assays confirmed the binding between C. myrrha metabolite(s) and PXR, while no binding to the other xenobiotic-sensing nuclear receptor, the constitutive androstane receptor (CAR), was observed, suggesting that C. myrrha metabolite(s) are potential PXR agonists. In conclusion, although in vivo studies are needed, this study cautions patients, healthcare providers, and governmental regulators against the consumption of C. myrrha and diayangambin-rich preparations with a high potential for herb-drug interactions through drug-metabolizing CYP 2C9 enzyme induction, which could affect drug efficacy.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

Background: Whole-body computed tomography (WBCT) is commonly employed for primary screening in pediatric patients experiencing out-of-hospital cardiac arrest (OHCA) without prehospital return of spontaneous circulation (ROSC). This study aimed to evaluate the cause of OHCA on WBCT and compare WBCT findings between ROSC and non-ROSC groups in non-traumatic pediatric OHCA cases in an emergency department (ED) setting. Methods: A retrospective analysis was conducted on 27 pediatric patients (mean age: 32.4 months; median age: 10 months) who experienced non-traumatic OHCA without prehospital ROSC and were transported to our tertiary care hospital between January 2013 and December 2023. WBCT scans were performed to investigate the cause of OHCA, with recorded findings in the head, chest, abdomen, and subcutaneous tissues. Results: In all cases, the direct causes of OHCA were undetermined, and WBCT identified no fatal findings. Statistical comparisons of CT findings between the ROSC and non-ROSC groups revealed significant differences. The non-ROSC group had a higher incidence of brain swelling, loss of cerebral gray-white matter differentiation, symmetrical lung consolidation/ground-glass opacity, cardiomegaly, hyperdense aortic walls, narrowed aorta, gas in the mediastinum, and hepatomegaly compared to the ROSC group. Conclusions: Although WBCT did not provide the direct cause of OHCA, it clarified several indicative findings for non-ROSC. These imaging findings could support clinical decision-making, offering objective criteria for discontinuing resuscitation in pediatric OHCA cases where prehospital ROSC is absent.

Clinical trials are essential in the development of new medical treatments, offering crucial data on their safety and effectiveness. This study provides a comprehensive analysis of clinical trials registered on ClinicalTrials.gov, examining trends, challenges, and innovations that have shaped the field over the past century. Data were extracted on July 15, 2024, and analyzed to identify patterns in trial design, sponsorship, participant demographics, and geographical distribution. The analysis reveals a significant increase in clinical trial registrations, peaking in 2021, driven by the COVID-19 pandemic. Most trials focus on cancer, reflecting its global burden, and are predominantly interventional, with randomized controlled trials (RCTs) being the most common study design. However, challenges persist, including underrepresentation of certain demographics, limited global distribution, and insufficient reporting of trial results. Additionally, the underrepresentation of pediatric, elderly, and minority populations in trials limits the generalizability of findings. The analysis underscores the need for more inclusive and globally distributed research to address disparities in health outcomes.

Background The metabolic syndrome increases the risk of developing various systemic cancers. The prevalence of the metabolic syndrome in newly diagnosed glioblastoma patients is unknown. Further, there have been contradictory reports about how the metabolic syndrome affects clinical outcomes. Therefore, the purpose of this study is to test the hypothesis that the metabolic syndrome is associ-ated with increased prevalence of glioblastoma and worsened survival outcomes. Methods This retrospective cohort study examines seventy-three patients with isocitrate dehydrogenase (IDH)-wild type glioblastoma as it provides for a relatively homogeneous population to examine. Patient characteristics, vital signs, lab results, tumor molecular markers, and overall survival were analyzed. Patients with the metabolic syndrome and individual risk factors were identified and survival outcomes were examined. Results Our results demonstrate that there is a higher prevalence of the metabolic syndrome in our cohort of patients with glioblastoma than the general population (41% vs 33%). We also demonstrate that after correction for confounding variables, the metabolic syndrome is not significantly asso-ciated with overall survival (p = 0.1). When analyzing individual metabolic risk factors, we demonstrate that there is a significant association between the accumulation of metabolic risk factors and decreased survival (p = 0.03), and hyperglycemia emerges as a significant independent risk factor for decreased survival (p = 0.05). Conclusion These results suggest that metabolic risk factors can affect survival in patients with glioblastoma, which can have significant implications for clinical practice. These findings need to be further ex-plored through further clinical and mechanistic studies.

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum-palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum-palladium. Platinum-palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients As the number of cases is expected to increase in the future, the substance is expected to be effective as a drug, although it is currently classified as a soft drink.

Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

Macular pigment optical density (MPOD) is an important clinical biomarker for ocular conditions like macular degeneration, diabetic eye disease, and digital eye strain. Additionally, its measurements can be essential in health assessment for visual function, systemic diseases, and brain health. We aimed to assess the repeatability, agreement, and effects of the learning curve of the new portable handheld heterochromatic flicker photometer, Zx Pro, in measuring MPOD in a wide age range of ocular-healthy adults, compared to the MPOD measurements obtained using the clinically available QuantifEye device. Seventy-six participants performed one practice at-tempt and two study-related MPOD measurements with the Zx Pro and the QuantifEye. The Pearson correlation between the study-related MPOD measurements for Zx Pro and QuantifEye devices was 90% and 85%, respectively. Altman and Bland plots show excellent agreement between the device's MPOD data, with 95% limits of an agreement being -0.10 to +0.11 du. The mean difference between the practice attempt and the study-related measurements was not statistically significant for Zx Pro but was significant for QuantifEye (Repeated measures ANOVA p=0.325 and p=0.015, respectively). The Zx Pro provides excellent repeatable MPOD measurements, has an insignificant learning curve, and is in good agreement with the predicate device.

Background and Purpose: Moyamoya disease is a rare cerebrovascular disorder characterized by stenosis of the carotid arteries and the formation of collateral vessels at the base of the brain. While advances have been made in understanding its genetics, diagnostic criteria, and treatment strategies, further research is needed. The purpose of this literature review is to synthesize current knowledge on Moyamoya disease and identify areas for future study. Materials and Methods: A literature search of databases including PubMed, Embase, and Web of Science was conducted. Search terms included "Moyamoya disease" and related terms. Only English articles were reviewed, with no date restrictions. Relevant data was extracted and synthesized. Results: Key findings indicate that genetic factors such as RNF213 variants play an important role in disease susceptibility. Imaging modalities such as MRI and CT angiography are crucial for diagnosis. Surgical revascularization shows superior outcomes compared to medical management for ischemic and hemorrhagic presentations. However, optimal treatment for asymptomatic cases remains unclear. Neurocognitive and psychiatric sequelae can negatively impact quality of life. Promising research directions include investigating ethnic differences, developing biomarkers, and exploring novel therapeutics targeting molecular pathways. Conclusions: In summary, comprehension of Moyamoya disease has significantly progressed but gaps remain regarding treatment of certain populations and underlying mechanisms. Further research addressing these areas can aid in developing personalized care approaches and new interventions to improve patient outcomes

(1) Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. (2) Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). (3) Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510 – 0.802) and Day 3 (AUC 0.698; 95% CI: 0.559 – 0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572 – 0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 g/L on Day 3, resulting in R2 of about 31% (p < 0.001). (4) Conclusion: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Summary: Hypertension is a public health problem with serious social, economic, and health consequences. The World Health Organisation (WHO) estimates that 1 in 3 adults worldwide suffers from hypertension. In Cameroon, the prevalence of hypertension is estimated at 35%, with nearly 17,000 deaths recorded each year. This study aimed to determine the factors associated with the occurrence and complications of hypertension at the Sangmélima Referral Hospital (HRS). A total of 528 patients treated in the cardiology department of the HRS were identified between January and December 2023. The data were analyzed using SPSS 28 software. Binary logistic regression determined the odds ratios and 95% confidence intervals associated with each variable. Differences were statistically significant for a p-value &lt; 0.05. At the HRS, the annual incidence of hypertension was 16.13%. Hypertension was present in 78.8% of patients. The factors associated with the occurrence and complications of hypertension were age (OR=1.028; p=0.003 ), level of education (OR=15.49; p=0.023), marital status (OR=3.859; p=0.04), hypercholesterolemia (OR=2.856; p=0.01), monthly income (OR=0.882; p=0.026), number of dependents (OR=1.231; p=0.025), food security (OR=16.666; p&lt;0.001), tobacco consumption (OR=8.592; p=0.041), fruit and vegetable consumption (OR=0.027; p=0.031), salt/sugar consumption (OR=8.129; p&lt;0.001), place of residence (OR=4.794; p=0.005), access to essential technologies (OR=8.851; p=0.002), and use of traditional care (OR=3.137; np=0.032). HTA at the HRS is associated with several factors. In order to limit the impact of hypertension, it is crucial to emphasize improving socioeconomic and health conditions.

Cardiac arrest (CA) is a life-critical condition. Patients who survive after CA, they go into a defined post-cardiac arrest syndrome (PCAS). In this clinical context, the role of the echocardiogram in recent years has become increasingly important to assess the causes of arrest, the prognosis, and any direct and indirect complications dependent on cardiopulmonary resuscitation (CPR) maneuvers. The aim of our review is to evaluate the increasingly important role of the transthoracic and transesophageal echocardiogram in the CA phase and especially post-arrest, analyzing the data already present in the literature.

Histone Deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing a wide range of cellular processes. Both the catalytic and non-catalytic functions of HDAC6 are implicated in cancer development and progression. Over a decade of clinical trials with catalytic domain inhibitors, such as Ricolinostat (ACY1215), has shown that these drugs are well tolerated and can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness in treating solid tumors remains uncertain due to the limited number of clinical trials and the small size of patient cohorts, leading to inconclusive results. HDAC6 activity is regulated by protein-protein interactions and post-translational modifications, which may allosterically influence its catalytic domains. Therefore, targeting HDAC6 in cancer therapy with small molecule inhibitors requires a more sophisticated understanding of its role within the tumor microenvironment, including whether its expression correlates with deacetylase activity. A comprehensive evaluation of both its enzymatic and non-enzymatic functions could be crucial in developing more effective strategies for targeting HDAC6 in cancer.

The aim of the article is to identify and illustrate the most used psychological techniques in the field of cystic fibrosis (CF) and to help clinicians choosing the appropriate strategy among the various possibilities. The disease and its medical treatments can be difficult to tolerate and can cause anxiety about health status or feelings of hopelessness and stress. The prevalence of depression and anxiety is 2.3 times higher in adults with CF than in community samples. A strong correlation has been identified between elevated psychological distress and unfavorable health outcomes, including, among others, impaired lung function, reduced BMI, an increased incidence of pulmonary exacerbations, and an elevated risk of transplantation. The use of psychological interventions is useful in addressing these common distress in CF patients. Aware of the necessity to identify efficacious interventions for all levels of depression and anxiety in CF patients, this study presents an overview of the research on psychological interventions for patients with CF, in order to complement the treatments suggested by the international guidelines on mental health in CF cases. In fact, the aim of this study is to conduct a review and quantitative synthesis of the psychological intervention techniques that are currently available for individuals with CF.

Introduction Allogeneic stem cell transplantation (allo-SCT) has been used less frequently as a treatment modality in patients with MM. Allo-SCT may have the potential of long-term survival or even cure due to graft versus myeloma effect, however, its use continues to remain controversial given the toxicity profile related to infectious complications and graft versus host disease (GVHD). Concern for exacerbation of GVHD has been raised following re-infusion of CAR-T cells in patients with prior Allo-SCT. Ciltacabtagene autoleucel (Cilta-cel) and Idecabtagene vicleucel (Ide-cel) are two engineered CAR-T products targeting specific B-cell receptors that are approved by the FDA for the treatment of relapsed/refractory (R/R) MM. A recent retrospective study conducted by Htut et al, using data from CARTITUDE-1 trial, showed favorable efficacy and safety in patients who received Cilta-Cel with prior allo-SCT. We report our experience for patients with prior Allo-SCT who underwent therapy with CAR-T in the real world setting. Objective To evaluate the safety and efficacy of CAR-T therapy in patients with R/R MM with a history of allo-SCT. Methods We conducted a retrospective chart review of adult patients (age 18-70 years old) with R/R MM who had received CAR-T on an institutional IRB approved protocol. We collected data for the eligible patients from our institution's database. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy criteria. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS). Survival analysis was performed using the Kaplan-Meir method including PFS. PFS was defined as time from initiation of treatment to progression of disease or death whichever occurred first. The IMW response criteria were utilized for response assessment. Results 8 out of 56 patients who received CAR-T (Cilta-cel or Ide-cel) had a prior allo-SCT. Pts with prior allo-SCT had received a median of 7 prior lines of therapy(LOT) compared with 5 prior LOT for pts who did not(non-Allo)(p=0.04). Median time of CAR-T infusion was 98.8 months following allo-SCT. 7 of 8 (85.7%) pts experienced CRS (any grade) in Allo-SCT vs. 37 of 48 pts (77.1%) in non-Allo (p=0.48); 1 pt with prior allo-SCT experienced HLH requiring intervention with anakinra. At a median follow-up of 4.8 months, 7 of 8 patients had a response (ORR= 87.5%) in allo-SCT vs. 75%(36 of 48) in non-Allo (p=0.4), mPFS was not reached in allo-SCT vs. 11.9-months in non-Allo (p=0.5), although f/u for our cohort was short. No TRM was observed in either group. None of the patients with prior allo-SCT experienced acute GVHD following CAR-T therapy. Baseline characteristics, safety and efficacy data are summarized in Table 1. Conclusion Our findings support the conclusion that prior Allo-SCT does not impact the safety and efficacy of CAR-T therapy in patients with R/R MM. More clinical studies with a higher number of subjects and longer duration of follow-up are warranted to further evaluate the impact of Allo-SCT on CAR-T therapy's safety and clinical outcome in patients with MM.

Recent mental health research has highlighted inflammation's critical role in conditions like depression and bipolar disorder, examining correlations with markers such as calcium levels, thyroid function, and inflammatory markers. The study aims to compare unipolar and bipolar d depression samples in terms of socio-demographic and clinical features. Prospective enrollment of patients hospitalized at the University of Insubria Psychiatric Unit. Patients were administered psychometric questionnaires (Beck Depression Inventory-II, Mental Pain Questionnaire, Beck Anxiety Inventory, Clinical Global Impressions Severity scale, and Reasons for Living Inventory). Thirty-six patients (17 males, 19 females) were enrolled. A statistically significant association emerged between calcium levels and bipolar depression (Pearson Chi square=0.050) and between CRP and bipolar depression (Pearson Chi-square=0.017). Additionally, a statistically significant association was observed between the unipolar and bipolar depression subgroups and current substance abuse (p=0.0275) A statistically significant difference between the BRLF scores and UDD subgroup emerged (p=0.0126). The results of the pilot study revealed significant associations between calcium/CRP levels with depressive symptoms, particularly in bipolar depression. Further research on inflammatory markers is needed to refine diagnostic subtypes and therapeutic strategies.

Training schedule is a factor that influences sports performance optimization. In a sport like soccer, there is often significant disparity in training schedules among different teams within the same club, without considering whether this may affect players' performance. The aim of this study was to describe differences in nutrient intake and body composition in elite youth soccer players from the Spanish league with different training schedules (morning and evening). A cross-sectional study was conducted to determine differences in anthropometric variables and dietary assessment in a sample of Spanish young soccer players. A total of 41 players participated in this study. After comparing the groups according to their training schedule, no differences were observed in body composition between both groups; the evening-night training group showed higher consumption of lipids and saturated fats. In summary, more experimental studies are needed to determine the effects on various health and performance parameters of different training schedules in young population.

Background: Studying patients carrying identical by descent (IBD) pathogenic gene variants allows to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated LDL-c levels, premature atherosclerosis and is often caused by defects in the LDLR gene. There is a high prevalence of FH in French Canada carry IBD FH-causing due to a founder effect from France in the 17th Century. Several FH patients currently living in French Canada (founder population) and in France (colonizing population) carry IBD FH-causing variants. The expression of FH is affected by environmental and genetic modifiers and patients with IBD variants may present different characteristics. Methods: In this study, we compared FH clinical expression patients carrying IBD LDLR pathogenic variants living in France or Canada. Four IBD variants, namely c.259T>G p.(Trp87Gly); c.2000G>A p.(Cys667Tyr); c.682G>A p.(Glu228Lys); and c.1048C>T p.(Arg350*) were selected. Untreated plasma lipid profiles, APOE genotype, cardiovascular risk factors and occurrence of symptomatic ASCVD were compared in 105 adult carriers (30 from France and 75 from French Canada). Results: All parameters were similar between the two populations, except for untreated total cholesterol (10.14 ± 1.89 mmol/L vs 8.65 ± 1.84 mmol/L, p=0.0006) and LDL-c concentrations (7.94 ± 1.86 mmol/L vs 6.93 ± 1.78 mmol/L, p=0.016) that were significantly higher in FH patients living in France, a trend that was observed in all studied LDLR variants. Conclusion: This study illustrates that FH patients sharing IBD pathogenic LDLR variants that have evolved in different geographic, cultural and socio-economic environments for hundreds of years, differ in term of cholesterol levels highlighting the importance of better understanding the interplay between genetic and environmental modulators of FH expression.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Background: Type 2 diabetes mellitus (T2DM) affects over 500 million people worldwide, and over 50% of this group experience the most common complication, diabetic peripheral neuropathy (DPN). The presence of advanced glycation end-products (AGEs) have been linked with the development of DPN. The present study assessed for AGE levels in participants with type 2 diabetes, and explored the hypothesis that there may be increased AGE levels in more severe DPN. Methods: 124 participants with T2DM were consecutively recruited, and underwent skin autofluorescence, clinical assessment for peripheral neuropathy, peripheral nerve ultrasound, nerve conduction studies and axonal excitability assessment. Results: Elevated levels of AGE did not correlate with higher clinical neuropathy scores, sural sensory nerve amplitude, median or tibial nerve cross-sectional area or measures of axonal excitability. While higher AGE readings correlated with diabetic kidney disease, these recordings were not associated with more severe peripheral neuropathy outcomes on multiple regression analysis. Conclusion: The present study suggests that accumulation of AGE is not associated with clinical, electrophysiological and morphological measures of neuropathy in T2DM.

Introduction: Arterial hypertension and obesity are two major risk factors for cardiovascular morbidity and mortality closely linked. The objective of this study was to describe the epidemiological and clinical characteristics of hypertensive patients according to their level of obesity as proposed by the classification of the World Health Organization (WHO). Patients and Methods: Retrospective study (January 2022-April 2023) involving 230 hypertensive and obese adult patients whose mean age was 52.5 ± 12.05 years [Extremes: 24-85 years] followed on an outpatient basis and classified into 3 Classes according to their body mass index (BMI). Epidemiological, clinical parameters and cardiovascular risk stratification were analyzed. The relevance of the risk stratification method was analyzed by area under the curve (AUC). Statistical analysis was performed using SPPS version 26 software (SPSS Inc., Chicago, IL, USA). Results: Classes 1 (n=170; 73.9%), 2 (n=43; 18.7%) and 3 (n=17; 7.4%) were identified. There were significantly more women than men in Class 3 (9.7% versus 2.7%; p=0.001). The risk of being diabetic (OR=0.135;95%CI=0.034–0.541;p=0.005), of having angina pain (OR=0.084;95%CI=0.009–0.790;p=0.030) or developing chronic renal failure (OR=2.416;95%CI=1.471–85.268;p=0.020) was significantly higher in Class 3 than in Class 1. According to cardiovascular risk stratification, 152 patients (66.1%) were at high and very high risk. The level of cardiovascular risk of our patients was not related to the degree of obesity based on body mass index (p=0.32). The risk stratification method was relevant (AUC˃0.70;p˂0.001). Conclusion: Morbid obesity exposes hypertensives more to cardiovascular, renal and metabolic complications.

After decades of studies, the pathogenesis of Autism Spectrum Disorder (ASD) remains unclear and there still lackseffective treatment strategies for core symptoms. Our recent work, combined with others’ research in a diversity ofmodels and clinical trials, suggested a concise, but potentially rational theory that can illustrate the key of the pathogenesis and treatment of ASD from the aspect of damage control.

The unravelling of the human genome created new perceptions on the origin and evolution of diseases and for cancer in particular, it established the notion that neoplasia has been a companion of life since its ap-pearance on earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today, begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century, generate new ther-apeutic opportunities with immunotherapy, oncolytic virotherapy and gene transfer, the latter especially in cases of hereditary cancer.

We are presenting a new method for the treatment of large macular holes (MH) with the use of an inverted flap consisting of both internal limiting membrane (ILM) and epiretinal proliferation (EP). A prospective interventional case series was conducted from September 2021 to January 2023. MH patients with coexistent EP visualized preoperatively in macula optical coherence tomography and MH minimum linear diameter larger than 400 microns underwent standard pars plana vitrectomy with the creation of an inverted petaloid flap (consisting of both ILM and EP) and gas tamponade. 16 eyes were included in our study. MH closure was successful in all the eyes with a single procedure. Preoperative minimum linear diameter was 707.63(±164.02μm) and preoperative best corrected visual acuity was 1.11±0.52. Postoperative BCVA was 0.51±0.20 (p=0.01) at 6weeks postoperatively and final BCVA was 0.45±0.20 (p=0.008). EP can be safely combined with ILM for the creation of an inverted, petaloid flap to cover and facilitate the closure of large MH.

Background/Objectives: interpretation of evidence on de-escalation of triple therapy with with-drawal of inhaled corticosteroids (ICS) to dual bronchodilator therapy with a long-acting musca-rinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstruc-tive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discon-tinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: we searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov and CENTRAL for RCTs and observational studies from inception to March 22, 2024, investigating the effect of triple therapy de-escalation with withdrawal of ICS to dual therapy on the risk of COPD exacerbation, pneumonia and lung function. This study was registered with PROSPERO, CRD42024527942. Results: 3335 studies were screened; three RCTs and three real-world non-interventional studies were ultimately identified as eligible. Analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80 to 1.15; I²=77%) for ICS withdrawal compared with triple therapy continuation. Analysis according eosinophil levels showed that COPD subjects with ≥300 eosino-phils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated from ICS/LABA/LAMA to LABA/LAMA (pooled HR: 1.35, 95% CI 1.00-1.82; I2: 56%). The ICS withdrawal in favour of LABA/LAMA did not significantly affect the risk of mortality and pneumonia. Conclusions: the main findings of this meta-analysis are consistent with current recommendations and suggest that the use of eosinophil counts may be of help in guiding maintenance therapy. However, methodological heterogeneity between the included studies is evident.

Background: Patients with mutations in the monocarboxylate transporter 8 (MCT8) suffer from Allan-Herndon-Dudley syndrome (AHDS), characterized by developmental delay and a highly disabling movement disorder. Despite the potential of thyroid hormone derivatives to overcome the transporter defect, current trials did not achieve patient-oriented therapeutic goals. Objectives: Since most neurological symptoms are related to the dopaminergic system, we investigated the role of dopamine and its metabolites in MCT8 deficiency with regard to pathophysiology and potential therapeutic strategies in an observational cohort study. Methods: We present longitudinal data from the DEEPTYPE registry of ten patients with video-documentation, standardized phenotyping, cerebrospinal fluid analysis, treatment response to levodopa/carbidopa supplementation, and neuroimaging data. To establish a cell-based model for pathophysiological studies, we differentiated healthy human induced pluripotent stem cells (hiPSCs) into dopaminergic neurons. Results: Children presented with signs of parkinsonism in childhood, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction along the classification of Leuzzi and colleagues. Cerebrospinal fluid homovanillic acid concentrations were decreased (n=11), suggesting isolated dopamine pathway impairment. Six out of seven patients responded favorably to levodopa/carbidopa supplementation and we did not see any adverse drug reactions. Our cell-based studies showed that hiPSC-derived dopaminergic neurons expressed MCT8 and produced quantifiable levels of biogenic amines. Conclusions: Parkinsonism is part of AHDS's clinical presentation and may be amenable to treatment. The precise impact of MCT8 deficiency on the dopamine metabolism needs to be further elucidated, e.g. by using patient iPSC-derived dopaminergic neurons in future studies.

Discoloration of endodontically treated anterior teeth poses a significant aesthetic concern for many individuals, impacting their confidence and self-image. Porcelain veneers have emerged as a popular solution for the aesthetic restoration of such teeth. This paper explores the role of porcelain veneers in addressing tooth discoloration, examining their efficacy, durability, and aesthetic outcomes, via a clinical case. Various factors influencing the selection of porcelain veneers as a treatment modality, including shade matching, preparation techniques, and adhesive bonding, are discussed. Additionally, advancements in materials and techniques have enhanced the versatility and aesthetic appeal of porcelain veneers, making them a valuable option for achieving natural-looking and durable aesthetic restorations in individuals with discolored endodontically treated anterior teeth.

The selection of the best allogeneic donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Besides the well-known patient’s characteristics, donor-related variables such as patient-donor histocompatibility and donor age are of utmost importance for the outcome after HSCT. However, there is still debate on the definition of the best stem cell donor when multiple suitable donors exist. By using own data from two transplant centers, we here developed a calculator able to provide the 2-year patients’ overall survival (OS) associated to each of the potential donor options during the selection process. Data on n=737 HSCTs performed from January 2010 to July 2022 have been retrospectively obtained. Donor types were HLA-identical siblings, unrelated or related haploidentical. Cox regression and parametric model indicates patients’ age, disease, comorbidity index and donor type as significant variables (p<0.05) able to predict 2-year OS with robustness (concordance index: 0.677). Estimates are provided with the three donor options for each single, specific patient. Of note, estimates express real data of the transplant centers and reflect their actual experience. In conclusion, we here present the prototype of a new tool for the calculation of patients’ outcome according to the stem cell donor type, guiding transplant physicians during the process of donor selection before HSCT. The novelty of this approach relies on the use of real data from the investigating centers, reflecting the local clinical experience. Improvements are planned by filling additional information and pooling data from more centers.

The human scalp is a common site of skin cancer in humans, with non-melanoma skin cancer being exceedingly common. In this review, two dermatologists with extensive experience in cutaneous oncology will discuss unique features of the epidemiology of cancer of the scalp. Clinical observations on these common skin cancers lead to insight into the pathogenesis and potential prevention and treatment of cutaneous scalp neoplasia. Our hypothesis is that the presence of hair protects against the development of skin cancer, but not by serving as a physical shield, but rather by providing a continuous IL-17 biased immunosurveillance. Loss of hair allow release from immunosurveillance, resulting in expansion of neoplastic cells towards skin cancer. Both hair follicles and metabolic changes in stroma allow permissiveness for tumor promotion.

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Low back pain (LBP) is a significant global health issue, contributing to considerable disability and socioeconomic burdens. The degeneration of the human intervertebral disc (IVD) is a critical factor in the pathogenesis of LBP. Recent studies have emphasized the significance of its specific set of genes and extracellular matrix (ECM) in IVD health. The Noggin gene has emerged as a critical factor due to its high expression levels in healthy nucleus pulposus cells (NPCs) observed in our previous research. In this study, we investigated the hypothesis that decreased Noggin expression in NPCs is associated with IVD degeneration, contributing to LBP development. A lentivirus-mediated RNAi was applied to knockdown Noggin expression in primary NPCs from six human donors. Cell viability analysis, XTT assay, and cell apoptosis were conducted to reveal the effect after transduction. After two weeks, colony formation unit (CFU) assay was used to examine the anchor-independent growth ability of transduced cells. Additionally, qPCR was performed to quantify cellular anabolism and catabolism makers at the transcript level. The results showed lentivirus-mediated downregulation of Noggin suppressed cell growth, cell viability, and colony formation, and induced apoptosis in human NPCs in vitro. Noteworthy, it hindered cellular anabolism and enhanced catabolism activity in human NPCs after transduction. Our findings indicated that the degeneration of human IVD is possibly related to decreased Noggin expression in NPCs. This research provides valuable insights into the role of Noggin in IVD homeostasis and its implications for LBP treatment.

Background and Objectives. The purpose of this study is to report on the results of treatment of distal and stem forms of hypospadias in boys with newly developed methods of surgical treatment compared with traditional methods of urethroplasty. Materials and Methods. A prospective non-randomized comparative study was conducted in January for the period 2014 to December 2023. All included patients were diagnosed with distal and stem hypospadias. 136 patients who met the inclusion and exclusion criteria were divided into 2 groups. Group I included 50 patients (study subgroup AI and comparison subgroup AI patients with distal hypospadias). Group II included 86 patients (study subgroup VI and comparison subgroup III patients with the stem form of hypospadias). Outcomes were assessed by the nature of postoperative wound healing, the presence of complications: neomeatus dystopia, formation of a cutaneous urethral fistula.Results. The average age of patients for the A(I) subgroup was 48 months (95%CI:45.29 – 60.64), CO=19.0. The average age of patients for subgroup A (II) was 51 months (95%CI:46.08-65.00), CO=22.4. The average age of patients for group B (I) was 56 months (95% CI:54.22 – 87.11), CO=46.3. The average age of patients for B (II) The period of the group was 60 months (95%CI:54.10 – 71.44), CO=31.4.The outcome of recovery was registered in 92.9% (13) of patients, repeated surgery in 7.1% (1) of patients. Neomeatus dystopia in group A (I) was not detected in any of the 100% (26) operated patients. Neomeatus dystopia in group A (II) was observed in 16.7% (4) of patients, at the same time in 83.3% (20) of patients. Neomeatus dystopia in subgroup B (I) was not observed in anyone–100% (33). Neomeatus dystopia in group B (II) was observed in 15.1% (8) of patients, was not observed in 84.9% (45). The differences are statistically significant (p=0.016, p=0.019). In group I, 80% (40) patients recovered, and 20% (10) patients underwent repeated surgery. In subgroup A (I), postoperative fistula was observed in 16.7% (1) cases, whereas in subgroup A(II), in patients after Snodgrass and MAGPI surgery, fistula developed in 20.8% (5) patients, neomeatus dystopia in 16.6% (4) cases (p=0.065; p=0.030;).According to the outcome in group II, 61.6% (53) of patients recovered, 38.4% (33) of patients underwent repeated surgery. Of these, in subgroup B (I), postoperative fistula was observed in 12.1% (4) cases, whereas in subgroup B (II), in patients after Snodgraft and Bracka surgery, fistula developed in 35.8% (19) patients, neomeatus dystopia in 15.1% (8) cases (p=0.016; p=0.019;). Wound healing in group (II): primary–82.1% (23), secondary–17.9% (5). Wound healing in group B (II): primary–70.1% (54), secondary–29.9% (23). Despite the fact that the duration of surgery is statistically significantly lower in the comparison group p<0.001, the frequency of primary wound healing is statistically significantly higher in the study group p<0.001. Conclusions. We came to the conclusion that after the use of traditional methods of urethroplasty, there is still a high percentage of postoperative complications that require the development of new methods of surgical treatment of hypospadias in boys.

Background/Objectives: Multiple sclerosis (MS) is a chronic neurological disorder characterized by various clinical presentations and manifestations that include biopsychosocial impediments. This study has three interrelated goals relevant to biopsychosocial functioning. The first is to compare cognitive, neuropsychological, and affective functioning and quality of life between patients with MS (PwMS) and a control group. The second is to examine whether cognitive and neuropsychological performance is affected by gender, and the third is to examine whether variation in QoL hinges on cognitive neuropsychological performance. Methods: This multicenter study was carried out among clinically stable PwMS under follow-up in two tertiary care units in urban Oman. Healthy controls, matched for age and sex, were also recruited as a comparison group. Data were collected using cognitive batteries sensitive to current reasoning ability and conventional neuropsychological batteries designed to measure verbal learning, visual-spatial ability, and processing speed. The affective range (anxiety and depressive symptoms) and quality of life (QoL) were also assessed. Results: The PwMS group scored lower on current reasoning ability, verbal learning, visual-spatial ability, and processing speed compared with the control group. The incidence of anxiety was higher in the PwMS group but there was no statistically significant difference in depressive symptoms. No significant differences were found in cognitive variables between the two sexes, except in visual-spatial ability, where women outperformed men. PwMS with low QoL scored lower on the attention and concentration indices than those with adequate QoL. According to QoL, no significant differences were observed in reasoning, verbal learning, and visual-spatial ability. Conclusions: The present sentinel study suggests that the Omani cohort with MS tends to have lower indices of current reasoning ability, visual and spatial memory and cognitive speed compared to control subjects. Gender differences are minimal, except for visual-spatial abilities where women outperform men. Quality of life significantly affects cognitive functioning. In general, the biopsychosocial impediment appears to be significant, indicating the need for comprehensive evaluation and care in the management of MS.

Artificial Intelligence (AI) is increasingly becoming integral to medical practice, potentially enhancing outcomes in thoracic surgery. AI-driven models have shown significant accuracy in diagnosing non-small cell lung cancer (NSCLC), predicting lymph node metastasis, and aiding in the efficient extraction of electronic medical records (EMR) data. Moreover, AI applications in robotic-assisted thoracic surgery (RATS) and perioperative management reveal potential in improving surgical precision, patient safety, and overall care efficiency. Despite these advancements, challenges such as data privacy, biases, and ethical concerns remain. This manuscript explores AI applications, particularly machine learning (ML) and natural language processing (NLP), in thoracic surgery, emphasizing their role in diagnosis and peri-operative management. It also provides a comprehensive overview of the current state, benefits, and limitations of AI in thoracic surgery, highlighting future directions in the field.

Recent epidemiologic studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigates demographic characteristics and survival trends in YONEN and compares these with those of young-onset colorectal adenocarcinoma (YOADC), the most common histologic subtype of YOCRC. A retrospective analysis was conducted from 2000 to 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were assessed using univariate and multivariable Cox proportional models, with demographic differences evaluated via Wilcoxon Rank Sum and Chi-square tests. Out of 61,705 patients aged 20-49 with colorectal cancer, 8% had NEN, and 92% had adenocarcinoma. The YONEN cohort had a higher proportion of Black patients and a lower proportion of White patients than the YOADC cohort (21% vs. 13% and 44% vs. 57%, respectively). NEN was more commonly found in the rectum (79%), and adenocarcinoma was mostly colonic (57%) in origin. YONEN patients had better survival than YOADC patients. Multivariate analysis in YONEN patients revealed that Hispanic patients had better overall survival compared to White patients (HR 0.67, 95% CI 0.47-0.95, p=0.024). Racial disparities should be investigated further to aid in policymaking and targeted interventions.

Aim: This study aims to analyze the evolution of co-author networks in Gastroesophageal Reflux Disease (GERD) research from 2000 to 2023, using data from the Web of Science (WoS) Core Collection. The objective is to provide a structural overview of researcher collaborations in this specialized field, highlighting key contributors and the impact of international cooperation. Method: I conducted a co-author network analysis on 19,463 GERD -related articles indexed in the WoS Core Collection between 2000 and 2023. Using Python (Version 3.10.5) within the PyCharm development environment (Software Version 2022.1.3), I assessed macro-level indicators including network density, clustering coefficient, number of components, and average distance. Micro-level indicators such as degree centrality, closeness centrality, and betweenness centrality were also evaluated to understand the roles of individual researchers in the network.Result: The GERD co-authorship network exhibited a sparse structure with low network density, indicating limited realized collaborations compared to potential connections. The clustering coefficient was consistently high across the analyzed periods, suggesting that researchers frequently formed tight-knit groups. The network was fragmented into numerous components, with significant disconnection between groups. Degree centrality highlighted key researchers such as Dent, J., and Shaheen, N.J., who had extensive collaborative reach. In contrast, closeness and betweenness centrality identified strategic intermediaries like Bredenoord, A.J. and Kahrilas, P.J., who facilitated connections across otherwise isolated segments of the network.Conclusion: The co-authorship network analysis revealed a persistently fragmented landscape in GERD research, with considerable room for enhancing collaboration among researchers. Identifying key contributors and understanding their roles within the network can guide future efforts to foster more integrated and comprehensive research collaborations. This study underscores the importance of strategic networking and partnership development in advancing GERD research and optimizing the field's collaborative potential.

Background/Objectives: Adolescence represents a period of heightened vulnerability to risky sexual behaviours. In Portugal, adolescents are initiating sexual activity at increasingly younger ages. Yet, there are no studies evaluating their knowledge about sexually transmitted diseases and prevention methods at an earlier stage of their development. Study how middle school ad-olescents define their sexuality and assess their level of information regarding sexuality, STI, and prevention methods. Additionally, it explores adolescents' sources of information on sexuali-ty-related issues. Methods: A cross-sectional observational study was conducted involving the application of a questionnaire to 750 9th-grade students of Vila Nova de Gaia, Porto, Portugal. The questionnaire covered topics such as perceptions of sexuality, knowledge of sexuality and STI, methods of transmission prevention, and sources of information. Results: The mean age was 14.4 years, with 19.9% reporting having already initiated sexual ac-tivity. Overall, the knowledge about sexually transmitted infections is low, pointing to 7.08 out of a maximum score of 18. Condoms and immunisation are well-recognized preventive measures, but many misconceptions persist. Better knowledge is associated with better attitudes in the likelihood of having sexual intercourse. Conclusions: This study reveals adolescents' limited sexually transmitted infections knowledge, misconceptions about prevention, and reliance on peers and the internet over trusted sources, highlighting the need for comprehensive sexual education in middle school.

Almost one fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumor and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

The stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is presented on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated but has been associated with the development of endometrial and ovarian cancer, we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflects the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial), CD45 (leukocyte), CD105/CD44 (mesenchymal-stemness) and by comparative RNA analysis. Similar to the situation in patients with cancer, levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with the highest Hsp70 level in a patient with lymph node endometriosis. Moreover, CECs could be isolated using the cmHsp70.1 mAb- and to a lesser extent EpCAM mAb-based bead approaches in all patients with endometriosis. The longevity in cell culture and the expression of cytokeratin, CD105 and CD44, together with differentially expressed genes related to EMT reveals similarities of mHsp70 expressing CECs with circulating tumor cells (CTCs) and suggest a mesenchymal-stemness origin. These findings may support the involvement of mHsp70 positive, stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 in the blood and CECs could serve as liquid biopsy markers for endometriosis and help to elucidate the underlying pathomechanism of the disease.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2 and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as time from drug initiation to treatment discontinuation. Kaplan-Meier analysis of treatment duration was performed using R for windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. Median treatment duration was 8.3 months (95% CI: 6.41-not reached) and the range was 1.0-47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being most common (9/18). At time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. This real-world data is comparable to the median PFS observed with HER2-directed therapies in phase II trials and supports the use of HER2-directed therapies in this group.

Background: Antimicrobial consumption data in Latin America is scarce and usually spread out within different sources for AMC calculations, making it difficult to both standardize and compare regions through similar time frames. The main objective was to analyze antimicrobial consumption trends in Social Security tertiary care hospitals in Costa Rica in the period spanning January 2017 to December 2021, using both defined daily doses (DDD)/100 bed days and DDD/100 discharges. Methods: Retrospective observational study of antimicrobial consumption. Global consumption trends were calculated and expressed in DDD/100 bed days and DDD/100 discharges. Trends in antimicrobial consumption were analyzed using a simple linear regression model to determine potential differences in antimicrobial usage throughout the study’s duration. Results: A statistically significant increase in the consumption expressed in DDD/100 discharges was observed in the following groups: carbapenems: 35.62% (p&lt;0.0001), trimethoprim-sulfamethoxazole: 62.50% (p&lt;0.0001), echinocandins: 20.73% (p=0.01) and azole antifungals: 61.58% (p&lt;0.0001). Additionally, a statistically significant increase of 40.43% in the consumption of azole antifungals expressed in DDD/100 bed days was observed (p=0.0008). In contrast, a statistically significant decrease in consumption expressed in DDD/100 discharges was identified for cephalosporins -21.97% (p&lt;0.0001) and macrolides -51.67% (p&lt;0.0001). Conclusions: This five-year analysis demonstrated trends over time in overall antimicrobial consumption measured in DDD/100 bed days do not correlate with trends in DDD/100 discharge rates. Continually, the comparison between DDD/100 bed days and DDD/100 discharges allows for complementary comparisons to be made regarding antimicrobial exposure in a clinical setting.

The purpose of this paper is to evaluate the possible application of a therapeutic carnivore diet regimen in the treatment of chronic inflammatory bowel disease (IBD). Based on current research and anecdotal reports, we hypothesized that the diet might potentially exhibit both anti-inflammatory and microbiome-modulating properties salutary to the IBD patient population. Our hypothesis demands comprehensive clinical validation. Therefore, in this paper, we review theories on ketogenic and carnivore diets, discussing their immunomodulatory effects and propose an experimental study to test the feasibility, safety, and clinical efficacy of the carnivore diet for IBD treatment.

Applied behavior analysis (ABA) interventions first introduced by Lovas in the 1960s have been proven historically effective in reducing challenging behaviors such as self-harm aggressive behaviors and improving communicative language skills in children with autism. While the interventions have evolved, focusing on restricting punishments and enforcing more reinforcements to teach skills, some concerns are yet to be evaluated. With the boom of ABA in Asia, this review focuses on understanding the techniques used and the progression of ABA by reviewing the existing literature. It aims to critically analyze the ABA strategies used to target challenging behaviors and teach new skills to gauge their long-term impact on children undergoing these interventions.

Harms of combustible cigarette (CC) use in pregnancy for fetal development are well-studied. Less understood is potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (EC). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n=26,394), CC (n=2,216), EC (n=493) were compared on birth outcomes, controlling for background differences. Compared to controls, the EC group had significantly lower birth weight, while CC had reduced birthweight and greater rates of arterial cord pH < 7.1. Compared to EC, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests EC are not safer alternatives to CC, and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average-risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

Background. Hypothyroidism is very common worldwide. It is known to be associated with frailty which in turn, is associated with increased morbidity and mortality in the elderlies. Low ALT blood activity is an established marker for sarcopenia and frailty. The incidence and outcomes of the association of low ALT values and hypothyroidism, as manifested in elevated blood TSH levels, is unknown. Methods. This was a retrospective analysis of hospitalized patients in a large, tertiary hospital. Results. Over a period of 21 years, an overall population of 16,827 patients were identified as eligible to participate in this study. Within the study population 726 (4.3%) were classified as suffering from hypothyroidism (TSH values > 6 MIU/L) and 2,184 (13%) were classified as patients with sarcopenia (ALT < 12 IU/L). Within our patients’ population, hypothyroidism was associated with sarcopenia in a statistically significant manner (p = 0.011). Patients classified as suffering from both hypothyroidism and sarcopenia had significantly shorter survival: A multivariate analysis showed that the frail and hypothyroid group of patients had a statistically significant risk of mortality in the for coming 5 years (HR = 3.6; CI 2.75-4.71; p < 0.001). Conclusions. Sarcopenia and frailty are common comorbidities, bearing negative long-term clinical outcomes. Low ALT values could serve as a useful biomarker for screening of patients already diagnosed with hypothyroidism.

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate de-carboxylase autoantibodies (GADA). LADA has intermediate features between type 1 diabetes and type 2 diabetes. In addition, genetic risk factors for both types of diabetes are present in LADA. Nonetheless, evidence about the genetics of LADA in non-European populations is scarce. This study aims to perform a genome-wide association study with a phenome-wide association study of LADA in a southeastern Mexican population. We included 59 patients diagnosed with LADA from a previous study and 3121 individuals without diabetes from the MxGDAR/ENCODAT database. We utilized the GENESIS package in R to perform the GWAS of LADA and PLINK for the PheWAS of LADA features. Nine polymorphisms reach the nominal association level (1x10-5) in the GWAS. The PheWAS showed that rs7305229 is genome-wide associated with serum GADA levels in our sample (p=1.84x10-8). rs7305229 is located downstream FAIM2 gene; previous reports associate FAIM2 variants with childhood obesity, body mass index, body adiposity measures, lymphocyte CD8+ activity, and anti-thyroid peroxidase antibodies. Our findings reveal that rs7305229 affects the GADA levels in patients with LADA from southeastern Mexico. More studies are needed to determine if this risk genotype exists in other populations with LADA.

Introduction: Patients with hematological malignancies undergo intensive treatment and prolonged hospitalization, thus having a variety of physical and psychosocial symptoms and worse quality of life (QOL). Aim: This study aimed to assess the QOL and investigate the symptoms of hospitalized hematological cancer patients. Methods: A cross-sectional study was conducted in the hematology clinics and day units of two general hospitals of Heraklion, Crete. Adult patients with hematological malignancy and an adequate understanding of the Greek language participated. A demographic questionnaire, the European Organization for Research and Treatment for Cancer quality assessment questionnaire (EORTC QLQ-C30), and the MD Anderson Symptom Inventory (MDASI) were used for data collection. The level of statistical significance was set at p &lt;0.05. Results: The sample consisted of 120 patients, 42.5% of whom were women, with a mean age of 65.6 years. The mean time from diagnosis was 33 months. The global health status of QoL had an average value of 47.1. The highest levels of QOL were found in the subscale of cognitive function (72.8) and the lowest in the role function (46.1). Among the of EORTC QLQ-C30 symptoms scale, the lowest score was found in nausea-vomiting (11.0) and the highest in fatigue (59.1). In the MDASI, in part I (core symptoms), higher levels, but also medium intensities were reported at fatigue (78.3%, mean 3.5), drowsiness (65.0, mean 3.3), and distress (65.8%, mean 2.8). In part II, enjoyment of life (85.8%, mean 5.1) had the highest and relation with other people (67.5%, mean 3.7) the lowest scores. The increase in the severity of the core symptoms (part I) was related to females (rho = 0.193, p &lt;0.05) and comorbidities (rho = 0.220, p &lt;0.05). It also related to a significant decrease in all functional domains and an increase in fatigue (rho = 0.571, p &lt;0.05) of the EORTC QLQ-C30 questionnaire. The increased global health status was related to males (rho = -0.185, p &lt;0.05) and physical functioning with younger age (rho = -0.331, p &lt;0.05), higher education (rho = 0.239, p &lt;0.05), fewer months from diagnosis (rho = -0.199, p &lt;0.05) and low comorbidity (rho = -0.209, p &lt;0.05). Finally, the increased global health status was significantly related to lower symptoms determined by the total average symptom score (-0.491, p &lt;0.05). Conclusions: The QoL of hematological cancer patients is significantly decreased during treatments due to a significant number of symptoms that must be taken into consideration for high-quality individualized care.

Background and aims: In recent years, a possible connection between HLA-Cw6 and a distinctive cardiometabolic (CM) profile in patients with psoriatic disease (PsD) has been proposed, although there is still little support for this. Our aim was to further investigate this possible association by studying a large population of PsD patients. Methods: For this study, three different cohorts of patients with PsD were analyzed: two with a majority of cutaneous psoriasis, pooled n: 600, and a third with only psoriatic arthritis -PsA- cases, n: 340. Potential relationships between HLA-Cw6 and the different CM risk factors (hypertension, diabetes, obesity, dyslipidemia) were analyzed using univariate and multivariate regression models, while the final net effect was assessed using fixed- or random-effects meta-analyses, as appropriate. Results: In the PsA cohort, no association was detected between HLA-Cw6 carriership and any of the CM comorbidity factors. In psoriasis cohorts, after correcting for age, sex, disease duration and arthritis, HLA-Cw6 carriers reduced diabetes risk (OR 0.49, 95%CI: 0.26-0.91, p = 0.026). This latter effect was confirmed by a fixed-effects meta-analysis of the included cohorts (pooled OR: 0.50, 95%CI: 0.27-0.90). Conclusion: This work demonstrates a potential protective effect of the HLA-Cw6 allele on the risk of diabetes in PsD. Our findings together with those of others seem to confirm the existence of a novel HLA-Cw6-linked cardiometabolic endotype in this disease.

Background: To investigate the association between enteral feeding and the risk of pneumonia in critical care adult patients. Methods: An updated literature review of studies discussing between 2016 and 2023. CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of science databases were used to explore studies regarding our subject, the association between enteral feeding and the risk of pneumonia in critical care adults. Results: Enteral nutrition (EN) has been linked to a significant reduction in pneumonia, as well as shorter ICU or hospital stays, and decreased mechanical-ventilation duration in numerous studies. Conversely, pneumonia risk and other infections, as well as the fatality rate, has been found to increase with EN. Early initiation of EN within 48 hours, along with a low-calorie diet containing (< 600 Kcal/day) demonstrated a notable decrease in the occurrence of Ventilator-Associated Pneumonia (VAP) when contrasted with delayed EN and a high-calorie diet. EN was associated with a marked decrease in adverse events including aspiration pneumonia, emesis, and the escalation of respiratory support. Conclusion: EN is safe and effective in critically ill patients. It is advisable for future research to investigate the monitoring of larger sample sizes to ascertain the most effective feeding methods in the intensive care unit.

The rapid development of specific-purpose Large Language Models (LLMs), such as Med-PaLM, MEDITRON-70B, and Med-Gemini, has significantly impacted healthcare, offering unprecedented capabilities in clinical decision support, diagnostics, and personalized health monitoring. This paper reviews the advancements in medicine-specific LLMs, the integration of Retrieval-Augmented Generation (RAG) and prompt engineering, and their applications in improving diagnostic accuracy and educational utility. Despite the potential, these technologies present challenges, including bias, hallucinations, and the need for robust safety protocols. The paper also discusses the regulatory and ethical considerations necessary for integrating these models into mainstream healthcare. By examining current studies and developments, this paper aims to provide a comprehensive overview of the state of LLMs in medicine and highlight the future directions for research and application. The study concludes that while LLMs hold immense potential, their safe and effective integration into clinical practice requires rigorous testing, ongoing evaluation, and continuous collaboration among stakeholders.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Changes during this period could contribute to inflammation and be associated with variations in the vascular smooth muscle (VSMC) phenotype. We studied changes in inflammatory pathways that could underlie the expressions of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. We analyzed histological changes in the aorta and expressions of the COX-2, TLR4, iNOS, eNOS, MMP-2, -9, β-, α-actin, and TNF-α, IL-6 and IL-1β expressions, and fatty acids by gas chromatography. The aortic wall presented disorganization, decellularization, wavy elastic fibers and increase in the lumen area. The COX-2, TLR4 expressions, TNF-α and IL-6 were increased, but iNOS, MMP-2 and -9 tended to increase and eNOS and arachidonic acid tended to decrease, con increase in oleic acid in CP in comparison with control group. There is a transient hypertension at the end of the CP that is accompanied by an inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the hypertension development during adulthood.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems. The gut microbiota plays a crucial role in in metabolism regulation and immune responses through its interaction with the external environment. This article explores the intricate interplay between intestinal flora and the pathogenesis of PCOS, focusing on the pivotal role of microbial metabolites, specifically short-chain fatty acids (SCFAs). SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria alongside a notable overgrowth of opportunistic microorganisms. An overproduction of acetic acid (AA) and valeric acid (VA) in fecal samples suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (BMI), insulin resistance (IR), and chronic inflammation. This finding points to the potential therapeutic value of maintaining optimal AA levels in the blood. Although serum SCFA levels showed non-significant changes following metformin treatment, the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. This treatment also led to an increase in beneficial gut bacteria and a reduction in opportunistic pathogens, suggesting a restoration of gut microbial balance. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Purpose: Our aim in this case is to report a new finding regarding Nutcracker syndrome (NCS), which is a variation of the left renal vein. Methods: We present a very rare anatomical variant of the left renal vein(LRV), with a preliminary diagnosis made by ultrasound and NCS as a differential diagnosis with computed tomography (CT) and diagnostic CT angiography. Results: The patient in our case was a 30-year-old woman with chronic abdominal and flank pain and increased sensitivity in the flank area. Neither hematuria nor proteinuria was detected in the urinalysis. Contrast-enhanced computed tomography(CT) showed that there were two separate LRVs draining the lower and upper poles. It was observed that the vein draining the lower pole narrowed significantly between superior mesenteric artery and abdominal aorta and then continued to widen. This view showed that we were faced with a typical NCS. What made our case different and unique from typical NCS was that it had renal intraparenchymal varicose veins. Treatment of NCS includes open, laparoscopic and robotic surgical repair and endovascular/extravascular stent placement. Treatment of symptomatic NCS includes open, laparoscopic, and robotic surgical repair and endovascular/extravascular stent placement. Except for the presence of hematuria causing severe anemia, deterioration in kidney functions and serious pain, patients are followed conservatively, and our patient is also followed conservatively. Conclusion: This case we present is the first case accompanied by renal parenchymal varices in the literature.

Aim: This study aims to analyze the evolution of co-author networks in Single-Balloon Enteroscope (SBE) research from 2000 to 2023, using data from the Web of Science (WoS) Core Collection. The objective is to provide a structural overview of researcher collaborations in this specialized field, highlighting key contributors and the impact of international cooperation. Method: I conducted a co-author network analysis on 149 SBE-related articles indexed in the WoS Core Collection between 2000 and 2023. Using Python (Version 3.10.5) within the PyCharm development environment (Software Version 2022.1.3), I assessed macro-level indicators including network density, clustering coefficient, number of components, and average distance. Micro-level indicators such as degree centrality, closeness centrality, and betweenness centrality were also evaluated to understand the roles of individual researchers in the network.Result: The analysis revealed that the co-author networks in SBE research have evolved over the studied period, with varying degrees of connectivity and collaboration. From 2000 to 2009, the network showed moderate clustering but high fragmentation, with a few key researchers like Nista, Enrico C., and Spada, Cristiano playing central roles. In the 2010-2019 period, network density decreased, indicating expansion in the author pool but less frequent co-authorships. However, the clustering coefficient remained high, suggesting localized collaboration. Central figures such as Itoi, Takao emerged as influential in bridging network gaps. In the most recent period (2020-2023), network density moderately increased, reflecting improved collaboration. Key contributors included Tanisaka, Yuki, and Ryozawa, Shomei, who enhanced connectivity within the network. Despite these advancements, the network remained fragmented with isolated components throughout all periods. Conclusion: The co-author networks in SBE research have shown an overall increase in collaboration over the past two decades, with key contributors playing pivotal roles in connecting disparate groups. However, the persistent fragmentation suggests a need for more integrated efforts to enhance international collaboration. Understanding these network dynamics can inform future strategies for fostering global cooperation and advancing SBE research.

The main objective is to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one-year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective is to study the changes in total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective sin gle-center observational study was conducted at Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into Time 0 (ETI treatment initiation), Time 1 (T1 – 3 months of ETI therapy), Time 2 (T2 - 6 months of therapy) and Time 3 (T3 - 12 months of therapy). Demographic and clinical data were collected. The results were then stratified by genotype (F508del in homozygosity or heterozygosity). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T1 and T2, but not at T3, as for HbA1c. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin dependent CFRD patients after one year of only ETI treatment.

Background: Atrial fibrillation (AF) is increasingly recognized in pediatric patients, presenting unique challenges in management due to its association with various underlying heart conditions. This study aimed to evaluate the prevalence, management strategies, and outcomes of AF in this population. Methods: A retrospective analysis was conducted at a tertiary pediatric cardiology center, including patients aged ≤18 years diagnosed with AF between January 2015 and December 2023. The study focused on demographic details, clinical presentations, treatments, and outcomes. Descriptive statistics were employed to assess treatment efficacy, recurrence rates, and complications. Results: The study included 36 pediatric patients (median age: 15 years, IQR: 13-17; 58% male). Of these, 52.8% had acquired heart disease, 16.7% had congenital heart anomalies, and 16.7% presented with lone AF. The initial management strategies involved electrical cardioversion in 53.3% of patients and pharmacological conversion with amiodarone in 46.7%. Rhythm control therapy was administered to over 80% of the cohort, and 63.9% were placed on oral anticoagulation, predominantly for rheumatic and congenital heart diseases. The overall success rate of rhythm control was 96.2%, with an AF recurrence rate of 3.8%. Ischemic stroke was the most common complication, occurring in three patients, all with underlying rheumatic heart disease. Conclusion: AF in pediatric patients is predominantly associated with rheumatic and congenital heart diseases, though a significant proportion of patients present with lone AF. Despite effective rhythm control in most cases, neurological complications, particularly ischemic strokes in patients with underlying heart disease, remain a critical concern. These findings underscore the need for more comprehensive studies to better understand the etiology, risk factors, and optimal management strategies for pediatric AF.

This study aimed to investigate the impact of specific single nucleotide polymorphisms (SNPs) on clinical and laboratory outcomes in COVID-19 patients receiving Paxlovid treatment. The primary focus was on genetic variants in IFNAR2, OAS1, OAS3, and ACE2. Laboratory parameters were assessed at admission and discharge, including oxygen saturation, white blood cell count, absolute neutrophil and lymphocyte counts, erythrocyte sedimentation rate, platelet count, hematocrit, and various liver and kidney function tests. The results demonstrated significant associations between certain SNPs and clinical outcomes. Patients with the IFNAR2 rs2236757 G allele exhibited improved oxygen saturation and lower eosinophil counts. The OAS3 rs10735079 and OAS1 rs10774671 G allele was associated with lower eosinophil and total bilirubin levels. Furthermore, patients with the ACE2 rs2074192 C allele showed increased segmented neutrophils and AST levels, while the T allele was associated with lower total bilirubin levels. These findings indicate that the efficacy of Paxlovid treatment may be influenced by genetic variations in IFNAR2, OAS1, OAS3, and ACE2. Further research is warranted to investigate the potential therapeutic implications of these genetic markers.

Background and Objectives: The deltopectoral (DP) flap represents a reconstructive option for head and neck. It is a fasciocutaneous flap raised from the anterior chest wall below the clavicle. Its role partially declined with the arise of free flaps. However, it still remains a valid option in patients that could not undergo a reconstruction with free flaps. The aim of this retrospective study was to evaluate the role of the DP flap in head and neck reconstruction, with a focus on surgical outcomes and complications. Materials and Methods: Thirty-one patients who underwent head and neck reconstruction with DP flap were included in the study. The delayed technique was not used in any procedure to harvest the flap beyond the deltopectoral groove. The patients’ characteristics, the recipient site, the closure of the donor site and the flap-related complications were recorded. Results: The median time to autonomization of DP flap was 23 days. Post-operative complications were observed in 10 subjects (32.3%). A partial necrosis was seen in 5 patients (16.1%), while a complete necrosis developed only in one case (3.2%). The diabetes mellitus was the only parameter associated to post-operative complications. In particular, the percentage of necrosis in subjects with or without diabetes was 66.7% and 8.0%, respectively. Conclusions: The DP has a wide range of applications in head and neck reconstruction and a low complication rate can be observed. The delayed technique does not necessarily need to be applied, and the flap can be extended beyond the deltopectoral groove when necessary. However, patients with diabetes mellitus have a higher risk of postoperative necrosis of the distal portion of the flap.

Current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. The emerging use of theranostic technologies to improve surgical outcomes can further augment the efficacy of adjuvant radiosurgery/radiotherapy and systemic therapies. Stanford Neurosurgery is a leader in the field of translational neuro-oncology. In this review, we provide an expert view of how theranostics can be integrated into future therapeutic treatment algorithms to help improve survival for patients with brain tumors.

Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (D_EP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, D_EP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by D_EP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by D_EP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated D_EP) at 20 V with 5 min intervals showed similar luciferase expression level to single D_EP application with 100 V. Histological observations showed the skin became thicker after a single D_EP at 100 V, whereas no apparent thickness changes was confirmed after repeated D_EP at 20 V with 5 min intervals. This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective in DNA vaccine delivery into skin tissue.

Damage to peripheral arteries by the atherosclerotic process accounts for about 3% of the world's population, which puts this problem in the category of major social problems. Modified lipoproteins and cholesterol crystals are known to accumulate in the arterial intima and cause the formation of proatherogenic macrophages, foam cells, and inflammation. Defective efferocytosis of apoptotic foam cells leads to the formation of a necrotic core, a sign of failure to resolve inflammation. Resolution of inflammation is mediated by specialized pro-resorption lipid mediators, proteins and signaling gases. Improving the balance between pro-inflammatory and anti-inflammatory factors contributes to the reverse development of local atherogenesis. Active direct intervention in the reconstruction of the adventitial layer of the arterial wall using cholesterol-affinity polysaccharide hydrogels containing a cocktail of growth factors creates conditions for the formation of additional extracellular matrix and reversal of cholesterol mass from the subintimal zone. Creating concentration and electrostatic gradients in the adventitia zone using a hydrogel may be one of the effective ways to degrade early soft atherogenic plaques and locally restore the damaged structure of the vessel wall. Growing scientific interest in the previously insufficiently studied adventitia indicates its important role in angionesis and atherogenesis.

Despite the existing effective treatment methods, tuberculosis (TB) is the second most deadly infectious disease globally, its carriers in the latent and active phases accounting for more than 20% of the world population. An effective method to control TB and reduce the mortality is regular population screening and diagnosis of the latent form of TB in order to take preventive and curative measures. Numerous methods allow diagnosing TB and directly detecting Mycobacterium tuberculosis (M.tb) biomarkers, including M.tb DNA, proteins, and specific metabolites, as well as antibodies produced by the host immune system in response to M.tb. PCR, ELISA, immunofluorescence and immunochemical analyses, flow cytometry, and other methods allow the detection of M.tb biomarkers or the host immune response to M.tb by recording the optical signal of fluorescent or colorimetric dyes included in the diagnostic tools. Current research in biosensors is aimed at increasing the sensitivity of detection, which can be achieved by using brighter and more photostable optical tags containing fluorescent quantum dots. Here, we review current methods for detection of M.tb biomarkers using optical sensor systems, primarily quantum dot–based nanosensors, and summarize M.tb biomarkers whose detection can be made significantly more sensitive by using quantum dot–based nanosensors.

Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer, comprising a disproportionate share of thyroid cancer-related mortalities despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for MTC patients. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. AI-driven precision oncology can significantly enhance the diagnostic work-up, staging, risk stratification, management, and follow-up care of MTC patients by processing vast amounts of complex data quickly and accurately. AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in MTC management enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being for all at all ages. By leveraging AI and holomics, we can strive towards making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. In conclusion, the integration of holomics and AI in the management of medullary thyroid carcinoma represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of MTC treatment and care.

Vitamin D and iron deficiencies are the most prevalent micronutrient deficiencies among women of reproductive age (WRA) in Morocco. Recent studies suggest that Vitamin D deficiency (VDD) may reduce iron bioavailability necessary for erythropoiesis, potentially leading to iron deficiency (ID) and anemia. This study investigates the association between vitamin D status, iron levels, and anemia risk among Moroccan WRA aged 18-49 years. A cross-sectional study was conducted with 463 participants. Serum levels of 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine were measured. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were evaluated using validated questionnaires, and anthropometric data were collected. Linear and logistic regression models assessed the relationships between variables, while Receiver Operating Characteristic (ROC) curve analysis evaluated the predictive accuracy of VDD for ID and anemia. VDD (25(OH)D &lt; 20 ng/ml) was significantly associated with lower levels of hemoglobin, hematocrit, red blood cells, and ferritin (all p &lt; 0.01), suggesting a role of vitamin D in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p &lt; 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate among all participants, with minimal protective effect against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p=0.037 respectively). ROC analysis demonstrated moderate discriminative power for VDD in diagnosing IDA and anemia (AUC: 0.643 and 0.603) but reduced accuracy for ID (AUC: 0.575). This study identifies VDD as a significant risk factor for impaired iron status and anemia among Moroccan WRA, underscoring the need for targeted nutritional interventions and further research to explore effective prevention strategies.

Septic arthritis (SA) represents an orthopedics urgency and mainly affects the knee joint. Due to its devastating effects on cartilage, immediate management is crucial. SA is characterized by an an-nual incidence of 2 to 10 cases per 100,000 individuals, with mortality rates fluctuating between 0.5% and 15%, with a substantially higher mortality rate observed in older people (15%) in con-trast to younger cohorts (4%). The etiology of septic arthritis is multifactorial: a spectrum of Gram-positive and Gram-negative bacteria can contribute to the development of this condition, especially Staphylococcus aureus. The treatment involves urgent (arthroscopic or arthrotomic) debridement associated with adequate antibiotic therapy. Intra-articular antibiotic carriers can also be used to increase their local concentration and effectiveness. The case of a 67-years-old woman affected by knee SA from methicillin-susceptible S. aureus is presented. She was treated with an arthroscopic debridement enhanced by intra-articular antibiotic-loaded calcium sulphate beads, together with antibiotic therapy. At 2-year follow-up, the infection has been eradicated and the patient fully recovered. This is the first description, to our knowledge, in English Literature of the use of antibiotic-loaded calcium sulphate beads as an adjuvant in the surgical treatment of SA of a native knee joint.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size and content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor respectively. Control group consisted of patients with risk factors for CHD, but no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, ADP 20, 5, 2.5 µM and in CHD/ACS groups, by TRAP 10 µM, ADP 20, 5 µM (+/- epinephrine 20 µM). Platelet size was assessed by mean volume, % large forms and forward scattering. RP were stained by thiazole orange. In the control group activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease of platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and reduced efficacy of antiplatelet therapy.

Background Cervical insufficiency, marked by recurrent painless cervix dilation leading to second-trimester pregnancy losses, is traditionally managed through cerclage placement and vaginal progesterone administration. However, a recent experimental approach targeted intra-amniotic inflammation or infection in a selected group of women with cervical dilation over 1 cm, intact membranes, and no uterine contractions in the second or third trimester. Case presentation We report a case of a 21 year old primigravid woman who experienced resolution of mid-trimester cervical insufficiency after the administration of triple antibiotic therapy, as confirmed by ultrasound monitoring. Remarkably, the patient successfully carried the pregnancy to term and delivered a healthy baby. Conclusions This case highlights the potential effectiveness of a novel combination of antibiotics, even in the presence of several high-risk pregnancy conditions, and underscores the possibility of a favorable outcome.

Background/Objectives: Cardiovascular diseases are one of the leading causes of morbidity and mortality worldwide. Health-related quality of life is crucial to assess the impact of cardiovascular diseases and to guide therapeutic strategies. The Short Form 36 Health Survey and the RAND 36-Item Health Survey questionnaires are common tools for measuring health-related quality of life in patients with cardiovascular disease, but their reliability may vary according to the population studied. The aim of this study is to compare the reliability of the SF-36 and the RAND-36 in a population with cardiac pathology, addressing the question of which of these instruments offers a more consistent and useful measurement in this specific group. Methods: Cross-sectional observational study carried out at the University Hospital of Burgos (Spain). 413 patients with cardiovascular pathology referred to the Cardiac Rehabilitation Unit were included. Patients with incomplete data or who did not participate in the program were excluded. Internal consistency (Cronbach’s alpha), item-total correlation and reliability and a half-half analysis were performed. Results: Both questionnaires showed similar and adequate reliability for patients with cardiovascular pathology. Internal consistency, as measured by Cronbach’s alpha, was above 0.80 for most dimensions, supporting its robustness. Significant inter-item and inter-dimension correlations were found in both scales, except in some specific cases in the dimension ‘Physical Functioning’. The half-half analysis confirmed the good reliability of both scales. Conclusions: Both the SF-36 and the RAND-36 are highly reliable tools for assessing health-related quality of life in patients with cardiovascular disease. The results may have significant implications for clinical practice, helping in the selection of health-related quality of life monitoring instruments and in the evaluation of the efficacy of therapeutic interventions.

Artificial intelligence (A.I.) is the key to process big amounts of data to useful information for operators. In the present study the suitability of a 24/7 A.I. sound based coughing monitoring system for early detection of respiratory distress caused by porcine respiratory disease complex (PRDC) associated pathogens was assessed in the nursery of a conventional pig farm. Screening for PRDC associated pathogens was conducted by PCR examination of oral fluids (OFs) and bioaerosol samples (AS). A significant correlation between A.I. and human gained health data was observed in both batches. An increase in coughing episodes, either measured by A.I. or human, was significantly correlated with decreasing Ct-values of swIAV. The Odds to detect nucleic acids of PRRSV or Actinobacillus (A.) pleuropneumonia was significantly higher for OFs compared to AS. Moreover, PCR examinations of OFs revealed significantly lower Ct-values for swIAV and A. pleuropneumonia compared to AS. The quantity of swIAV RNA in OFs and AS was significantly associated with the A.I. calculated respiratory health score and thus, with clinical disease. Due to its reliable data A.I. based health monitoring is beneficial for early recognition of respiratory distress and thus can assist farmer’s daily work.

This study evaluated the impact of rough, smooth, and very smooth Titanium (Ti) and zirconia (Zr) surfaces on the neutrophil expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9 and extracellular traps (NETs). Ti and Zr disks with a diameter of 10mm and a thickness of 1.5mm were processed using diamond-impregnated polishing burs and paste to generate rough (R; Ra= > 3µm), smooth (S; Ra= ≥1 to 1.5µm) and very smooth (VS; Ra= <0.1µm) surfaces. Peripheral neutrophils from Wistar rats were cultured on these surfaces and the culture supernatants subsequently analyzed for the presence of NE, MMP-8, and MMP-9 by ELISA, while NETs formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expression of NE and MMP-8 were significantly higher from neutrophils cultured on both on Ti and Zr rough surfaces compared to the very smooth surface (R>S>VS) after 2h and 4h of culture. The expression of MMP-9 also increased with culture time however no significant surface effects on expression were observed. Similarly, rough Ti and Zr surfaces (R & S) also showed significantly larger NETs formation compared to the very smooth surface (VS) after 4h and 8h culture. Our findings suggest that increasing surface roughness on Ti and Zr triggers higher secretion of NE, MMP-8 and NETs formation.

It has been suggested that parasitic infections, common in Latin American populations, may amplify the inflammatory response of the airways. There are several reports in atopic and asthmatic patients, but few reports of parasitic infection in COPD patients. The study aimed to determine the prevalence of parasitic infections in COPD patients as compared to atopic and asthmatic patients attending the outpatient clinics of the Institute of Immunology and the pneumonology service of the University hospital. A case-control study was conducted: 100 patients with bronchial asthma, 100 patients with COPD, 100 individuals with atopy without respiratory symptoms, and 100 healthy individuals. Serum specific IgG antibody against the parasites Ascaris lumbricoides (Al), Strongyloides stercolaris (Ss) and Toxocara canis (Tc) were measured: by ELISA. IgE levels were used as an indirect indicator of atopy. Positive IgG for Al was observed in all groups, predominantly in atopic cohort, Ss positiveness was recorded only in 4 COPD patients and Tc positiveness was observed in all groups except in controls. There are significant correlations between the values of Al and IgE in controls, atopic and asthmatic patients not with COPD. No correlation was found for Tc. IgE levels and FEV1 correlate only in atopic and asthmatic patients. Parasitic infections are common in atopic patients and in moderate and severe asthmatic and COPD patients. Anti-inflammatory treatment may be responsible for the increase frequency of infection.

Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS), associated with a poor prognosis. The standard treatment for GBM includes surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet despite these interventions, overall treatment outcomes remain suboptimal. The blood-brain barrier (BBB), which plays a crucial role in maintaining the stability of brain tissue under normal physiological conditions of the CNS,also poses a significant obstacle to the effective delivery of therapeutic agents to GBM. Recent preclinical studies have demonstrated that nanomedicine delivery systems (NDDS) offer promising results, demonstrating both effective GBM targeting and safety, thereby presenting a potential solution for targeted drug delivery. This review explores the various strategies employed in preclinical studies to overcome the BBB for drug delivery. Subsequently, the results of clinical translation of NDDS has been summarized, highlighting the progress made. Finally, we discuss potential strategies for advancing NDDS development and accelerating their translational research through well-designed clinical trials in GBM therapy.

Compared to agonists, radiolabeled somatostatin receptor (SSTR) antagonists have advantages in neuroendocrine tumors (NETs). Articles on radiolabeled somatostatin receptor agonists or antagonists in NETs were included by searching the Web of Science (WoS) database. The included literature has been subjected to data collection and bibliometric study. A detailed analysis of the included clinical articles was also performed. 123 publications were identified for biblio-metric analysis. The number of publications on radiolabeled somatostatin receptor agonists and antagonists in the theranostics of NETs has increased significantly after 2014, with Germany publishing the most papers (39), followed by the United States (33) and Switzerland (28). The Swiss paper was cited the most, with 1783 quotations, followed by the USA (1338) and Germany (1330). The most common keywords were NETs (89), Peptide receptor-mediated radionuclide therapy (PRRT) (62), and antagonists (53). Antagonists had lower uptake in normal tissue and higher uptake in tumor tissue compared to agonists, with a high tumor-to-liver ratio. Research on radiolabeled somatostatin receptor agonists and antagonists in theranostics of NETs is increasing, with significant contributions from Europe and the United States. Radiolabeled somatostatin receptor antagonists are likely to be a hot topic in NETs theranostics.

Little is known about skeletal muscle thickness, echogenicity, and muscle quality (handgrip strength /muscle thickness) in breast cancer-related lymphedema (BCRL). Using B-mode ultrasound, we recorded the raw radiofrequency data of the affected (AA) and unaffected (UA) arms of women (n=20) with BCRL, and in 20 control women with no lymphedema (CA). The data were converted into images and measurements of skin, subcutaneous fat and muscle thickness were obtained. Within a designated region of interest, muscle echo-intensity was assessed using computer graded grey scale and muscle thickness was measured using ImageJ2. Handgrip strength was measured using standard dynamometry. We found that forearm muscle thickness was similar among AA, UA, and CA. When compared to the unaffected and control arms, the affected arm had a significantly higher (p 0.013) muscle echo-intensity. When compared to the AA, handgrip strength was similar to UA (p 0.401) but lower than CA (p 0.05). We conclude that the use of B-mode ultrasound is a reliable method to assess muscle thickness and EI in BCRL. When comparing AA to UA, the elevated levels of muscle EI in AA did not influence strength or muscle quality. The elevated EI in AA is a marker of abnormal health that needs to be further explored.

The field of personalized medicine is undergoing a transformative shift through the integration of multi-omics data, which encompasses genomics, transcriptomics, proteomics, and metabolomics. This synergy allows for a comprehensive understanding of individual health by analyzing genetic, molecular, and biochemical profiles. The generation and integration of multi-omics data enable more precise and tailored therapeutic strategies, improving the efficacy of treatments and reducing adverse effects. However, several challenges hinder the full realization of personalized medicine. Key hurdles include the complexity of data integration across different omics layers, the need for advanced computational tools, and the high cost of comprehensive data generation. Additionally, issues related to data privacy, standardization, and the need for robust validation in diverse populations remain significant obstacles. Looking ahead, the future of personalized medicine promises advancements in technology and methodologies that will address these challenges. Emerging innovations in data analytics, machine learning, and high-throughput sequencing are expected to enhance the integration of multi-omics data, making personalized medicine more accessible and effective. Collaborative efforts among researchers, clinicians, and industry stakeholders are crucial to overcoming these hurdles and fully harnessing the potential of multi-omics for individualized healthcare.

Background. Of as yet, flow in the internal jugular veins has not been quantitatively studied in lateral decubitus position. Optimal venous outflow during sleep has been hypothesized to be potentially protective against neurodegeneration. Methods. Using ultrasonography, we measured the cross-sectional areas and flow volumes in middle parts of the internal jugular veins in group of 25 healthy individuals. These measurements were performed in the supine, upright and lateral decubitus positions. Results. In lateral decubitus positions we revealed collapse of the internal jugular vein located higher, and dilatation of the opposite vein; yet there was also a high heterogeneity of the cross-sectional area changes and in many participants this pattern was not observed. Regarding flow volumes, there was a shift of flow from one vein to the opposite one, depending on which side the person was lying, but in comparison with the supine position the total outflow through both internal jugular veins was not significantly different. Conclusions. In terms of venous outflow, the lateral decubitus position does not differ significantly from the supine one. Working hypothesis of potentially protective effect of this body position during sleep against neurodegeneration, through improved venous outflow, has not been proven, at least in healthy persons.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV.

Approximately 10–20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare cost vs controls without a COVID-19 diagnosis over ≥15 months, with a 7.6%–13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4–10% increase in long-term total HCRU over 6–8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.

The combination of nanoemulgel and phytochemistry has resulted in several recent discoveries in the field of the topical delivery systems. The present study aimed to prepare turmeric (Curcuma longa) and neem (Azadirachta indica) based nanoemulgel against microbial infection as topical drug delivery. Olive oil (oil phase), Tween 80 (surfactant), and PEG600 (co-surfactant) were used for the preparation of nanoemulsion. Carbopol 934 was used as gelling agent to convert the nanoemulsion to nanoemulgel and promote to control the release of biological properties of turmeric and neem. The nanoemulsion were characterized based on particle size distribution, PDI values and compatibility using FTIR analysis. In contrast, the nanoemulgel was evaluated based on pH, viscosity, spreadability, plant extract and excipients compatibility or physical state, in-vitro study, ex-vivo mucoadhesive study, antimicrobial properties and stability. The resulting nanoemulsion was homogeneous, stable during the centrifugation process, with the smallest droplets and low PDI values. FTIR analysis also confirmed good compatibility and absence of phase separation between the oil substance, surfactant, co-surfactant with both plant extracts. The improved nanoemulgel also demonstrated a smooth texture, good consistency, pH, desired viscosity, ex-vivo mucoadhesive strength with highest spreadability, and an 18-hour in-vitro drug release study. Additionally, it exhibited better antimicrobial properties against different microbial strain. Stability studies also revealed that the product had good rheological properties and physicochemical state for a period of over 3 months. The present study has affirmed that turmeric and neem based nanoemulgel as a promising alternative for microbial infection particularly associated by microorganisms via topical application.

Background: The development of new technologies, interpretation of amputations as therapeutic failures by society, and high morbidity and mortality associated with external hemipelvectomies make these mutilating surgical procedures appear obsolete. Herein, we review the scientific literature on the topic and present two cases of high-grade ulcerated soft tissue sarcomas in the gluteal region showing exceptional behavior and different outcomes. Methods: We performed a literature review of the PubMed databases from 2022 to April 2024. Additionally, we present two cases of soft tissue sarcomas in 18- and 71-years old female patients, which were treated with extended external hemipelvectomies with anterior flap and in combination with abdomino-perineal amputation and colostomy in one case. Results: At 4 years of follow-up, case one is living a relatively normal life. She had an uncomplicated pregnancy and a cesarean section delivery. Case two underwent emergency surgery for intestinal perforation and sepsis. She died 2.5 months following the surgery. Conclusion: External hemipelvectomy for soft tissue sarcoma treatment is a demanding surgical procedure with purpose in selected cases after review by multidisciplinary committees and with informed patient consent. This should be similarly individualized and extended to other pathologies when possible

Abstract Background The advent of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a e challenge. Objective This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results Our search included 55 pertinent studies conducted between 2019 and 2023. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, disability), high responder rates, and optimal safety and tolerability profiles. Conclusion Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an unprecedented finding in clinical neurology.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation and unnecessary NETosis impair DW healing. This theoretical problem commands the necessity of developing a novel strategy focused on targeting the 'specific' molecular modalities of DW. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, there is reinvigorated interest in identifying selective inhibitors for the effective management of DW. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule as a dual-inhibitor of MMP-9 and PKC-βII using protein-protein docking and molecular dynamics simulation studies. Residue-residue interactions and binding affinity were investigated using Z-dock. Chemical bonding behavioral changes, structural dynamics, and functional changes were determined using GROMACS by analyzing RMSD, ROG, RMSF, SASA, FEL, and PCA. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, which can be an ideal therapeutic for the accelerated healing of DW. The study provides valuable insights into the molecular mechanisms underlying hBD-2's potential therapeutic effects, offering new avenues for the development of innovative treatment strategies. The clinical relevance of our findings lies in their potential to inform the development of new approaches for diabetic wound management, addressing a significant healthcare concern.

Background and Objectives: Fibrillinopathies have different phenotypic expression: Marfan- like skeleton features, MLSF; mitral valve prolapse syndrome, MVPS; MASS phenotype, M= mitral valve prolapse, MVP, A= aortic root dilation, S= skeletal features, and the second S= (cutaneous) striae; Marfan syndrome, MS. These are inherited connective tissue diseases, provoked by a mutation of the encoding gene for a protein(fibrillin 1, FBN1) which has major importance in the formation of elastic fibers.The study had the following main objectives: the correlation between disc displacement, DD( a major sign for temporomandibular joint dysfunction, TMD) on magnetic resonance imaging, MRI, and aortic Z score(a major sign for aortic root dilation) on echocardiography; the predictive value of DD towards aortic Z score. DD had 2 types of severity: DD with reduction(the mild type, DDwR) , and DD without reduction( the severe type, DDwoR). Materials and Methods: The type of fibrillinopathy was precised by clinical exam( systemic score), ophthalmic exam(for ectopia lentis), and echocardiography(aortic Z score, MVP). Medical treatment consisted in betablockers, BB(for patients with tachycardia), or angiotensin II receptor blockers, ARB. Surgical treatment was addressed to aortic root aneurysm, and severe MR. DD benefited by dental conservatory treatment, or surgical restoration.Results: DD- Z score had a powerful correlation in MASS(Rho= 0.787, p&lt; 0.01), and in MS patients(Rho=0.819, p&lt; 0.01). For the entire sample, both DDwR- Z score, and DDwoR- Z score had a moderate correlation(Rho= 0.469, and respectively 0.669). Muchmore, DD was an important predictor for Z score. DDwoR had a double power of prediction for Z score, comparative with DDwR(B coefficient= 1.661 for DDwR, and 3.281 for DDwoR). Conclusions: TMD had a powerful correlation with aortic root dilation, in MASS, and MS patients from the sample. Likewise, TMD was a major predictor for aortic root dilation, in the entire sample. We can utilize in clinical practice, an extracardiac finding, TMD, obtained by a non-invasive technique, MRI, for cardiac severity stratification of fibrillinopathies.

According to evolutionary cancer cell biology ECCB, cancer stem cells do not arise from normal stem cells, but rather from the functional ACD phenotype of the germline. This phenotype proliferates through asymmetric cell division, producing self-renewing cells and non-proliferating daughter cells with cancer stem cell qualities (CSCs). ECCB posits that cancer stem cells themselves do not proliferate. Similar to protists, there is a close reciprocal relationship between both sister cells that collectively form a germ and stem cell lineage. These sister cells share functional roles: the proliferating cancer germline cells generate stem cells, while the non-proliferating cancer stem cells accumulate progenitor cells for new germline clones. ECCB distinguishes between primary CSCs, which are associated with carcinogenesis and primary tumors, and secondary CSCs, which are linked to metastases. This unicellular stem cell system is homologous to that of parasitic protists, such as amoebae. Both cancer stem cells and amoebae stem cells are generated by an oxygen-sensitive germline and are vulnerable to damage when oxygen levels exceed 6.0% (germline hyperoxia). Oxygen concentrations above this threshold can damage the germline genome. Dysfunctional germline cells do not undergo senescence; instead, they continue to cycle through defective symmetric cell cycles However, to regain functionality, the germline genome requires repair by hyperpolyploid giant cells known as native PGCCs, which are homologous to the multinucleated genome repair structures MGRS found in protists. Native PGCCs differ in some respects from genotoxic-induced PGCCs

Cancer, a complex group of diseases marked by uncontrolled cell growth and invasive behavior, is characterized by distinct hallmarks acquired during tumor development. These hallmarks, first proposed by Douglas Hanahan and Robert Weinberg in 2000, provide a framework for un-derstanding cancer's complexity. Targeting them is a key strategy in cancer therapy. It includes inhibiting abnormal signaling, reactivating growth suppressors, preventing invasion and me-tastasis, inhibiting angiogenesis, limiting replicative immortality, modulating the immune sys-tem, inducing apoptosis, addressing genome instability, and regulating cellular energetics. Usnic acid (UA) is a natural compound found in lichens that has been explored as a cytotoxic agent against cancer cells of different origins. Although the exact mechanisms remain incom-pletely understood, UA presents a promising compound for therapeutic intervention. Under-standing its impact on cancer hallmarks provides valuable insights into the potential of UA in developing targeted and multifaceted cancer therapies. This article explores UA activity in the context of disrupting hallmarks in cancer cells of different origins based on articles that emphasize the molecular mechanisms of this activity.