This paper presents the rationale for using ultra low intensity transcranial light photodynamic treatment (LIT-PDT) for treating glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide and ionizing irradiation. Mortality in 2024 remains at over 80% within several years from diagnosis. 5-aminolevulinic acid (5-ALA) is a heme precursor that is selectively taken up preferentially by malignant cells, including glioblastoma. Photon energy can be transduced to molecular oxygen by a 5-ALA metabolite, PpIX, transforming oxygen to the singlet state, a reactive oxygen species (ROS) that destroys or damages vital glioblastoma cell structures. In PDT, light energy ~ 100 to 200 J / cm2, at 630 nm is delivered intraoperatively after resection and preoperative oral 5-ALA. This generates ROS cytotoxicity in residual glioblastoma cells within the resection cavity wall. 630 nm light poorly penetrates skin, skull, and brain tissue. That currently restricts PDT to a single intraoperative session using high flux light. LIT-PDT addresses some current shortcomings of 5-ALA PDT treatment. Part 1 analyzes published data indicating that continuous ultra low light flux, 17 μW / cm2, over 24 hours for a total delivery of 1.5 J / cm2, is effective for 5-ALA PDT treatment. That opens the way for repetitive, extracranial light to deliver enough energy for low flux, long duration PDT to any deep brain structure using less than 12 W total distributed over the entire scalp area. In Part 2, by analysis of 5-ALA and PpIX physiology, it became apparent that four non oncology drugs - ciprofloxacin, deferiprone, telmisartan and ziprasidone, will increase energy capture by GB cells, thereby increasing PDT treatment cytotoxicity. A phased pilot study of LIT-PDT treatment is being planned.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from <50 µm to >1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

Community Acquired Urinary Tract Infections account for 15% of all outpatient use of antibiotics, women are primarily affected; major causative microorganisms are uro-pathogenic E. Coli. Treatment is indicated for cystitis and pyelonephritis and includes B-lactams (amoxicillin-clavulanic acid or third generation cephalosporins), fluoroquin-olones (ciprofloxacin or levofloxacin), nitrofurantoin, fosfomycin, and trime-thoprim-sulfamethoxazole. Resistance to antibiotic treatment is of concern, several mecha-nisms have been associated with the acquisition of genes that confer antimicrobial re-sistance to fluoroquinolones, which often are associated with other patterns of resistance, especially in extended spectrum beta lactases (ESBL) producers. Several studies have ad-dressed the prevalence of uropathogens producing ESBL, but only a few have focused on resistance against fluoroquinolones and to our knowledge, none has been addressing the prevalence of isolates mutations that confer antimicrobial resistance to fluoroquinolones. The focus of the present review was to analyze recent published papers that describe the E. coli phylotype causing community acquired UTIs in association to fluoroquinolones re-sistance.

Hereditary cardiomyopathies (CMPs), including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Dilated Cardiomyopathy (DCM), and Hypertrophic Cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in Next-Generation Sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated to CMPs. Nowadays, a set of core genes is included in diagnostic panels for ARVC, DCM, HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines, provides a thorough overview of the genetic landscape of minor genes in CMPs and offers insights for future research and translation to clinical practice. Given the increasing knowledge on these less-understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

Objective: The primary objective of this study was to develop a logistic regression model to predict post-operative in-hospital mortality rates for patients undergoing emergency cardiac surgeries, with the aim of improving predictive accuracy over traditional risk assessment tools and enhancing patient outcomes and clinical decision-making. Methods: Data were collected from 4,855 patients who underwent emergency cardiac surgeries at a tertiary hospital between 2008 and 2017. The analysis incorporated demographic, anthropomet- ric, and clinical factors, including the ASA classification, emergency status, and various preoperative laboratory values. A logistic regression model was developed, and the Elixhauser Comorbidity Index was calculated using standard ICD-10 codes for its comprehensive assessment of comorbidities. Model performance was evaluated using metrics such as AUROC, AUPRC, accuracy, precision, recall, and F1 score. Results: The logistic regression model demonstrated strong predictive performance, with an AUROC of 0.939 and an AUPRC of 0.350. Key pre-operative factors identified included emergency operation status, ASA classification, and preoperative prothrombin time. The model significantly outperformed the traditional ASA classification system, which showed an AUROC of 0.524 and an AUPRC of 0.010. These findings suggest a substantial improvement in predicting post-operative mortality. Conclusion: The logistic regression model significantly improves the prediction of post-operative mortality in emergency cardiac surgeries compared to the ASA classification system. These findings highlight the potential of incorporating comprehensive pre-operative factors into predictive models to enhance clinical decision-making and patient outcomes. Implementing such models in routine clinical practice could lead to more accurate risk assessments, better resource allocation, and improved patient care.

The global need for rapid diagnostic methods for pathogen identification and antimicrobial susceptibility testing (AST) is underscored by the increasing bacterial resistance and limited therapeutic options, especially critical in sepsis management. The evolution from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly decreased result turnaround times, improving patient outcomes. Despite advancements, the complex decision-making in antimicrobial therapy often exceeds the capacity of many clinicians, highlighting the importance of antimicrobial stewardship programs (ASP). These programs, integrating mHealth and eHealth, leverage technology to enhance healthcare services and patient outcomes, particularly in remote or resource-limited settings. However, the application of such technologies in antimicrobial management remains underexplored in hospitals. The development of platforms combining antimicrobial prescription data with pharmacotherapeutic algorithms and laboratory integration can significantly reduce costs and improve hospitalization times and mortality rates. Yet, the effectiveness of empirical antibiotic therapy, influenced by rapid diagnostic tests, becomes cost-effective when error rates exceed 20%, emphasizing the need for technological integration in ASPs to combat the rising challenge of antimicrobial resistance (AMR) and healthcare sustainability.

(1) Background: Heart rate variability (HRV) has emerged as a potential prognostic tool in cardiovascular diseases, offering individualized insights into autonomic nervous system activity. However, real-time HRV data during the acute phase of STEMI, particularly during percutaneous coronary intervention (PCI), was not previously explored. (2) Methods: This single-center, observational cohort study included 104 STEMI patients undergoing primary percutaneous coronary intervention (PCI). HRV parameters were measured using a wearable device (CE marked) during PCI, capturing dynamic responses. The association between HRV parameters and adverse outcomes, including in-hospital mortality and major adverse cardiovascular events (MACE), were assessed. (3) Results: HRV parameters significantly decreased after myocardial revascularization, particularly SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio. Significant associations were found between reduced SD2/SD1 ratio, approximate entropy, and adverse outcomes, including increased in-hospital mortality and MACE. The SD2/SD1 ratio was significantly lower in patients who died during the hospital stay (p = 0.008) compared to survivors. Approximate entropy was also significantly lower in deceased patients (p = 0.019). (4) Conclusions: Real-time HRV monitoring using wearable technology offers valuable data regarding dynamic physiological changes during primary PCI. The integration of HRV into routine clinical practice, facilitated by wearable devices, could improve the risk stratification and event prediction in STEMI patients.

Substance use disorder (SUD) is a global health crisis that is becoming increasingly prevalent among younger generations and impacting the overall health of millions of people worldwide. Traditional treatment methods, including cognitive-behavioral therapies and medicinal-assisted treatments, often face limitations such as inconsistent efficacies and varying degrees of accessibility. Thus, there is a clear need for a new and innovative treatment strategy. Music therapy has recently gained attention through research as a promising non-pharmacological supplement to strengthen conventional SUD treatment methods. This review explores the potential benefits of music therapy in reducing substance cravings, alleviating depressive symptoms, and improving emotional expression among patients in the rehabilitation phase of SUD recovery. We review evidence from various studies and clinical trials to evaluate the efficacy of music therapy in improving standard treatment outcomes, with the results indicating that music therapy could be an effective complement to traditional treatment methods while noting that its efficacy could vary depending on the individual and type of intervention provided. The benefits of music therapy include accessibility of treatment for diverse patient groups and the potential for highly individualized care, although more research is needed to compare the efficacies of specific music treatment types for certain conditions and patient populations. Further research is also needed to validate the neurobiological mechanisms of music therapy, as well as increased communication between music therapists worldwide to enforce consistency in treatment methods and share learnings in this growing field.

Achieving effective haemostasis is crucial for successful outcomes and optimal patient care in contemporary oral surgery. Control of bleeding is essential in procedures like extractions, implant placements, periodontal surgeries, and soft tissue interventions. Efficient management ensures a clear surgical field, reduces post-operative complications, and promotes healing. Local haemostatic agents are essential tools for oral surgeons, offering targeted and controlled methods to achieve haemostasis. These agents include diverse materials and technologies, each with unique mechanisms of action suited to specific surgical scenarios. This review explores the spectrum of local haemostatic agents in contemporary oral surgery, focusing on their efficacy, safety, and practical utility. By examining the characteristics and clinical performance of various haemostatic agents, this review provides valuable insights to guide dentists and oral surgeons in selecting the most appropriate agent for specific situations. A literature search in electronic databases such as Medscape, PubMed-Medline, Science Direct, and EBSCO Host identified 46 publications from 1990 to 2023. This comprehensive examination aims to enhance understanding of local haemostatic agents and their role in advancing the standards of care in contemporary oral surgery.

This communication is to summarize our single center experience on applications of anti-IL-1 biologic response modifiers on autoimmune and autoinflammatory conditions in children. We present our rationale for off-label utilization of Anakinra and discuss evolving treatment paradigms that warrants further research and validation. Based on our observations and successful treatment outcomes, we advocate future multilateral efforts to liberate access to anti-IL-1 medications to control inordinate and detrimental inflammation in children.

Background and aim: Apigenin (API), a dietary flavone subclass of flavonoid found in herbs, fruits, and vegetables, exhibits various pharmacological effects. However, its role in triggering oxidative stress- induced apoptosis in uterine cells remains unclear. This study aimed to evaluate the oxidative stress-mediated apoptosis induced by apigenin in rat uterine leiomyoma ELT3 cells. Material and methods: ELT3 cells were treated with 50 and 100 µM API for 48 hours. We assessed oxidative stress markers (reactive oxygen species, malondialdehyde), antioxidant defense (glutathione reductase activity), cell proliferation, and apoptotic gene expression (p53, Bax, Bcl-2, caspase-3, caspase-9) using relevant assays and real-time PCR. Results: API treatment decreased cell proliferation and glutathione reductase activity in ELT3 cells. This coincided with increased levels of reactive oxygen species, malondialdehyde, and lactate dehydrogenase activity, indicating oxidative stress and cell damage. Furthermore, apigenin upregulated pro-apoptotic genes (p53, Bax, caspase-3, caspase-9) and downregulated the anti-apoptotic gene Bcl-2, suggesting activation of the intrinsic apoptotic pathway. Conclusion: API induces apoptosis in rat uterine leiomyoma cells through a mechanism involving oxidative stress-mediated activation of the intrinsic apoptotic pathway.

A multicenter retrospective analysis of 408 patients diagnosed with onychomycosis and attended at three tertiary care Spanish hospitals was conducted to assess the effectiveness and safety of a combined treatment with ciclopirox 8% hydroxypropyl chitosan (CPX 8% HPCH) nail lacquer and oral antifungal agents (terbinafine, itraconazole, and fluconazole). Data were extracted and analyzed using the EHRead® technology based on natural language processing and machine learning and using SNOMED CT terminology. The median age was 51 years with a ratio male: female close to 1. Repeated nail trauma was the most common risk factor (7.1%). More than half of patients (56.6%) underwent fungal culture. Terbinafine was used in 67.7% of patients, itraconazole in 20.8%, and fluconazole in 11.5%. Treatment synchronicity distribution revealed that 59.1% of patients started concomitant treatment with CPX 8% HPCH and oral antifungals, 27.9% had initial oral antifungals, and 13% had initial nail lacquer. The response to treatment (positive response 15.7%, presumed positive 59.8%) was unrelated to treatment synchronicity or type of antifungal agent. Erythema (5.6%), diarrhea (4.9%) and fever (4.2%) were the most frequently registered potential adverse events. The present findings provide valuable insights for physicians paving the way for better management of patients with onychomycosis.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

Endoscopic ultrasound (EUS) and intraductal ultrasound (IDUS) play very important roles in the field of biliary tract disease. Because of their excellent spatial resolution, the detection of small lesions and T-staging of tumors have become possible. Additionally, contrast-enhanced EUS and the new imaging technique of detective flow imaging are reported to be useful for differential diagnosis. Furthermore, EUS-guided tissue acquisition is used not only for pathological diagnosis, but also to collect tissue samples for cancer genome profiling. Although percutaneous transhepatic biliary drainage (PTBD) was traditionally performed in cases where endoscopic retrograde cholangiopancreatography is not feasible, treatments using EUS have recently become increasingly common, and EUS-guided biliary drainage was recently suggested to be superior to PTBD in terms of a higher success rate, less adverse events, and lower reintervention rate. This review provides an overview of diagnosis and treatment utilizing the features and techniques of EUS and IDUS.

The climate change constitutes nowadays an enormous global threat for human health and environmental sustainability. The expanding world population and the increased global needs for food production have an important negative impact upon environment. Diet can link human health with environmental sustainability. Food production systems are closely related to anthropogenic greenhouse gas emissions and the aggravation of climate change, and current western type, animal-based, dietary patterns may lead to adverse environmental footprints. In the present narrative review, we address the interconnection of the Mediterranean diet (MD) with climate change and sustainability. MD is a highly recommended dietary intervention for the prevention and management of various endocrine and cardiometabolic diseases. Beyond its evidence-based, health-promoting effects, it also has beneficial environmental impact, reducing greenhouse gas emissions and enhancing biodiversity, food security and sustainability. Based on the evidence reviewed herein, MD should be incorporated within the framework of a “One Health” model, which involves the improvement not only of human health but also of planetary health and food system sustainability. Our review aims to provide a stimulus for health pro-fessionals to strongly recommend the implementation of MD under the current pressure of climate change, despite all barriers, targeting both human health preservation and the planetary well-being.

Objective: To evaluate audiological outcomes, quality of life, and complications in patients implanted with Active middle ear implants (AMEI). The secondary objective is to investigate the required duration after implantation to reach satisfactory outcomes. Methods: This retrospective study included 31 patients implanted with Active middle ear implants (AMEI) with different methods of floating mass transducer attachment. Patients with incomplete medical records and those who did not respond to postoperative follow-up were excluded. Patients were assessed preoperatively, and at one, three, and six months postoperatively. The assessment included Pure Tone Average (PTA4), Speech Reception Threshold (SRT) and Speech Discrimination Score (SDS). The Speech Spatial and Qualities of Hearing scale (SSQ12) was also used to evaluate levels of satisfaction. Result: There are no significant differences found in PTA and SRT between the 3-, 6-, and 12-month visits. The speech reception threshold (SRT) showed a statistically significant improvement at 3, 6, and 12 months post-operative measures compared to pre-operative. Additionally, the SDS exhibited a significant increase only after 12 months, compared to the 3-month time point. However, satisfaction levels did not significantly differ between the 6-month and 12-month measurements following surgery. Conclusion: Vibrant Sound bridge improves subjective satisfaction scores and audiological test scores in patients with different types of hearing loss. AMEI has a low risk of medical or surgical complications, the ease of using a hearing implant, and the social benefits of good hearing and communication.

The management of erectile dysfunction (ED) shows several grey zones, especially in terms of patient satisfaction and adherence to the treatment. The main and first-line treatment for ED is drug therapy, mainly phosphodiesterase-5 inhibitors (PDE-5is) but the adherence to the therapy is not optimal due to the low patient satisfaction reported in several cases. To address this issue, different administration routes and PDE-5is pharmacological formulations have been introduced in the pharmacological market. The pharmaceutical market has recently seen the introduction of a novel sildenafil oral suspension. This device offers access to all therapeutic regimens in one device, releasing 0.5 mL of suspension containing 12.5 mg of sildenafil with each pulse. This formulation enables tailored dosing based on clinical requirements and the demands of ED patients. Here, we aim to give a brief narrative review of the management of this new oral suspension in order to provide the readers with some suggestions to use in everyday clinical practice, on the basis of the recent evidence, by using an easy and rapid-to-consult questions and answers form. Also included are the conclusions of a board meeting of experienced andrologists regarding the most recent developments in this area.

Background: Lutein and zeaxanthin are fat-soluble antioxidant nutrients that have evidence of beneficial effects on vision and eye health. The purpose of this study was to examine the effects of supplementation with lutein and zeaxanthin isomers (Lute-gen®) on eye health, eye strain, sleep quality, and attention in high electronic users. Study design: Two-arm, 6-month, parallel-group, randomized, double-blind, placebo-controlled trial. Methods: Seventy volunteers aged 18 to 65 who used electronic screens for more than 6 hours daily were supplemented with 10 mg of lutein and 2mg of zeaxanthin-isomers or a placebo. Outcome measures included several ophthalmic examinations comprising the Schirmer tear test, photo-stress recovery time, contrast sensitivity, tear film break-up time, and self-report measures of visual fatigue, computer vision, sleep quality and attention. Results: Compared to the placebo, lutein and zeaxanthin supplementation was associated with greater improvements in the Schirmer tear test, photo-stress recovery time, and tear film break-up time. However, there were no group differences in the change in self-report measures or contrast sensitivity. Lutein and zeaxanthin supplementation was well-tolerated, with no reports of serious adverse reactions or clinically significant changes in safety blood measures, including liver function, renal function, blood lipids, and full blood examination. Conclusions: The results from this study provide support for the beneficial effects of 6 months of lutein and zeaxanthin supplementation on visual health and dry eyes in regular users of electronic screens. However, these findings were not corroborated by group differences in the administered self-report questionnaires.

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women suggesting that there are serious errors in our preventive and therapeutic measures.Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defect in liganded estrogen receptor (ER) signaling demonstrating its role in genomic instability and cancer initiation. 2. In breast cancers, the increased expression of certain receptor family is an effort for self directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast tumors, non responsive to endocrine therapy, show HER2 overexpression for compensation the complete blockade of liganded ER activation. 5. In breast tumors, somatic mutations serve upregulation of liganded or unliganded activation of ERs helping genome stabilization and apoptotic death. 6. The dynamic communication between breast cancer and its microenvironment is a wonderful collaboration among molecular players fighting for genomic repair and apoptosis in the tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather the non responsive tumor cells exhausted all compensatory possibilities against therapeutic damages. Conclusion: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying a supportive care instead of genotoxic measures.

The amplified production of reactive oxygen species (ROS) or reduced oxidant protection is described as oxidative stress, which contributes to the increase in several disorders, notably obesity and neurodegenerative diseases. Flavonoids are polyphenol compounds found in a variety of foods of plant origin, such as berries, with a basic chemical structure consisting of an aromatic ring linked to a benzene ring and a pyran ring. Flavonoids have neuroprotective activity and promote synaptogenesis and neurogenesis and are also capable of inhibiting oxidative stress and neuroinflammation. Anthocyanins are water-soluble natural pigments that belong to the flavonoid class and have antioxidant and anti-inflammatory properties, helping to reduce chronic inflammation associated with various health conditions, including obesity. In addition, flavonoids and anthocyanins can modulate the expression of genes involved in lipid metabolism, promoting the oxidation of fatty acids and the reduction of lipid synthesis, contributing to the reduction of body fat accumulation. One of the most abundant flavonoids in the natural environment, quercetin, is found mainly in the form of O-glycoside derivatives and rarely as an aglycone. Quercetin has antioxidant properties, against diseases such as cancer; It also acts to combat allergic reactions, inflammatory processes, platelet disorders, obesity, hypertension and atherosclerotic and hypercholesterolemic disorders. Anthocyanins can activate intracellular signaling pathways, such as the AMPK (AMP-activated protein kinase) pathway, which has a crucial role in regulating energy metabolism and glycemic homeostasis. Activation of this pathway increases glucose uptake and fatty acid oxidation, favoring weight loss and improving insulin sensitivity. This review article aims to analyze the effects of using berries in controlling obesity and its role as a reducing factor for mild cognitive decline. A systematic review will be carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyze. We will search the following electronic databases: PubMed (Medline), Science Direct, Scopus and Web of Science.

Several factors contribute to stigma associated with migraine, such as the lack of objective diagnostic tests and biomarkers or traditional gender stereotypes. Patients with migraine can perceive the stigma from different sources: other people (public stigma), organisations (structural stigma) or themselves (internalised stigma), and even neurologists may harbour stigma towards patients with headache. At a social level, repeated migraine attacks lead to restricted participation in work and family life, inducing anxiety, depression and reduced self-esteem. Regarding the workplace, the impact of migraine on their proffesional lives is significant. Individuals who were acquainted with people with migraine at job tended to behave more negatively towards them, and over half of the managers did not consider headache as a valid reason for being absent from work. Effectiveness at work is reduced during a migraine attack, but also because of the interictal symptoms these patients go through. Regarding presenteeism, migraine was the second most expensive disease in the USA, with an annual cost of approximately $240 billion. For all these facts, destigmatisation should take place at the level of healthcare providers, patients and the general population. Implementing educational programmes, training more neurologists in a specialised headache approach, listening to the patients and taking their concerns seriously, or recognizing the disability that the disease causes are strategies that may help minimizing the stigma of migraine.

Background/Aim: Performing emergency surgery for bowel obstruction continues to place a significant strain on the healthcare system. Conventional assessment methods for outcomes in bowel obstruction cases often concentrate on isolated factors, and the evaluation of results for individuals with bowel obstruction remains poorly studied. This study aimed to examine the risk factors associated with major postoperative complications. Methods: We retrospectively analyzed 99 patients undergoing surgery from 2015 to 2022. We divided the patients into two groups: 1) benign related obstruction (n=68), 2) cancer related obstruction (n=31). We used logistic regression, KNN and XGBOOST. We calculated the receiver operating characteristic curve, and accuracy of the model. Results: Colon obstructions were more frequent in the cancer group (p=0.005). Operative time, intestinal resection and stoma were significantly more frequent in the cancer group. Major complications were 41% for the cancer group vs. 20 in the benign group (p=0.03). Uni-and multivariate analysis shows that significant risk factors for major complication were cancer related obstruction and CRP. The best model was KNN with an accuracy of 0.82. Conclusion. Colonic obstruction is associated with a tumor-related blockage. Malignant cancer and an increase in C-reactive protein (CRP) are significant risk factors for patients who have undergone emergency surgery due to major complications. KNN could improve the process of counseling and the perioperative management of patients with intestinal obstruction in emergency settings.

Beginning in December 2019, a novel coronavirus known as SARS-CoV-2 has caused an international outbreak of respiratory illness termed COVID-19. This disease may cause mild to moderate respiratory illness. However, older individuals and those with underlying medical conditions like diabetes, cancer, and cardiovascular disease are more likely to develop serious illnesses (progressive pneumonia, multi-organ failure, and even death) (1). The main target for antiviral therapy for COVID-19 is the 3CL protease (3CLpro, Main protease, Mpro, Nsp5). The 3CL protease plays an integral role in viral replication and is often known as the “Achilles heel” of the SARS-CoV-2 virus (2). Thus, NLC Pharma utilized a unique and novel technology termed Quantum Core Technology (QCT) to design a mechanism-based potent inhibitor against the SARS-Cov-2 3CL protease. 3CL Pharma has designed an oral anti-viral for COVID-19 called Tollovir. Biochemical assays have revealed that 40uM of Tollovir in PBS can achieve 90% maximum inhibition of 3CL protease. Furthermore, the oral anti-viral has completed clinical trial phase 2b/3. Tollovir has proven to be safe and significantly decreases mortality rates of hospitalized patients with COVID-19 infection.

Background: The utilization of nutrient supplementation as a tool to address issues such as iron and vitamin A deficiencies among children in Sub–Saharan Africa (SSA) has been beneficial. Nevertheless, there is a dearth of evidence on the effect of vitamin A and iron supplementation on infectious diseases in pre–school children in SSA. We aimed to assess the association of vitamin A and iron supplementation on the incidence of major clinical features of infectious diseases (diarrhea, cough, and fever) in children aged 6–59 months in Ghana. Methods: A cross–sectional study that utilized data from the Ghana Demographic and Health Survey, involving a sample size of 2,408 children. The collected data was analyzed using binomial logistic regression. Results: Dual supplementation with vitamin A and iron was associated with an increased risk of fever (OR: 1.68 95% CI: 1.22–2.32) and cough (OR: 1.43, 95% CI: 1.02–1.99) in children 6–59 months. Iron supplementation alone was associated with an increased risk of fever (OR: 1.32, 95% CI: 1.01–1.72) while Vitamin A alone significantly increased the risk of diarrhea (OR: 1.73, 95% CI: 1.03–2.92). Conclusions: Dual supplementation of vitamin A and iron is associated with an increase in childhood morbidity, endorsement of combined supplementation should be done with caution.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

Backround: The purpose of this study was to evaluate the outcomes of different radiotherapy techniques used in routine clinical practice for the radical treatment of hypopharyngeal cancer and to assess improvements over the last few decades. Methods: We compared the outcomes of patients with hypopharyngeal squamous cell carcinoma treated with curative radiotherapy (RT) or chemoradiotherapy between January 1992 and December 2020, using 2D-RT, 3D-CRT/IMRT, and VMAT techniques. A retrospective analysis was conducted on eighty-one patients with hypopharyngeal cancer. Results: The median follow-up time was 26 months (range: 6-290). In multivariate analysis, radiotherapy technique, Karnofsky Performance Status (KPS), nodal stage, and clinical stage were identified as statistically significant factors affecting overall survival and local-regional relapse-free survival. Grade 2-4 early and late side effects were significantly more frequent in Group I patients (treated with 2D Conventional Radiotherapy) (20.3%) compared to Group II patients (treated with 3DCRT/IMRT and VMAT techniques) (3.1%) Conclusion: KPS, stage, and advanced RT techniques independently significantly affected outcomes. Moreover, advanced RT techniques were associated with a significant reduction in side effects.

Type 2 diabetes mellitus (T2DM) poses a significant economic and clinical burden. Clinical inertia is defined as the failure of healthcare providers to modify therapy in the presence of clear indications. This study aimed to identify patient opinions on insulin to understand the barriers preventing type 2 diabetes patients from initiating insulin treatment when recommended by their physician. This cross-sectional observational study included 671 individuals with poorly controlled T2DM and HbA1c levels exceeding 10%. These patients required either the initiation or escalation of their existing insulin therapy. The participants were referred to Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) for consultation between January 2022 and July 2022.Results: During discussions between the researcher (clinician) and the inadequately controlled T2DM patients, the primary reasons for refusing insulin therapy were identified. These reasons included fear of injections, the belief that insulin induces dependence and is a last resort, concerns about hypoglycemia and complications, cost, difficulty in computing doses, social stigma, inconvenience and disruption to life and work, storage challenges, fear of weight gain, dependence on others, and lack of confidence.The study concludes that the clinical barriers faced by individuals who refuse the initiation of insulin therapy are diverse. The most common belief among the patients was that insulin leads to dependence (38%), while the smallest percentage cited a lack of confidence in insulin as an effective treatment for lowering hyperglycemia.

In the context of restorative dentistry and the use of different techniques and dental adhesive systems, this study was to designed to assess the degree of adhesive absorption and wetting for each dental micro applicator; and also quantify the amount of lost fiber flocks after three applications of dental adhesive on the inside surface of a plastic veneer tooth in order to reveal a potential contaminating factor at the adhesive interface. Initially, one drop of dental adhesive was dispensed into a glass dental mixing well. The dental adhesive was then applied onto the inside surface of the veneer restoration for 30s using a dental micro applicator which was weighed afterwards. For each dental micro applicator, this sequence was repeated three times and measured again by the same operator. Each adhesive application was analyzed separately, to show the values independently and compare them to the initial weight. The samples of Fiber-Free Elastomer Bristle Micro Applicators (FEBM) demonstrated the best performance with a good degree of absorption and wetting of the dental adhesive without the loss fiber flocks and release-induced weight loss. The samples of Conventional Fiber Flocked Micro Applicators (CFFM) demonstrated good initial absorption and wetting of the dental adhesive, but visually shed several fiber flocks which resulted in significant weight loss and can also be considered a contaminating factor at the adhesive interface.

Objective. The present study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for the assessment of bone density in postmenopausal women with low bone mass. Study design. We enrolled 104 postmenopausal women who performed dual energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT using NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between DXA parameters: lumbar, femoral neck and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS) and the panoramic mandibular indices: computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)) and computed tomography mental index (CTMI). Results. We found important correlations between the CTI(I), CTI(S) and CTMI and bone mass, quantitative evaluated as BMD and T-score and also quality using TBS score. Conclusion. CBCT measured indices CTI(S), CTI(I), CTMI are useful in assessing patients with low bone mass.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients, and healthy subjects with (GBA-C) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn & Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-C and HC were also considered. Clinical assessment included the MDS-UPDRS and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-C (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p<0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p<0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-DHP. Allopregnanolone was the only neurosteroid significantly lower (p<0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Background and objective: The impairments and duration of PASC (Post-acute sequelae of COVID-19) symptoms in mental health have up to date not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course. Methods: Mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University-Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID-Syndrome-Score), depression (Patient-Health-Questionnaire 9), somatic symptoms (Patient-Health-Questionnaire 15), anxiety (Generalized-Anxiety-Disorder 7), fatigue (Fatigue-Severity-Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional-Malaise Screening) was conducted in the home environment. Results: 80% of patients experienced severe PASC at follow up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety, and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained on an unchanged high level. Risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre. Conclusion: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for mental health implications of PASC is needed for planning health services and disease prevention.

The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination is impaired in nasal polyp (NP) mucosae due to suppressed expression of a series of CPLANE (ciliogenesis and planar cell polarity effector) complex proteins in chronic rhinosinusitis (CRS) patients. To inves-tigate this hypothesis, we subjected sinonasal mucosal samples to live video recording to measure mucociliary transport velocity (MCTV) and scanning electron microscopy to evaluate surface morphology. The expression and distribution of a panel of PCP proteins, e.g. WDPCP and FUZ, were investigated in relation to inflammatory cytokine levels and clinical features. The mean MCTV of NP mucosae was significantly lower than that of the inferior turbinate mucosae. The CRS group with NPs (CRSwNP group) (n=28) showed increased expression of IL-13 and CCL26 mRNA compared to CRS patients without NPs (n=25) and controls (n=30). WDPCP and FUZ mRNA levels were significantly decreased in NP mucosae compared to ethmoid sinus mucosae in CRSwNP patients. WDPCP protein distribution was reduced in the cytoplasmic region of ciliated cells in CRSwNP patients. We conclude that suppression of WDPCP in ciliated cells is responsible for the impaired MCC of nasal polyps with type-2 inflammation. This mechanism might explain the decreased clearance and the potential for worsening symptoms of CRSwNP.

Background: This is a propensity matched, single centre study of limited versus extended resections for Type A acute aortic dissections (AAAD). Methods: Retrospective data for 440 patients with acute Type A aortic dissection repairs (Limited Resection, LR-215, Extended Resection, ER-225). 109 pairs were propensity matched to LR versus ER. Multivariate analysis was performed for inpatient death, long term survival and composite of inpatient death/TIA/stroke. Kaplan Meier survival curves were compared at 1, 3, 5, 10 and 15 years using the log-rank test. Results: Mean age was 66.9±13 years and mean follow up was 5.3±4.7 years. 48.9% had LR. In-hospital mortality was 10% (LR;6% vs ER;13.8%, p<0.01). ER, NYHA class, salvage surgery and additional procedures were predictors of increased mortality in unmatched data. Propensity matched data showed no difference in TIA/stroke rates, LOS, in-patient mortality or composite outcomes. LR had better survival (LR; 77.1% vs ER; 51.4%, p<0.001). ER (OR; 1.97, 95%CI; 1.27, 3.08, p=0.003) was a significant predictor of worse long term survival. At 15 years, aortic re-operation was 17% and freedom from re-operation and death was 42%. Conclusions: Type A aortic dissection repair has high mortality and morbidity although results have improved over two decades. ER was predictor of worse perioperative results and long term survival.

Capsinoids (CAP) are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, the aim of this study was to investigate the effects of CAP on adiposity and biomarkers of cardiac oxidative stress in rats with obesity induced by a high-fat diet. Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After characterization of obesity (week 19), some of the obese (Ob) animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury and biomarkers of oxidative stress were determinated. The treatment did not reduce the adiposity induced d by obesity, but they were efficient in reducing cholesterol levels. CAP treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capisinoids did not reduce the increase in advanced oxidation of proteins products (AOPP) and carbonylated proteins (CBO) caused by obesity in cardiac tissue. Besides that, it was observed that ObCap rats presented high levels of malondialdehyde and greater activity of antioxidant enzymes compared to Ob. In conclusion, treatment with capsinoids did not lead to significant positive effects in reducing obesity-induced oxidative stress.

Introduction: Management of hypoxic-ischemic encephalopathy (HIE) has been the subject of international recommendations. However, some aspects remain within the realm of service practices and appear to vary greatly from one center to another. Objectives: To achieve a multidisciplinary consensus in France regarding management of HIE newborns that are not covered by international and national guidelines. Methods: This is a prospective, multicenter study using the Delphi method from April 21, 2021, to July 15, 2021. Perinatal professionals were contacted through professional societies. Participants received a questionnaire in three successive rounds. Each proposal was rated using a Likert scale from 1 (completely disagree) to 8 (completely agree). An item was considered consensual if at least 70% of responses were in agreement or disagreement. Results: 58 french neonatal professionals participated. A consensus was reached in the first round concerning the use of passive hypothermia in maternity ward, with 84% agreement and to define the target temperature between 35.0°C and 35.5°C at the third round. Regarding hypoglycemia in the delivery room, 79.2% agreed in the first round to correct blood glucose levels below a threshold of <2.2 mmol/l. Parenteral route was the preferred correction method for 91.4% of respondents, while enteral route via nasogastric tube did not reach consensus. Conclusion: This study highlights the variability in definitions and practices among professionals in the management of HIE. Consensus was found regarding certain care practices performed without formal guidelines. The work to harmonize definitions and practices for the management of HIE likely needs to continue.

Breast cancer (BC) is a prevalent malignancy with various subtypes, each presenting unique diagnostic and therapeutic challenges. Triple-negative breast cancer (TNBC), which comprises 12-17% of breast cancers, is particularly aggressive due to its lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. This case report details the management of a 64-year-old woman with TNBC. Initially presenting with a left breast nodule, she underwent a biopsy that confirmed triple-negative infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and a newly detected right breast lesion led to a bilateral mastectomy. Post-surgery imaging revealed multiple hypodense nodules and a spiculated pulmonary nodule, prompting further investigation. An endoscopic lung biopsy identified a primary pulmonary carcinoma with histological features similar to the breast cancer, indicating the lung as the primary source. This case underscores the complexity of TNBC, the importance of comprehensive diagnostic evaluations, and the need for considering extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated evaluations in atypical BC presentations.

Background: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery associated-AKI (CSA-AKI). Methods: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-β-D-glucosaminidase (NAG) and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in Intensity Care Unit (ICU) after cardiac surgery. Sensitivity, specificity, positive and negative predictive value for diagnosis of stages 1, 2 and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-months glomerular filtration rate (GFR) and other long-term events over the next 5 years. Results: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0 to 75 %. Besides, GluAp and DPP4 was related to the decrease in GFR at 6- or 12-months after surgery. Conclusions: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, being GluAp the most effective marker for diagnosing stages 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for the decrease in GFR.

Evidence suggests that COVID-19 infection increases the risk of type 1 (T1D) and type 2 diabetes (T2D). Diabetes, in turn, increases COVID-19 susceptibility and contributes to increased COVID-19 morbidity and mortality. Oxidative stress (OxS) has emerged as a common factor driving the pathogenesis of diabetes and COVID-19 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The mechanistic links between OxS, T2D, and COVID-19 have primarily been studied in adults and will be summarized in this review. However, we suggest that studying these interconnections in children and young adults is critical since early intervention is optimal for improving outcomes. At the height of the pandemic, COVID-19 was a leading cause of death in children and young people, and people in this age group are as susceptible to COVID-19 as adults and the elderly. Glutathione (GSH) is the primary water-soluble intracellular antioxidant and can be deficient in both diabetes and COVID-19. GSH is a tripeptide containing cysteine (CYS), glutamic acid (GLU), and glycine (GLY). Strategies to increase GSH levels may be beneficial in helping to manage COVID-19-induced diabetes as well as diabetes-induced COVID-19 risk. Dietary supplementation with GlyNAC may be optimal since it contains two metabolic GSH precursors, i.e., n-acetyl-l-cysteine (NAC) and GLY.

Conclusion: The study highlights the high prevalence of depression among caregivers of geriatric patients in Jeddah and underscores the significant impact of caregiving burden on mental health. These findings emphasize the need for targeted interventions, such as mental health support, respite care programs, and culturally sensitive educational training, to mitigate caregiver burden and enhance the well-being of caregivers.

In this study, Cu2O nanoparticles were synthesized using the sol-gel technique and subsequently functionalized with extracts from plants of the Rauvolfioideae subfamily and citrus fruits. Com-prehensive characterization techniques, including UV-Vis spectroscopy, FT-IR, XRD, BET, SEM, and TEM, were employed to evaluate the structural and surface properties of the synthesized nanoparticles. The results demonstrated that both functionalized Cu2O nanoparticles exhibit mesoporous structures, as confirmed by nitrogen adsorption-desorption isotherms and pore size distribution analysis. The Green Extract functionalized nanoparticles displayed a more uniform pore size distribution compared to those functionalized with the Orange Extract. The study un-derscores the potential of these functionalized Cu2O nanoparticles for applications in drug de-livery, catalysis, and adsorption processes, highlighting the influence of the functionalization method on their textural properties and performance in antibacterial efficacy.

Lidocaine hydrochloride (HCl) 2% with 1:100,000 epinephrine (LW/E) is widely used to prevent pain during dental procedures and has been associated with injection sting, jittering effects, slow onset, and a bitter aftertaste. Since LW/E’s introduction in 1948, no significant modifications have been proposed. This study aims to design and characterize an improved dental lidocaine HCl injectable formulation without epinephrine (LW/O/E) via buffers, sweeteners, and amino acids. LW/O/E injections were prepared with pH and osmolality values of 6.5 – 7.0 and 590-610 mOsm/kg. Using the electronic tongue (ETongue), the LW/O/E injectable formulations were characterized for viscosity, injectability, and taste analysis. The results were compared with the LW/E control. In vivo efficacy and anesthetic duration of the samples were measured through radiant heat tail-flick latency (RHTFL) and hot plate (HP) tests and local toxicity was assessed after a single intra-oral injection in Sprague Dawley rats (SDR). The viscosity and injectability values of the LW/O/E samples were found to be comparable to the LW/E injection. ETongue taste analysis showed an improvement in bitterness reduction of the LW/O/E samples compared to the LW/E formulation. Toxicity studies of samples in SDR showed minor and transient signs of erythema/eschar and edema. Anesthetic duration via RHTFL and HP paw withdrawal latency time in SDR were found to be comparable for the LW/O/E Sample 3A and the LW/E injection (p<0.05). In conclusion, the buffered, higher osmolality and reduced bitterness developed LW/O/E formulation (Sample 3A) could be considered a promising alternative to the LW/E formulation for dental use.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

Bluetongue is not a contagious disease. It spreads very quickly and uncontrollably, considering that it is a vec-tor-borne disease transmitted by the genus Culicoides. Climate change has led to the fact that vectors and dis-eases have spread to the top of Northern Europe, causing great economic losses in livestock production. Even greater problem is controlling the disease, because numerous species of domestic and wild ruminants are sus-ceptible to bluetongue. The most effective tool against bluetongue disease is vaccination. There is no ideal vaccine against bluetongue virus (BTV) due to the serotype diversity of the strains. Thus, there is need for a vaccine for at least for 24 clinically significant serotypes. Sometimes it is difficult to obtain the desired amount of vaccine against a defined serotype on the market, and this led to the need for a new vaccine against blue-tongue disease. We tested an experimental inactivated novel vaccine against BTV4. Master seed BTV4 has been examined and characterized by sequencing. The novel BTV4 vaccine induce the onset of immunity at least at day 21 after the application of the first dose in more than 80% of vaccinated individuals, while specific antibodies against BTV are detected by the ELISA test for more than a year. Along with our laboratory results, the preliminary results of safety and efficacy trials are also presented. The side effects of novel vaccine are within the limits of permissible local reactions without generalized changes of health status, while the serology and challenge test leads to the conclusion that novel vaccine protects high percentage of vaccinated individuals against BTV4 or causes a significant reduction in the intensity and duration of the clinical signs in the vac-cinated sheep. Based on the trial results, new vaccine has given encouraging results in quality, safety and pre-liminary efficacy tests. Thus, we believe that a new vaccine against BTV is on the horizon. Keywords: bluetongue virus, inactivated vaccine, candidate, quality of vaccine, safety, efficacy We confirm that neither the manuscript nor any parts of its content are currently un-der consideration for publication with or published in another journal. All authors have approved the manuscript and agree with its submission to Vaccines.

Background Compliance with research ethics legislation is crucial for protecting people's rights in clinical trials. Researchers can alert publishers when they have concerns about possible non-compliance with this legislation by other authors, and this opportunity for independent scrutiny is important. Nevertheless, some alerts may turn out to be unfounded due to a misunderstanding of the legislation. Methods We present the analysis of the article by F. Franck et al., « Raising concerns on questionable ethics approvals - a case study of 456 trials from the Institut Hospitalo-Universitaire Méditerranée Infection», in which the authors explain having sent numerous emails to different publishers to express their concerns about potential ethical breaches in publications from a single French institution. We analyzed in detail the 248 studies that the authors present as suspects. We have also studied the texts of French law. Results Our detailed analysis of these 248 studies discovered that only 8 of them report research involving humans. All the others are secondary research on existing biological samples. In France, as in many other countries, secondary research on biological samples does not involve human subjects. Conclusions Assessing the ethical conformity of scientific publications must be based on a precise knowledge of the legislation and a rigorous analysis of these publications. When researchers who alert publishers confuse research involving the human person with research not involving the human person, the publishers are in danger of being misled by these unfounded alerts. This can have deleterious consequences.

Seroprevalence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies in the postvaccination period in Kenya remains to be elucidated. This study aimed to determine the seroprevalence of anti-SARS-CoV-2 IgM and IgG and evaluate vaccination uptake in Nairobi, Kenya. This was a cross-sectional study conducted in a university setting. Serum anti-SARS-CoV-2 IgM and IgG levels were assayed using enzyme-linked immunosorbent assays. Mann–Whitney U test was used for binary comparisons and Kruskal–Wallis Test for multigroup comparisons. Statistical significance was set at p &lt; 0.05. A total of 189 participants were enrolled (median age, 21 years; female, 50.8%). The seroprevalence of anti-SARS-CoV-2 was 12.7% for IgM and 87.8% for IgG. Anti-SARS-CoV-2 IgG titers were higher among the vaccinated vs. non-vaccinated individuals (p &lt; 0.001, U = 2817.5), females vs. males (p = 0.024, U = 3616), and those vaccinated &lt; 6 months before the study vs. those vaccinated &gt;1 year earlier (p = 0.002, H = 12.359). The vaccination hesitancy rate was 43.4% and the underlying reasons included mistrust (22.4%), health concerns (19.7%), and lack of information (18.4%). Despite the high seroprevalence of anti-SARS-CoV-2 IgG, the high vaccine hesitancy rate necessitates community engagement and education prior to vaccines roll out.

Background: Resistant hypertension (HTN) is associated with high risk of cardiovascular complications. Our study aimed to assess prevalence, characteristics and treatment of patients with resistant HTN; Methods: We screened 4340 consecutive cardiovascular patients and identified 3762 with HTN. Of them 128 fulfilled criteria for resistant HTN and were included in our study. We matched these patients to 128 hypertensive patients with controlled HTN; Results: Resistant HTN patients were 3.4% of all hypertensives. Most of these patients (67.2%) were at high or very high cardiovascular risk compared to controlled HTN patients (40.6%), p&lt;0001. Resistant HTN patients had more frequently concomitant chronic kidney disease (CKD) (60.9%), overweight/obesity (52.3%), dyslipidemias (35.2%), smoking (27.3%) and diabetes (21.9%) compared to controlled HTN patients (37.5%, 29.7%, 28.1%, 14.1% and 7.8% respectively), p&lt;0.001. Regression analysis showed strongest association of resistant HTN with CKD (OR 6.64), stage III HTN (OR 3.07) and obesity/overweight (OR 2.60). In contrast, single-pill combinations (SPCs) were associated with lower likelihood of uncontrolled HTN (OR 0.58); Conclusions: Resistant HTN represented a small proportion of all hypertensives in our study, but it was characterized by high/very high cardiovascular risk. Optimized therapy including increased usage of SPCs could improve blood pressure control and long-term prognosis of these patients.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of tri-ple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs, so that the distinct pH of tumor cells, would stimulate the release of the drug and/or genetic materi-al. The current revision summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Background/Objectives: Conventional surgery gland using the naked eye remains the standard for submandibular gland resection. Owing to its excellent automatic focus and high magnification, the ORBEYE 3D system introduces precise submandibular resection with less stress. Therefore, we examined the usefulness of the exoscope in submandibular gland resection for the first time. Methods: This retrospective study enrolled 12 patients who underwent submandibular gland resection using an ORBEYE exoscope at the Department of Head and Neck Surgery and Otorhinolaryngology at Kansai Medical University from April 2021 to March 2024. Surgical outcomes were retrospectively reviewed. Results: The mean age of the 12 patients (six females and six males) was 58.5 years (23–83 years). The final histopathology showed pleomorphic adenoma in eight cases, non-sebaceous-type lymphadenoma and carcinoma ex pleomorphic adenoma in one case each, and sialolithiasis with chronic inflammation in two cases. We performed facial artery and vein sparing in all cases except one in which level I neck dissection, including the submandibular gland, was performed. In all cases, we identified the marginal mandibular branches of the facial, hypoglossal, and lingual nerves, as well as the submandibular duct. No postoperative complications occurred in any patient. The mean operative time was 104 min (80–129 min). The mean blood volume lost was 20 mL (5–43 mL). Conclusions: Using ORBEYE in submandibular gland resection will contribute to preserving the mandibular marginal branch of the facial and lingual nerves and the facial artery and vein, and visualizing the submandibular duct, which are important structures surrounding the submandibular gland.

With increasing numbers of older adults worldwide, multimorbidity and polypharmacy are on the rise, highlighting the risks of harmful drug-drug interactions (DDIs) to patients. As cardiovascular agents are among the most prescribed medications, we performed an observational cross-sectional study to determine the prevalence of DDIs in a cardiology department of a secondary hospital. Patient data was obtained from medical records and screened for DDIs using the Micromedex drug interaction software. Descriptive statistics, Chi-square (χ2) test, Student's t test and Pearson's correlation test were used to analyse the results. Out of 50 participants, 45 (90%) had at least one DDI. A total of 266 DDIs were identified, with more than half classified as major. At least one major DDI was found in 78% of patients. 42% of patients were at an increased risk of bleeding due to DDIs. A statistically significant relationship was found between the detection of DDIs and both patient age (p = 0.005) and the number of drugs used (p &lt; 0.001). Our findings pose questions about the wider prevalence and risks of drug-drug interactions among patients with cardiovascular disease.

Objectives: To analyze the clinical characteristics and factors associated with adverse drug reactions (ADR) in liver cancer patients receiving oxaliplatin‐based hepatic arterial infusion chemotherapy (HAIC). Methods: A retrospective analysis was performed on the clinical data of 137 patients with liver cancer who received oxaliplatin‐based HAIC. Changes in baseline characteristics, inflammatory factors, and other laboratory indicators in the no‐ADR and ADR groups were analyzed. Results: The incidence of serious ADR (CTCAE ≥ 3) was 21.9% (30/137). There was no significant difference in the cumulative dose of oxaliplatin between the two groups [157.3 (80.3, 322.4) vs. 206.6 (139.1, 324.2), P=0.161]. The increase in NEUT and IL‐6 was greater in the group treated with ADR than in the group not treated with ADR. Changes in NEUT [4.1 (1.5, 6.2) vs. 2.5 (0.5, 4.9), P=0.045] and changes in NEUTIL‐6 [4.2 (‐0.2, 22.9) vs. 0.8 (‐3.9, 7.7), P=0.026]. TBIL, ALT, AST, ALP, WBC, NEUT, PCT, CRP, TNF, IL‐2R, IL‐6, and IL‐10 were significantly higher after treatment than before in the ADR group (P < 0.05). In contrast, ALB and AFP were decreased. Conclusions: The severe ADR (CTCAE ≥ 3) associated with oxaliplatin‐based HAIC may be closely related to increased inflammatory factors such as NEUT and IL‐6. We should be vigilant for allergic reactions to oxaliplatin and increase monitoring during treatment

Traditional photodynamic therapy (PDT) is often limited in its efficacy by insufficient light penetration, inefficient photosensitizer energy transfer, and inadequate target tissue oxygenation. X-ray activated PDT (XPDT), using nanoparticle (NPs) photosensitizers comprised of europium-doped yttrium oxide cores encased within silica shells (Y₂O₃:Eu@SiO₂), offers the potential of overcoming most of these limitations. Aimed at maximizing the generation of reactive oxygen species (ROS), this study reports methodologies for investigation of the effects of synthesis conditions on the characteristics of Y₂O₃:Eu@SiO₂ NP. Transmission electronic microscope (TEM) revealed that the NP core diameter was linearly, positively correlated with condensation time (R2 = 0.7357, p < 0.05) and linearly, negatively correlated with urea concentration (R2 = 0.958, p < 0.05). The addition of cetyltrimethylammonium bromide (CTAB) during core synthesis demonstrated enhanced particle dispersion. Silica coating via APTES-1 and TEOS-3 conditions resulted in Y₂O₃:Eu@SiO₂ NPs that generated the highest ROS, with 8.7-fold and 8.9-fold increase respectively in relative fluorescence intensity at 8 Gy irradiation compared to a 5.2-fold increase in PBS under the same condition. In vivo evaluation using 18F-fluorothymidine positron emission tomography (18F-FLT PET) of mouse xenografts of a human prototypical cancer (ovarian) revealed a 55% reduction in tumor proliferation of radiation-sensitive CAOV3 tumors treated with Y₂O₃:Eu@SiO₂ NPs compared to a 19% reduction in tumor proliferation of radiation-resistant SKOV3 tumors on the fourth day post-treatment. Taken together, these findings suggest Y₂O₃:Eu@SiO₂ NPs can serve as effective photosensitizers for XPDT and their performance characteristics can be optimized by selecting synthesis conditions and parameters to deliver the desirable therapeutic effects, offering novel approaches to circumventing many of the limitations of conventional PDT in the treatment of cancer.

Freezing of Gait (FoG) is a disabling motor complication in Parkinson’s disease (PD), affecting approximately 50% of advanced PD patients. It is characterized by sudden and transient inability to initiate or maintain walking, leading to falls and reduced quality of life. This study investigates the relationship between white matter integrity and step initiation impairments in FoG. Forty-three PD patients (26 with FoG) underwent diffusion-weighted imaging to assess white matter DTI metrics and kinematic analysis during step initiation tasks. Multiple regression analyses were conducted to explore the connection between white matter tract integrity and step initiation behavior. The multiple regression analysis shows that (1) Right Inferior Longitudinal Fasciculus RD explained 31% of APA duration’s variance; (2) Corpus Callosum Forceps Major explained 25% of the step length's variance. There was a positive correlation between the Right Inferior Longitudinal Fasciculus RD and APA duration and a negative correlation between Corpus Callosum Forceps Major RD and step length. The findings suggest that compromised white matter integrity in RILF and CC contributes to impaired motor control during step initiation in FoG. These regions are critical for inhibitory control and interhemispheric coordination, crucial for APA execution and step length regulation.

Background: Glutathione and its related enzymes constitute one of the most important antioxidant defense mechanisms against oxidative stress and cancer formation in the body. Bladder cancer is the second most common urological malignancy after prostate cancer. Oxidative stress plays a significant role in the development and prognosis of bladder cancer. The aim of this study was to examine the effect of glutathione on the prognosis of non-muscle-invasive bladder cancer. Methods: The 98 patients with bladder tumors were those with T1G3 pathology who had undergone intravesical Bacillus Calmette-Guérin therapy, while the 30 controls were healthy individuals with no history of transitional cell carcinoma of the bladder. The 128 participants were divided into four groups: Group 1 comprised 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, Group 3 consisted of 29 patients who progressed to muscle-invasive stages, and Group 4 was composed of 30 healthy volunteers. Blood samples were collected from all participants. Glutathione levels were measured, and statistical analysis were performed. Results: There was a statistically significant difference in reduced glutathione levels among the groups (p < 0.001), attributed to Group 4 exhibiting higher reduced glutathione levels compared to Groups 1, 2, and 3 (p < 0.001). No significant differences were observed in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.999). Total glutathione levels varied significantly among the groups (p < 0.001), with Group 4 having higher levels than Groups 1, 2, and 3 (p < 0.001). However, there were no significant differences between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in terms of total glutathione levels (p = 0.473, p = 0.747, and p > 0.999, respectively). Regarding oxidized glutathione levels, a significant difference was observed (p < 0.001), with Group 4 showing lower levels than the remaining three groups (p < 0.001). No significant differences were found between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in relation to oxidized glutathione levels (p > 0.999, p = 0.171, and p > 0.999, respectively). Conclusions: The current study revealed that glutathione is a factor influencing the development of new bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the effect of glutathione on the prognosis of bladder cancer.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

Liver cancer imposes a pervasive global health challenge, ranking among the most prevalent cancers worldwide. Its prevalence and mortality rates are on a concerning upward trajectory and exacerbated by the dearth efficacious treatment options. The Hippo signaling pathway, originally discovered in Drosophila, comprises four core components: MST1/2, WW45, MOB1A/B, and LATS1/2. This pathway regulates the cellular localization of the transcriptional coactivator YAP/TAZ (Yes-associated protein/PDZ-binding motif) through a series of enzymatic reactions. The Hippo/YAP/TAZZ pathway maintains a balance between cell proliferation and apoptosis, regu-lates tissue and organ sizes, and stabilizes the internal environment. Abnormalities of any genes within the Hippo signaling pathway, such as deletion or mutation, disturb the delicate balance between cell proliferation and apoptosis, creating a favorable condition for tumor initiation and progression. Mutations or epigenetic alterations in the Hippo signaling pathway components can lead to its inactivation. Consequently, YAP/TAZ becomes overexpressed and activated, promoting excessive cell proliferation and inhibiting apoptosis. This dysregulation is closely associated with the development of liver cancer. This review discusses the pivotal role of the Hippo signaling pathway in the pathogenesis and progression of liver cancer. By elucidating its mechanisms, we aim to offer new insights into potential therapeutic targets for effectively combating liver cancer.

Background: Rectal prolapse is usually self-limiting in early childhood. Laparoscopic rectopexy has become a safe and effective method for treating children with rectal prolapse recurrence, especially those older than 4 years of age. We present the clinical case of an infant with recurrent rectal prolapse and secondary complications. The infant required surgical intervention with laparoscopic rectopexy after the failure of conservative management. Case presentation: A 2-year- and 7-month-old infant with a 15-month history of rectal prolapse who did not respond to conservative management developed bloody diarrhea, intestinal infection and electrolyte imbalance. Laparoscopic surgical correction was performed via anterior ventral rectopexy, and the results were satisfactory. Conclusion: Infants with recurrent rectal prolapse and associated complications who do not respond to conservative measures may benefit from laparoscopic rectopexy.

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.

We conducted a study to determine if antenatally collected maternal urine cotinine (a me- 13 tabolite of nicotine) measurements can be used to assess the neonatal impact of nicotine exposure 14 during pregnancy. This was a prospective longitudinal cohort of mother-infant dyads. Only term 15 singleton pregnancies were included. The primary outcome measure was the correlation between 16 maternal urine cotinine and infant birth weight. We analysed data from 238 mother-neonates' dy- 17 ads. Urine cotinine was detected in 50.4 % (120/238) women from the whole cohort, but only 16% 18 (38/238) self-reported as smokers (chi-square 39.7, p<0.0001), and these women had significantly 19 smaller babies (p=0.010). There was a significant negative correlation between maternal urine co- 20 tinine and birth weight (Spearman's coefficient = -0.0226, p=0.013). Female babies born to women 21 with nicotine in the urine were significantly smaller (p= 0.001). The number of women exposed to 22 nicotine during late pregnancy (measured in urine) was markedly higher than self-reported and 23 National smoking percentages, suggesting an urgent need for improvement of medical record re- 24 porting on smoking habits to better assess neonatal outcomes.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global inci-dence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked leading to vision loss either from destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised treatment of cutaneous melanoma, which share some similarities to Co-M. A better understanding of Co-M and its precursor lesions is urgently needed to lead the development of novel targeted and immuno-therapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge of Co-M, its epidemiology, pathogenesis, presentation, diagnosis, management, and recent advances in novel biological therapies for personalised treatment of this disease.

Background and objectives: Due to resistance and lack of treatment options, hospital-acquired Acinetobacter baumannii (A. baumannii) infections are associated with high mortality. The aim of this study was to identify the characteristics and outcomes of patients with infections caused by multidrug resistant A. baumannii in a tertiary-care teaching hospital and to determine the risk factors for in-hospital mortality. Materials and methods: A retrospective cohort study including 196 patients with A. baumannii strains isolated from different clinical specimens in the Hospital of the Lithuanian University of Health Sciences in 2016, 2017 and 2020, 2021 was conducted. Data on patients’ characteristics, comorbid diseases, treatment, length of hospital and ICU stay, outcome were collected. To determine risk factors for in-hospital mortality, logistic regression analysis was performed. Results: There were 60 (30.6%) women 136 (69.4%) men with a mean age of 61.7 ± 16.6 years (range, 52–74). More than three-fourths (76.5%, n = 150) of the patients had at least one comorbid disease. The highest number of A. baumannii strains were isolated from patients hospitalized in ICUs (43.4%, n = 85). A. baumannii strains producing three types of β-lactamases were more frequently isolated from women than men (77.8 % vs. 22.2%, p = 0.006). Infections caused by A. baumannii strains producing two types of β-lactamases were significantly more often treated with combination therapy than infections caused by strains producing one type of β-lactamase (78.9% vs. 60.0%, p = 0.019). Patients with A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) stayed significantly shorter at the ICU compared to patients with A. baumannii strains not producing β-lactamases (median of 9, IQR 2–18, vs. median of 26, IQR 7–38, p = 0.022). Death occurred in 58.7% (n = 115) of patients. Logistic regression analysis showed that combination therapy, length of hospital stay of < 10 days after A. baumannii infection, age of > 58 years, and absence of co-infection were independent predictors of in-hospital mortality. Conclusions: Patients with infection caused by A. baumannii strains producing two different types of β-lactamases were more frequently treated with combination therapy. Mortality of patients with multidrug resistant A. baumannii infection was high, and it was associated with patient’s age, length of hospital stay after the diagnosis of A. baumannii infection, absence of co-infection, and combination treatment.

Wetlands are ecosystems that are essential to ecological balance and biodiversity, never-theless human activity is a constant threat to them. Excess nutrients are caused by inten-sive livestock and agricultural operations, pollution, and population growth, which in turn leads to uncontrolled microbiological development. This impairment in water quality can constitute a risk to animal, human, and environmental health. To thoroughly charac-terize the microbial communities, shotgun metagenomics was used to characterize the taxonomic and functional pattern of microorganisms that inhabit urban wetlands in the Los Lagos Region of Chile. The main objective was to identify microorganisms of veteri-nary relevance, assess their potential antibiotic resistance, and characterize the main vir-ulence mechanism. As expected, a high diversity of microorganisms was identified, in-cluding bacteria described as animal or human pathogens. Also, a diverse repertory of an-timicrobial-resistant genes (ARGs) was detected, which confers mainly resistance to be-ta-lactams, consistent with the families of antibiotics most used in Chile. Besides, a di-verse collection of virulence mechanisms was also identified. Given the significance of the relationship between environmental, animal, and human health—a concept known as One Health—there is a need to establish molecular surveillance programs. This work is the first report of the presence of these harmful biological elements in urban wetlands subjected to anthropogenic pressure, located in the south of Chile.

Urinary incontinence after Radical prostatectomy (RALRP) has been associated with older age, longer operative time, higher BMI, short membranous urethral length and preoperative erectile function. We sought to assess the association between the neuromuscular characteristics and postoperative urinary incontinence. Methods: RALRP specimens from 29 men who underwent bilateral nerve sparing were reanalyzed. Urinary incontinence was evaluated using the International Consultation on Questionnaire-Short Form (ICIQ-SF) at 6 weeks post surgery and last follow-up. Linear and logistic regression analyses were performed to assess neuromuscular characteristics and incontinence. Results: At a median follow-up of 11 months (IQR 9-12), 11 patients (38%) reported on severe incontinence (>12 ICIQ-SF score). Median number of peripheral nerves observed at the base and apex of the specimens were 52 (IQR 13-139) and 59 (IQR: 28-129), respectively. Ganglia were present in 19 patients (65%) at the base and 12 patients (41%) at the apex. Additionally, the median proportional area of detrusor smooth muscle fibers at the base was 0.54 (IQR 0.31-1), while the median proportional area of striated muscle fibers at the apex was 0.13 (IQR 0.08-0.24). No statistical significant associations were found. Conclusion: Histologic neuromuscular characteristics were not associated with postoperative urinary incontinence. Enhanced intraoperative evaluation and larger scale studies may prove useful for prediction of post prostatectomy incontinence.

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy, characterized by progressive and asymmetric muscle atrophy, primarily affecting muscles of the face, shoulder girdle, and upper arms before affecting muscles of the lower extremities with age and greater disease severity. FSHD is a disabling condition, and patients may also present with various extramuscular symptoms. FSHD is caused by the aberrant expression of double homeobox 4 (DUX4) in adult skeletal muscle, arising from compromised epigenetic repression of the D4Z4 array. DUX4 encodes the DUX4 protein, a transcription factor that activates myotoxic gene programs to produce the FSHD pathology. Therefore, sequence-specific oligonucleotides aimed at reducing DUX4 levels in patients is a compelling therapeutic approach, and one that has received considerable research interest over the last decade. This review aims to describe the current preclinical landscape of oligonucleotide therapies for FSHD. This includes outlining the mechanism of action of each therapy and summarizing the preclinical results obtained regarding their efficacy in cellular and/or murine disease models. The scope of this review is limited to oligonucleotide-based therapies that inhibit the DUX4 gene, mRNA, or protein in a way that does not involve gene editing.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacody-namics and pharmacokinetics of many medicaments used in clinical care. The ability of medica-tions to cross the blood-brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various central nervous system (CNS) medications at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with various CNS medications. These transporters appear to have a role in BBB pharmacogenetics. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

Melanoma is the most aggressive and deadly form of skin cancer, and its incidence has been steadily increasing over the past few decades, particularly in the Caucasian population [1]. Current treatment strategies, the combination of BRAF and MEK inhibitors (BRAF/MEKi) in BRAFV600 mutant melanoma, and immune checkpoint inhibitors (ICI), have changed the clinical evolution of this disease [2]. However, a significant percentage of patients do not benefit from these therapies. Therefore, to improve patient selection, it is imperative to look for novel biomarkers. Immune subsets, particularly the quantification of lymphoid populations, could contribute to the identification of ICI responders. The aim of this review is to thoroughly examine significant published data on this topic in melanoma patients and to evaluate the potential role of lymphoid subsets as prognostic and predictive response biomarkers.

Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is not consensus on optimal management. Prostate-specific membrane antigen-positron emission tomography (PSMA PET) has emerged as highly sensitive imaging, distinguishing local recurrences from distant metastases, crucially influencing treatment decisions. Genomic biomarkers such as Decipher, Prolaris, and Oncotype DX contribute to refining recurrence risk profiles, guiding decisions on intensifying adjuvant therapies like radiotherapy and androgen deprivation therapy (ADT). This review assesses PSMA PET and biomarkers utility in post-radical prostatectomy BCR scenarios, highlighting their impact on clinical decision-making. Despite their promising roles, routine integration of biomarkers is limited by availability and cost, requiring further evidence. PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

Idiopathic pulmonary fibrosis remains a relevant problem in the field of healthcare with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the reactions damaging the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and Nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of application of other approaches aimed at regulating the immune response, cellular aging processes, programmed cell death and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential application points and effects of vitamin D and its metabolites.

Objectives: To develop a machine learning-based model for the identification of features involved in the prediction of long-term erectile dysfunction (ED) after COVID-19 recovery. Methods: We performed an observational prospective multicentre study. Participants were divided into 2 groups: I) Patients with a past history of COVID-19; II) Patients without a previous microbiological diagnosis of COVID-19. A total of 361 patients (COVID-19 group, n=166, Control group; n=195) were assessed from January 2022 to March 2023. COVID-19 group patients were assessed 12 months after COVID-19 recovery; Control group patients were assessed within the same time window. The primary outcome measure was ED. A machine learning-based model including three algorithms (random forest, logistic regression and support vector machines [SVM]) was applied to perform the automatic selection of those features involved in the prediction of ED. The algorithm SVM-recursive feature elimination (RFE) was also executed. Results: The median age was 55 years in both groups. The final selection of variables in our model was: group, SARS-CoV-2 vaccination status, hypertension, diabetes, beta blocker treatment, antiplatelet therapy and coffee intake. The algorithm SVM-RFE showed that a past history of COVID-19 and SARS-CoV-2 vaccination were both long-term ED predictors in our model. Conclusions: We developed a machine learning-based model for the prediction of long-term ED following COVID-19 recovery. A past history of COVID-19 and SARS-CoV-2 vaccination were both predictors in our model. The application of our predictive tool in a community setting could avoid the adverse effects of ED and the unfavourable economic impact associated.

Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies, but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy was particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity (not all tumor cells express the target antigen), the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising anti-tumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies.

Sepsis-induced cardiomyopathy (SICM) may be defined as a non-ischemic cardiac dysfunction associated with sepsis. SICM is characterized by a decrease in left ventricular contractility, ultimately associated with left ventricular dilation, with or without right ventricular dysfunction. Echocardiography stands as the current gold standard in diagnosis of SICM. Left ventricular ejection fraction (LVEF) is the most frequently utilized parameter for evaluating left ventricular systolic function, but some traditional parameters, including LVEF, are dependent on cardiac preload and afterload, limiting their clinical application. Advanced echocardiography techniques, such as speckle-tracking analysis, have the potential to diagnose and evaluate myocardial dysfunction even in the early phases of sepsis, facilitating risk stratification for proactive personalized treatment of patients. This article reviews the progress in the application of various echocardiographic parameters in SICM.

We evaluated the dentofacial characteristics and temporomandibular disorder (TMD) symptomatology of patients with orthopedic instability before and after deprogramming with a stabilization splint. Sixty patients with the signs and symptoms of TMD were assessed using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and underwent stabilization splint therapy to place the condyles in a more stable musculoskeletal position. The amount of condylar displacement was evaluated using the condylar position indicator (CPI). Six-teen angular and linear hard tissue landmarks were traced and compared from lateral cephalo-grams taken in the maximum intercuspation (MI) position before and in the centric relation (CR) position after the splint therapy. Following the splint therapy, the signs and symptoms of TMD were significantly reduced or completely eliminated in more than 90% of the patients. Compared with the values registered before the splint therapy, a significant reduction in the mean values of condylar displacement was observed on both sides of the vertical, horizontal, and transverse planes of space after the splint therapy. A comparison of pre- and post-splint lateral cephalograms revealed that, following the splint therapy, the mandible moved more posteriorly and rotated more in a clockwise direction. In patients with orthopedic instability and signs and symptoms of TMD, deprogramming of the neuromuscular system with a stabilization splint is highly recommended to provide a correct orthodontic diagnosis and improve the health of temporomandibular joint structures.

The objective of this research was to analyze the evolution and trend of the generation gap and nursing education from 1968 to 2021 through bibliometric indicators. The method used is a bibliometric, descriptive and retrospective study of documents in Scopus, with descriptors “Nursing educat*”, “generation* and the Boolean operator “AND”, N= 653 web documents from 1968 to 2021, and filters of the type bib, csv. The search was carried out on October 9, 2021, using the Bibliometrix R Package software and the Biblioshiny tool. The Results indicate high scientific production in 2020 (54 articles disclosed). This study demonstrates patterns and lines of research in nursing education, such as educational models, interpersonal relationships, and organizational innovation.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

This study investigated the effects of a ten-visit individual coordinative locomotor training (CLT) program, including both a hands-on and a hands-off approach, on static and dynamic trunk stability in healthy adults with sedentary occupations. During the ten-visit program, the performance of eight subjects was monitored using a modified one-leg stance test in the sprinter and skater position, the Y-balance test, and the scapula and ischial tuberosity control test in the four-legged position. The data were analyzed using parametric and nonparametric statistics at an overall level of significance α=0.05. In the one-leg stance test, all subjects achieved a maximum value of 60 s on all ten visits. The improvement over time in the Y-balance test results was statistically significant for all directions (p<0.001). In addition, a statistically significant improvement in the Y-balance test composite score was observed between the first and the last visit (p=0.015-0.041). Subject-specific patterns were observed in the results of the Y-balance test. Significant improvements were observed over time in the four-legged position test score (p=0.008-0.010). Overall, the CLT program led to a significant improvement in trunk stability and leg extension in the anterior and posterolateral directions, as well as a reduction in instability as determined by the composite score of the Y-balance test.

Background: Neuroinflammation has long been implicated in the progression of amyloid beta (Aβ) accumulation and the decline of cognitive function in Alzheimer's disease (AD). Currently, many transcription factors, downstream signaling pathways, and molecular mechanisms that regulate the polarization of microglia have been explored. Furthermore, microglia may also exert a complex role in AD through the transformation of Aβ plaques or debris clearance, reflected in Aβ phagocytosis. One of the mediators of neuroinflammation in AD is the activated microglia. Therefore, the regulation of microglial function may be the key to successfully treating AD. Methods: This is a review article. PubMed, Embase, Scopus, and research meeting abstracts were searched up to 2024 for studies of microglia and neuroinflammation in Alzheimer's Disease. Systematic information retrieval was performed and appropriate studies were isolated based on important information available in the studies. The information from each of the articles was un-derstood and extracted to form a database. Results: The similar neuropathological results between several animals and AD cases show the possibility to implement microglia-related changes as an earlier diagnostic marker for AD in humans. The gene sets identified in various transcriptomic studies further foster this avenue of research by offering potential targets for therapeutic development. Multiple studies suggest that microglia-associated neuroinflammation at a special stage could also be protective, and there-fore, intervention should be delicate so that a beneficial response is retained. Conclusion: The phenotype balance between A1 (toxic) and A2 (safe) microglial phenotypes to toxic illness in AD has become a hot research topic at present. Substantial evidence, both in vitro and in vivo, has suggested that the loss of the normal A2 phenotype and the activation of toxic A1 microglia contribute to neurodegeneration in AD. Promoting or restoring the polarization of mi-croglia towards the A2 phenotype may thus represent an effective therapeutic strategy for ame-liorating neuroinflammation and progressive neurocognitive impairments.

Galectin-3 (Gal-3) is a lectin associated with fibrosis and inflammation, and increased circulating concentrations are considered a risk factor for atrial fibrillation (AF) in humans. This retrospective study aimed to evaluate the serum concentration of Gal-3 in dogs with cardiac disease, both with and without AF. Dogs with AF associated with congenital and acquired heart diseases were selected, while clinically healthy dogs and dogs with heart diseases but without AF served as controls. We statistically compared the serum concentration of Gal-3, assessed using a commercial canine-specific ELISA kit, among healthy dogs and dogs with heart disease with and without AF. Additionally, associations between Gal-3 and clinical and echocardiographic variables were evaluated. A total of 80 dogs were included, of which 17/80 (21.2%) were clinically healthy and 63/80 (78.8%) had heart disease, with 30/63 (47.6%) having AF. No significant difference in Gal-3 concentration was found between healthy dogs (3.90 ± 0.38 ng/mL) and dogs with heart disease, either with or without AF (3.45 ± 0.28 ng/mL, P=0.226 and 4.46 ± 0.27 ng/mL, P=0.286, respectively). Gal-3 showed a significant positive correlation with age (r=0.46, P &lt; 0.001). The results of this study suggest that Gal-3 does not have predictive value for the development of AF in dogs, but it is associated with advanced age.

Competent authorities of many countries, including Belgium, impose control measures (preventing wild bird access to feeders and water facilities, indoor confinement of captive birds, or fencing off outdoor ranges with nets) to professional and non-professional keepers of birds to prevent the spread of avian influenza (AI). Flemish laying hen farmers (FAR, n = 33) and private keepers of captive birds (PRI, n = 263) were surveyed about their opinion on, and compliance with, AI-measures legally imposed during the most recent high-risk period before this survey in 2021. Participants answered questions on a 5-point Likert scale (1 = the worst, 3 = neutral, and 5 = the best). FAR indicated better compliance with the AI-measures compared to PRI, except for confinement with nets. PRI and FAR perceived the level of compliance with AI-measures by other private bird keepers to be lower compared to themselves. FAR regarded the AI-measures as more effective than PRI. To prevent the spread of AI more effectively, national authorities could focus on information campaigns explaining to private bird keepers, in particular, the need for the various control measures that they impose, implement alternative control measures that have broader support or implement stricter enforcement of the control measures.

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein, and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a prote-ase promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphoryla-tion. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor, and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors.

Background. A direct clinical and morphological comparison of non-COVID myocarditis than was diagnosed before the SARS-CoV-2 pandemic and post-COVID myocarditis has not been performed so far. Purpose: to compare morphological activity, toll-like receptors expression and response to the immunosuppressive therapy in patients with non-COVID and post-COVID myocarditis. Metodhs. Seventy-seven patients (52 male and 25 female, 48.7±11.7 y.o.) with biopsy proven myocarditis, NYHA class 2 or more heart failure, ejection fraction (EF) <45% were included. A history of myocardial infarction, verified cardiomyopathies, systemic autoimmune diseases, viral DNA in the myocardium, except parvovirus B19, were exclusion criteria. The right ventricular endomyocardial biopsy with hematoxylin and eosin, Van Gieson stains, PCR for virus (herpes viruses, parvovirus B19, adeno-, enteroviruses and SARS-CoV-2), immunohistochemical study for CD3, CD45, CD68, CD20, nucleocapsid / spike proteins of SARS-CoV-2 and in addition toll-like receptors (TLR) type 4 and 9 expression (in 38 patients) were performed. The steroids (methylprednisolone 24-40 mg per day), azathioprine, mycophenolate mofetil were prescribed. The mean follow-up was 16 [6; 30] month. Results. In 45 patients, myocarditis was diagnosed before the SARS-CoV-2 pandemic (giant-cell in one case and lymphocytic in the others). Other 32 patients had post-COVID myocarditis positive for RNA or/and proteins of SARS-CoV-2 (giant-cell in one case, eosinophilic in three cases and lymphocytic in the others). There were no differences in age, NYHA class, CRP and anti-heart antibodies level, echocardiographic parameters (mean EF 30.2±7.8 vs 28.7±6.7%), parvovirus B19 positivity (22 vs 34%), doses of methylprednisolone (24-40 mg/day) and death / transplantation rate (11.1 vs 9.4%). Differences between non-COVID vs post-COVID myocarditis focused on higher CD3, CD 45*, TLR 4 (4+ vs 6+), TLR 9 (0 vs 2+) expression and better response to therapy [10% or more increase in EF in 53 vs 86%* of patients, mean EF (43.9±12.3 vs 49.8±7.6%*) by the end of follow-up], *p<0.05. Conclusion. Post-COVID myocarditis is characterised by different morphological types, higher morphological activity, tendency to higher TLR expression and the best response to the immunosupressive therapy in comparison with non-COVID myocarditis.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

Oral cancer (OC) presents a significant global health burden with rising incidence rates. Despite advancements in diagnosis and treatments, the survival rate for OC patients, particularly those with advanced or recurrent disease, remains low at approximately 20%. This poor prognosis is often due to a small population of cancer stem cells (CSCs) that are capable of self-renewal and immune evasion, thus playing pivotal roles in proliferation, tumor initiation, progression, metastasis, and therapy resistance. Exosomes, nano-sized extracellular vesicles (EVs), have emerged as crucial mediators of cell-to-cell communication within the tumor microenvironment (TME). These vesicles carry diverse molecules such as DNA, RNA, proteins, lipids, and metabolites, influencing various cellular processes. Emerging evidence suggests that CSC-derived EVs are significant in promoting tumor progression and metastasis and maintaining the balance between CSCs and non-CSCs, which is vital for intracellular communication within the TME of oral cancer. Recent reports indicate that oral cancer stem cell-derived EVs (OCSC-EVs) influence stemness, immune evasion, metastasis, angiogenesis, tumor reoccurrence, and drug resistance. Understanding OCSC-EVs could significantly improve oral cancer diagnosis, prognosis, and therapy. In this mini-review, we explore OCSC-derived exosomes in oral cancer, examining their potential as diagnostic and prognostic biomarkers that reflect CSC characteristics, and delve into their therapeutic implications, emphasizing their roles in tumor progression and therapy resistance. However, despite their promising potential, several challenges remain, including the need to standardize isolation and characterization methods and to elucidate exosome-mediated mechanisms. Thus, a comprehensive understanding of OCSC-EVs could pave the way for innovative therapeutic strategies that have the potential to improve clinical outcomes for OC patients.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and 11 inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their 12 inflammatory functions. This study analyzed the subtype-specific prognostic significance 13 of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex- 14 pression analysis. Correlations between these interleukin signatures and immune cell 15 markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. 16 Materials and Methods: The study investigated the prognostic significance of an anti- 17 inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory interleu- 18 kin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) 19 using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with 20 early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef- 21 ficient. 22 Results: Kaplan-Meier curves revealed that the prognostic significance of the anti-inflam- 23 matory signature was specifically pronounced in the basal-like subtype (p=0.004, Log 24 Rank). This signature retained independent prognostic significance in multivariate Cox 25 regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti- 26 inflammatory interleukin signature was associated with longer MFS. The pro-inflamma- 27 tory interleukin signature showed a significant prognostic effect in the whole cohort, with 28 higher expression associated with shorter MFS (p=0.034). Strong correlations were found 29 between the anti-inflammatory signature and CD8 expression (ρ=0.391; p<0.001) and be- 30 tween the pro-inflammatory signature and PD-1 expression (ρ=0.627; p<0.001).

Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in females, remains unclear. This study examined the KD's effect on increasing ethanol intake due to vicarious social defeat (VSD) in female mice. Sixty-four female OF1 mice were divided into two dietary groups: standard diet (n=32) and KD (n=32). These were further split based on exposure to four VSD or exploration sessions, creating four groups: EXP-STD (n=16), VSD-STD (n=16), EXP-KD (n=16), and VSD-KD (n=16). KD-fed mice maintained ketosis from adolescence until the fourth VSD/EXP session, after which they switched to a standard diet. The Social Interaction Test was performed 24 hours after the last VSD session. Three weeks post-VSD, the Drinking in the Dark test and Oral Ethanol Self-Administration assessed ethanol consumption. The results showed that KD blocked the increase in ethanol consumption induced by VSD in females. Moreover, among other changes, KD increased the expression of the ADORA1 and CNR1 genes, which are associated with mechanisms modulating neurotransmission. Our results pointed to KD as a useful tool to increase resilience to social stress in female mice.

The recent COVID-19 pandemic has significantly challenged Blood Transfusion Services (BTS) for providing blood products and for keeping blood supplies available. The possibility that similar pandemic event may occur again has induced researchers and transfusionists to investigate the adoption of new tools to prevent and reduce these risks. Similarly, increased donor travelling and globalization, with consequent donor-deferral and donor pool reduction, have contributed to raise awareness on this topic. Although recent studies have validated the use of pathogen reduction technology (PRT) for the control of Transfusion Transmitted Infections (TTI) this method is not a standard of care despite increasing adoption. We present a critical commentary on the role of PRT for platelet and on associated problems for blood transfusion services (BTS). The balance of cost effectiveness of adopting PRT is also discussed.

Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We investigated the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Children aged &lt; 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range undergoing cardiac surgery without DHCA were included as the control group. All patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician. Seventeen of 25 DHCA and six of 10 control patients completed the BSTID assessment. The groups showed no preoperative, operative, or postoperative significant differences. In adjusted multivariable analysis, prematurity and age at assessment were significant changing predictors of each of the BSTID components (p &lt; 0.001), other than the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Use of DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes if DHCA has a long duration.

(1) Background: a study was undertaken to determine the prevalence of chronic diseases and health conditions that affect oral health and oral health self-care among independent living older adults in rural areas of Victoria, Australia; (2) Methods: The study analysed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants self-completed questionnaires about health conditions, service use, and demographics. 572 attended a 2-hour health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD=9.2) years. Participants had a high prevalence of medical conditions, the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, with potential impact on oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.

Thoracic aortic aneurysms (TAAs) pose critical health risks, often asymptomatic until a rupture or dissection occurs. Guidelines recommend surgical repair based on specific aortic diameters and risk factors, emphasizing the importance of early detection and intervention. Despite established clinical risk factors for early detection in TAAs, the influence of racial and ethnic disparities on TAAs remains underexplored. This study aims to provide a comprehensive summary of existing research on racial and ethnic disparities in the presentation and outcomes of TAAs. Methods: This literature review was conducted using a systematic search strategy, in order to explore racial and ethnic differences in the presentation and surgical outcomes of patients with TAAs. Results: The findings demonstrated that black patients were younger at presentation and had a higher incidence of ruptured TAAs than non-black patients. Furthermore, compared to non-black patients, black patients had higher rates of cardiac arrhythmia and COPD, as well as comorbidities such as diabetes, hypertension, and renal insufficiency. For black patients undergoing open surgery, the surgical results showed improved 5-year survival rates after repair but higher perioperative mortality rates. All-cause or in-hospital mortality did not significantly differ between the racial groups, according to four studies. Discussion: This review highlights significant racial and ethnic disparities in TAA presentation and outcomes, underscoring the need for personalized risk stratification models. Standardized racial and ethnic definitions are essential for consistent and reliable research. Future studies should focus on refining risk assessment models to enhance diagnostic and therapeutic strategies, ultimately improving patient outcomes across diverse populations.

A 70-year-old female with a significant medical history of hypertension, hypothyroidism, chronic back pain, and a left hip prosthetic joint infection experienced complications following a total hip replacement. After multiple revisions and eventual discharge to a rehabilitation facility, she developed surgical site bleeding and a femoral head dislocation extending into the pelvis. At our hospital, imaging revealed a failed hip arthroplasty with extensive damage and infection, necessitating complex revision surgery and an antibiotic regimen. During her treatment, she developed a diffuse rash diagnosed as vancomycin-induced hypersensitivity reaction (DRESS), prompting a switch to oral linezolid and systemic corticosteroids. Despite transient eosinophilia and elevated inflammatory markers, her condition stabilized, and she was discharged with instructions for follow-up. This case underscores the importance of vigilant monitoring and timely intervention in managing complex postoperative infections and drug reactions.

Many studies utilize sensors to measure foot plantar pressure and analyze gait patterns, often focusing on assessing weight-bearing symmetry or asymmetry compared to control groups. However, a critical question arises: does the selection of the control group significantly impact study outcomes? Does chronic low back pain affect foot plantar pressure measurements? This experimental study involved 23 participants, including healthy individuals and those without foot disorders but with chronic low back pain. Dynamic foot pressure measurements were conducted using the Ortopiezometr, and data were analyzed using the "Steps" program. Participants were divided into two groups: Group 1 comprised completely healthy individuals, while Group 2 consisted of individuals without foot problems but with moderate chronic low back pain. The findings highlight a prevalence of energy release in the forefoot sensors compared to the hindfoot for both the right and left legs in most cases. Even among healthy volunteers, achieving perfect symmetry in the maximum values on the sensors for the right and left feet was a challenge. Results showed no statistically significant differences in energy released on specific sensors or duration of gait phases between the groups. Essentially, this suggests that foot pressure patterns are comparable between healthy individuals and those with low back pain. The use of sensor-equipped inserts for pedobarographic examinations indicates that, in cases of degenerative changes in the lumbar and sacral spine without accompanying acute pain, gait patterns resemble those of the healthy population.

Leukocyte migration is an essential function of innate and adaptive immune responses. Chemokines and their receptors control the migration system. The abundance of chemokines is controlled by atypical chemokine receptors (ACKRs), chemokine receptor-like molecules that do not couple to the G protein signaling pathways. Among them, ACKR4 regulates dendritic cell migration by controlling the ligands and is involved in tumor development in mouse models. Because no anti-mACKR4 mAb for flow cytometry has been reported, this study aimed to develop a novel monoclonal antibody (mAb) for mouse ACKR4 (mACKR4). Among the established anti-mACKR4 mAbs, A₄Mab-1 (rat IgG_2b, kappa), A₄Mab-2 (rat IgG_2b, kappa), and A₄Mab-3 (rat IgG_2b, kappa) recognized mACKR4-overexpressed Chinese hamster ovary-K1 (CHO/mACKR4) by flow cytometry. The dissociation constant (K_D) values of A₄Mab-1, A₄Mab-2, and A₄Mab-3 for CHO/mACKR4 were determined as 3.5 × 10⁻⁹ M, 6.0 × 10⁻⁹ M, and 1.6 × 10⁻⁹ M, respectively. Furthermore, A₄Mab-1 and A₄Mab-2 could detect mACKR4 by western blotting. These results indicated that A₄Mab-1, A₄Mab-2, and A₄Mab-3 help to detect mACKR4 by flow cytometry and western blotting and obtain the proof of concept in preclinical models.

Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

Lactate, an important metabolic product, provides energy to neural cells during energy depletion or high demand and acts as a signaling molecule in the central nervous system. Recent studies revealed that lactate-mediated protein lactylation regulates gene transcription and influences cell fate, metabolic processes, inflammation, and immune responses. This review comprehensively examines the regulatory roles and mechanisms of lactylation in neurodevelopment, neuropsychiatric disorders, brain tumors, and cerebrovascular diseases. This analysis indicates that lactylation has multifaceted effects on central nervous system function and pathology, particularly in hypoxia-induced brain damage. Highlighting its potential as a novel therapeutic target, lactylation may play a significant role in treating neurological diseases. By summarizing current findings, this review aims to provide insights and guide future research and clinical strategies for central nervous system disorders.

A Europe-wide outbreak of invasive pediatric Group a streptococcal infections (iGAS) began in fall 2022. Here we report the evolution of GAS hospitalizations in children and adolescents during the second outbreak year in 2023-2024 at a tertiary center in Switzerland. Using prospective monitoring of all in-patient GAS cases below 16 years of age including those with iGAS, we compared case frequencies and clinical characteristics in three time periods (2013-2020; 2022-2023; 2023-2024). Annual GAS hospitalizations increased from a median of 25 case (range 11-28) in 2013-2020 to 89 and 63 cases, respectively, in 2022-2023 and 2023-2024. iGAS cases evolved similarly (2013-2020, 4 cases (3-8); 2022-2023, 32 cases; 2023-2024, 21 cases). The decline in cases from 2022-2023 to 2023-2024 included all types of GAS organ involvement except suppurative infections in the head area, which remained largely unchanged (48 vs. 45 cases). Pleural empyema declined from 13 to 7 cases, possibly explained by a poor overlap of the GAS and influenza curves, respectively, in 2023-2024 compared to 2022-2023. These data document the prolongation of the GAS outbreak into its second winter season in 2023-2024, however with a decline of iGAS, pleural empyema, skin and soft tissue infection and infections of bone, joint and muscle.

Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN) and 396 controls. Sixteen tag-SNPs in OPRD1 were identified. Psychometric evalu-ations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Dis-orders Inventory Test-2 (EDI-2). P-values obtained by regression models were corrected for mul-tiple testing by the FDR method. Results: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower BMI values (FDR-q=0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0±0.28, 17.22±0.18 and 16.59±0.39 for TT, TC and CC carriers, FDR-q=0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in Interpersonal distrust (FDR-q=0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in Ineffectiveness (FDR-q=0.041 and FDR-q=0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448/rs204077/rs223491, FDR-q=0.028), which was also associated with the global PST index of SCL-90R (FDR-q=0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q=0.004-0.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q=0.011 and PSDI: FDR-q=0.003 for the last s204077/rs2234918/rs169450 combination). No associations with ED risk were observed. Conclusions: Genetic variation in the OPRD1 gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients.

B-cell lymphoid malignancies is a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling. To bypass the C481S mutation, non-covalent BTK inhibitors, such as pirtobrutinib, were developed and are active against both wild-type and the C481S mutation. In this review, we discuss the molecular and genetic mechanisms which contribute to acquisition of resistance to covalent and non-covalent BTK inhibitors. In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTK inhibitors and the development of new therapeutic strategies highlight the ongoing advances, that are being made towards the pursue of cure of B-cell lymphoid malignancies.

This case report presents a 63-year-old male patient who developed deep vein thrombosis (DVT) shortly after undergoing retroperitoneal laparoscopic nephroureterectomy for ureteral and renal pelvis tumors. Despite early postoperative mobilization and administration of low molecular weight heparin, the patient developed DVT, highlighting the limitations of current postoperative management strategies. The patient was promptly treated with the placement of an inferior vena cava filter and continued anticoagulation therapy, preventing the progression to pulmonary embolism and leading to a successful discharge.The report emphasizes the importance of vigilant postoperative monitoring and timely intervention in preventing complications such as DVT. It suggests that current strategies, including early mobilization and standard anticoagulation therapy, may not be sufficient to fully prevent DVT, necessitating further optimization of postoperative care. Regular monitoring of D-Dimer levels and ultrasound examinations, as well as appropriate limb protection measures during surgery, are recommended to detect and manage potential DVT early.This case contributes valuable insights into the early detection and management of postoperative DVT, providing useful references for similar cases and stressing the need for enhanced postoperative monitoring and timely intervention.