Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

An application of CO2/HCO3--free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in the beating frequency (CBF) or bend distance (CBD, an index of amplitude). This study demonstrated that the pHi of the c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while that of the ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). Upon applying Zero-CO2, an extremely high level of pHi caused the pHi, CBF and CBD to decrease, while a low level of pHi caused them to increase. The high pHi was generated by a high rate of HCO3- influx via interac-tions between CAIV and Na+/HCO3- cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased the pHi and CBF, and Zero-CO2 application increased the CBF in S0859-treated c-hNECs. In conclusion, the interactions of CAIV and NBC maximize the HCO3- influx to increase the pHi in c-hNECs. This novel mechanism causes the pHi to decrease, leading to no increase in CBF and CBD in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBD in c-hNECs periodically exposed to air (0.04% CO2) with respiration.

Barrett’s esophagus (BE) is a known precursor to Esophageal Adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered an acceptable alternative to esophagogastroduodenoscopy (EGD). This study presents analytical validation of EsoGuard® (EG), a two gene DNA methylation biomarker assay, in esophageal cell samples collected with the 510(k)-cleared, swallowable EsoCheck® (EC) device. EG is a Next Generation Sequencing (NGS) assay that evaluates methylated Vimentin (VIM) and Cyclin A1 (CCNA1) genes, clinically validated biomarkers for detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for analytical validation of molecular assays. Comparison to Sanger sequencing showed EG was 100% accurate at all 31 CpG sites evaluated by the assay. Analytical sensitivity, specificity and accuracy of the assay was 89%, 100% and 96% respectively. Intra- and inter-assay precision was 100%. Limit of detection (LOD) was 1 in 400 methylated cells and reference range was 84%. In summary, EsoGuard is a robust DNA methylation test to detect BE with high accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device.

The severity and invasiveness of clinical outcomes from organic responses to trauma are influenced by individual, surgical and anesthetic factors. A stress response elicits neuroendocrine and immune reactions that may lead to multi-organ dysfunction. The degree of neuroinflammatory reflex activation from trauma can increase pro-inflammatory cytokine production, leading to endothelial dysfunction, glycocalyx damage, neutrophil activation and multisystem tissue destruction. A shift in patient treatment towards a neuroinflammatory perspective has prompted a new evaluation protocol for surgical patients, required to understand surgical pathogenesis and its link to chosen anesthesia-surgical methods. This study aims to provide a description of the mechanisms involved in the immune and neuroendocrine response and below is a summary of the main mediators, focusing on video laparoscopic surgeries, by examining its frequency usage by researchers. We performed a narrative review of data from databases like PubMed, MEDLINE, EMBASE, high-impact journals, and studies from the past decade that used inflammatory mediator analysis to compare anesthetic and surgical strategies. Results showed preference for certain biomarkers more sensitive to tissue trauma. These markers display distinct behaviors, temporal fluctuations and their dosages serve as a tool to measure and validate therapeutic approaches in perioperative systemic inflammation.

The Mediterranean Diet, characterized by high intake of plant foods and unsaturated fats, has been suggested to improve assisted reproductive technology (ART) outcomes. This literature review aimed to summarize the evidence from observational studies on the associations between preconception Mediterranean Diet and ART outcomes. PubMed/MEDLINE, Embase, ScienceDirect, and Google Scholar databases were searched to identify relevant studies. Seven observational studies (n=2,321 women on ART) were included. Adherence to the Mediterranean Diet was assessed by food frequency questionnaires with 6-195 items. Three studies found that higher Mediterranean Diet scores improved Clinical Pregnancy or Live Birth rates, while two studies showed a positive effect on ART eggs and embryos. However, two studies reported no significant associations with ultimate ART success, and four studies found no effects on oocyte and embryo number or quality. Evidence for the effects of greater adherence to the Mediterranean Diet on ART outcomes is limited but promising. Additional rigorous research is needed to clarify and weigh the degree of association between the Mediterranean Diet and ART success.

Infantile Neuroaxonal Dystrophy (INAD) is a rare neurodegenerative disorder, affecting 1:1,000,000 population. It results from pathogenic variants in the PLA2G6 gene located on chromosome (22q13.1). The onset of symptoms usually occurs between 6 to 18 months, causing developmental regression leading to debilitating symptoms such as muscle weakness, dementia, and loss of basic skills. Eventually, it progresses to life-threatening symptoms including breathing difficulties, which limits the life expectancy to 5-10 years. While potential genetic therapy for treatment is are being developed, they are yet to be approved for use, and management remains essentially supportive. This case report is of a 9-year-old Pakistani girl with INAD. She presented with recurrent chest infections, developmental regression, loss of speech, paralysis, hypertension, and eventually breathing difficulties. Brain magnetic resonance imaging and genetic testing con-firmed the diagnosis. This case posed diagnostic challenges in view of its overlapping clinical presentation. Through this report, we aim to raise awareness about the condition among practitioners, outline the importance of genetic counseling in susceptible couples and suggest potential areas of further research.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding. So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort. This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs’ sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3. 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5mm,) AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE (p = 000.1). All grades of AWE were significantly associated with reperfusion. Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion.

Even despite rapid advances in colorectal surgery, morbidity and mortality rates in elective gastrointestinal surgery play a significant role. For decades, there have been tempestuous discussions on preventive measures to minimize the risk of anastomotic dehiscence. When mechanical bowel preparation before elective procedure, one of the key hypotheses, has been introduced into practice, it was assumed that it would decrease number of infectious complications and anastomotic dehiscence. The advancements in antibiotic treatment supported concomitant administration of oral antibiotics and mechanical bowel preparation. In the prospective study conducted at our clinic, we performed left-side colorectal procedures without the prior mechanical preparation. All patients enrolled in the study underwent the surgery and had been observed in the 3rd Surgical Clinic, Faculty of Medicine, Comenius University in Bratislava, Slovakia, from January 2019 to January 2020. As a control group we used similar group of patients with MBP. Our observed group included 87 patients with tumors in the left part of their large intestine (lineal flexure, descendent colon, sigmoid colon, and rectum). Dixon laparoscopic resection was performed in 26 patients. Sigmoid laparoscopic resection was performed in 27 patients. In 12 patients, the procedure was started laparoscopically but had to be converted due to adverse anatomical conditions. The conservative approaches mostly included Dixon resections (19 patients), sigmoid colon resection (5 patients) and left side hemicolectomy (6 patients), and Miles´ tumor resection with rectal amputation (4 patients). Our study highlighted the fact that MBP does not have the unequivocal benefit for patients with colorectal infection, which has an impact on development of anastomotic dehiscence.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by multiple risk factors and associated conditions. HFpEF prevalence is rising, and its prognosis remains poor after the first hospitalization. Using a two-hit HFpEF murine model, we aimed at studying cardiac reverse remodelling after stopping the causing stress (Angiotensin II [AngII]) and a high-fat diet [HFD]; MHS) and introducing voluntary exercise. We studied in young male and female C57Bl6/J mice fed or not with an HFD (60% calories from fat) the cardiac response to AngII (1.5 mg/kg/day for 28 days). Then, MHS was stopped, and VE was started for another four weeks (RR). We studied the effects of MHS and RR on the circulatory microRNA (miR) profile (miRNome) and the myocardial miRNome to characterize the cardiac and non-cardiac response of small RNAs. AngII alone and MHS but not the HFD caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in male mice. HFD-induced CH and LV concentric remodelling only in female mice. Four weeks after RR, CH, LV concentric remodelling and atrial enlargement were reversed. We performed bulk circulatory and LV miR sequencing. We did not observe differences linked to biological sex. RR restored normality for circulatory miRNome, whereas LV miRNome remained relatively similar to the one after MHS. Among the 25 most abundant circulatory miRs, ten were modulated by MHS (9 upregulated). In the LV, 8 of the 25 most abundant miR were upregulated by MHS, and 10 were downregulated. MiRNomes from AngII, HFD or MHS shared many common modulated miRs (32), suggesting that the overall response of organs producing the bulk of circulatory small non-coding RNA was similar even for seemingly different stress.

Bile acids (BAs) play a crucial role in the human body's defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolases (BSHs) activity but also directly combat infections. Building upon our research group's previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and microbiota. Leveraging existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile, Staphylococcus aureus, Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, Lactic Acid Bacteria), fungi (e.g., Candida albicans), and viruses (e.g., Coronavirus SARS-CoV-2, influenza virus, norovirus). Our research underscores the critical role of the interplay between BAs and intestinal microbiota, including Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, and Lactic Acid Bacteria, in maintaining intestinal homeostasis and combating infections. It is imperative to note that Primary bile acid (PBA) and Secondary bile acid (SBA) often exhibit distinct roles in the anti-infection process. In the antimicrobial action of BAs, SBA demonstrate antagonistic properties against a wide range of microbiota, with the exception of Norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating intestinal microbial infections.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Aim: To evaluate the clinical findings of glucose 6 phosphate dehydrogenase(G6PD) and pyruvate kinase(PK) deficiency in prolonged jaundice. To determine whether systemic-immune-inflammation index(SII), neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio (PLR) can be used in the diagnosis of neonatal prolonged jaundice. Methods: In full term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 10 mg/dL, whose jaundice persisted after the 10th day, were included in the study. Results: G6PD was negatively correlated with NLR, SII, age, and Hct. There was a negatively poor correlation between G6PD and NLR and a negatively moderate correlation between G6PD and SII when adjusted for age and Hct. PK showed no significant correlation with G6PD, NLR, PLR, SII, age, and Hct. A linear relationship was observed between G6PD and SII and NLR. Conclusions: NLR and SII can be easily calculated in the evaluation of prolonged jaundice in G6PD deficiency has a considerable advantage. NLR and SII levels may contribute by preventing further tests for prolonged jaundice and regulating its treatment. It may be useful to form an opinion in emergencies and in the early period.

Severe deficiency of ADAMTS13 (<10 iu/dL) is diagnostic of thrombotic thrombocytopenic purpura (TTP) and leads to accumulation of ultra-large VWF multimers, platelet aggregation and widespread microthrombi, which can be life-threatening. However, the clinical implications of a low ADAMTS13 activity level are not only important in an acute episode of TTP. In this article, we discuss the effects of a low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation, but once in a clinical remission. Evidence is emerging of the clinical effects of a low ADAMTS13 activity in other disease areas outside of TTP and here we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states.

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly com-bined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterised by inflammation and immune activation that persists despite cART and that may contribute to the development of co-morbid conditions. Toxicity associated with cART contributes to persistent immune dysregulation. Therefore, we aimed to compare current cART regimens in the light of premature aging to evaluate residual immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and af-fordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show less fa-vorable regimen profile containing protease inhibitor. Our data suggests incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the inter-est in various biomarkers related to immune activation and inflammation as predictors of clini-cal outcomes among PLHIV will increase in the future.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

This retrospective study aimed to assess coronary artery calcium (CAC) progression in serial computed tomography measurements according to risk factor changes. In 448 asymptomatic adults who underwent CAC measurements with more than one-year intervals, CAC progression was assessed according to age, sex, variable traditional risk factors (diabetes mellitus, hypertension, hyperlipidemia, and smoking), and initial CAC score (0, 0.1–100, and &gt;100). Univariate and multivariate logistic regression analyses were assessed for independent predictors of rapid CAC progression (△CAC/year&gt;20). During the 3.5-year follow-up, coronary artery calcifications occurred in 43 (12.8%) of 336 individuals with an initial CAC score of zero. Of 112 individuals with initial CAC presence, 60 (53.6%) had △CAC/year&gt;20. Age, male sex, body mass index, and all risk factors were significantly associated with △CAC/year&gt;20, but recently diagnosed hypertension (odds ratio [OR], 11.3) and initial CAC score (OR, 1.05) were significant independent predictors in multivariate regression analyses. CAC progression was affected by demographic and traditional risk factors, but adjusting for these factors, recently diagnosed hypertension and initial CAC score were the most influential factors for rapid CAC progression. These findings suggest that patients with higher initial CAC scores may benefit from more frequent follow-up scans and checks regarding risk factor changes.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Balance is important in lifesaving competitions. We aimed to investigate the relationship between dynamic balance and physical function in elite lifesavers by measuring the foot muscle cross-sectional area, ankle joint muscle strength, toe grasp strength, plantar superficial sensation, and dynamic balance. In this observational study, we measured the foot muscle cross-sectional area, ankle dorsiflexion, plantar flexion, external flexion, isometric muscle strength, toe grasp strength, and superficial foot sensation of 15 adult lifesavers (12 males). The results showed that toe grasp strength and ankle plantar flexion isometric muscle strength are particularly important for the dynamic balance function of elite lifesavers working on sandy surfaces. Sand training improves intrinsic muscle training and dynamic balance function. However, high training intensity may cause a decrease in plantar surface sensation, which needs to be verified with sand training interventions in the future.

Pregnancy-related morbidity and mortality remains high across the United States and the majority of deaths are preventable. Misdiagnosis and delay in diagnosis are thought to be contributors to preventable harm. These diagnostic errors in obstetrics are understudied. We present selected research methods to ascertain rates of and harm associated with diagnostic errors, the challenges in investigating them, and present future steps toward achieving diagnostic excellence in obstetrics.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC). cHCC-ICC is generally considered to exhibit a more aggressive clinical course compared to ICC; however, its risk factors and outcomes remain largely undefined. A single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC from June 2011 and January 2023, all of whom underwent surgical resection. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 vs. 46; ALT median 165.5 vs. 48; p=0.012 and p=0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 vs. 104; p=0.03). CA 19-9 values (p=0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (p=0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p=0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p=0.007). cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Our study showed that RFS is lower in the cHCC-ICC group as compared to ICC patients alone. Further studies are warranted and possibly suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.

Ectopic eruption of teeth rarely occurs in the mandibular condyle, orbit, nasal cavity, skin, and maxillary sinus. Ectopic eruption of teeth in the maxillary sinus can be accompanied by chronic and recurrent sinusitis, including headache, facial pain, and numbness. Fibro-osseous lesions in the paranasal sinuses are discovered incidentally on X-ray images and are often asymptomatic. Osteoma is the most common fibro-osseous lesion that develops in the paranasal and nasal sinuses. Herein, we report a rare case of osteoma (exostosis) containing supernumerary teeth within the maxillary sinus. A characteristic pedicled bone lesion with a clear border on computed tomography was the undefined orthopantomogram radiopacity in the left maxillary sinus, and the lesion contained teeth. The tumor was excised using the Caldwell–Luc procedure. Pathologically, the surgical specimen revealed an osteoma. The patient’s symptoms of chronic sinusitis disappeared, and the patient had no symptoms 2 years after the surgery. Because the patient had no history of midface trauma or surgery, the supernumerary teeth were speculated to have migrated during a reactive osteogenic process caused by chronic sinusitis.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are in order, a viral infection, a metabolic disorder, an ischemic event, and a neurodegenerative disorder. OS may be an early initiator or a significant promotor of their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology may avoid subsequent severe and irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, and autoimmunity. Past clinical studies that addressed OS have had equivocal results. It may be due to the use of ineffective antioxidants, an untimely delay in their use, or an inefficient delivery system. Experimental studies have used antioxidants that are not available for clinical trials. Although GSH can significantly reduce OS, its exogenous use is hampered by the lack of an effective delivery system. By incorporating GSH into cyclodextrin (CD) through nanotechnology, there is recent evidence that exogenous GSH can be delivered more effectively to prevent or mitigate injury from OS [1]. Future studies using the GSH/cyclodextrin (GC) complex will be needed to confirm its effectiveness and, hopefully, offer a path to treat many sub-optimally managed or currently untreatable illnesses.

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range, 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Limited number of long-term responders in R/M HNSCC cases treated with nivolumab exists. Given that PFS plateaued at 3 years, we propose that the optimal duration of treatment for this subset of patients is 3 years.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proved to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in treatment of HCC. This review summarizes impact of hypoxia on HCC tumor biology, adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Background: Endoplasmic reticulum (ER) stress is a significant player in the pathophysiology of various neurodegenerative and neuropsychiatric disorders. Despite the established link between ER stress and inflammatory pathways, there remains a need for deeper exploration of the specific cellular mechanisms underlying ER stress-mediated neuroinflammation. Methods: This study aimed to investigate how severity of ER stress can impact the release of proinflammatory cyto-kines IL-6 and IL-8 from astrocytes and microglia, comparing the effects with those induced by well-known immunostimulants - tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Results: Mild ER stress has a distinct effect on the cytokine release compared to more intense stress levels, i.e. diminished IL-6 production was accompanied by an increase in IL-8 level, which was significantly more pronounced in astrocytes than in microglia. On the contrary, prolonged or more severe ER stress induced inflammation in glial cells, leading to a time- and concentration-dependent buildup of pro-inflammatory IL-6 but unlike inflammatory agents, ER stress inducer diminished IL-8 secretions by glial cells. Conclusion: The differences could hold importance in identifying ER stress markers as potential drug targets for treatment of neurodegenerative diseases or mood disorders, yet it requires confirmation in more complex animal studies.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Background/Objectives: Postoperative intraocular lens (IOL) is a risk associated with IOL scleral fixation. However, the cause of IOL tilt during IOL suturing remains unclear. Therefore, this study aimed to evaluate the surgical outcomes of a modified IOL suturing technique and investigate the factors contributing to postoperative IOL tilt and decentration. Methods: We included 25 eyes of 22 patients who underwent IOL suturing between April 2018 and February 2020. A modified IOL suturing technique that decreased the need for intraocular suture manipulation was used. Factors contributing to IOL tilt and decentration were investigated using an intraoperative optical coherence tomography (iOCT) system. Results: The mean postoperative best-corrected visual acuity improved from 0.15 ± 0.45 to -0.02 ± 0.19 (p = 0.02). The mean IOL tilt angle at the last visit after surgery was 1.84 ± 1.28 degrees. The study revealed that the distance of the scleral puncture site from the corneal limbus had a stronger effect on IOL tilt; while, the suture position of the haptics had a greater effect on IOL decentration. Conclusions: The modified IOL suturing technique, which avoids intraocular suture handling, had favorable surgical outcomes with improved postoperative visual acuity and controlled IOL tilt and decentration. Accurate surgical techniques and careful measurement of distances during surgery are crucial for preventing postoperative IOL tilt and decentration.

Background: Donor shortage limits the utilization of heart transplantation making it available for only a fraction of the patients on the transplant wait list. Continuous flow left ventricular assist devices have therefore risen in importance as a standard of care for end-stage heart failure. Short, mid and long-term survival rates as well as quality of life are now being studied with newer and more sophisticated machines. This study attempts to assess the impact of several commonly associated risk factors on long-term survival of LVAD recipients. Methods The TriNetX dataset comprises de-identified patient information across healthcare organizations. The study assesses the impact of demographics, infections, comorbidities, types of cardiomyopathies, arrhythmias, and end-organ dysfunction on long-term LVAD survival. The Log-rank test was used to assess post-implant survival effects, while Cox regression was used in univariate analysis to obtain Hazard Ratio (HR). Patients with unknown lab results were removed before the univariate analysis and K-M survival curves were generated. Samples with missing values or data errors (e.g., implantation is after recorded death) were excluded. All analyses were conducted using the Python programming language and the lifelines library. This study is IRB-exempt Results This study identified common risk factors that significantly impact survival such as CMV, hepatitis A exposure, atrial fibrillation, paroxysmal ventricular tachycardia, ischemic cardiomyopathy, renal dysfunction, diabetes, COPD, mitral valve disease, and hypertension. Conclusions This is the first report of a detailed long-term survival assessment of several risk factors that impact the LVAD population.

MiR-204 is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC known as hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.

Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigates the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy

Vascular rings are a rare congenital anomaly of the aortic arch in which a ring-shaped structure forms surrounding the trachea and/or esophagus, potentially causing compression. We describe the case of a 14-month-old female patient with failure to thrive secondary to dysphagia, and a vascular ring formed by a right aortic arch, an aberrant left subclavian artery, and a left liga-mentum arteriosum. Surgical repair involved ligamentum arteriosum division, Kommerell’s di-verticulum obliteration, and left subclavian artery re-implantation into the left carotid artery. Endoscopy and EndoFLIPTM evaluated intraoperative improvement in esophageal narrowing and impedance, respectively. Postoperative period was uneventful and follow-up visits demonstrated dysphagia resolution and a patent re-implanted left subclavian artery.

This critical review revisited the new classification system for periodontitis, specifically for staging, suggesting modifications, and introducing a new flowchart for a better clinical evaluation. It evaluated articles published between 2018 and 2024 in the English language, which had an educational motivation focused on staging periodontitis. PubMed/MEDLINE, Web of Science, and Embase databases were used to retrieve the articles. The focus questions involved the analysis of all parameters for staging periodontitis. A total of 836 articles were initially found; 388 duplicated were excluded; 448 were evaluated by title and abstract; 26 articles followed for full-text reading, and 6 articles were included in this critical review (k=0.98). All articles included detailed parameters and steps about how to diagnose periodontitis. Therefore, it was possible to observe instability and “gray zones” in the staging step, which was due to a lack of priority and an organized order sequence. This review suggests the severity parameters cannot be overcome by complexity parameters, following a cumulative sequence: CAL (1^st), RBL (2^nd), TLP (3^rd), and, after, complexity parameters. An exception must be permitted only for complexity factors between Stages III and IV that can change the initial Stage (III or IV) obtained through the severity analysis, but only between themselves. Moreover, for patients without tooth loss or with TLP of ≤4 teeth (without need for complex rehabilitation) and presenting any type of drifting or flaring or a secondary traumatic occlusion, it cannot be a justification for moving the diagnosis from Stage III to Stage IV.

Backgorund and Objectives: In this study, we aimed to evaluate and compare the changes in visual and structural outcomes in patients with intravitreal aflibercept (IVA)-resistant neovascular age-related macular degeneration (nAMD) switched to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This obser-vational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab for aflibercept-resistant nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant im-provement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (μm) was significantly thinner at A1 (IVBr; 240.55 ± 51.82, IVF; 234.91 ± 47.29) and at A3 (IVBr; 243.21 ± 76.15, IVF; 250.50 ± 72.61) compared to at A0 (IVBr; 303.55 ± 79.18, IVF; 270.33 ± 77.62) in IVBr group (A1; p = 0.0093, A3; p = 0.0026) and in IVF group (A1; p = 0.0161, A3; p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusion: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical ef-fect on eyes with aflibercept-resistant nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.

Creatine has been linked to the development of kidney damage since 1998. However, uncertainties persist regarding the actual impact of creatine supplementation on individuals with kidney disease before supplementation or with pathological conditions that have an increased risk of developing kidney dysfunction. This study performed a comprehensive review of the literature and utilized bioinformatics tools to investigate the effects of creatine on renal tissue and function. Moreover, we identified 44 genes modulated explicitly in response to creatine exposure using the Comparative Toxicogenomics Database, including IGF1, SLC2A4, and various creatine kinase genes. The analysis revealed associations with metabolic processes such as amino acid metabolism, indicating a connection between creatine and tissue physiology. Gene expression analysis using the Genotype-Tissue Expression Portal highlighted tissue-specific expression patterns in kidney and pancreas tissues. Furthermore, the study explored creatine metabolism pathways and kinase regulation through biological databases and Gene Expression Omnibus data, shedding light on the potential regulatory roles of creatine in cellular processes during kidney diseases. Understanding the impact of the balance between the endogenous creatine synthesis and the creatine uptake, particularly the genes GATM, GAMT, SLC6A8 and IGF1, insights into molecular mechanisms underlying creatine's physiological effects on renal tissues. Overall, this work provides new insights into the molecular interactions and pathways influenced by creatine in renal function.

ABSTRACT: Background: Virtual Reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and patients' perception of the chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of the chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity and vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves beneficial in minimizing the perceived length of chemotherapy session for lung cancer patients, enhancing their overall treatment experience. The intervention showed to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body's immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using Receiver Operating Characteristic (ROC) curve and AUC (Area Under the Curve) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT with a value of r=0.933 and p &lt;0.001. The value ≥37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, positive, and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

Introduction: Left ventricular dysfunction in an independent predictor of mortality in Chagas disease. Global longitudinal strain (GLS) is an emerging echocardiographic modality with possible incremental value in early detection of cardiac involvement. Objective: Compare left ventricular function with multiple echocardiographic parameters between patients with the indeterminate and chronic forms of Chagas and perform a literature review. Methods: In this observational study, 11 patients with a confirmed diagnosis of Chagas disease were evaluated. Individuals were distributed as follows: 5 with the indeterminate and 6 with the chronic forms. Conventional echocardiographic evaluation was followed by GLS measurement. Results: The mean left ventricle ejection fraction LVEF was 33 ± 2.88 and the mean GLS of the left ventricle was - 10.76 ± 2.20 in the chronic form as compared to 57.80 ± 6.49 and - 17.34 ± 3.82, respectively in the indeterminate group. Contractility was reduced in segments of the inferior, inferoseptal and anteroseptal walls in both groups. Conclusion: Analysis of longitudinal strain in the indeterminate form has potential incremental value to the conventional analysis of ejection fraction when compared to patients with chronic Chagas cardiomyopathy, especially with individual segmental analysis but the impact and clinical significance of these techniques is still unknown.

Depressive disorders represent the leading contributors to mental health-related global burden, and they are often diagnosed in the context of many comorbid disorders, such as cardiovascular disorders, Stroke, Parkinson’s Disease, Major Neurocognitive Disorders and Headache, thus worsening their outcomes. Depression is a challenge for “real-world” clinicians, due to the low rates of remission despite the increasing number of antidepressant strategies currently available. Indeed, current antidepressant strategies often fail to achieve acceptable rates of remission. One of the main challenges of “real-world” management of depression is represented by geriatric depression, which is common and under diagnosed. The challenge of diagnosis and treatment of geriatric depression in real world calls for the need of a deeper exploration of its management in clinical practice. This is the purpose of the present cross-sectional survey, aimed at evaluating the clinical approach to late-life depression in a sample of expert physicians working in geriatric settings in Italy, thus trying to provide useful insights on geriatric depression care.

The associations between dietary sodium intake (DSI), dietary potassium intake (DPI), and kidney stone disease (KSD) are not clear. We examined The National Health and Nutrition Examination Survey 2011-2018 to determine the independent associations between daily DSI, DPI, DSI/DPI and prevalent KSD. 19,405 participants were included for analysis, of which 1,895 had KSD. Higher DSI was not associated with increased odds of KSD in regression analysis when DSI was modeled as a continuous variable (OR=0.99, 95% CI: 0.99-1.00, p=0.2), or when comparing highest quartile of DSI to lowest quartile (OR=0.84, 95% CI: 0.68–1.04, p=0.1). Unlike DSI, higher DPI associated strongly with reduced odds of KSD in regression analysis when DPI was modeled as a continuous variable (OR=0.99, 95% CI: 0.99-0.99, p=0.02), or when comparing highest quartile of DPI to lowest quartile (OR =0.75, 95% CI: 0.60–0.94, p=0.01). Lastly, higher DSI/DPI also associated strongly with increased odds of KSD in regression analysis when DSI/DPI was modeled as a continuous variable (OR=1.1, 95% CI: 1.01-1.20, p=0.03), or when comparing highest quartile of DPI to lowest quartile (OR =1.30, 95% CI: 1.10–1.70, p=0.008). All the observed relationships were independent of total calorie intake. In conclusion, both lower DPI and higher DSI/DPI associate with an increased risk of KSD. Future prospective studies are needed to clarify these causal relationships.

Early detection of PDAC remains challenging due to the lack of early symptoms and absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics sig-natures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used western blot-ting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal dis-tributions were performed using one-way ANOVA followed by Tukey’s post hoc test and pair-wise tests were performed using t tests. P≤0.05 was considered statistically significant. Protein cluster of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described in the literature target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166 and S100A13 as potential meaningful biomarker candi-dates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with identifier PXD053169.

Lately, radiomic studies featuring the development of a signature to use in prediction models in diagnosis or prognosis outcomes are being published increasingly. While the results are shown to be promising, these studies still have many pitfalls and limitations. One of the main issues of this methodology is that radiomic features depend on how the images are preprocessed before their computation. Since, in widely known and used software for radiomic features calculation, it is possible to set these preprocessing parameters before the calculation of the radiomic feature, there are ongoing studies assessing the stability and repeatability of radiomic features to find the most suitable preprocessing parameters for every used imaging modality. This review examines the impact of preprocessing parameters on the reproducibility and reliability of radiomic features extracted from multimodality imaging (CT, MRI, CBCT, PET/CT). Standardized preprocessing is crucial for consistent radiomic feature extraction. Key preprocessing steps include voxel resampling, normalization, and discretization, which influence feature robustness and reproducibility. From our work, we highlighted the need to harmonize the use of preprocessing parameters and their values, especially in light of future studies of prospective studies, which are still lacking in the current literature.

Background: Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors. Material and methods: 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. A representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use t-test to test the significance and use receiver operating characteristic curve method to fund optimal cut-point for these significant features. After splitting 80% data into training set and 20% data into testing set, we use five machine learning models k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANN) and supportive vector machine (SVM) to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors. Results: This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign from malignant tumors (p&lt;0.05). On ML, the overall accuracy rates are 74.3% (95%CI: 59.8-88.8%), 94.3% (86.6-100%), 72% (54-89%), 84% (69.5-97.3%) and 73.5% (58.7-88.4%) for kNN, Naïve Bayes, Logistic regression, one node ANN and SVM, respectively. Conclusion: US texture analysis with ML has potential as an objective and valuable tool for assessment of salivary gland tumors.

Conclusions: The quantitative method provides a large-scale overview of the biometry measurements of an entire practice. Image audits can then be focused on sonographers whose measurements are outliers, avoiding the time, complexity, and expense of auditing those whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative review.

Schizophrenia is a disease with a complex etiology that significantly impairs the functioning of patients. In recent years, there has been increasing focus on the importance of the gut microbiota in the context of the gut-brain axis. In our study, we analyzed data on the gut-brain axis in schizophrenia, as well as the impact of eating habits, the use of various supplements, and diets on schizophrenia. Additionally, the study investigated the impact of antipsychotics on the development of metabolic disorders such as diabetes, dyslipidemia, and obesity. There may be significant clinical benefits to be gained from therapies supported by supplements such as omega-3 fatty acids, B vitamins, and probiotics. The results suggest the need for a holistic approach to the treatment of schizophrenia, incorporating both drug therapy and dietary interventions.

Secondary prevention after SCA (acute coronary syndrome) is of paramount importance to reduce the incidence of MACE and improve prognosis in follow-up. The control of avoidable risk factors, lifestyle modifications, but especially careful control of cholesterolemia (with a target of LDL-C

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Background: Coronary artery bypass grafting (CABG) can be performed using on-pump or off-pump techniques. The optimal approach remains debated. Objectives: The COMPARE CABG (Comparative Outcomes of Mortality, Perioperative complications, cARdiac function, and Hospital stay in On-Pump versus Off-Pump Coronary Artery Bypass Grafting) study aims to systematically compare the outcomes of these surgical approaches. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, and other databases. Studies with a sample size > 4000 were included. Outcomes analyzed included mortality, complications, cardiac function, and hospital stay. Results: Meta-analysis of 5 studies with 58,232 patients showed that off-pump CABG was associated with a slightly lower complication rate: 15% for on-pump CABG and 13.5% for off-pump CABG with a pooled effect size of 0.90 (95% CI: 0.85-0.95). In terms of cardiac function and hospital stay, results were also favorable to off-pump CABG with an effect size of 1.12 (95% CI: 1.05-1.19) and 1.15 (95% CI: 1.10-1.20), respectively. The pooled mortality rate was 2.5% for on-pump and 2.4% for off-pump CABG, with an effect size of 1.05 (95% CI: 0.98-1.12), indicating no significant difference between the groups. Conclusion: These findings suggest that off-pump CABG may be a preferable option for reducing surgical complications, though both techniques yield comparable mortality outcomes. Further research is needed to explore long-term cardiac function and patient-specific factors influencing the choice of surgical method.

Background. Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. Case presentation. We identified across different Cancer Centers six cases of both BRCA wild-type and BRCA-mutated EOC spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as by clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Conclusion. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for optimal disease control of this unfortunate patient’s subset. Albeit not being directly investigated in BM patients, the PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

The syndrome of inappropriate antidiuresis (SIAD) is a rare and significant side effect of a variety of medications such as antidepressants, chemotherapeutic medications, and non-steroidal anti-inflammatory drugs. Regarding dipyrone, only a few cases have been mentioned in the world. The non-opioid analgesic metamizole (dipyrone) is used for the treatment of acute or chronic pain and fever and is one of the most frequently prescribed over-the-counter medications in Israel, Brazil, and Mexico. Dipyrone has low anti-inflammatory properties yet inhibits prostaglandins to some degree. In this case report, we present a case of a post-operative patient, who was on an analgesic cocktail containing dipyrone. The patient developed a new and sudden hyponatremia, namely, a drop of 12 meq/L of sodium in less than 24 hours. Dipyrone was found to be the culprit drug. Our case report demonstrates the importance of considering dipyrone in the diagnosis of medication-induced SIAD in patients taking analgesics.

Preventing or treating infections at implantation sites where the risk of bacterial contamination is high requires the development of intelligent drug delivery systems. In this work, honeycomb structures as a potential drug carrier were obtained for the first time in a fast, one-step anodization process of titanium grade 4, lasting only 60 seconds. Fourth generation oxide nanotube layers were obtained from an aqueous solution of 0.5% AgNO3 in the voltage range from 50 to 80 at 15(1) °C. The FE-SEM method showed the length of the oxide nanotubes from 1.02(2) µm at 50 V to 230(8) nm at 80 V. The EDS analysis revealed that during anodizing, silver particles are deposited on the Ti G4 up to 2.2(5) wt.%. Electrochemical measurements by open circuit potential and anodic polarization curves methods proved the improvement of in vitro corrosion resistance as a result of Ti G4 anodizing. Assessment of the anodized Ti G4 as gentamicin sulfate carrier carried out using ATR-FTIR and UV-VIS absorption spectroscopy revealed that the obtained oxide nanotube layers can be used for application of drugs directly to the tissue around the implant. This method of application allows full use of the therapeutic dose of the antibiotic used.

Primary bone lymphoma of the spine (PBL) is a rare entity and the most shared type of non-Hodgkin lymphoma (LNH) appearing in bone lesions deprived of nodal or extra-nodal in-volvement and accounting for approximately 2% of all lymphomas. Most PBL are diffuse large B-cell lymphomas (DLBCL) and commonly involve the appendicular skeleton. Due to its atypical location and non-specific clinical imaging features mimicking certain neoplastic or infectious processes, this pathology may be misdiagnosed, thus complicating and delaying diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia and fever. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed significant inflammatory syndrome, a pattern of spondylodiscitis at the L3-L4 level associated with morphological and metabolic invasion extending posteriorly, raising suspicion of epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation with different prognosis and therapeutic management.

The targeted compounds in this research, resveratrol analogs 1–14 were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. Molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

Acute myeloid leukemias (AMLs) are heterogeneous hematologic cancers that occur prevalently in older patients as the result of a complex pathobiology. The clinical outcomes of older patients with AML, often unsuitable for intensive chemotherapy and allogeneic stem cell transplantation, are generally disappointing. However, recent advances in understanding molecular pathogenesis and other biological mechanisms recognized in AML development and progression have changed the treatment approach, especially for this particularly vulnerable category of patients. Indeed, non-intensive biologically tailored approaches, such as combining venetoclax with hypomethylating agents, have changed the therapeutic paradigm in this field. Moreover, other promising compounds and treatment strategies are currently under advanced clinical development. This article delves into the latest biological understanding and therapeutic advances in the clinical management of older AML patients into new conceptual frameworks that progressively transform the clinical practice in this challenging setting.

Leptin, acting centrally or peripherally, has complex effects on cardiac remodeling and heart function. We previously reported that central leptin exerts an anti-hypertrophic effect in the heart via cardiac PPARβ/δ activation. Here, we assessed the impact of central leptin administra-tion and PPARβ/δ inhibition on cardiac function. Various cardiac properties, including QRS du-ration, R wave amplitude, heart rate (HR), ejection fraction (EF), end-diastolic left ventricular mass (EDLVM), end-diastolic volume (EDV), and cardiac output (CO) were analyzed. Central leptin infusion increased cardiac PPARβ/δ protein content and decreased HR, QRS duration and R wave amplitude. These changes induced by central leptin suggested a decrease in the ventricu-lar wall growth which was confirmed by MRI. In fact, the EDLVM was reduced by central leptin, while increased in rats co-treated with leptin and GSK0660, a selective antagonist of PPARβ/δ ac-tivity. In summary, central leptin plays a dual role in cardiac health, potentially leading to ven-tricular atrophy and improving heart function when PPARβ/δ signaling is intact. The protective effects of leptin are lost by PPARβ/δ inhibition, underscoring the importance of this pathway. These findings highlight the therapeutic potential of targeting leptin and PPARβ/δ pathways to combat cardiac alterations and heart failure, particularly, in the context of obesity

Aim: To determine the prevalence of skeletal muscle alterations (SMA) in patients with meta-bolic dysfunction-associated steatotic liver disease (MASLD) and to assess the significance of circulating myokines as potential biomarkers of SMA in patients with MASLD. Material and methods: Measurements of both skeletal muscle strength and skeletal muscle mass parameters, anthropometric and metabolic features as well as serum levels of different myokines were per-formed in a cohort of 62 MASLD patients and then compared according to the stage of liver fi-brosis and hepatosteatosis degree both diagnosed by transitional elastography. Results: No sig-nificant differences were found in skeletal muscle strength and skeletal muscle mass in MASLD patients stratified according to the stage of liver fibrosis. Noteworthy, serum levels of FGF21 were significantly higher in MASLD patients with advanced hepatic fibrosis (F3-F4) than in those with lower stages of hepatic fibrosis (F0-F2) (197.49±198.27 pg/ml vs 95.62±83.67 pg/ml, p=0.049, respectively). MASLD patients with severe hepatosteatosis (S3) had significantly higher serum levels of irisin (1116.87±1161.86 pg/ml) than those with lower grades (S1-S2) (385.21±375.98 pg/ml, p=0.001). Conclusion: SMA were uncommon in our MASLD patients, particularly in those with lower stages of liver fibrosis. An increase in serum FGF21 was detected in patients with a higher stage of fibrosis with possible therapeutic implications in MASLD.

Current epidemiological data about interstitial lung disease (ILD) are still poor. The principal cause of the discordant data is associated with a heterogeneous group of respiratory diseases that includes a large number, about 200 families, with low frequency, distinct and sometimes unknown etiology, and different progression. Furthermore, epidemiological data are limited. Scope of the narrative review is to report ILD incidence and prevalence in Registries from different Countries in the second millennium. We identified 16 ILD Registries (14 prospective and 2 retrospective) from major Countries in Europe (n = 10), Asia (n = 7), North America (n =2) and Oceania (n = 1). Significant discrepancies in ILD and ILD subtypes prevalence and incidence among countries are reported in Registries. These discrepancies could be determined by different ethnicities and socio-economic conditions as well as by updates in disease diagnosis and classification. ILD epidemiological Registries are progressively ameliorating through a better adherence to updated Guidelines and Classification codes. An accurate and definite compilation of ILD epidemiological Registries will be useful for a more precise monitoring of disease progression and treatment.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial blood flow reserve (MFR), and myocardial blood flow volume fraction (MBF), and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 male, 1 female) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86±0.13 vs. 1.08±0.09, p=0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23±0.23 vs. 1.88±0.29, p=0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

Plants from the Myrtaceae family are well known to contain considerable amounts of volatile compounds, ranging from oxygenated monoterpenes to hydrogenated sesquiterpenes, and others, which exhibit antimicrobial activity. One such plant includes Syzygium aromaticum that has been extensively used to treat a number of disorders, including bacterial and fungal infections. Thus, the scientific validation of the essential oil (EO) of Syzygium aromaticum vis-à-vis Candida and Cryptococcus species is valuable. To this end, the present study sought to investigate the antifungal activity of EO from S. aromaticum (clove) leaves and flower buds against Candida and Cryptococcus species. The antioxidant activity of S. aromaticum’s essential oils is also elucidated. The EO was extracted from fresh leaves and floral buds of S. aromaticum using a Clevenger-type apparatus. The as-prepared essential oils were further evaluated for antifungal activity against Candida and Cryptococcus species using a microdilution method. The phytochemical analysis of the EOs was assessed by gas chromatography/mass spectrometry (GC-MS). Antioxidant activities of the EOs were evaluated using standard methods. As a result, the GC-MS analysis revealed the presence of volatile compounds, such as eugenol (87.08%), β-caryophyllene (6.40%) and acetyleugenol (4.45%) as the major constituents of EO from the flower buds ; and eugenol (90.54%) and β-caryophyllene (24.65%) as the major components of the leaf’s EO. The eugenol-rich essential oils exhibited significant antifungal effects against Candida species (common MIC value: 200 ppm) and Cryptococcus neoformans (MIC value: 50 ppm), as well as antioxidant activity. Overall, essential oils of S. aromaticum demonstrated an-tioxidant and antifungal effects, thus validating the ethnopharmacological use of this plant in the treatment of fungal infections. However, antifungal mechanisms of action, in-depth toxicity and in vivo experiments, and pharmacokinetics are warranted to support the use of this plant in ethnomedicine.

Abstract: (1) Background: to find out how COVID-19 infection during pregnancy affects the outcome of the pregnancy; (2) Methods: 166 SARS-CoV-2-positive pregnant women formed the study group. 128 SARS-CoV-2-negative pregnant women formed the control group. Anatomopathological study of the placenta was performed in all cases; (3) Results: Placental insufficiency appeared in 38 patients (22.9%) of the study group and in 17 patients (13.2%) in the control group (p=0.016). Villitis appeared in 50 patients (30.1%) of the study group and in 16 (12.6%) in the control group (p=0.000). 166 COVID-19 positive patients were further subdivided, into those with anatomopathological affection of the placenta, and those without. When gestational age between patients with placental insufficiency and those without it are compared, a difference of 4.38 days is obtained (p=0.0393). If we compare neonatal weight between patients with placental insufficiency and those without it, a difference of 406.4 grams is obtained (p=0.0000). When gestational age between patients with villitis and those with-out it are compared, a difference of 3.2 days is found (p=0.0919). When neonatal weight between patients with villitis and those without it are compared, a difference of 242.2 grams is obtained (p=0.0018). (4) Conclusions: COVID-19 infection during pregnancy may produce lower fetal weight and shorter gestational length.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of pulsatilla decoction (BEPD) of the traditional Chinese medicine herbal formula has been shown to be effective in treating UC. We aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL)1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. Our results showed that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduce the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

Robotic-assisted hip and knee arthroplasty represents significant advancements in orthopedic surgery. Artificial intelligence (AI) - driven chatbots, such ChatGP, plays a significant role in healthcare education. This study aims to evaluate the quality of responses provided by ChatGPT to the top 20 questions concerning robotic-assisted hip and knee arthroplasty.We have asked ChatGPT to select the top 20 questions on Google concerning robotic hip and knee arthroplasty and to provide a detailed answer to each of them. The accuracy of the information provided were examined by three orthopedic surgeons with scientific and clinical experience in hip and knee replacement surgery. The accuracy was assessed through a 5-point Likert scale (from 1 – completely incorrect to 5 – correct); the completeness through a 4-point Likert scale (from 0 – comprehensiveness not assessable for completely incorrect answers to 3 – exhaustive information) on two different occasions to ensure the consistency of the assessment. Our analysis reveals that ChatGPT provides a relatively high degree of accuracy, moreover the explanations can be considered satisfy, especially for factual questions. The findings suggest that ChatGPT can serve as a valuable initial resource for general information on robotic hip and knee arthroplasty but the integration with human expertise remains essential.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by abnormal growth of mature B cells in the blood, bone marrow, and lymphoid tissues. Although CLL primarily affects the hematopoietic system and lymph nodes, renal involvement is exceptionally rare and presents diagnostic and treatment challenges. Potential causes of renal failure in CLL patients include sepsis, dehydration, tumor lysis syndrome (TLS), compression of the ureter by enlarged lymph nodes, and side effects of cancer therapy. This report presents a case of CLL with renal infiltration leading to severe renal failure, discussing the clinical presentation, diagnostic workup, and management of this condition.

Introduction: The disease caused by Coronavirus-2019 (COVID-19) was initially described in December 2019. Severe acute respiratory syndrome type 2 (Sars-Cov-2) is responsible for an important multisystem inflammatory spectrum. Cardiovascular conditions have been reported with an estimated frequency of 8-28%. In this context, transthoracic echocardiography associated with the analysis of the two-dimensional Global Longitudinal Strain (GLS) of the left ventricle derived from Speckle Tracking emerges as a promising modality. Objective: This study aims to evaluate the applicability of GLS and segmental deformity assessment in detecting subclinical myocardial dysfunction in patients that recovered from COVID-19 infection. Methods: The observational study involved 18 patients (mean age 52 years) with recent evidence of COVID-19 infection that underwent detailed echocardiographic evaluation with GLS, and cardiac magnetic resonance (CMR) according to segmental assessment results. The degree of correlation between the methods was analyzed and a systematic literature review was also conducted. Results: The mean left ventricular ejection fraction (LVEF) was 57.50 ± 9.98%. Only 16.6% of patients had reduced LVEF. The average GLS was – 18.70 ± 3.54% and in 44% of cases only one myocardial segment was affected, particularly the inferolateral basal. CMR revealed inflammatory cardiomyopathy. Discussion: Subclinical myocardial involvement is associated with major adverse cardiac events. Literature review supports the use of GLS for detecting early cardiac involvement. Conclusion: Speckle-tracking echocardiography has been shown to have clinical utility in a variety of settings and to offer superior prognostic value with a potential to enhance subclinical detection of myocardial changes in patients after COVID-19 infection.

Epithelial ovarian cancer significantly contributes to cancer-related mortality in women, often recurring post-treatment with chemotherapy resistance. Dietary interventions have demonstrated influence on cancer progression; for instance, caloric restriction has exhibited tumor growth reduction and enhanced survival in animal cancer models. This study aims to calculate a transcriptomic signature based on caloric-restriction for ovarian cancer patients and explore its correlation with disease progression. We identified proteins modulated by fasting, intermittent fasting or caloric restriction in human females. Based on their gene expression, we calculated a Non-Fasting Genomic Signature score for ovarian cancer samples from the TCGA database. We examined the association between this genomic profile and clinical characteristics. The non-fasting signature, comprising eight genes, demonstrated higher prevalence in primary ovarian tumors compared to normal tissue. Patients with elevated signature expression exhibited reduced overall survival and increased lymphatic invasion. The mesenchymal subtype, associated with chemotherapy resistance, displayed the highest signature expression. Multivariate analysis suggested the non-fasting genomic signature as a potential independent prognostic factor. Ovarian cancer tumors expressing a “non-fasting” transcriptional profile correlate with poorer outcomes, emphasizing the potential impact of caloric restriction on improving patient survival and treatment response. Further investigations, including clinical trials, are warranted to validate these findings.

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumour cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83+-20 nm and 49+-12 nm, respectively. For RT alone, a reduction in cell viability of up to 33+-12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 μM showed a reduction in cell viability of 20+-4% and 35+-4%, respectively, while for BBN-AuNPs, at 50 and 200 μM, a reduction in cell viability of 25+-3% and 37+-3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26+-3% and 22+-2% between RT+HAOA-AuNPs at 400 μM and RT+BBN-AuNPs at 50 μM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Despite advances in our knowledge of systemic lupus erythematosus (SLE) has increased over time, there are still many challenges in deciphering the precise mechanisms involved in the development and progression of the disease. Recent evidence has raised questions about the effectiveness of the programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during the autoimmune response. Research has ventured into investigate the potential impact of PD-1 on various CD4+ T cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and have been closely related with several autoimmune disorders including SLE. This review aims to highlight the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell response. Additionally, we address the potential of PD-1 or its ligands as a possible therapeutic target in SLE.

Approximately more than 120 transthyretin mutations are known whose variation in clinical presentation is heterogeneous, as the course of disease onset depends on genetic variation and level of penetrance. It is little known in Ecuador, and some of the reported cases; suggest to the family tree analysis that they come from a province that is possibly considered endemic. The main objective is to carry out a descriptive cross-sectional analysis on the presentation of transthyretin amyloidosis in families carrying the p.Ser43Asn gene from the index case identified.

Background & Objective: Acne Vulgaris is a common skin disease, with 5 % prevalence in Pakistan and has a significant physiological, psychological, emotional and social impact on the population, our study aims to estimate its annual economic burden per person in Pakistan.Methodology: Economic burden was estimated by using Cost of Illness analysis. All types of costs, including direct medication costs, direct non-medical costs and indirect costs due to loss of work. Data were collected from online databases and literature reviews. Results: Cost of illness analysis estimated that the cost of Acne Vulgaris treatment varies for mild, Moderate and severe acne. Acne is causing an annual economic burden of PKR 1,92,366 PKR per person (direct cost is PKR 1,86,366 and indirect cost 6,000) for an expensive treatment and PKR 53,550 (direct cost is PKR 47550 and indirect cost 6,000) for a cheap treatment. Limitation: Being an LMIC, Pakistan needs extensive study on the pharmacoeconomic analysis of Acne for proper and rational allocation of resources. Conclusion: Acne has a significant economic burden in Pakistan. Even with significant impact of Acne, there is very minute work done about Acne in Pakistan.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Objective: Evaluation of patients with prosthetic valves who developed infective endocarditis by comparing treatment outcomes in both early- and late-onset IE episodes following prosthetic valve replacement surgery. This study sought to conduct a comprehensive assessment of the efficacy of these methodologies. The insights derived from this assessment will be utilized to enhance the quality of care for individuals with infective endocarditis who have received prosthetic valve replacement surgery. Results: During the period of investigation (January 2018 - December 2022), 78 patients diagnosed with infective endocarditis (IE) on prosthetic valve were admitted to the Infectious Diseases Department of the "Dr. Carol Davila" Central Military Emergency University Hospital in Bucharest. In 28 cases (35.8%), the onset of PVE occurred within 12 months of surgery (early onset), whereas in 50 patients (64.2%), the onset occurred more than 12 months after surgery (late onset). The mortality rate was 35.9% (53.6% among the early onset patients and 26% among the late-onset patients). Among patients who received surgical and medical therapy, the mortality rate was 29.6%, whereas among those who underwent only medical therapy, a 39.2% mortality rate was reported. According to the extracted data, antibiotic therapy was successful in 72.6% of patients. In contrast, a combination of surgical and drug-based approaches resulted in a cure in 76.1% of the patients. The most common etiological agent was Staphylococcus aureus (38.5%), followed by Enterococcus faecalis (26.9%), and Streptococcus mitis (10.3%). The mortality rate of patients with S. aureus was 29.2%, indicating the severity of this infectious agent. Conclusions: Prosthetic valve endocarditis (PVE) is a serious condition associated with a high mortality rate both in the short and long term. Regardless of the therapy used, the risk of death remains high. All patients with PVE who survived received effective early treatment, highlighting the need for prophylactic measures.

Objective-Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Method- This cross-sectional study was conducted on 326 women of reproductive age using hormonal contraceptives for a week to one year referred to as "hormonal contraceptive (HC) users" (n=165), and those using non-hormonal methods and not using contraceptives referred to as "HC non-users" (n=161). Beck's depression inventory (BDI-II) was used to measure depression. Result-There was no discernible difference in mean Beck's depression inventory score and degree of depression between the two groups. However, individual symptoms of depression such as sadness(p=0.01), reduced libido(p=0.0002) feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly high in the HC user group. Conclusion- We conclude that there was no significant difference in mean depression scores between groups. However, few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

Arduino microcontrollers are being used for a wide range of technological and biomedical applications such as image classification, computer vision, brain-computer interaction and vision experiments. Here I present a new cost-effective mini-device based on RGB LED flicker stimulation for the assessment of polychromatic temporal resolution of visual function. The visual device configuration allows for relative luminance thresholding, mono- and polychromatic critical flicker fusion frequency assessment. The results demonstrate the steady white visual perception of a trichromatic flicker stimulus beyond the critical flicker fusion frequency, as predicted by Talbot´s law for monochromatic stimuli. The trichromatic critical flicker fusion frequency (tFCC) depends on the relative luminance threshold at the light-adaptation level. Finally, wavefront measurements demonstrate that high-order aberrations improve the temporal resolution of visual function.

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

Background. Coronary artery disease (CAD) with extensive stenosis presents significant clinical challenges. This case report details the management and outcomes of a 61-year-old male with a notable history of CAD, initially treated with coronary artery bypass grafting (CABG), followed by an innovative intravenous hydrogen and oxygen nanobubble therapy due to recurrent symptoms.Case Presentation. Mr. BH was diagnosed with significant stenosis in the left anterior descending (LAD) artery and left circumflex (LCx) artery, initially managed by CABG. Recurring symptoms led to the adoption of a novel treatment involving hydrogen and oxygen nanobubbles. Following treatment initiation, Mr. BH experienced substantial improvements in physical capacity and symptomatic relief, with an ability to climb 22 flights of stairs and resolution of previous symptoms such as dyspnea and cough. Despite these improvements, subsequent imaging revealed in-stent restenosis and progression of graft disease.Discussion. The application of hydrogen and oxygen nanobubbles as a therapy in CAD is explored, highlighting potential mechanisms such as reduction of oxidative stress and improvement in endothelial function. This case contrasts the effects of conventional surgical and pharmaceutical interventions with the novel nanobubble therapy, illustrating both the benefits and complexities of managing advanced CAD with innovative treatments.Conclusion. While Mr. BH showed clinical improvement with nanobubble therapy, the development of new severe stenosis and restenosis underscores the need for further research to understand the long-term efficacy and mechanisms of nanobubble therapy in complex CAD cases. This case suggests that while innovative therapies may provide symptomatic relief and functional improvement, they do not obviate the need for ongoing surveillance and possibly further intervention.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

The severest form of muscular dystrophy (MD) termed Duchenne MD (DMD) remains to this day an incurable disease, hence the continued effort to further develop supportive therapies. Perturbation of autophagy, a degradative yet protective mechanism activated when tissues face severe and persistent stress, is critically involved in DMD, consequently, treatments harnessing autophagic capacities represent an amenable therapeutic strategy. We studied the effects of the protective osmolyte ectoine in the standard mouse model of DMD, the MDX, zooming in on the autophagy-related proteome. From birth, mice were treated with ectoine in the drinking water (150mg/kg) or through daily intraperitoneal injection (177mg/kg) until 5 weeks old. Hind limb muscles were dissected, performing western blotting for protein quantification and immunofluorescence to investigate tissue distribution. We report significant alterations of total levels of autophagy related 5 (ATG5), Ser366 phosphorylated sequestosome 1 (SQSTM1) and heat shock protein 70 (HSP70), and of activated microtubule-associated protein 1A/1B-light chain 3 (LC3 II) in mitochondrial fractions. Ectoine tends to restore the shifted balance between LC3 II and SQSTM1 levels observed in MDX muscle, and LC3 II upregulation was most pronounced on muscle fibers of MDX treated with ectoine in the drinking water. Findings from this explorative study support a possible beneficial effect of ectoine on the autophagic deficit in the MDX, which warrants its further exploration as a therapeutic supplement for DMD.

ABSTRACT Introduction: Traditional penile venous surgery and enhancement have been controversial. Based on De Novo penile fibrovascular assembly, we report on penile venous stripping (PVS) and factual penile girth enhancement (FPGE). Methods: From 2013 to 2023, 18 men underwent PVS and FPGE, all confirmed with veno-occlusive dysfunction (VOD). PVS involves the stripping of erection-related veins. FPGE was performed along the tunica albuginea bilaterally; then, the two tunic defects were repaired with a 70.0x30.0 mm venous stripe and covered with either autologous venous walls (AVW, n=10) or Surgiform (SF, n=8). The penile girth was measured, and radio-opaque contrast was used. The abridged 5-item version of the International Index of Erectile Function (IIEF-5) score and the Erection Hardness Scale (EHS) were used yearly during follow-up via the Internet. Results: The follow-up period was 5.3±1.5 years. Radiopacity was consistently enhanced. Although there was indifference between AVW and SF, there was a significant improvement (both P＜0.01) in IIEF-5 and EHS scores (9.7±2.8 vs. 20.8±2.3; 1.7±0.6 vs. 3.2±0.2, respectively). Both the diameters of the glans and penile shaft increased (28.0±2.3mm and 28.3±2.1mm vs 35.3±2.2mm and 36.3±2.1mm respectively). The satisfaction rate was 81.3% (13/16). Conclusions: This novel combination of PVS and FPGE is promising, although a larger sample size is needed for further validation.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. The study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had a significantly higher cytoplasmic E-cadherin score (P=0.043), they were significantly less differentiated (P=0.007), more advanced (P=0.005), and predominately affected right colon (P=0.030) in comparison to non-mucinous tumors. Epithelial tumors were significantly better differentiated (P=0.034) and with less prominent tumor budding (P < 0.001) than mesenchymal tumors. The process of EMT appears to be more prominent in tumors of younger patients regardless of mucinous histology. EMT status may represent a useful prognostic tool in early-onset CRC.

Our world is rife with challenges, many of which arise from both natural phenomena and human-made issues. While natural problems like diseases and environmental changes often elude our immediate control, a troubling number of today's issues are unintended consequences of human innovations. A striking example is the evolution of drug resistance. The discovery of antibiotics in the early days of modern medicine marked a monumental breakthrough, drastically reducing mortality rates and improving quality of life. Pioneers like Alexander Fleming, who discovered penicillin in 1928, ushered in a new era of medical treatment, transforming healthcare by effectively combating bacterial infections.However, the widespread and often indiscriminate use of these drugs has led to the emergence of drug-resistant pathogens. This natural phenomenon, accelerated by human practices such as overprescription and the misuse of antibiotics in agriculture, exemplifies a double-edged sword—initially celebrated solutions have now become significant challenges. The same drugs that once cured deadly infections are losing efficacy, making us vulnerable to diseases previously thought under control.The inventors of these drugs acted with the intent to save lives and alleviate suffering, unaware of the long-term consequences. Today, the responsibility to address drug resistance lies with us, armed with hindsight and a deeper understanding of microbial resistance complexities. This review explores the origins and evolution of drug resistance, the role of scientific knowledge, and the implications for future actions.

Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, represents a global health concern associated with various conditions, including cardiovascular diseases, gout, hypertension, metabolic syndrome, renal dysfunction, and neurodegenerative diseases. This review offers a contemporary analysis of HU, encompassing its causes, associated health risks, diagnosis, treatment, and future outlook. Recent studies have underscored the multifaceted origin of HU, implicating genetic predisposition, dietary patterns, lifestyle choices, and environmental influences. Genetic variations affecting enzymes and transporters involved in purine metabolism and UA excretion have been identified, laying the groundwork for personalized treatment strategies. Advances in diagnostic imaging and omics technologies provide enhanced precision in the detection and evaluation of risks. While pharmacological interventions remain central to managing HU, persistent challenges such as treatment resistance prompt exploration of novel drug targets and lifestyle modifications. Chinese herbal medicines offer a potentially alternative approach with fewer side effects. Emerging research on the impact of gut microbiota on UA metabolism opens new therapeutic avenues. Despite progress, challenges such as optimizing treatment duration and understanding long-term effects persist. Collaborative efforts are crucial to address these challenges and advance our comprehension of HU. The integration of precision medicine and holistic patient care approaches holds promise for improving outcomes and enhancing quality of life for individuals with HU.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of modified RoPE score for PFO presence in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without PFO (median 63 years vs. 71 years, p&lt;0.001) and fewer were female (46.1% vs. 49.7%, p&lt;0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p&lt;0.001). The area under the curve for the RoPE score in predicting PFO was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut point of ≥5 increased specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFO was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

BackgroundLiving donor liver transplantation offers comparable long-term results to cadaveric donor transplantation. This study analyzes the selection process of living liver donors at a Western transplant center that utilizes both donation forms. MethodsThis retrospective analysis examined potential living donors, collecting medical data and reasons for refusal, and divided patients by indication and urgency for transplantation. ResultsFrom January 2013 to December 2023, 594 potential living donors were assessed at Jena University Hospital. Of these, 124 living donor transplants were performed. During outpatient evaluation, 357 potential donors were excluded. Subsequently, 238 individuals underwent inpatient assessment, with 100 more being excluded. Main reasons for donor refusal included medical or psychological issues (n=160), disease progression in recipients (n=90), and recipient refusal or donor withdrawal (n=54). The evaluation process showed a trend towards considering more distant relatives and acquaintances as donor candidates with increasing severity of the recipient's disease.

Simple Summary: Breast cancer is the most common invasive cancer among women. Triple-negative breast cancer (TNBC) accounts for 15–20% of newly diagnosed breast cancers and has the worst prognosis. However, TNBC patients are not a homogeneous group, and there are differences in the course of the disease as well as in response to treatment. For this reason, differentiation of subtypes of this tumor is important for optimal therapeutic decision and risk prediction. The presented study focuses on the expression of the androgen receptor (AR) and the infiltration of T-lymphocytes in the tumor stroma (TILs) of TNBC patients. Correlation of these tested biomarkers with standard prognostic factors. Defining new prognostic factors for 3-year overall survival (OS). Abstract: Background: Analysis of the practical benefit of testing the expression of AR and the TILs in patients with TNBC and their correlation with standard prognostic factors. Methods: The study group consisted of 86 female patients treated for TNBC. T-lymphocyte infiltration was examined in H+E staining. AR expression, CD8 and CD4 T-lymphocytes were evaluated in immunohistochemistry. Results: Significantly negative correlation was found between AR expression and the CD8 T-lymphocyte infiltration levels. A significant negative correlation was found between the AR expression and G and Ki 67, and a positive correlation between the TILs levels and G and Ki 67. Patients with AR expression and low TILs levels had the highest percentage of diagnosed distant metastases and 3-years OS. Patients with high TILs no distant metastases or deaths were diagnosed. The level of TILs turned out to be a significant independent prognostic factor. Conclusions: Based on the assessment of AR expression and TILs infiltration, the group of highest and lowest risk was determined. The prognostic factor of known parameters such as TNM and a new factor - TILs was confirmed. On the other hand, parameters such as G and Ki 67 and the tested factor - AR had no effect on the prognosis.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity ≥ 20% and tissue area ≥ 4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Background Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was insulted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusion This study demonstrated that oral diet training combined with NGT feeding was safe in patients with prolonged dysphagia who had sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review the relationship between smoking and sleep is investigated, based on the existing literature. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnoea-hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, restless legs but also non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric. This review aims to consolidate all the existing knowledge about the relationship between smoking and sleep.

Cystic artery bleeding (CAB), a relatively uncommon entity, can arise from both traumatic and non-traumatic etiologies. This pictorial essay aims to elucidate the computed tomography (CT) findings associated with CAB in these distinct contexts. In traumatic CAB, particularly blunt or penetrating trauma, a cystic artery lesion is the culprit behind the hemoperitoneum characteristically located within the gallbladder fossa. Prompt diagnosis is crucial. Fortunately, trans-arterial embolization offers a successful treatment option for traumatic cystic artery lesions, especially in settings where non-operative management is preferred. Non-traumatic CAB, on the other hand, often stems from inflammation in the hepatobiliary and pancreatic system, gallbladder tumours, or iatrogenic injuries. The underlying mechanism typically involves cystic artery wall damage, either due to inflammation or procedural complications, leading to the formation of a cystic artery pseudoaneurysm (CAP). Notably, CAP bleeding can manifest long after the causative event, posing a diagnostic challenge with a variable clinical presentation. This pictorial essay serves to illustrate the CT signs and features of CAB in both traumatic and non-traumatic scenarios. Additionally, it will delve into the characteristic CT appearance of CAP.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is often linked to deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.