Adverse Outcome Pathways Mechanistically Describing Hepatotoxicity.

Adverse outcome pathways (AOPs) describe toxicological processes from a dynamic perspective by linking a molecular initiating event to a specific adverse outcome via a series of key events and key event relationships. In the field of computational toxicology, AOPs can potentially facilitate the design and development of in silico prediction models for hazard identification. Various AOPs have been introduced for several types of hepatotoxicity, such as steatosis, cholestasis, fibrosis, and liver cancer. This chapter provides an overview of AOPs on hepatotoxicity, including their development, assessment, and applications in toxicology.

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

The influence of occupational noise exposure on blood pressure and hearing loss among female workers of childbearing age.

OBJECTIVES: Women exposed to occupational noise experience adverse pregnancy outcomes. Therefore, we initiated a large, population-based, cross-sectional study to further investigate the effects of occupational noise on hearing and blood pressure among female workers of childbearing age. STUDY DESIGN AND SETTING: A total of 6981 childbearing-aged female workers were selected for this cross-sectional study. Basic characteristics of participants were analyzed by comparing the exposed and control groups. Logistic regression models were employed to calculate the odds ratios (ORs) and 95% confidences intervals (CIs) for the associations of occupational noise with levels of hearing loss and blood pressure. The associations were further explored through stratification by age and duration of noise exposure. RESULTS: Compared with participants not exposed to occupational noise, increasing years of occupational noise exposure were independently associated with an elevated risk of hypertension after adjustment of age, industry classification, enterprise size and economic type. Compared to participants not exposed to occupational noise, only the prevalence of bilateral hearing loss was significantly higher after adjustments for age, industry classification, enterprise size and economic type. Compared with those with normal hearing, the ORs and 95% CIs were 1.97 (0.95-4.07), 2.22 (1.05-4.68) and 1.29 (1.06-1.57) for bilateral, unilateral and any ear hearing loss, respectively. CONCLUSIONS: Occupational noise exposure is positively associated with both hypertension and bilateral hearing loss among female workers of childbearing age. Those exposed to occupational noise show an increased risk of hypertension after adjusting for potential confounders.

Risk and determinants of sarcopenia in people with diabetes: a case-control study from Qatar Biobank cohort.

BACKGROUND: Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors. METHODS: Using a case-control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia. RESULTS: Cases with diabetes were older (55 vs. 36 years; P < 0.001), had higher BMI (31.6 vs. 28.3 kg/m2; P < 0.001), lower cardiorespiratory fitness (50.0% "Moderate" fitness for cases, 62.9% "High" fitness for controls), and consumed less total (59.0 vs. 64.0; P = 0.004) and animal protein (39.0 vs. 42.0; P = 0.001), compared to controls based on a computed score. Participants with diabetes also had lower appendicular lean mass/BMI, handgrip strength, and higher probability of sarcopenia/probable sarcopenia (P < 0.005). Adjusted multiple logistic regression revealed that elevated cardiorespiratory fitness (ß = 0.299, 95%CI:0.12-0.74) and blood triglycerides (ß = 1.475, 95% CI: 1.024-2.124), as well as being a female (ß = 0.086, 95%CI: 0.026-0.288) and having higher BMI (ß = 0.908, 95%CI: 0.852-0.967) and ALM/BMI (ß = 0.000, 95% CI: 0.000-0.007) are independent predictors (p < 0.05) of sarcopenia risk. CONCLUSIONS: This study highlights the intricate relationship between diabetes and sarcopenia, revealing modifiable risk factors. Individuals with diabetes were found to have a higher likelihood of sarcopenia, which was associated with lower fitness levels and higher blood triglycerides. Protective factors against sarcopenia included being female and having higher BMI and ALM/BMI ratios.

Functional movement disorder similar to Parkinson's disease: a case report.

INTRODUCTION: Functional neurological disorder challenges conventional medical understanding, presenting neurological symptoms without organic explanations. This report delves into the intricate interplay between psychological and physical manifestations, emphasizing the importance of timely diagnosis and intervention and its impact on a patient's mental health and quality of life. CASE PRESENTATION: A 40-year-old single Iranian man was admitted for the third time owing to exacerbation of mood symptoms, including depression, irritability, aggression, suicidal ideation, and movement and sensory problems. The patient's symptoms began with psychological stressors and family conflict, leading to muscle weakness and tremors in the left hand. Over a year, muscle weakness escalated, leading to slow movement, motor impairment in the lower limbs, and reliance on a cane for walking. The patient still exhibited symptoms, such as a mask-like face, stooped walking posture, and a relative improvement of symptoms periodically. At first, the patient was suspected of Parkinson's disease and was placed on levodopa and amantadine. However, the medication was discontinued owing to an unsatisfactory response and the lack of strong evidence in favor of neurological problems on frequent examinations and reviews. Despite multiple hospitalizations, the patient's symptoms remained unresolved. Finally, after years of investigations, based on specialists' recommendations, he was admitted to the psychosomatic ward for diagnostic evaluationele, and he was diagnosed with functional neurological disorder (psychogenic parkinsonism). He underwent pharmacotherapy, electroconvulsive therapy, and psychotherapy. He was discharged with partial improvement of symptoms, but showed periods of relapse and remission during the following years. CONCLUSION: This case study illuminates functional neurological disorder complexities, emphasizing the need for a holistic diagnostic approach. Timely interventions, including psychological support, can alleviate symptoms, reduce healthcare costs, and improve the overall prognosis. The report contributes to evolving functional neurological disorder understanding in psychiatry and neurology. The report underscores early recognition, advocating for comprehensive interventions involving psychiatric support, cognitive-behavioral therapy, and patient psychoeducation.

Identifying high-risk groups for deep vein thrombosis after primary total knee arthroplasty using preoperative Caprini scores and D-dimer levels.

BACKGROUND: Caprini score and D-dimer are well-recognized markers in deep vein thrombosis (DVT) assessment. However, their utility in guiding post-arthroplasty DVT risk is hampered by susceptibility to various post-operative factors, limiting their effectiveness as reminders. Conversely, these markers exhibit greater stability in the pre-operative setting. Despite this, research on the pre-operative predictive value of Caprini score and D-dimer for DVT following primary total knee arthroplasty (TKA) remains scarce. METHODS: In a retrospective study, we analyzed data from patients who underwent primary TKA, between August 2015 and December 2022. Upon admission, Caprini scores were assessed, and comprehensive blood panels were obtained from fasting blood samples. For all patients, lower limb vascular Doppler ultrasonography was performed pre-operatively to exclude those with pre-existing DVT, and all patients underwent DVT examination again post-operatively. RESULTS: Our study included 2,873 patients, averaging 67.98 ± 7.54years, including 676 men and 2,197 women. In this study, 303 (10.55%) patients developed postoperative DVT, and 57 (1.98%) cases presented with lower limb symptoms. DVT incidence in patients with pre-operative Caprini scores of 1-2 (6.50%), 3 (10.28%), and ≥ 4 (18.05%) showed significant differences (P < 0.05). DVT rates were 14.80% in patients with pre-operative D-dimer levels of ≥ 1 mg/L, higher than the 8.98% in those with levels of < 0.5 mg/L, and 10.61% in those with levels 0.5-1 mg/L (P < 0.05). In patients with Caprini scores of 1-2 and D-dimer levels ≤ 0.5 mg/L, the occurrence rate of postoperative DVT was only 5.84%. For patients with Caprini scores ≥ 4 and D-dimer levels ≥ 1.0 mg/L, the postoperative DVT occurrence rate soared to 24.81%, with the OR(odds ratio) was 4.744 compared to the former group. CONCLUSION: Patients with preoperative higher Caprini scores and D-dimer are more likely to develop DVT after TKA. Additionally, those with a preoperative Caprini score ≥ 4 and D-dimer level ≥ 1.0 mg/L have a significantly increased risk (24.81%) of developing DVT, identifying them as a high-risk group for DVT following TKA. These findings hold significant value for DVT risk stratification in primary TKA patients and the formulation of preoperative interventions to mitigate the risk of DVT.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome.

BACKGROUND: This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. AIM: To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. METHODS: Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. RESULTS: IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. CONCLUSION: The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM: To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS: In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS: This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION: The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.

Causal pathways in lymphoid leukemia: the gut microbiota, immune cells, and serum metabolites.

Background: We employed Mendelian randomization (MR) to investigate the causal relationship between the gut microbiota and lymphoid leukemia, further exploring the causal relationships among immune cells, lymphoid leukemia, and potential metabolic mediators. Methods: We utilized data from the largest genome-wide association studies to date, encompassing 418 species of gut microbiota, 713 types of immune cells, and 1,400 serum metabolites as exposures. Summary statistics for lymphoid leukemia, acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL) were obtained from the FinnGen database. We performed bidirectional Mendelian analyses to explore the causal relationships among the gut microbiota, immune cells, serum metabolites, and lymphoid leukemia. Additionally, we conducted a two-step mediation analysis to identify potential intermediary metabolites between immune cells and lymphoid leukemia. Results: Several gut microbiota were found to have causal relationships with lymphoid leukemia, ALL, and CLL, particularly within the Firmicutes and Bacteroidetes phyla. In the two-step MR analysis, various steroid hormone metabolites (such as DHEAS, pregnenolone sulfateprogestogen derivatives, and androstenediol-related compounds) were identified as potential intermediary metabolites between lymphoid leukemia and immune cells. In ALL, the causal relationship between 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) and ALL was mediated by CD62L-plasmacytoid DC%DC (mediated proportion=-2.84%, P=0.020). In CLL, the causal relationship between N6,n6,n6-trimethyllysine and CLL was mediated by HLA DR+ CD8br AC (mediated proportion=4.07%, P=0.021). Conclusion: This MR study provides evidence supporting specific causal relationships between the gut microbiota and lymphoid leukemia, as well as between certain immune cells and lymphoid leukemia with potential intermediary metabolites.

Redefining hemorrhoid therapy with endoscopic polidocanol foam sclerobanding.

Hemorrhoids are a common and painful condition, with conventional treatments such as endoscopic rubber band ligation (ERBL) and injection sclerotherapy often falling short due to high recurrence rates and significant post-operative pain. A clinical trial by Qu et al introduces a novel approach called endoscopic poli-docanol foam sclerobanding (EFSB). This multicenter randomized trial involved 195 patients with grade II and III internal hemorrhoids and demonstrated that EFSB significantly reduced recurrence rates and post-procedural pain while improving symptom relief and patient satisfaction compared to ERBL. The study's strengths include its robust design, comprehensive outcome evaluation, and patient-centered approach. Despite limitations such as the single-blind design and relatively short follow-up period, the findings suggest that EFSB could enhance clinical practice by offering a more effective and patient-friendly treatment option. Further research is needed to validate these results and explore the long-term benefits and cost-effectiveness of EFSB.

Computed tomography-based multi-organ radiomics nomogram model for predicting the risk of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: Radiomics has been used in the diagnosis of cirrhosis and prediction of its associated complications. However, most current studies predict the risk of esophageal variceal bleeding (EVB) based on image features at a single level, which results in incomplete data. Few studies have explored the use of global multi-organ radiomics for non-invasive prediction of EVB secondary to cirrhosis. AIM: To develop a model based on clinical and multi-organ radiomic features to predict the risk of first-instance secondary EVB in patients with cirrhosis. METHODS: In this study, 208 patients with cirrhosis were retrospectively evaluated and randomly split into training (n = 145) and validation (n = 63) cohorts. Three areas were chosen as regions of interest for extraction of multi-organ radiomic features: The whole liver, whole spleen, and lower esophagus-gastric fundus region. In the training cohort, radiomic score (Rad-score) was created by screening radiomic features using the inter-observer and intra-observer correlation coefficients and the least absolute shrinkage and selection operator method. Independent clinical risk factors were selected using multivariate logistic regression analyses. The radiomic features and clinical risk variables were combined to create a new radiomics-clinical model (RC model). The established models were validated using the validation cohort. RESULTS: The RC model yielded the best predictive performance and accurately predicted the EVB risk of patients with cirrhosis. Ascites, portal vein thrombosis, and plasma prothrombin time were identified as independent clinical risk factors. The area under the receiver operating characteristic curve (AUC) values for the RC model, Rad-score (liver + spleen + esophagus), Rad-score (liver), Rad-score (spleen), Rad-score (esophagus), and clinical model in the training cohort were 0.951, 0.930, 0.801, 0.831, 0.864, and 0.727, respectively. The corresponding AUC values in the validation cohort were 0.930, 0.886, 0.763, 0.792, 0.857, and 0.692. CONCLUSION: In patients with cirrhosis, combined multi-organ radiomics and clinical model can be used to non-invasively predict the probability of the first secondary EVB.

Recurrent laryngeal nerve monitoring by flexible laryngoscopy during thyroid radiofrequency ablation in the awake patient.

Objective: Although radiofrequency ablation (RFA) is a safe and effective non-surgical treatment for benign thyroid nodules, injury to the recurrent laryngeal nerve (RLN), is a potential and feared complication. Intermittent voice checks have been proposed to monitor vocal cord (VC) function during RFA, but such assessment is highly subjective and effort-dependent. Methods: We are here reporting the methodological use of flexible laryngoscopy (FL) for VC monitoring during bilateral thyroid RFA treatment. The patient, a 35-year-old woman, was referred to the Endocrinology Unit for subclinical hyperthyroidism due to bilateral autonomously functioning thyroid nodules. Results: At the end of the treatment of the first nodule, the FL performed by an otorhinolaryngologist specialist allowed evaluating VC function and ruling out possible paralysis before proceeding with the contralateral RFA treatment. The patient was awake during the entire procedure and well tolerated the laryngoscopic examination. The TSH serum evaluations performed one month and 9 months after the procedure assessed an euthyroid state (TSH 3.2 mIU/L and 2.8 mIU/L, respectively). Conclusion: During bilateral thyroid RFA the use of FL for VC monitoring treatment resulted in a safe, easy-to-perform, and effective strategy to minimize and anticipate RLN injury risk in the awake patient. The prevention of RLN damage is advisable in the case of single RFA treatment, while it should be strongly recommended when RFA is performed on bilateral nodules.

Genistein mitigates diet-induced obesity and metabolic dysfunctions in gonadectomized mice with some sex-differential effects.

Background: Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome. Methods: Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment. Results: Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as Fasn, Srebf1, Saa1, Cd36, Col1a1, Pck1, and Ppargc1a. Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice. Conclusion: Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.

Genetic support of causal association between lipid and glucose metabolism and stress urinary incontinence in women: a bidirectional Mendelian randomization and multivariable-adjusted study.

Background: Stress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in women is higher than in men, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in women and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in women and lipid and blood metabolism. Methods: Using bidirectional univariate Mendelian randomization (MR), we investigated the causal association between SUI liability in women (case/control = 5,924/399,509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N = 61,166), low-density lipoproteins (LDL, N = 58,381), high-density lipoproteins (HDL, N = 60,812), triglycerides (TG, N = 60,027), fasting glucose (FG, N = 19,745), and fasting insulin (FI, N = 38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism. Results: We found that increased genetically proxied TC, LDL, and HDL levels were associated with an elevated risk of SUI in women (OR: 1.090-1.117, all P < 0.05), These associations were further supported by MVMR analyses with adjustment for BMI (OR: 1.087-1.114, all P < 0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in women (OR: 0.731-0.815, all P < 0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting the causal effect of SUI in women on lipid and blood metabolism (all P > 0.05). Conclusions: Our results reported that increased TC, LDL, and HDL are linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL, and HDL levels and SUI indicate a higher risk.

Partial role of volatile organic compounds in behavioural responses of mice to bedding from cancer-affected congeners.

Tumours induce changes in body odours. We compared volatile organic compounds (VOCs) in soiled bedding of a lung adenocarcinoma male mouse model in which cancer had (CC) versus had not (NC) been induced by doxycycline at three conditions: before (T0), after 2 weeks (T2; early tumour development), after 12 weeks (T12; late tumour development) of the induction. In an earlier study, wild-derived mice behaviourally discriminated between CC and NC soiled bedding at T2 and T12. Here, we sought to identify VOCs present in the same soiled bedding that could have triggered the behavioural discrimination. Solid phase micro-extraction was performed to extract VOCs from 3 g-sample stimuli. While wild-derived mice could discriminate the odour of cancerous mice at a very early stage of tumour development (T2), the present study did not identify VOCs that could explain this behaviour. However, consistent with the earlier behavioural study, four VOCs, including two well-known male mouse sex pheromones, were found to be present in significantly different proportions in soiled bedding of CC as compared to NC at T12. We discuss the potential involvement of non-volatile molecules such as proteins and peptides in behavioural discrimination of early tumour development (T2), and point-out VOCs that could help diagnose cancer.

Thyroid Status in Children with Transfusion Dependent Thalassemia in a Tertiary Level Hospital.

Most of the thalassemic children of Bangladesh are receiving repeated blood transfusion. But they do not receive chelation therapy due to financial constraints. As a result, iron overload occurs in various organs of these children. Extra iron that is loaded in thyroid gland causes thyroid dysfunction. This study was undertaken to evaluate thyroid status in children with transfusion dependent Thalassemia patient. This cross-sectional analytical study was conducted in the Department of Pediatrics, Mymensingh Medical College Hospital, Bangladesh from September 2016 to April 2018. Children having thalassemia diagnosed by Hb electrophoresis, aged 3-12 years of both sexes were included as study group. Children of same age and sex admitted in indoor of Mymensingh Medical College Hospital with minor illness and without thalassemia were taken as comparison group. Purposive Sampling technique was applied. Serum FT4, TSH and ferritin level were estimated in all children. Data analysis was done with Statistical Package for Social Science (SPSS) version 21.0. A total of 60 patients were enrolled as study group and another 60 patients were compared as comparison group. Mean ages of study group was 7.88±2.55 years and comparison group were 7.22±2.48 years. The mean pre-transfusion hemoglobin, serum ferritin, serum FT4 and serum TSH level were found 6.23±0.60 gm/dl, 2658.33±879.39 ng/ml, 15.14±4.40 fmol/mL, 4.29±4.60 µIU/mL respectively in study group. The mean serum FT4 was found significantly lower and mean serum TSH was significantly higher in thalassemic children in comparison to non-thalassemic children (p= <0.05). Frequency of subclinical hypothyroidism was found significantly higher in study group (25.0%) compared to comparison group (3.3%) (p=0.001). Mean serum ferritin level was found significantly higher in hypothyroid cases. Mean FT4 level was significantly lower and mean TSH level was significantly higher in hypothyroid thalassemic patients (p= <0.001). Significant positive correlation between serum ferritin level and serum TSH level was found. Higher serum ferritin level was found significantly associated with the development of hypothyroidism in thalassemic patients.

Clinicopathological Evaluation of the Patients with Febrile Illness and Altered Consciousness Admitted in a Tertiary Level Hospital.

This is important to note that altered mental status is not a disease in itself, but rather a symptom with a wide range of potential diagnoses. But a structured approach to assessing the patients with this symptom frequently leads to helpful information and can rule out worst-case scenarios. In cases where fever is followed by changes in consciousness, quick assessment of the patient's level of consciousness and potential causes is decisive. A focused history and physical assessment can help differentiate between structural or medical causes. Asymmetrical neurological findings, such as a dilated and fixed pupil, dysconjugated extraocular movements and asymmetrical motor findings, suggest brainstem dysfunction due to a structural lesion, while symmetrical neurological findings usually indicate a medical disorder. A recent study aimed to identify features of different etiologies, demographic patterns, and common causes of both acute and prolonged febrile illness in patients. This cross-sectional type of observational study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Bangladesh from April 2014 to October 2015. Over the study period patients admitted with satisfying the inclusion and exclusion criteria of study and purposively selected (non-probability) from the hospitalized patients. Total 100 cases with febrile illness and altered consciousness meeting the exclusion and inclusion criteria were examined and investigated to find out the actual etiology. Out of 100 patients, it was observed that 26(26.0%) of patients were suffering from pneumonia, 22(22.0%) urinary tract infection, 18(18.0%) meningitis, 14(14.0%) typhoid fever, 8(8.0%) meningo-encephalitis, 6(6.0%) cerebral malaria, 4(4.0%) tuberculosis and 2(2.0%) from tuberculoma. The result revealed that large number of patients with febrile illness and altered consciousness were suffering from pneumonia and urinary tract infection.