Transthyretin orchestrates vitamin B12-induced stress resilience.

BACKGROUND: Chronic stress significantly contributes to mood- and anxiety disorders. Previous data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood. METHODS: Using the chronic variable stress mouse model coupled with RNA-sequencing, we determined vitamin B12-induced transcriptional changes related to stress resilience. By viral-mediated gene transfer and in vivo epigenome editing, we reveal a functional pathway linking vitamin B12, DNA methylation, and depressive-like symptoms. RESULTS: We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology, and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we establish a direct causal link between DNAme on Ttr and stress-associated behaviors. DISCUSSION: Using state-of-the-art techniques, this study uncovers a mechanistic link between vitamin B12 supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.

The effects of photoactivated ciprofloxacin and bile acids on biofilms on bile duct catheters.

OBJECTIVES: This study examined the potential of a novel photoactivatable ciprofloxacin to act against bacterial infections and microbiomes related to biliary diseases. It also evaluated treatment by combining the impact of bile acids and antibiotics on biofilms. Innovative strategies were evaluated to address the elusive bile duct microbiome resulting in biofilm-related infections linked to biliary catheters. The healthy biliary system is considered sterile, but bile microbiomes can occur in disease, and these correlate with hepatobiliary diseases. Causes include biofilms that form on internal-external biliary drainage catheters. These biliary catheters were used to noninvasively study the otherwise elusive bile microbiome for a pilot study. METHODS: A new photoactivatable antibiotic was tested for efficacy against human-derived pathogenic bacterial isolates - Salmonella enterica and Escherichia coli - and catheter-derived bile duct microbiomes. In addition, the effect of bile acids on the antibiotic treatment of biofilms was quantified using crystal violet staining, confocal laser scanning microscopy, and biofilm image analysis. Two novel approaches for targeting biliary biofilms were tested. RESULTS: A photoactivated antibiotic based on ciprofloxacin showed efficacy in preventing biofilm formation and reducing bacterial viability without harming eukaryotic cells. Furthermore, combination treatment of antibiotics with bile acids, such as ursodesoxycholic acid, mildly influenced biofilm biomass but reduced bacterial survival within biofilms. CONCLUSION: Bile acids, in addition to their endocrine and paracrine functions, may enhance antibiotic killing of bacterial biofilms compared with antibiotics alone. These approaches hold promise for treating biliary infections such as cholangitis.

The Relationship Between Myocardial Infarction and Estrogen Use: A Literature Review.

This thorough literature evaluation was prompted by significant research into the complex interactions between estrogen use and myocardial infarction (MI). Estrogen has fascinated researchers because of its possible cardioprotective benefits and its impact on cardiovascular health. In order to clarify the connection between estrogen use and the risk of MI, this review critically examines the body of prior evidence. This review focuses on estrogen and its pivotal role in cardiovascular health, concentrating on lipid metabolism, vasodilation, inflammation, and endothelial function. It examines contentious data about estrogen therapy's heart-protective effects, taking into account age, initiation timing, dosage, and dosage of administration. Genetic and epigenetic influences on MI risk among estrogen users highlight intricate, personalized estrogen effects. The conclusion summarizes the main findings and emphasizes the need for an all-encompassing strategy for initiating and managing estrogen medication. It is crucial to consider patient-specific traits and risk factors to successfully customize treatment regimens. This review sheds vital light on the potential directions for better cardiovascular treatment for postmenopausal women by shedding light on the complex link between estrogen use and myocardial infarction. The review also identifies research gaps and future objectives in this area, highlighting the demand for novel medicines and individualized strategies to improve cardiovascular outcomes.

Starvation Protects Hepatocytes from Inflammatory Damage through Paradoxical mTORC1 Signaling.

Background and aims: Sepsis-related liver failure is associated with a particularly unfavorable clinical outcome. Calorie restriction is a well-established factor that can increase tissue resilience, protect against liver failure and improve outcome in preclinical models of bacterial sepsis. However, the underlying molecular basis is difficult to investigate in animal studies and remains largely unknown. METHODS: We have used an immortalized hepatocyte line as a model of the liver parenchyma to uncover the role of caloric restriction in the resilience of hepatocytes to inflammatory cell damage. In addition, we applied genetic and pharmacological approaches to investigate the contribution of the three major intracellular nutrient/energy sensor systems, AMPK, mTORC1 and mTORC2, in this context. RESULTS: We demonstrate that starvation reliably protects hepatocytes from cellular damage caused by pro-inflammatory cytokines. While the major nutrient- and energy-related signaling pathways AMPK, mTORC2/Akt and mTORC1 responded to caloric restriction as expected, mTORC1 was paradoxically activated by inflammatory stress in starved, energy-deprived hepatocytes. Pharmacological inhibition of mTORC1 or genetic silencing of the mTORC1 scaffold Raptor, but not its mTORC2 counterpart Rictor, abrogated the protective effect of starvation and exacerbated inflammation-induced cell death. Remarkably, mTORC1 activation in starved hepatocytes was uncoupled from the regulation of autophagy, but crucial for sustained protein synthesis in starved resistant cells. CONCLUSIONS: AMPK engagement and paradoxical mTORC1 activation and signaling mediate protection against pro-inflammatory stress exerted by caloric restriction in hepatocytes.

Evaluation of Convalescent Plasma in the Management of Critically Ill COVID-19 Patients (with No Detectable Neutralizing Antibodies Nab) in Kashmir, India.

BACKGROUND: For centuries, convalescent plasma (CP) has been recommended to treat a diverse set of viral diseases. Therefore, the present study was undertaken to evaluate the effectiveness of CP in critically ill COVID-19 patients. METHODS AND MATERIALS: From 23 March 2021 to 29 December 2021, an open-label, prospective cohort, single-centre study was conducted at Chest Disease Hospital, Jammu and Kashmir, Srinagar. Patients with severe manifestation of coronavirus disease 2019 (COVID-19) under BST (best standard treatment) +CP were prospectively observed in order to evaluate effectiveness of CP therapy and historical control under BST were used as the control group Results: A total of 1667 patients were found positive for COVID-19. Of these, 873 (52.4%), 431 (28.8%), and 363 (21.8%) were moderately, severely, and critically ill, respectively. On 35th day post-infusion of CP, all-cause mortality was higher in the BST (best standard treatment) +CP group 12 (37.5%) compared to 127 (35%) in the BST group with an odds ratio (OR) of 1.4 and hazard ratio (HR) (95% CI: 1.08-1.79, p = 0.06). Similarly, 7 (21.9) patients in the BST+CP group and 121 (33.3) patients in the BST group showed the transition from critically ill to moderate disease with subhazard ratio (s-HR 1.37) (95% CI: 1.03-2.9). CONCLUSIONS: In the present study, we could not find any significant difference in the CP group and BST +CP in primary outcome of reducing all-cause mortality in critically ill patients with negligible Nabs levels. However, beneficial results were observed with use of CP in a limited number of secondary outcomes which includes days of hospitalization, negative conversion of SARS-CoV-2 on basis of RT-PCR on 7th day and 14th day, need for invasive mechanical ventilation on 14th day post-CP treatment, and resolution of shortness of breath.

Perception of massage application among clinicians and parents in spastic cerebral palsy: Qualitative study.

OBJECTIVE: To explore the perceptions about traditional massage and its modified techniques among clinicians and families of the patients with spastic cerebral palsy. METHODS: The qualitative, cross-sectional study was conducted from November 2019 to August 2020 in Sialkot, Pakistan, after approval from the ethics review committee of Riphah College of Rehabilitation Sciences, Islamabad, and comprised neuro paediatricians and paediatricians in Group A, parents of children with spastic cerebral palsy aged 8-15 years in Group B, and musculoskeletal physiotherapists and orthopaedic manual physical therapists in Group C. The professionals in groups A and C had a minimum of 5-year paediatric experience in government and teaching hospitals. Data was collected using a semi-structured pilot-tested questionnaire. Qualitative approach and thematic code analysis was used to analyse the collected data. RESULTS: Of the 26 subjects, 10(38.5%) were in Group A, 8(30.7%) in Group B and 8(30.7%) in Group C. Overall, there were 16(61.4%) males and 10(38.5%) females. Among the professionals, experience ranged 5-38 years in Group A, and 5-9 years in Group C. The identified themes were reforms in recommendations, and application of massage techniques, with the participants overwhelmingly favouring termination markers to prevent increase in hypertonicity in spastic cerebral palsy. CONCLUSIONS: Termination markers of massage should be considered in interventions to improve outcomes in children with spastic cerebral palsy.

Human BK and JC polyomaviruses: Molecular insights and prevalence in Asia.

Polyomaviridae family consists of small circular dsDNA viruses. Out of the 14 human polyomaviruses described so far, BKPyV and JCPyV have been studied extensively since their discovery in 1971. Reportedly, both BKPyV and JCPyV are widely distributed across the globe with the frequency of 80-90 % in different populations. The primary infection of these viruses is usually asymptomatic and latent which is activated as a consequence of immunosuppression. Activated BKPyV and JCPyV viruses lead to the development of BK Virus Associated Nephropathy and Progressive Multifocal Leukoencephalopathy, respectively. Immense progress has been made during the last few decades regarding the molecular understanding of polyomaviruses. Epidemiology of polyomaviruses has also been studied extensively. However, most of the epidemiological studies have focused on European and American populations. Therefore, limited data is available regarding the geographical distribution of these potentially oncogenic viruses in Asian countries. In this article, we have presented a compendium of latest advances in the molecular understanding of polyomaviruses and their pathobiology. We also present a comprehensive review of published literature regarding the epidemiology and prevalence of BKPyV and JCPyV in Asian regions. For this purpose, a thorough search of available online resources was performed. As a result, we retrieved 24 studies for BKPyV and 22 studies for JCPyV, that describe their prevalence in Asia. These studies unanimously report high occurrence of both BKPyV and JCPyV in Asian populations. The available data from these studies was categorized into two groups: on the basis of prevalence (low, medium and high) and disease development (healthy and diseased). Altogether, Korean population hasbeen evidenced to possess highest frequency of BKPyV (66.7 %), while JCPyV was found to be most prevalent in Taiwan (88 %). Due to high and ubiquitous distribution of these viruses, frequent studies are required to develop a better understanding regarding the epidemiology and pathobiology of these viruses in Asia.

Merkel cell polyomavirus DNA sequences in the blood of healthy population of Pakistan.

Aim: This study aimed at detecting and quantifying Merkel cell polyomavirus (MCPyV) viral loads in the peripheral blood of healthy Pakistani individuals. Patients & methods: A total of 221 whole blood samples obtained from healthy individuals were examined by qPCR. Results & conclusion: MCPyV was detected in the peripheral blood of 31.2% healthy individuals. The rate of MCPyV positivity decreased from young (36%), to middle (33.7%) and elder (25.3%) age groups. Our data revealed higher prevalence of MCPyV in women (43.93%) than men (25.80%). The MCPyV viral load was calculated in the range of 0.06 -11 copies/ng of isolated DNA. The MCPyV viral load increased from young (median = 3.35) to elder (median = 5.66) age groups. The MCPyV circulate at a higher frequency by residing dormant in certain blood cells, which might act as potential vehicles for the spread of MCPyV infection among general population.

Effect of a Novel Patient Garment on Perceived Privacy during Colonoscopy: A Simple Approach to Minimize Embarrassment.

BACKGROUND: In the United States, patients wear a one-piece, reusable cloth gown during colonoscopy procedures. Many patients report embarrassment related to bodily exposure during colonoscopy. This may limit participation in colorectal cancer screening programs. AIMS: To assess whether the use of a novel, disposable patient garment (Privacy Pants, Jackson, MS), which increases patient coverage, can reduce embarrassment related to bodily exposure and increase colonoscopy acceptance rates. METHODS: Patients were offered a novel gown, and they completed questionnaires before and after colonoscopy. RESULTS: A total of 120 patients participated. 54% were female and 82% were Caucasian. The novel gown had high overall satisfaction (8.3) and was associated with a sense of respect during the procedure (9.4). 67% (80) of the patients had a prior colonoscopy, and of these, 76% would request a novel gown over a traditional gown for future procedures. Among all study participants, a high rate of acceptability for repeat colonoscopy if recommended by their doctors was reported (mean of 9.4). Nonwhites were more likely to have a concern for embarrassment addressed by using novel gowns as compared to whites (P value 0.02). CONCLUSION: All participants, particularly women and nonwhite participants, reported high rates of respect and satisfaction and decrease in embarrassment utilizing the novel gown during colonoscopy. Patients who had prior colonoscopy with a traditional gown preferred the novel garment. A novel procedure gown may enhance colonoscopy acceptance by minimizing embarrassment.

Specific and quantitative detection of Human polyomaviruses BKPyV and JCPyV in the healthy Pakistani population.

BACKGROUND: The BK Polyomavirus (BKPyV) and JC polyomavirus (JCPyV) infections are widespread in human population and have been associated with severe kidney and brain disorders, respectively. The viruses remain latent primarily in reno-urinary tract, reactivating only in case of a compromised immune system. The seroepidemiology and molecular prevalence of BKPyV and JCPyV have been widely studied both in healthy and immunocompromised patients worldwide. However, data regarding the prevalence of these viruses in the immunocompetent or apparently healthy Pakistani population is lacking. Herein, we present the first ever report on quantitative prevalence of BKPyV and JCPyV in the peripheral blood of a randomly selected cohort of healthy Pakistani population. METHODS: A total of 266 whole blood samples were examined. The subjects were divided into three age groups: ≤ 25 years (young), 26-50 years (middle) and ≥ 51 years (elder). Absolute real time PCR assay was designed to quantify the BKPyV and JCPyV viral copy numbers in the range of 106 to 100 copies/mL. RESULTS: Overall, BKPyV was detected in 27.1% (72/266) individuals while JCPyV in 11.6% (31/266) indicating significant difference (p < 0.005) in the distribution of these two viruses. The prevalence of BKPyV significantly decreased from 51% (49/96) in young age group to 8.2% (7/85) in eldest age group. Whereas, JCPyV positivity rate slightly increased from 8.3% (8/96) in young age group to 11.8% (10/85) in elder age group. The median viral load was calculated as 6.2 log and 3.38 log copies/mL of blood for BKPyV and JCPyV, respectively. Notably, no significant difference in viral load of either of the subtypes was found between different age groups. CONCLUSION: The current study provides an important baseline data on the prevalence and viral load of circulating BKPyV and JCPyV in Pakistani population. The prevalence and viral load of BKPyV was comparatively higher than JCPyV. The prevalence of BKPyV significantly decreased with increase in age while JCPyV positivity rate slightly increased with increasing age. Viral load of both BKPyV and JCPyV was not correlated with the individual ages.

Nutritional guidelines for school lunch programs: a survey of islamic schools and recommendations for creating a culture of healthful eating.

OBJECTIVE: To determine the status of lunch programs in Islamic schools in the United States and develop recommendations for improving them. STUDY DESIGN: The Islamic Medical Association of North America (IMANA) conducted a survey of lunch programs by mailing questionnaires to 100 Islamic schools in the United States. Muslims in Dietetics and Nutrition (MIDAN) developed lunch menus using American and ethnic foods conforming to nationally recommended guidelines. RESULTS: Forty-eight Islamic schools responded to the survey, revealing that 20 schools follow guidelines and only six have dietitians advising on menu planning. Based on this survey, IMANA, with the assistance of MIDAN, has developed a summary of guidelines that schools can follow. These guidelines include sample menus of American and ethnic foods, recommendations for creating a n environment for healthful eating, and sources for funding school lunch programs. CONCLUSIONS: IMANA and MIDAN, recognizing the scientific significance and religious relevance of a nutritious diet, have developed these recommendations. This information is provided to aid Islamic schools in implementing guidelines for nutritionally balanced school lunch menus and in creating a culture that fosters a healthful lifestyle.