Interactions between age, sex and visceral adipose tissue on brain ageing.

AIM: To examine the associations between visceral adipose tissue (VAT) and brain structural measures at midlife and explore how these associations may be affected by age, sex and cardiometabolic factors. METHODS: We used abdominal and brain magnetic resonance imaging data from a population-based cohort of people at midlife in the UK Biobank. Regression modelling was applied to study associations of VAT volume with total brain volume (TBV), grey matter volume (GMV), white matter volume, white matter hyperintensity volume (WMHV) and total hippocampal volume (THV), and whether these associations were altered by age, sex or cardiometabolic factors. RESULTS: Complete data were available for 17 377 participants (mean age 63 years, standard deviation = 12, 53% female). Greater VAT was associated with lower TBV, GMV and THV (P < .001). We found an interaction between VAT and sex on TBV (P < .001), such that the negative association of VAT with TBV was greater in men (ß = -2.89, 95% confidence interval [CI] -2.32 to -10.15) than in women (ß = -1.32, 95% CI -0.49 to -3.14), with similar findings for GMV. We also found an interaction between VAT and age (but not sex) on WMHV (P < .001). The addition of other cardiometabolic factors or measures of physical activity resulted in little change to the models. CONCLUSIONS: VAT volume is associated with poorer brain health in midlife and this relationship is greatest in men and those at younger ages.

Systematic Review of Women Leading and Participating in Nephrology Randomized Clinical Trials.

Introduction: Women are underrepresented in the leadership of and participation in randomized controlled trials (RCTs). We conducted a bibliometric review of nephrology RCTs to examine trial leadership by women and participation of women in nephrology RCTs. Methods: A bibliometric review of RCTs published in top medical, surgical, or nephrology journals was conducted using MEDLINE and EMBASE from January 2011 to December 2021. Leadership by women as corresponding authors, women trial participation, and trial characteristics were examined with duplicate independent data extraction. Logistic regression was used to examine associations between trial characteristics and women leadership and trial participation. Results: A total of 1770 studies were screened and 395 RCTs met eligibility criteria. The number (%) of women in corresponding, first, and last authorship positions were as follows: 89 (22%), 109 (28%), and 74 (19%), respectively, without change over time (P = 0.94). The median percentage (interquartile range [IQR]) of women trial participants was 39.0% (13.5%) with no difference between women or men lead authors (P = 0.15). Men lead authors were statistically less likely to enroll women in RCTs. Women lead authors were less likely to be funded by industry (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14-0.63; P = 0.002) or lead international trials (OR: 0.11; 95% CI: 0.01-0.83; P = 0.03). Trials with sex-specific eligibility criteria were more likely to have women leaders (OR: 2.56; 95% CI: 1.19-5.49; P = 0.02) than those without. Discussion: Gender inequalities in RCT leadership and RCT participation exist in nephrology and did not improve over time. Strategies to improve inequalities need to be implemented and evaluated.

Effect and outcome of equity, diversity and inclusion programs in healthcare institutions: a systematic review protocol.

BACKGROUND: Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients' viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions. METHODS: We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation. ANTICIPATED RESULTS: We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions. ETHICS AND DISSEMINATION: No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice. REVIEW REGISTRATION: This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

Secondary Hemochromatosis Leading to Acute Coronary Syndrome in a Thalassemic Patient.

Thalassemia, a congenital hemoglobinopathy, is characterized by impaired erythropoiesis and peripheral hemolysis, leading to anemia. Thalassemia major, in particular, necessitates regular blood transfusions, resulting in iron accumulation in the body. Iron overload primarily affects the heart and can induce cardiac disorder, including defects in the pump and conduction system, which is one of the leading causes of mortality among thalassemics. The existing literature has revealed limited support for the occurrence of acute coronary syndrome (ACS) due to hemochromatosis. However, it does show that elevated troponin levels can be observed even in cases not associated with ACS. Here, we offer a rare case study of acute coronary syndrome in a patient with thalassemia major who also had elevated ferritin levels and abnormal troponin I values. The difficulty of cardiac problems in thalassemia major is highlighted by this case, as well as the necessity for more clinical attention and study to better comprehend and handle such instances.

A remarkable response to palliative treatment in metastatic breast cancer: A case report and comprehensive literature review.

The case report describes a patient with stage IV breast cancer which metastasized to the lungs. The patient's initial computed tomography (CT) scan revealed a malignant lesion in the upper outer quadrant of the left breast and multiple pulmonary nodules, suggesting pulmonary metastasis. After starting palliative chemotherapy with intravenous paclitaxel and subcutaneous injections of Herceptin, a follow-up CT scan 3 months after the initiation of treatment showed the disappearance of metastasis, and her cancer regressed to stage II breast cancer that could be surgically resected. This case report highlights the importance of timely and appropriate palliative treatment measures, which can lead to unexpected outcomes, such as the regression of metastatic lesions and the possibility of curative treatment in such advanced cancer.

Membrane mechanics dictate axonal morphology and function.

Axons are thought to be ultrathin membrane cables of a relatively uniform diameter, designed to conduct electrical signals, or action potentials. Here, we demonstrate that unmyelinated axons are not simple cylindrical tubes. Rather, axons have nanoscopic boutons repeatedly along their length interspersed with a thin cable with a diameter of ∼60 nm like pearls-on-a-string. These boutons are only ∼200 nm in diameter and do not have synaptic contacts or a cluster of synaptic vesicles, hence non-synaptic. Our in silico modeling suggests that axon pearling can be explained by the mechanical properties of the membrane including the bending modulus and tension. Consistent with modeling predictions, treatments that disrupt these parameters like hyper- or hypo-tonic solutions, cholesterol removal, and non-muscle myosin II inhibition all alter the degree of axon pearling, suggesting that axon morphology is indeed determined by the membrane mechanics. Intriguingly, neuronal activity modulates the cholesterol level of plasma membrane, leading to shrinkage of axon pearls. Consequently, the conduction velocity of action potentials becomes slower. These data reveal that biophysical forces dictate axon morphology and function and that modulation of membrane mechanics likely underlies plasticity of unmyelinated axons.

Coronary Artery Tortuosity Found in a Marathon Runner.

Coronary artery tortuosity (CAT) is an anatomical anomaly in which the coronary arteries contain kinks or coils. It is usually found incidentally in elderly patients with long-standing uncontrolled hypertension. This case illustrates a 58-year-old female marathon runner who was found to have CAT, originally presenting with chest pain, hypotension, presyncope, and a severe cramping sensation in her legs.

Automated detection of GFAP-labeled astrocytes in micrographs using YOLOv5.

Astrocytes, a subtype of glial cells with a complex morphological structure, are active players in many aspects of the physiology of the central nervous system (CNS). However, due to their highly involved interaction with other cells in the CNS, made possible by their morphological complexity, the precise mechanisms regulating astrocyte function within the CNS are still poorly understood. This knowledge gap is also due to the current limitations of existing quantitative image analysis tools that are unable to detect and analyze images of astrocyte with sufficient accuracy and efficiency. To address this need, we introduce a new deep learning framework for the automated detection of GFAP-immunolabeled astrocytes in brightfield or fluorescent micrographs. A major novelty of our approach is the applications of YOLOv5, a sophisticated deep learning platform designed for object detection, that we customized to derive optimized classification models for the task of astrocyte detection. Extensive numerical experiments using multiple image datasets show that our method performs very competitively against both conventional and state-of-the-art methods, including the case of images where astrocytes are very dense. In the spirit of reproducible research, our numerical code and annotated data are released open source and freely available to the scientific community.

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

BACKGROUND: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed. SUMMARY: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas. CONCLUSION: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.

Extreme Heat and Pregnancy Outcomes: A Scoping Review of the Epidemiological Evidence.

BACKGROUND: Extreme heat caused by climate change is a major public health concern, disproportionately affecting poor and racialized communities. Gestational heat exposure is a well-established teratogen in animal studies, with a growing body of literature suggesting human pregnancies are similarly at risk. Characterization of extreme heat as a pregnancy risk is problematic due to nonstandard definitions of heat waves, and variable study designs. To better focus future research in this area, we conducted a scoping review to assess the effects of extreme heat on pregnancy outcomes. METHODS: A scoping review of epidemiological studies investigating gestational heat-exposure and published 2010 and 2020, was conducted with an emphasis on study design, gestational windows of sensitivity, adverse pregnancy outcomes and characterization of environmental temperatures. RESULTS: A sample of 84 studies was identified, predominantly set in high-income countries. Preterm birth, birthweight, congenital anomalies and stillbirth were the most common pregnancy outcome variables. Studies reported race/ethnicity and/or socioeconomic variables, however these were not always emphasized in the analysis. CONCLUSION: Use of precise temperature data by most studies avoided pitfalls of imprecise, regional definitions of heat waves, however inconsistent study design, and exposure windows are a significant challenge to systematic evaluation of this literature. Despite the high risk of extreme heat events and limited mitigation strategies in the global south, there is a significant gap in the epidemiological literature from these regions. Greater consistency in study design and exposure windows would enhance the rigor of this field.

Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses.

Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently.

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections.

Pneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs' mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against a bacterial pathogen and provide mechanistic insights into means to protect vulnerable patients against lethal infections.

Reel Syndrome: An Atypical Cause for Inappropriate Shocks in a Patient with Automated Implantable Cardioverter Defibrillator (AICD).

A 71-year-old woman, with the past medical history of heart failure with reduced ejection fraction (EF) and automated implantable cardioverter defibrillator (AICD) placement (for low EF 5-10%) in 2015, presented in February 2017 with the complaint of AICD shocks following an episode of vomiting. She denied any chest pain, abdominal pain, shortness of breath, palpitation, or dizziness. Electrocardiogram (EKG) on admission showed ectopic atrial rhythm with premature ventricular contractions in bigeminies, anterior fascicular block, and left axis deviation. On examination of the cardiovascular system, there was a normal S1 heart sound with a loud A2. There was no jugular venous distention on the neck or pitting edema on the legs. Laboratory studies showed no elevation of cardiac enzymes. Evaluation with chest x-ray showed the right ventricular lead had migrated to the right atrium and the defibrillator generator was flipped with leads coiled around it in transverse axis. AICD interrogation was performed which revealed inappropriate shocks were due to atrial fibrillation with rapid ventricular rate and loss of capture of the right ventricular lead. The diagnosis of Reel syndrome was made, and an electrophysiologist was consulted for replacement of the AICD. Reel syndrome is a variant of Twiddler's syndrome, which is a rare complication of pacemaker implantation. It manifests with the rotation of generator on transverse axis with leads coiling around it. Twiddler's syndrome, on the other hand, is the rotation of the generator on its long axis, which causes damage to the leads by twisting. Reel syndrome is usually observed within months from the placement of the generator compared to Twiddler, which takes years to occur. Twiddler and Reel's syndromes have similar contributing factors, such as female gender, obesity, large pocket, old age, dementia, and deep brain stimulation. Our patient only had two risk factors, namely, the sex and age. We propose that every patient with a pacemaker malfunction and AICD shocks should have a posterior-anterior (PA) chest x-ray and a lateral chest x-ray in addition to AICD interrogation. Twiddler's syndrome is effortlessly observed because of the twisting of dual leads compared to Reel syndrome, which is not straightforward because of the lack tortuosity of the leads.

Examining the Role of Familial Support During Prison and After Release on Post-Incarceration Mental Health.

A significant number of prisoners experience mental health problems, and adequate social support is one way that facilitates better mental health. Yet, by being incarcerated, social support, particularly family support, is likely to be strained or even negative. In this study, we examine whether familial support--either positive or negative--in-prison and after release affects mental health outcomes post-release. Using the Serious and Violent Offender Reentry Initiative (SVORI) dataset, we regress post-release mental health on in-prison familial support, post-incarceration familial support, and changes in familial support. We find that while in-prison family support does not affect mental health, post-release familial support does. Also, experiencing an increase in negative familial support is associated with lower post-incarceration mental health. We conclude with a discussion of policies which may facilitate better familial support environments.

Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.

Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. We used a MYC target gene signature that predicts poor neuroblastoma prognosis to identify the histone chaperone FACT (facilitates chromatin transcription) as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small-molecule curaxin compound CBL0137 markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma.

The Chikungunya Epidemic: A look at five cases.

Chikungunya is an infection caused by the Chikungunya virus and transmitted by the bite of infected mosquito. The most common symptoms of Chikungunya virus infection are fever, joint pain or rash. Chikungunya virus outbreaks had been identified in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. In late 2013, the first local transmission of Chikungunya virus in the Americas was identified in Caribbean countries and territories. Chikungunya virus disease became a nationally notifiable condition in 2015. There is a threat that Chikungunya will continue to spread to new areas in the Americas. We describe 5 patients who presented to our hospital with Chikungunya infection, shortly after returning from endemic areas. Fever and travel history to endemic areas were documented in all of our cases. Skin rash, arthralgia and contact history were also reported by these patients. Persons with suspected Chikungunya infection should be counseled to avoid mosquito bites during illness to decrease the risk of local transmission. The transmitting mosquitos are present in the US, and limiting the viral spread is essential. In this report, we describe the clinical presentation, risk factors and laboratory tests of each patient, and attempt to ensure awareness on the risk of potential spread of the disease.