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This article from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used to inform the final guidance outlined in the accompanying summary and recommendations article for strategies to manage endoscopically placed gastrostomy tubes. This article was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and specifically addresses the utility of PEG versus interventional radiology–guided gastrostomy (IR-G), the need for withholding antiplatelet and anticoagulant medications, appropriate timing to initiate tube feedings, and appropriate selection of the gastrostomy technique in patients with malignant dysphagia. In patients needing enteral access, the ASGE suggests PEG as the preferred technique for initial gastrostomy over IR-G. The ASGE recommends that tube feeding can be safely started within 4 hours of the gastrostomy without the need for an intentional delay. The ASGE suggests that a PEG can be performed without the need to withhold antiplatelet medications. In patients on anticoagulants who need to undergo PEG placement, the ASGE suggests that the periprocedural management of anticoagulants should be based on a multidisciplinary discussion with the patient regarding the risk of bleeding versus cardiovascular adverse events. In patients with malignant dysphagia, either transoral “Pull” PEG or transcutaneous “Direct” PEG can be performed for initial enteral access.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions. Multi-group confirmatory factor analysis indicated that configural and metric invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional SWLS model has universal applicability. Full scalar invariance was achieved across gender identities and age groups. Based on alignment optimisation methods, partial scalar invariance was achieved across all but three national groups and across all languages represented in the BINS. There were large differences in latent SWLS means across nations and languages, but negligible-to-small differences across gender identities and age groups. Across nations, greater life satisfaction was significantly associated with greater financial security and being in a committed relationship or married. The results of this study suggest that the SWLS largely assesses a common unidimensional construct of life satisfaction irrespective of respondent characteristics (i.e., national group, gender identities, and age group) or survey presentation (i.e., survey language). This has important implications for the assessment of life satisfaction across nations and provides information that will be useful for practitioners aiming to promote subjective well-being internationally.

BackgroundSex and gender can affect all aspects of health-related behavior, yet there is limited information on how they influence diagnosis of any health condition. This scoping review examined the extent to which sex- and gender-disaggregated data on diagnostics are available for five tracer conditions: tuberculosis, coronavirus disease 2019 (COVID-19), diabetes, malaria, and schistosomiasis.MethodsPublications were searched between 2000 and 2022 on PubMed and Google Scholar and screened for relevance. Extracted data were analysed using descriptive quantitative and qualitative approaches.ResultsWe identified 29 relevant articles for tuberculosis, four for diabetes, six for schistosomiasis, eight for COVID-19, and three for malaria. For tuberculosis, most studies looked at gender-based barriers to diagnosis and disparities in health-seeking behaviors that predominantly affected women. For diabetes, studies noted that women had lower odds of being screened for prediabetes and potentially lower quality of care versus men. For schistosomiasis, studies suggested lower sensitivity diagnostic methods among women than men and low awareness of the disease. Studies suggest that women are less likely to be diagnosed for COVID-19 in certain settings. Studies on malaria reported that women show different health-seeking behaviors to men.ConclusionThis scoping review highlights a concerning lack of sex- and gender-disaggregated data on diagnostics. Consequently, further work is required to develop and implement an appropriate framework to assess gender and sex-related data around testing and diagnosis.

BackgroundGlobally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.Methods and findingsWe performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available.ConclusionsMultiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

Background and aim: A class of anti-diabetic medications, namely Sodium Glucose Co-Transporter-2 (SGLT2) inhibitors, has shown their potential effects beyond glucose tolerance in Type 2 Diabetes Mellitus (T2DM) patients. These inhibitors may affect inflammatory indicators, including monocyte chemoattractant protein-1 (MCP-1), which contributes to insulin resistance and vascular inflammation. Furthermore, uromodulin levels, a kidney-specific protein linked to renal function and tubular health, may be impacted by SGLT2 inhibitors. The study aimed to assess the role of inflammatory biomarkers in patients with renal dysfunction and T2DM who were receiving SGLT2 inhibitors compared to those receiving antidiabetic medications other than SGLT2 inhibitors. Methodology: It was a cross-sectional, observational, prospective, and single-centric study that was done to assess serum MCP-1 and uromodulin levels in T2DM patients with early renal dysfunction on SGLT2 inhibitors (n = 28), other antidiabetic medications (n = 28), and healthy controls (n = 30). The study also evaluated associations with glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), estimated glomerular filtration rate (eGFR), serum creatinine, serum urea, serum uric acid, body mass index (BMI), and age. Results: Serum MCP-1 and uromodulin levels were considerably lower in T2DM patients with early renal impairment who were on SGLT2 inhibitors than in those taking other antidiabetic drugs. Serum uromodulin was found to be negatively correlated with both serum urea and FPG in patients using SGLT2 inhibitors. FPG and serum MCP-1 were significantly correlated negatively in these patients. However, no significant correlation was observed between serum MCP-1 and HbA1c, eGFR, serum creatinine, or serum uric acid. Conclusion: It has been concluded that patients taking SGLT2 inhibitors are at lower risk of inflammation and renal dysfunction. However, further research is needed to strengthen the evidence of the associations between SGLT2 inhibitors and inflammation.

Purpose: To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile. Design: In vivo preclinical investigation in mice. Subjects: C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice. Methods: Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 × 109 viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost. Main Outcome Measures: Intraocular pressure assessment. Results: Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, P

Autism spectrum disorder (ASD) affects approximately 1% of the population, presenting a significant healthcare challenge due to limited resources, particularly a shortage of clinicians, which impedes timely ASD detection and management in children. This study investigates stakeholder viewpoints regarding the effectiveness of integrating machine learning (ML) into the information and communications technology (ICT) platform for ASD detection and intervention. Primary stakeholders, including parents and clinicians, provide first hand experiences with this technology during and after the COVID‐19 pandemic. The research identifies critical technology adoption factors by synthesizing stakeholder input based on user experiences, technology design, technology utility, and its impact. Additionally, the study gathers insights from potential investors interested in assistive technologies. Stakeholders unanimously acknowledge the pivotal role of technology in enhancing current ASD detection and management. However, their attitudes toward technology adoption exhibit divergent trends during and after the COVID‐19 pandemic. The study highlights a shift toward a technology‐enabled, human‐centred framework, which gained prominence post‐pandemic. Various factors contributing to this shift in stakeholder perspective were identified, including caregiver stress, technostress, and pandemic‐induced environmental factors affecting stakeholders' stress levels and motivating them to shift towards a human‐centric model. Stakeholders emphasize the paramount importance of human‐centred approaches in ASD detection and intervention, with technology serving as an empowering tool. Stakeholders also highlight the imperative ethical and legal considerations to foster trust and enhance the adoption of ML‐based technology. Consequently, future research should delve into stakeholder perspectives within the framework of fairness, accountability, transparency, and ethics (FATE) to ensure these technologies' responsible development and implementation. [ABSTRACT FROM AUTHOR]

Background: Limited population-based data as well as proposed mechanisms of retinal ganglion cell (RGC) loss suggest autoimmune disease may be a risk factor for glaucoma, the leading cause of irreversible blindness worldwide. Though intraocular pressure (IOP) is the leading risk factor for glaucoma onset and progression, a subset of glaucoma referred to as normal tension glaucoma (NTG) may be more likely to be associated with IOP-independent mechanisms of RGC injury including those of an inflammatory or immune nature. Methods: This retrospective case-control study enrolled 277 patients with NTG and the same number of age- and sex-matched controls to determine whether autoimmune disease diagnosis, treatment thereof, or relevant laboratory markers are associated with NTG. Results: There was no significant difference between the two groups in frequency of autoimmune disease overall, autoimmune disease catagorized by mechanism or organ involvement, or individual autoimmune disease including psoriasis (6% vs. 5%), rheumatoid arthritis (5% vs. 4%), inflammatory bowel disease (2% vs. 3%), Sjögren's syndrome (1% vs. 1%), sarcoidosis (1% vs. 1%), autoimmune thyroiditis (1% vs. 0%), type 1 diabetes (1% vs. 0%), or systemic lupus erythematosus (1% vs. 0%). There was also no significant difference in laboratory values or treatment of identified autoimmune conditions. Conclusions: Our study found no significant association between autoimmune disease and NTG, suggesting that other factors may play a more significant role in the pathogenesis of NTG. [ABSTRACT FROM AUTHOR]

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine. This neomorphic activity results from substitutions at key residues involved in the interactions with the mC base, including Asn1387 and His1904. Recombinant human TET2 proteins harboring the mutation of these residues can catalyze the oxidation of thymine to 5-hydroxymethyluracil (hmU) and 5-formyluracil (fU). Exogenous expression of the mutant TET2 Asn1387Thr (N1387T) in HEK293T cells leads to hmU accumulation, with levels further increased in cells lacking the glycosylase SMUG1. Endogenous knock-in of N1300T, the murine equivalent of N1387T, in mouse embryonic stem cells induces hmU production, causing DNA lesions and transcriptional activation of DNA damage response genes. N1300T cells accumulate more additional mutations with extended culture and exhibit heightened sensitivity to ATR inhibition compared to Tet2 knockout cells. Our study reveals that certain patient-derived TET2 mutations can acquire unexpected gain-of-function activities beyond impairing mC oxidation, offering a fresh perspective on the diverse molecular etiology of mutant TET2-related leukemogenesis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Neurogenic lower urinary tract dysfunction (NLUTD) is a condition characterized by bladder or urinary sphincter control issues due to neurologic dysregulation. NLUTD commonly causes symptoms like urinary incontinence and retention that impact both urinary health and quality of life. Current NLUTD treatment primarily manages symptoms, as restorative interventions are limited by a lack of diagnostic approaches to understand its underlying neurologic mechanisms. Neuroimaging may help identify neurologic pathways associated with bladder control, providing insights into functional and structural neural changes in NLUTD. This report reviews current neuroimaging modalities and their efficacy in detecting NLUTD. Recent Findings: Evaluated modalities include functional magnetic resonance imaging, positron emission tomography, functional near-infrared spectroscopy, functional ultrasonography, electrocorticography, and deep brain stimulation. Each modality's unique characteristics, such as resolution and invasiveness, shape its application in studying neurologic mechanisms of NLUTD. Collectively, they reveal a consistent finding: reduced brain activation in circuits related to bladder voiding and storage in patients with NLUTD. Summary: By examining each method's mechanism, effectiveness, advantages, and limitations, we aim to aid clinicians and researchers in selecting the best techniques for exploring the mechanisms of NLUTD and developing restorative treatments. [ABSTRACT FROM AUTHOR]

Background: College students in the United States are disproportionately impacted by food insecurity, which is associated with diminished health outcomes and poor academic performance. One key resource to support students through periods of food insecurity are on-campus food pantries, which distribute food, personal hygiene products, and other essential items. But as colleges and universities navigated through the COVID-19 pandemic, many campuses closed their food pantries as the demand for their services among students grew. Few studies, however, have assessed how food pantries at academic institutions navigated through the COVID-19 pandemic to support students. With this knowledge gap in mind, our study objectives included the following: (1) to compare staff members' perceptions on the impact of COVID-19 on food pantries of academic institutions; and (2) to provide recommendations to improve campus food pantries in navigating through future public health threats. Methods: The research team conducted a qualitative study involving semi-structured interviews with staff members, including directors and supervisors, of food pantries located on the campuses of colleges and universities in the state of Connecticut. Participants also completed a short post-interview survey assessing demographic information and perspectives on food insecurity-related issues impacting their respective college or university. A template organizing approach was used to allow members of the research team to create a codebook of both inductive and deductive codes and identify emergent themes from the qualitative data. Results: Twelve interviews were conducted, of which 7 participants represented four-year and 5 from 2-year institutions. Based on our thematic analysis if the interviews, we identified four central themes: (1) Persistent Pre-COVID-19 Pandemic Barriers to Food Pantry Utilization; (2) Innovative responses to the COVID-19 pandemic; (3) International Students' Reliance on Food Pantries at Four-Year Colleges and Universities; and (4) Demand for Non-Food-Related Items. Conclusions: Our research underscores the importance of lessons gleaned by the COVID-19 pandemic, particularly through the lens of on-campus food pantry workers. Their unique insight and lessons learned ought to be considered when academic institutions deliberate allocating resources and making key decisions to help mitigate food insecurity concerns on their campuses. [ABSTRACT FROM AUTHOR]

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative. Methods and findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available. Conclusions: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics. Sun Kim and colleagues conducted a systematic review and individual patient data meta-analysis to investigate the factors that influence a clinician's decision to initial TB treatment when bacteriological tests are negative. Author summary: Why was this study done?: Tuberculosis (TB) remains one of the leading causes of infectious disease death worldwide. Despite advancements in TB diagnostics, many diagnoses are still based on clinical judgment rather than bacteriological evidence. Understanding why clinicians decide to initiate TB treatment despite negative bacteriological test results can improve diagnostic accuracy and treatment outcomes. What did the researchers do and find?: We conducted a systematic review and meta-analysis of individual patient data from studies conducted between January 2010 and December 2022, where individuals were evaluated for TB. Key factors associated with initiating TB treatment after a negative bacteriological test included male sex, history of prior TB, reported cough and night sweats, and having HIV infection but not on antiretroviral therapy. Clinicians were less likely to initiate treatment if the initial test was a PCR-based diagnostic like Xpert MTB-RIF (as compared to sputum smear microscopy (SSM)). What do these findings mean?: The study identifies several factors that influence clinicians' decisions to treat for TB despite negative bacteriological test results. These findings can help refine TB diagnostic and treatment protocols, improving patient outcomes and enhancing public health strategies. More evidence is needed on clinicians' decision-making processes, which we did not assess in this study. [ABSTRACT FROM AUTHOR]

Introduction: The escalating longevity facilitated by medical advancements has led to a surge in elderly individuals grappling with chronic kidney disease (CKD) and progressing to end-stage renal disease (ESRD). Objectives: Our study addresses the paucity of research on octogenarians undergoing dialysis, a highly co-morbid and frail subset, particularly in the context of a resource-limited setting like India. Patients and Methods: A retrospective observational study at Kasturba Medical College and Hospital in Manipal, India, examined 18 octogenarian dialysis patients from 2017 to 2022. Clinical details, including age, co-morbidities, dialysis patterns, and laboratory data, were collected. The Coxproportional hazards model assessed factors influencing survival. Results: The majority-initiated dialysis in emergencies (72%), predominantly via central venous catheters. Hospitalizations post-dialysis were common (median 2.5). Survival rates at 1, 3, and 5 years were 61%, 54%, and 44%, respectively. Sudden cardiac death (64%) emerged as the predominant cause, with a significant impact of a higher Charlson comorbidity index on survival (HR 3.11; 95% CI [1.21-7.89]; P = 0.018). Conclusion: Octogenarian dialysis patients, marked by substantial co-morbidities, exhibit reduced survival, particularly with higher comorbidity scores. Hospitalizations contribute significantly to morbidity. Our study underscores the need for nuanced care strategies tailored to this vulnerable population. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium channel α-subunits (NaV1.1–1.9) initiate and propagate action potentials in neurons and myocytes. The NaV β-subunits (β1–4) have been shown to modulate α-subunit properties. Homo-oligomerization of β-subunits on neighboring or opposing plasma membranes has been suggested to facilitate cis or trans interactions, respectively. The interactions between several NaV channel isoforms and β-subunits have been determined using cryogenic electron microscopy (cryo-EM). Interestingly, the NaV cryo-EM structures reveal the presence of N-linked glycosylation sites. However, only the first glycan moieties are typically resolved at each site due to the flexibility of mature glycan trees. Thus, existing cryo-EM structures may risk de-emphasizing the structural implications of glycans on the NaV channels. Herein, molecular modeling and all-atom molecular dynamics simulations were applied to investigate the conformational landscape of N-linked glycans on NaV channel surfaces. The simulations revealed that negatively charged sialic acid residues of two glycan sites may interact with voltagesensing domains. Notably, two NaV1.5 isoform-specific glycans extensively cover the α-subunit region that, in other NaV channel α-subunit isoforms, corresponds to the binding site for the β1- (and likely β3-) subunit immunoglobulin (Ig) domain. NaV1.8 contains a unique N-linked glycosylation site that likely prevents its interaction with the β2 and β4-subunit Igdomain. These isoform-specific glycans may have evolved to facilitate specific functional interactions, for example, by redirecting β-subunit Ig-domains outward to permit cis or trans supraclustering within specialized cellular compartments such as the cardiomyocyte perinexal space. Further experimental work is necessary to validate these predictions. [ABSTRACT FROM AUTHOR]

Polyuria-polydipsia syndrome is composed of arginine vasopressin deficiency, arginine vasopressin resistance and primary polydipsia and are characterised by severe polyuria with hypotonic urine. The water deprivation test is commonly used to indirectly assess the vasopressin response to water deprivation. We report a woman in her 20s who demonstrated severe polyuria (11–12 L/ day) on submitting a 24-hour urine sample for analysis. She subsequently mentioned having had polyuria and polydipsia for 10 years after an Epstein-Barr virus infection. A water deprivation test with copeptin measurement confirmed arginine vasopressin deficiency. Treatment with desmopressin transformed her life. Further investigation revealed possible concurrent subclinical mixed connective tissue disease. We suspect Epstein-Barr virus infection to be the cause of the arginine vasopressin deficiency and possibly the trigger for the subclinical mixed connective tissue disease. This case also highlights the utility of copeptin measurements in differentiating the various polyuria-polydipsia syndromes. [ABSTRACT FROM AUTHOR]