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Introduction: The frequency and importance of vulval diseases are often underestimated due to the multifactorial nature of disease on the vulva. Dermoscopy can help provide clues for early diagnosis and insight into dermoscopic patterns. The present study was done with the objective to study the clinico-dermoscopic pattern of dermatosis and correlate the dermatoses with the age of the patient. Materials and Methodology: This was a prospective cross-sectional observational study conducted in the department of dermatology at a tertiary health care center over a period of 1½ year. All females with dermatosis affecting genital areas attending the skin outpatient department or ward were recruited after taking written consent. A detailed history was taken to collect demographic data. A thorough clinical examination and dermatoscopy were done. Descriptive statistics was used to depict the profile and dermatoscopic pattern. Results: Out of the 103 patients with vulvar dermatoses, 24 (23.30%) patients were in the age group of 41–50 years. A total of 43 (41.74%) patients had infective conditions, followed by 16 (15.53%) patients of papulosquamous group of disorders and 11 (10.67%) patients of eczema. Dermatoscopic findings had a surface scale in 40 (38.83%), vascular patterns in 22 (21.36%), red dots in 19 (18.45%), and structureless patterns in 13 (12.62%) with different vulvar dermatosis. In tinea cruris, out of 30 cases, 28 (93.33%) had surface scales, followed by 5 (16.67%) showing vascular pattern, whereas in lichen sclerosus et atrophicus, out of total of 10 cases, 8 (80%) had structureless pattern and 6 (60%) had vascular patterns. Discussion and Conclusion: Genital diseases represent a diagnostic challenge for clinicians. The use of dermoscopy improves the diagnostic accuracy by recognizing specific dermoscopic patterns. Limitation: Small sample size was the only limitation.

Background: Parents and families have a role to play in helping children develop healthy behaviours that will carry over into adulthood. The sugary drink and fruit juice consumption is significantly related to unhealthy weight gain in childhood. Hence, this study was planned to assess parental knowledge, attitudes, and practices about juice and sugar-sweetened beverages (SSBs) among parents of children (2–24 months) and identify factors that contribute to their early introduction. Methods and Material: A cross-sectional study was conducted on 400 children-parent dyads (2–24 months). A questionnaire regarding the knowledge and attitudes about initiating fruit juice and SSB among children was prepared with 6 statements that were validated for contents by two subject experts. Each of the questions was designed to be answered on a Five-point Likert-type scale. STATA 14.2 version was used to analyse data. Results: Out of 400, 14 (26.9%) and 125 (68%) parents planned to introduce SSBs and juices respectively in the first year life of their child. None of the parents had an excellent knowledge score. There was no significant difference reported between parents with less than high school and those with high school/graduation educated in their intention to introduce juice and SSBs (P = 0.68) to their babies in the first year of life and about its knowledge (P = 0.82). Most parents with lower socio-economic status (58.6%) showed less likeliness to introduce juices and SSBs to their child’s diet as reflected by a statistically significant (P = 0.01) knowledge score. Conclusion: There was a knowledge gap among parent’s of children irrespective of their education level and socio-economic status.

A total of 9 million veterans receive care in a unique healthcare system, the Veterans Healthcare Administration (VHA), with nearly 50% reporting at least one cardiovascular disease. Despite evidence for high quality of health care in the VHA, more veteran care is being moved to the non-VHA community. An assumption of this shift in care is that the quality of non-VHA care is at least comparable to VHA care. This paper reviews the quality of cardiovascular care delivered by the VHA in comparison to community care, which is care delivered in non-VHA facilities by non-VHA providers and is authorized and paid for by VHA, examining quality metrics and highlighting novel national care programs. The critical examination of this data is valuable for deriving health care policy, sharing novel and effective quality initiatives throughout the healthcare sector, and will help veterans and their providers make important healthcare decisions.

Introduction: Colloid cysts of the third ventricle are benign brain lesions that may obstruct cerebrospinal fluid flow within the ventricular system and cause symptoms like headaches, deterioration of vision, and acute hydrocephalus. Research question: What is the clinical outcome of surgical treatment of third ventricle colloid cysts, and what factors are influencing long-term complications? Material and methods: In this multicenter retrospective cohort study performed between 2008 and 2023, we assessed the preoperative clinical status, the colloid cyst risk score, surgical techniques, and the clinical outcome of patients undergoing surgical cyst resection for incidental and symptomatic colloid cysts of the third ventricle. We specifically focused on long-term data such as shunt dependency and postoperative complications. Results: In total, 190 patients were included. Most presented with headaches (75,3%), while 25% showed signs of acute and 36% signs of chronic hydrocephalus. In 23% of the patients, short-term memory was impaired. The surgical treatment presented a safe and definite treatment, with wound healing disorders (6.3%) and CSF leakage (4.7%) being the most frequently encountered complications. Only 5.3% showed a postoperative shunt dependency. Discussion and conclusion: The surgical treatment of colloid cysts of the third ventricle represents a safe procedure. Acute hydrocephalus was observed more frequently than previously described, and shunt dependency after surgery was low. (211/250 words)

Conclusions: Multiple preoperative serum values were predictive of postoperative medical complications, and laboratory value thresholds were identified in this carpal tunnel decompression cohort to aid in risk stratification.

The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis.

Background This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction. Methods and Results Data from 809 patients in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion

Purpose: To report a case series of 4 patients with poor visual outcomes from concurrent fulminant idiopathic intracranial hypertension (IIH) and malignant arterial hypertension with bilateral optic disc edema. The diagnosis of fulminant IIH was delayed given the bilateral optic disc edema was attributed initially to hypertensive optic neuropathy. Observation: All 4 patients (3 males, 3 African Americans, mean BMI 27.6 kg/m2 (range 19.5–36 kg/m2) presented to the emergency department with bilateral vision loss, optic disc edema, and blood pressure (BP) of greater than 180/120. The patients were treated initially to control BP and the optic disc edema was either attributed to the hypertension or the ophthalmic examination was not performed. The patients were subsequently diagnosed with IIH with Brain MRI, MR venogram, and lumber puncture (mean cerebrospinal fluid (CSF) opening pressure 42 cm, range 40–43 cm). The mean time from presentation to diagnosis of IIH was 3.2 months (range 1–6 months). The final visual acuity ranged from 20/400 to hand motions in the better eye and count fingers to hand motions in the worse eye despite bilateral optic nerve sheath fenestrations (3 patients), ventriculoperitoneal shunts (3 patients), and treatments with acetazolamide (3 patients) and furosemide (1 patient). Conclusion: Our case series underscores the need to promptly include IIH in the differential diagnosis in patients with bilateral optic disc edema including patients with malignant hypertension, particularly in those experiencing progressive visual loss, regardless of gender or BMI. Prompt work-up with brain MRI with contrast and MR or CT venogram to detect neuroimaging signs of intracranial hypertension followed by a lumbar puncture with CSF opening pressure are essential to initiate rapid treatment of fulminant IIH to avoid poor outcome.

Background: Despite aggressive multimodal treatment for locally advanced esophagogastric cancer (LA-EGC), many patients experience early disease progression/death. We aimed to explore the role of Geriatric Assessment (GA) in optimizing patient care in older patients with LA-EGC. Materials and methods: A retrospective cohort study was conducted in patients aged ≥60 years with LA-EGC referred to the geriatric oncology clinic at our institute between June 2018 and November 2022, who were planned for curative treatment. We explored the role of GA-guided therapy modifications on survival, identification of factors predicting potential ‘overtreatment’ (arbitrarily defined as patients in whom disease recurrence or death occurred within 6 months of treatment completion), and utility of the GA in identification of this patient subset. Results: We enrolled 199 patients. The median age was 68 years (interquartile range 64-73 years). There were 131 (65.8%) males and 157 patients (78.9%) had a performance status of 0-1. Based on the GA, 110 (55.3%) patients were deemed fit (≤2 domains affected). Therapy modification (primarily de-intensification) occurred in 72 (36.2%) patients. At a median follow-up of 34.1 months [95% confidence interval (CI) 31.5-36.7 months], median event-free survival with de-intensified treatment was 12.2 months (95% CI 9.1-15.3 months) versus 18.8 months (95% CI 14.7-22.9 months) with standard treatment; P = 0.113. Median overall survival was 15.4 months (95% CI 9.3-21.5 months) with de-intensified treatment versus 21.1 months (95% CI 16.1-26.1 months) with standard treatment, P = 0.116. Six months following treatment completion, 79 (39.7%) patients were potentially overtreated. Initial GA failed to identify patients who were potentially overtreated (P = 0.923). Conclusion: GA-tailored treatment de-escalation does not impair survival in older patients with LA-EGC but fails to identify the patient cohort at risk for overtreatment.

Small cysteine-rich antifungal peptides with multi-site modes of action (MoA) have potential for development as biofungicides. In particular, legumes of the inverted repeat-lacking clade express a large family of nodule-specific cysteine-rich (NCR) peptides that orchestrate differentiation of nitrogen-fixing bacteria into bacteroids. These NCRs can form two or three intramolecular disulfide bonds and a subset of these peptides with high cationicity exhibits antifungal activity. However, the importance of intramolecular disulfide pairing and MoA against fungal pathogens for most of these plant peptides remains to be elucidated. Our study focused on a highly cationic chickpea NCR13, which has a net charge of +8 and contains six cysteines capable of forming three disulfide bonds. NCR13 expression in Pichia pastoris resulted in formation of two peptide folding variants, NCR13_PFV1 and NCR13_PFV2, that differed in the pairing of two out of three disulfide bonds despite having an identical amino acid sequence. The NMR structure of each PFV revealed a unique three-dimensional fold with the PFV1 structure being more compact but less dynamic. Surprisingly, PFV1 and PFV2 differed profoundly in the potency of antifungal activity against several fungal plant pathogens and their multi-faceted MoA. PFV1 showed significantly faster fungal cell-permeabilizing and cell entry capabilities as well as greater stability once inside the fungal cells. Additionally, PFV1 was more effective in binding fungal ribosomal RNA and inhibiting protein translation in vitro. Furthermore, when sprayed on pepper and tomato plants, PFV1 was more effective in reducing disease symptoms caused by Botrytis cinerea, causal agent of gray mold disease in fruits, vegetables, and flowers. In conclusion, our work highlights the significant impact of disulfide pairing on the antifungal activity and MoA of NCR13 and provides a structural framework for design of novel, potent antifungal peptides for agricultural use.

We present a case of a young woman who presented with blurring of vision in her right eye, worsening on near work. Detailed ophthalmic and neurological evaluation was done, which revealed light near dissociation, vermiform iris movements, constriction to diluted pilocarpine with absent deep tendon reflexes. Laboratory investigation indicated mild iron deficiency anemia and reduced vitamin D3 level. On orthopedic evaluation she was diagnosed with right knee joint arthritis and grade 1 patellar chondromalacia. Neuroimaging was within normal limits. Magnetic resonance imaging (MRI) pelvis and lumbar spine showed left ovarian cyst, small periurethral cyst and small hemagioma in left sacral ala. A diagnosis of Holmes-Adie syndrome was made and she was prescribed photochromatic glasses.

Background Cigarette smoking has been associated with incident heart failure (HF). However, the association between cigarette smoking and smoking cessation with HF subtypes has not been well elucidated, particularly among Black people. Methods and Results We investigated 4189 (never smoker n=2934, former smoker n=761, current smoker n=464) Black participants (mean age 54 years, 64% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the association of cigarette smoking with incident HF hospitalization and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction). After adjustment for confounding factors, current smoking was associated with incident HF (both subtypes) compared with never smoking. Smoking intensity among those who identified as currently smoking and smoking burden among those who ever smoked were associated with higher incidence of HF with preserved ejection fraction compared with never smoking. Lung function evaluated by spirometry at baseline did not significantly influence these associations. The risk of developing HF decreased with more years after smoking cessation, and more than 20 years of smoking cessation were required to reach a risk comparable to that of never smoking. Conclusions Smoking cigarettes was associated with developing both subtypes of HF and it was independent from the influences on baseline lung function. Long‐term smoking cessation is necessary to prevent the onset of HF in people who smoke cigarettes.

Summary: The accumulation of damaged mitochondria in the heart is associated with heart failure. Mitophagy is an autophagic degradation system that specifically targets damaged mitochondria. We have reported previously that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells. However, the in vivo function of Bcl2-L-13 remains unclear. Here, we demonstrate that Bcl2-L-13-deficient mice and knockin mice, in which the phosphorylation site (Ser272) on Bcl2-L-13 was changed to Ala, showed left ventricular dysfunction in response to pressure overload. Attenuation of mitochondrial fission and mitophagy led to impairment of ATP production in these mouse hearts. In addition, we identified AMPKα2 as the kinase responsible for the phosphorylation of Bcl2-L-13 at Ser272. These results indicate that Bcl2-L-13 and its phosphorylation play an important role in maintaining cardiac function. Furthermore, the amplitude of stress-stimulated mitophagic activity could be modulated by AMPKα2.

Objective: The pathway to cardiothoracic surgery is often obscure for premedical students and aspiring applicants and requires navigating various known and unknown obstacles. Recognizing the challenges encountered on the path to a career in cardiothoracic surgery in the United States, we present this guide for students interested in the field to maximize success in their premedical, preclinical, and preresidency years. Methods: This is a joint collaboration between the Thoracic Surgery Residents Association and the Thoracic Surgery Medical Student Association. Drawing from firsthand experiences and insights gathered from numerous student applicants and current surgical residents, a comprehensive guide was constructed for students from the point of undergraduate school to advanced training options, including super-fellowship training. Results: Several intricacies to cardiothoracic surgery career planning were discussed, including differences between traditional and integrated/fast-track pathways, college and medical school selection, networking, performing during clinical rotations, extracurricular and research activities, building mentorship relationships, and pursuing alternate career and advanced training opportunities. Conclusions: For premedical students and aspiring applicants, the road to cardiothoracic surgery requires meticulous planning, grit, and thoughtful dedication. This document consolidates firsthand insights and advice from numerous aspiring and matched applicants to serve as a comprehensive guide for students seeking a career in cardiovascular and thoracic surgery.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

Abstract Background Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. Methods 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. Results Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p

Abstract Background Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. Objectives We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. Methods We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory’s 99th -percentile upper limit of normal (xULN). Results 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs.

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors. The co-occurrence of meningioma and oligodendroglioma is particularly uncommon, posing unique diagnostic and therapeutic challenges. We describe the case of a patient diagnosed with concurrent meningioma and oligodendroglioma and review the existing literature on this rare phenomenon. Case Presentation: A 55-year-old female patient with a history of seizures presented to the emergency department with worsening headaches, nausea, and vomiting. She had a known right frontoparietal intracranial mass but had previously declined surgery. Magnetic resonance imaging revealed extensive fluid-attenuated inversion recovery /T2 hyperintensity around the lesion, which had slowly increased over 5 years; the growth of the lesion was producing a mass effect with a significant midline shift. The patient underwent urgent hemicraniectomy with subsequent resection. Clinical evaluation, imaging studies, and histopathological examination were conducted to confirm the diagnosis. Genetic and molecular analyses were also performed to explore potential underlying mechanisms. Histopathological findings confirmed a diagnosis of an isocitrate dehydrogenase-mutated World Health Organization Grade II oligodendroglioma with 1p/19q codeletion, along with a Grade I meningioma. Conclusion: The coexistence of meningioma and oligodendroglioma represents a rare clinical event. Surgical management remains the cornerstone of treatment. Further investigation into the genetic and environmental factors that contribute to the co-occurrence of such tumors could pave the way for more targeted therapeutic strategies.

Dermatologic diagnosis depends on the careful observation and documentation of signs, which can be highly pathognomonic for a certain condition. Most of the signs appear either de novo or have to be elicited by the physician. It refers to important physical finding or observation made by the physician when examining the patient. In this article, we have included total 154 signs including clinical, dermoscopic, and histopathological signs. We have divided them in 13 groups including signs seen in infectious conditions, vesiculobullous disorders, papulosquamous disorders, dermatitis, connective tissue diseases, and diseases of appendages for the ease of readers.

Summary: Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett’s esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (1) known/plausible links to BE/EAC pathogenesis (n = 493) or (2) prior evidence of biological interactions (n = 4,196). Approximately 75 × 106 SNP×SNP interactions were screened via hierarchical group lasso (glinternet) using BEACON GWAS data. The top ∼2,000 interactions retained in each scan were prioritized using p values from single logistic models. Identical scans were repeated among males only (78%), with two independent GWAS datasets used for replication. In overall and male-specific primary replications, 11 of 187 and 20 of 191 interactions satisfied p

Background The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA.Methods We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model.Results Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001).Conclusions Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies.PROSPERO registration number CRD42021275070.

Background Approximately 50% of women referred for invasive coronary angiography have angina and nonobstructive coronary arteries, which includes coronary microvascular dysfunction, vasospastic angina, and other vasomotor disorders. We sought to determine the real‐world diagnostic yield of invasive coronary angiography and coronary function testing in women with angina and nonobstructive coronary arteries. Methods and Results From 2018 to 2023, we enrolled 198 women who underwent either coronary angiography (CA) alone (n=99) or coronary function testing (CFT; n=99). Mean±SD age was 62±10 years (CA alone) compared with 57±10 years (CFT). Coronary angiography was interpreted as nonobstructive coronary artery disease more frequently after CA alone (79% versus 52%). Of the women who underwent CFT, 82% (N=81) were found to have vasomotor disorders, including coronary microvascular dysfunction (27%), vasospastic angina (32%), mixed coronary microvascular dysfunction/vasospastic angina (16%), endothelial dysfunction (10%; without spasm), elevated resting flow (2%), or symptomatic myocardial bridging (4%). Compared with women undergoing CA alone, medications were changed more frequently after CFT at 24 hours (41% versus 65%; P=0.001) and between 24 hours and 30 days (30% versus 44%; P=0.04) with intensification of antianginal therapy (79% versus 92%; P80% of women undergoing CFT received a specific diagnosis of a coronary vasomotor disorder and greater intensification of antianginal therapy.

AimsPatients with severe aortic stenosis (AS), low transvalvular flow (LF) and low gradient (LG) with normal ejection fraction (EF)—are referred to as paradoxical LF-LG AS (PLF-LG). PLF-LG patients develop more advanced heart failure symptoms and have a worse prognosis than patients with normal EF and high-gradient AS (NEF-HG). Despite its clinical relevance, the mechanisms underlying PLF-LG are still poorly understood.MethodsLeft ventricular (LV) myocardial biopsies of PLF-LG (n = 5) and NEF-HG patients (n = 6), obtained during transcatheter aortic valve implantation, were analyzed by LC-MS/MS after sequential extraction of cellular and extracellular matrix (ECM) proteins using a three-step extraction method. Proteomic data are available via ProteomeXchange with identifier PXD055391.Results73 cellular proteins were differentially abundant between the 2 groups. Among these, a network of proteins related to muscle contraction and arrhythmogenic cardiomyopathy (e.g., cTnI, FKBP1A and CACNA2D1) was found in PLF-LG. Extracellularly, upregulated proteins in PLF-LG were related to ATP synthesis and oxidative phosphorylation (e.g., ATP5PF, COX5B and UQCRB). Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p

Background In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Methods Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions–Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI −0.026–0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change −0.12±0.22 versus −0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Interpretation Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

Primary tumours of the optic nerve are relatively rare. Optic nerve gliomas are usually seen in children under the age of 10 and present with gradual vision loss followed by proptosis. A 19-year-old female presented to our neuro-ophthalmology clinic with chief complaints of disturbances in vision in both eyes and headache. Ocular examination showed best corrected visual acuity (BCVA) of 6/6 in both eyes and visual field analysis revealed bitemporal hemianopia. Urgent neuroimaging was advised and her MRI brain revealed optic pathway glioma involving the intracranial segment of right optic nerve and optic chiasma. Improvement in vision was noted during post-surgical follow-up. We present this case to highlight the importance of visual field examination in a young patient with headache, even with a BCVA of 6/6.

Abstract Background Glycolytic flux is regulated by the energy demands of the cell. Upregulated glycolysis in cancer cells may therefore result from increased demand for adenosine triphosphate (ATP), however it is unknown what this extra ATP turnover is used for. We hypothesise that an important contribution to the increased glycolytic flux in cancer cells results from the ATP demand of Na+/K+-ATPase (NKA) due to altered sodium ion homeostasis in cancer cells. Methods Live whole-cell measurements of intracellular sodium [Na+]i were performed in three human breast cancer cells (MDA-MB-231, HCC1954, MCF-7), in murine breast cancer cells (4T1), and control human epithelial cells MCF-10A using triple quantum filtered 23Na nuclear magnetic resonance (NMR) spectroscopy. Glycolytic flux was measured by 2H NMR to monitor conversion of [6,6-2H2]d-glucose to [2H]-labelled l-lactate at baseline and in response to NKA inhibition with ouabain. Intracellular [Na+]i was titrated using isotonic buffers with varying [Na+] and [K+] and introducing an artificial Na+ plasma membrane leak using the ionophore gramicidin-A. Experiments were carried out in parallel with cell viability assays, 1H NMR metabolomics of intracellular and extracellular metabolites, extracellular flux analyses and in vivo measurements in a MDA-MB-231 human-xenograft mouse model using 2-deoxy-2-[18F]fluoroglucose (18F-FDG) positron emission tomography (PET). Results Intracellular [Na+]i was elevated in human and murine breast cancer cells compared to control MCF-10A cells. Acute inhibition of NKA by ouabain resulted in elevated [Na+]i and inhibition of glycolytic flux in all three human cancer cells which are ouabain sensitive, but not in the murine cells which are ouabain resistant. Permeabilization of cell membranes with gramicidin-A led to a titratable increase of [Na+]i in MDA-MB-231 and 4T1 cells and a Na+-dependent increase in glycolytic flux. This was attenuated with ouabain in the human cells but not in the murine cells. 18FDG PET imaging in an MDA-MB-231 human-xenograft mouse model recorded lower 18FDG tumour uptake when treated with ouabain while murine tissue uptake was unaffected. Conclusions Glycolytic flux correlates with Na+-driven NKA activity in breast cancer cells, providing evidence for the ‘centrality of the [Na+]i-NKA nexus’ in the mechanistic basis of the Warburg effect.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2023 Annual Conference. The conference was held in-person, 31 May–2 June 2023, in Halifax, Nova Scotia at the Westin Nova Scotian hotel. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 1 June, and oral abstract authors were featured during the oral abstract session in the afternoon of Friday, 2 June 2023. Twenty-three (23) abstracts were selected for presentation as posters and four (4) as oral presentations. Abstracts were submitted within four categories: (1) Basic/Translational Sciences, (2) Clinical Trials/Observations, (3) Laboratory/Quality, and (4) Pharmacy/Nursing/Other Transplant Support. The top four (4) oral abstracts and top four (4) poster abstracts were selected to receive an award. All of these were marked as “Award Recipient” within the relevant category. We congratulate all the presenters on their research and contributions to the field.

Abstract Aims Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk‐factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi‐racial populations. Methods and results Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31% cumulative incidence) HF cases developed over 30 years of follow‐up. PRSs of AF, BMI, and CHD were associated with incident HF (P

By considering the limited energy of Internet of Things (IoT) devices. We take the resource allocation to guarantee the stringent Quality of Service (QoS) depending on the joint optimization of power control and finite blocklength of channel. To achieve large volumes of arrival rates, we propose Adversarial Training based Generative Adversarial Networks (AT-GANs), which utilize a significant number of extreme events to provide high reliability and adjust real data in real-time. Simulation results show that Deep-Reinforcement Learning (Deep-RL) for AT-GAN could eliminate the transient training time. As a result, the AT-GAN keeps the reliability higher than 99.9999%.

Condensation heat transfer is involved in many industrial applications. Therefore, it is important to know the relative accuracy of the available methods for predicting heat transfer. Condensation can occur with saturated as well as superheated vapors. Predictive methods for both conditions were evaluated using a wide range of data. Twelve well-known correlations for the condensation of saturated vapor, including the most recent ones, were compared with data for 51 pure fluids and mixtures from 132 sources in horizontal and vertical channels of many shapes. Channel hydraulic diameters were 0.08–49 mm, the mass flux was 1.1–1400 kg/m2s, and the reduced pressure range was 0.0006–0.949. The fluids included water, CO2, ammonia, hydrocarbons, halocarbon refrigerants, various chemicals, and heat transfer fluids. The best predictive technique was identified. The three most commonly used models for heat transfer during the condensation of superheated vapors were studied. They were first compared with test data using measured saturated condensation and forced convection heat transfer coefficients to select the best model. The selected model was then compared with test data using various correlations for heat transfer coefficients needed in the model. The best correlations to use in the model were identified. The results of this research are presented, as are recommendations for use in design.

Background: For intraocular surgery, the optimal local anesthetic agent must have a rapid onset of action and a sufficient duration of effect so as to enable a painless, motionless procedure without prolonging akinesia. Aims and Objective: This prospective, comparative observational study compares ropivacaine and 0.5% bupivacaine for cataract surgery peribulbar block. Hyaluronidase is utilized in both groups because it promotes local anesthetic diffusion. Material and Methods: Present prospective, observational, comparative study performed at the Department of Anesthesia Tertiary Care Teaching Institute of India for the duration of 1 year. All eligible patients were allocated in two groups as GROUP B and GROUP R. GROUP B: 10 mL of 0.5% bupivacaine and 15 I.U./mL of hyaluronidase. GROUP R: 10 mL of 0.5% ropivacaine and 15 I.U./mL of hyaluronidase. Patients were assessed for sensory block, eyelid, and ocular movements at an interval of 2 min, and Visual Analog Scale score for pain assessment. Results: Age and gender did not differ significantly between the two study groups, according to the findings. Comparable and similar patient characteristics distinguished the two study groups. (P>0.05). The difference in onset of eyelid motor blockade between the two groups was not statistically significant. The difference in the onset of motor blockade [ocular movement] between the two groups was not statistically significant (P>0.05). (P>0.05) Analgesia duration differed significantly between the two groups in a statistical sense. Ropivacaine exhibits a significantly prolonged duration of analgesic effect than bupivacaine (P≤0.05). Conclusion: Peribulbar block utilizing 0.5% ropivacaine is a more favorable and secure option for a local anesthetic that effectively extends postoperative pain alleviation, in comparison to the use of 0.5% bupivacaine.

Abstract Introduction The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun’s ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Methods This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun’s ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). Results Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun’s ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at −1% (−2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun’s ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun’s ranibizumab group and 14.6 letters in the reference ranibizumab group (p

Background: Revisions to the heart allocation criteria in 2018 motivated an increased use of extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation. Studies have demonstrated inferior post-transplant outcomes in patients bridged with ECMO but do not account for underlying diagnosis. Our objective was to elucidate the differential impact of ECMO on outcomes by heart failure (HF) etiology. Methods: The United Network of Organ Sharing database was queried for adults who underwent isolated heart transplantation after October 2018. Patients were stratified by ECMO utilization at the time of transplantation and then by HF etiology. After baseline statistical comparisons, survival analysis relied on Kaplan-Meier estimates and Cox proportional models. Results: A total of 13,203 patients were included, of whom 761 (5.8%) were supported with ECMO. ECMO patients were younger (48 vs 54 years, p

Aim: Examining how pre-cooling affects children’s experience of pain during local anesthetic administration is the primary goal of this study. Material and Methods: This study was conducted in vivo and involved 60 child patients who required local anesthetic in order to undergo dental procedures. Patients were divided into two groups based on a random chance: Group I was the control group, which did not receive any pre-cooling. Group II was the pre-cooling group, which allowed the injection site to be chilled with an ice pack for one minute prior to the administration of anesthesia. The Wong-Baker FACES Pain Rating Scale was used to evaluate the participants’ level of pain perception immediately following the administration of the anesthetic injection. Results: The group that received pre-cooling showed a reduction in pain levels that was statistically significant when compared to the group that received control (P < 0.05). Conclusion: Pediatric dental patients may decrease local anesthesia pain by pre-cooling the injection site. This technique can be simply used in dental practices to improve patient experience, especially for children with dental anxiety or needle phobia.

Backgroundobjectives: To compare the structural anatomy of the anterior segment in pediatric Trisomy 21 (T21) subjects with and without cataracts to age-matched controls. Design: Prospective case-control study. Participants: 40 subjects (57 eyes) age 0–25 years old (9.1 ± 10.6 years). Methods: This prospective case-control study evaluated anterior segment measurements from ultrasound biomicroscopy (UBM) imaging on 342 images. Results: Among persons with T21 cataract, the iris was significantly thinner than T21 individuals without cataract (0.28 vs 0.32 mm, p = 0.0181). T21/cataract subjects also had significantly thinner lenses than subjects without cataract, regardless of whether they have T21 or are controls (3.1 mm vs 3.5 mm, p = 0.0074).Thinner lens (

# Background The rotator cuff (RC) plays a pivotal role in the performance and health of the shoulder and upper extremity. Blood flow restriction training (BFRT) is a modality to improve strength and muscle hypertrophy with even low-load training in healthy and injured individuals. There is minimal evidence examining its effect proximal to the occluded area, and particularly on the RC. # Hypothesis & Purpose The purpose of this case series is to explore the effects of low-load BFRT on RC strength, hypertrophy, and tendon thickness in asymptomatic individuals. # Study Design Case series. # Methods Fourteen participants with asymptomatic, untrained shoulders were recruited to participate. They performed an eight-week low-load shoulder exercise regimen where BFR was applied to the dominant arm only during exercise. The dependent variables were maximal isometric strength of the shoulder external rotators(ER) and elevators (in the scapular plane in full can position) (FC) measured via handheld dynamometry, cross sectional area (CSA) of the supraspinatus and infraspinatus muscles, and supraspinatus tendon thickness measured via ultrasound imaging (US). Mean changes within and between arms were compared after training using paired t-tests. Cohen's d was used to determine effect sizes. # Results All participants were able to complete the BFRT regimen without adverse effects. Mean strength and CSA increased for all variables in both arms, however this increase was only significant (p\

Machines have a long-demonstrated ability to find statistical relationships between qualities of texts and surface-level linguistic indicators of writing. More recently, unlocked by artificial intelligence, the potential of using machines to identify content-related writing trait criteria has been uncovered. This development is significant, especially in formative assessment contexts where feedback is key. Yet the extent to which writing traits can be validly scored by machines remains under-researched, especially in the K-12 context. The present study investigated the validity of machine learning (ML) models designed for students in grades 3-6 to score three writing traits: task fulfillment, organization and coherence, and vocabulary and expression. The study utilized an argument-based approach, focusing on two primary inferences: evaluation and explanation. The evaluation inference investigated human-machine score alignment, the ability for the models to detect off-topic and gibberish responses, and the consistency of human-machine score alignment across grades and language backgrounds. The explanation inference investigated the relevance of features used in the models. Results indicated that human-machine score alignment was sufficient for all writing traits; however, validity concerns were raised regarding the models' performances detecting off-topic and gibberish responses and the consistency across sub-groups. Implications for language assessment professionals and other educators were discussed.

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide. Moreover, severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis. In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis, the implications for the neonate, as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment. Finally, we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.