Srsf2 co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia-like disease in mice.

Recurrent mutations in RNA splicing proteins and epigenetic regulators contribute to the development of myelodysplastic syndrome (MDS) and related myeloid neoplasms. In chronic myelomonocytic leukemia (CMML), SRSF2 mutations occur in ~50% of patients and TET2 mutations in ~60%. Clonal analysis indicates that either mutation can arise as the founder lesion.

Delivering hypertension care in private-sector clinics of urban slum areas of India: the Mumbai Hypertension Project.

In India, the private sector provides 70% of the total outpatient medical care. This study describes the Mumbai Hypertension Project, which aimed to deliver a standard hypertension management package in private sector clinics situated in urban slums. The project was conducted in two wards (one "lean" and one "intensive") with 82 private providers in each.

Telemedicine Use by Older Adults in a COVID-19 Epicenter.

Background: In early 2020, New York City was the epicenter of the Coronavirus disease 2019 (COVID-19) pandemic in the United States. Older adults were at especially high risk. Telemedicine (TM) was used to shift care from overburdened emergency departments (EDs) to provide health care to a community in lockdown.

Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.

Background: Valosin-containing protein (VCP) disease, caused by mutations in the gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in gene and investigates genotype-phenotype correlations.

Cotrimoxazole guidelines for infants who are HIV-exposed but uninfected: a call for a public health and ethics approach to the evidence.

WHO first recommended cotrimoxazole prophylaxis for all infants who are HIV-exposed but uninfected (HEU) in 2000, given the ability of this treatment to prevent mortality from pneumocystis pneumonia in adults living with HIV. Over the last 21 years, evidence has been generated from the use of cotrimoxazole prophylaxis in infants who are HEU, including two randomised controlled trials, which have shown no clinical benefit and an increase in antibiotic resistance and microbiome dysbiosis. Additionally, improvements in health care over the last two decades in terms of antiretroviral treatment and prophylaxis for mothers and infants, and notably improved vaccination programmes, have substantially reduced the risk of HIV transmission and the overall morbidity and mortality of infants who are HEU from pneumonia and diarrhoeal diseases.

COVID-19 vaccination and breakthrough infections in patients with cancer.

Background: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer.

Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary.

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development.

Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [ C]PBR28 and Machine Learning Analysis.

Background: The clinical diagnosis of multiple system atrophy (MSA) is challenged by overlapping features with Parkinson's disease (PD) and late-onset ataxias. Additional biomarkers are needed to confirm MSA and to advance the understanding of pathophysiology. Positron emission tomography (PET) imaging of the translocator protein (TSPO), expressed by glia cells, has shown elevations in MSA.

Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke.

Ischemic stroke is the third leading cause of mortality worldwide, but its medical management is still limited to the use of thrombolytics as a lifesaving option. Multiple molecular deregulations of the protein kinase family occur during the period of ischemia/reperfusion. However, experimental studies have shown that alterations in the expression of essential protein kinases and their pharmacological modulation can modify the neuropathological milieu and hasten neurophysiological recovery.

Bone outcomes in virally suppressed youth with HIV switching to tenofovir disoproxil fumarate.

Background: Tenofovir disoproxil fumarate (TDF) is included in first-line antiretroviral treatment (ART) for adolescents living with HIV (ALWH). Associated toxicities remain a concern.

Objective: We evaluated bone and renal safety outcomes in virologically suppressed South African ALWH after switching to TDF.

Nonpharmacological interventions to reduce respiratory viral transmission: an evidence-based review with recommendations.

Background: Viral respiratory infections are a leading cause of worldwide mortality and exert the potential to cause global socioeconomic crises. However, inexpensive, efficacious, and rapidly deployable strategies to reduce viral transmission are increasingly important in the setting of an ongoing pandemic, though not entirely understood. This article provides a comprehensive review of commonly employed nonpharmacological interventions to interrupt viral spread and provides evidence-based recommendations for their use.

Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome.

Discovering drugs that efficiently treat brain diseases has been challenging. Genetic variants that modulate the expression of potential drug targets can be utilized to assess the efficacy of therapeutic interventions. We therefore employed Mendelian Randomization (MR) on gene expression measured in brain tissue to identify drug targets involved in neurological and psychiatric diseases.

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa.

Objectives: Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa.

Materials And Methods: Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30-65 years, participated in the study.

Incidence and outcomes of infective endocarditis following transcatheter aortic valve implantation.

Introduction: Prosthetic valve infective endocarditis is a feared and potentially catastrophic complication of valvular intervention. Transcatheter aortic valve implantation has transformed the modern management of aortic stenosis and vastly altered the demographics of those patients undergoing valve replacement.

Areas Covered: As a relatively nascent development, what TAVI means for the epidemiology of infective endocarditis, how to identify those patients undergoing the procedure at greatest risk, and how best to prevent and manage the condition remains the subject of fervent research activity.

Editor's Choice - Mortality is High Following Elective Open Repair of Complex Abdominal Aortic Aneurysms.

Objective: To evaluate the 30 day mortality of elective open complex abdominal aortic aneurysm (cAAA) repair and identify factors associated with death.

Methods: This was a retrospective cohort study using a Targeted Vascular Module from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP). All patients undergoing elective repair for juxta- and suprarenal abdominal aortic aneurysm (AAA), or type IV thoraco-abdominal aneurysms (TAAA) from 2011 to 2017 were identified.

Inherited cardiac arrhythmias.

The main inherited cardiac arrhythmias are long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. These rare diseases are often the underlying cause of sudden cardiac death in young individuals and result from mutations in several genes encoding ion channels or proteins involved in their regulation. The genetic defects lead to alterations in the ionic currents that determine the morphology and duration of the cardiac action potential, and individuals with these disorders often present with syncope or a life-threatening arrhythmic episode.

Iliocaval Venous Obstruction, Cardiac Preload Reserve and Exercise Limitation.

Cardiac output during exercise increases by as much as fivefold in the untrained man, and by as much as eightfold in the elite athlete. Increasing venous return is a critical but much overlooked component of the physiological response to exercise. Cardiac disorders such as constrictive pericarditis, restrictive cardiomyopathy and pulmonary hypertension are recognised to impair preload and cause exercise limitation; however, the effects of peripheral venous obstruction on cardiac function have not been well described.

The role of nutrition in pediatric oncology.

: Obesity compromises survival in children with cancer in high-income countries (HICs) and is accompanied often by sarcopenia. In low and middle-income countries (LMICs), where the great majority of children live, the prevalence of under-nutrition is as high as 95% in those with cancer. Nutritional support improves clinical outcomes, including survival.

Early Life Maternal Separation and Maternal Behaviour Modulate Acoustic Characteristics of Rat Pup Ultrasonic Vocalizations.

Early separation of preterm infants from their mothers has adverse, long-term neurodevelopmental consequences. We investigated the effects of daily maternal separation (MS) of rat pups from postnatal days 2-10 (PND2-10) on neurobehavioural responses to brief isolation at PND12 compared with pups receiving controlled handling without MS. Ultrasonic vocalizations (USV) were measured at PND12 during two, 3-minute isolations occurring immediately before and after a 3-minute maternal reunion.