Magnetic resonance imaging features in 283 patients with primary biliary cholangitis.

Objectives: To evaluate magnetic resonance imaging (MRI) features of the liver in primary biliary cholangitis (PBC).

Methods: We conducted a multicenter retrospective review on 283 patients with PBC who underwent an MRI between 2007 and 2018. Patients with overlap syndromes were excluded.

The relationship between mental health conditions and hearing loss in low- and middle-income countries.

Objective: Hearing loss can have far-reaching effects on social, emotional and cognitive development, but few studies have addressed the link with mental health conditions. We conducted a systematic review of the association between hearing loss and mental health conditions in low- and middle-income countries (LMICs).

Methods: We searched six electronic databases using predetermined criteria to retrieve original research reporting mental health in people with hearing loss.

Partnership for the implementation of mental health policy in Nigeria: a case study of the Comprehensive Community Mental Health Programme in Benue State.

Background: 71% of countries in the World Health Organisation's (WHO's) African Region have a stand-alone mental health policy or plan, but only 14% have fully implemented it. In Nigeria, integration of mental health into primary care has been a stumbling block to the implementation of the 1991 National Mental Health Policy, 2013 Policy on Mental Health Services Delivery and the National Mental, Neurological and Substance Use Programme and Action Plan. A partnership between public and private not-for-profits in Benue State, the Comprehensive Community Mental Health Programme (CCMHP) has successfully integrated mental health into primary care in alignment with the national mental health policy and the WHO's mental health Gap Action Programme Intervention Guide (mhGAP-IG).

Survival and Functional Outcomes at Discharge After Traumatic Brain Injury in Children versus Adults in Resource-Poor Setting.

Background: More than 90% of trauma mortality occurs in low- and middle-income countries, especially in sub-Saharan Africa. Head injury is the primary driver of trauma mortality in the prehospital and in-hospital setting.

Methods: An observational study was performed on patients presenting with traumatic brain injury (TBI) from October 2016 through May 2017 at Kamuzu Central Hospital, Malawi.

Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis.

Ferroptosis is widely involved in degenerative diseases in various tissues including kidney, liver and brain, and is a targetable vulnerability in multiple primary and therapy-resistant cancers. Accumulation of phospholipid hydroperoxides in cellular membranes is the hallmark and rate-limiting step of ferroptosis; however, the enzymes contributing to lipid peroxidation remain poorly characterized. Using genome-wide, CRISPR-Cas9-mediated suppressor screens, we identify cytochrome P450 oxidoreductase (POR) as necessary for ferroptotic cell death in cancer cells exhibiting inherent and induced susceptibility to ferroptosis.

Prevalence of a Good Perinatal Outcome With Cryopreserved Compared With Fresh Donor Oocytes.

Objective: To compare the odds of a good perinatal outcome between cryopreserved and fresh donor oocytes.

Methods: We used the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System to conduct a retrospective cohort study of women undergoing donor oocyte in vitro fertilization (IVF) from 2012 to 2015. Cycles using cryopreserved embryos, a gestational carrier, or preimplantation genetic testing were excluded.

Nursing Management of Patients Requiring Acute Mechanical Circulatory Support Devices.

Topic: The growing use of acute mechanical circulatory support devices to provide hemodynamic support that has accompanied the increasing prevalence of heart failure and cardiogenic shock, despite significant improvement in the treatment of acute myocardial infarction.

Clinical Relevance: The critical care nurse plays a crucial role in managing patients receiving acute mechanical circulatory support devices and monitoring for potential complications.

Purpose: To review the anatomical placement and mechanics of each type of device so that nurses can anticipate patients' hemodynamic responses and avoid complications whenever possible, thereby improving patients' clinical outcomes.

Efficacy of psychosocial interventions for mental health outcomes in low-income and middle-income countries: an umbrella review.

Background: Mental health conditions are leading causes of disability worldwide. Psychosocial interventions for these conditions might have a key role in their treatment, although applicability of findings to poor-resource settings might be a challenge. We aimed to evaluate the strength and credibility of evidence generated in low-income and middle-income countries (LMICs) on the efficacy of psychosocial interventions for various mental health outcomes.

An update on primary sclerosing cholangitis epidemiology, outcomes and quantification of alkaline phosphatase variability in a population-based cohort.

Background: Contemporary primary sclerosing cholangitis (PSC) population-based cohorts describing the epidemiology, natural history, and long-term fluctuations in serum alkaline phosphatase (SAP) and their prognostic relevance are lacking. Therefore, we investigated the incidence and natural history of PSC and quantified SAP fluctuations among those with PSC in Olmsted County, Minnesota over the last 41 years.

Methods: The Rochester Epidemiology Project was used to identify 56 subjects diagnosed with PSC between 1976 and 2017 in Olmsted County.

Comparison of liver stiffness measurement with MRE and liver and spleen volumetry for prediction of disease severity and hepatic decompensation in patients with primary sclerosing cholangitis.

Purpose: To compare liver stiffness measurement (LSM) with magnetic resonance elastography (MRE) and liver and spleen volumetry for prediction of disease severity and hepatic decompensation in primary sclerosing cholangitis (PSC).

Methods: This retrospective study was approved by the institutional review board. Magnetic resonance imaging (MRI) and MRE studies were reviewed, and mean LSM of entire liver, right lobe and left lobe, total liver, right lobe, left lobe, caudate lobe, and spleen volumes were calculated.

Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently.

GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. Although most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein's catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules have uncovered novel electrophilic warheads that bind and inhibit GPX4. Here, we report our discovery that diacylfuroxans can act as masked nitrile oxide prodrugs that inhibit GPX4 covalently with unique cellular and biochemical reactivity compared to existing classes of GPX4 inhibitors.

Structural and Dynamical Signatures of Local DNA Damage in Live Cells.

The dynamic organization of chromatin inside the cell nucleus plays a key role in gene regulation and genome replication, as well as maintaining genome integrity. Although the static folded state of the genome has been extensively studied, dynamical signatures of processes such as transcription or DNA repair remain an open question. Here, we investigate the interphase chromatin dynamics in human cells in response to local DNA damage, specifically, DNA double-strand breaks (DSBs).

Dynamic rodent behavioral response to predation risk: implications for disease ecology.

Prey modify their behavior in response to variation in predation risk, and such modifications can affect trophic processes such as disease transmission. However, variation in predation risk is complex, arising from direct risk from the predator itself and indirect risk due to the environment. Moreover, direct risk typically stems from multiple predators and varies over timescales (e.

A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes.

The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is important. Here, we describe a single mechanism incorporating features of both models.

HIV surveillance based on routine testing data from antenatal clinics in Malawi (2011-2018): measuring and adjusting for bias from imperfect testing coverage.

Objective: The use of routinely collected data from prevention of mother-to-child transmission programs (ANC-RT) has been proposed to monitor HIV epidemic trends. This poses several challenges for surveillance, one of them being that women may opt-out of testing and/or test stock-outs may result in inconsistent service availability. In this study, we sought to empirically quantify the relationship between imperfect HIV testing coverage and HIV prevalence among pregnant women from ANC-RT data.

Global variations in mortality in adults after initiating antiretroviral treatment: an updated analysis of the International epidemiology Databases to Evaluate AIDS cohort collaboration.

Background: UNAIDS models use data from the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration in setting assumptions about mortality rates after antiretroviral treatment (ART) initiation. This study aims to update these assumptions with new data, to quantify the extent of regional variation in ART mortality and to assess trends in ART mortality.

Methods: Adult ART patients from Africa, Asia and the Americas were included if they had a known date of ART initiation during 2001-2017 and a baseline CD4 cell count.

The Estimation and Projection Package Age-Sex Model and the r-hybrid model: new tools for estimating HIV incidence trends in sub-Saharan Africa.

Objectives: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA).

Design: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance (ANC-SS) data.

Methods: We modified EPP to incorporate age and sex stratification (EPP-ASM) to more accurately capture the shifting demographics of maturing HIV epidemics.

National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the 'first 90' from program and survey data.

Objective: HIV testing services (HTS) are a crucial component of national HIV responses. Learning one's HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load.

A Compendium of Genetic Modifiers of Mitochondrial Dysfunction Reveals Intra-organelle Buffering.

Mitochondrial dysfunction is associated with a spectrum of human conditions, ranging from rare, inborn errors of metabolism to the aging process. To identify pathways that modify mitochondrial dysfunction, we performed genome-wide CRISPR screens in the presence of small-molecule mitochondrial inhibitors. We report a compendium of chemical-genetic interactions involving 191 distinct genetic modifiers, including 38 that are synthetic sick/lethal and 63 that are suppressors.

Summarizing the results and methods of the 2019 Joint United Nations Programme on HIV/AIDS HIV estimates.

: UNAIDS and other partners provide support to countries to develop estimates of HIV and related indicators on an annual basis. These estimates are used to monitor epidemic trends, guide program planning and resource allocation, and inform policy decision-making. The collection of articles in this AIDS supplement provide the headline results for the 2019 UNAIDS estimates and describe the new developments in the methods used to produce these estimates.

Avoiding anaesthetics after multiple failed drug-induced comas: an unorthodox approach to management of new-onset refractory status epilepticus (NORSE).

New-onset refractory status epilepticus (NORSE) is a rare, poorly understood and often catastrophic condition. There is little guidance available for management. Here, we describe the course of a 19-year-old man with NORSE who was treated successfully with a new approach.

Dataset for dose and time-dependent transcriptional response to ionizing radiation exposure.

Exposure to ionizing radiation associated with highly energetic and charged heavy particles is an inherent risk astronauts face in long duration space missions. We have previously considered the transcriptional effects that three levels of radiation (0.3 Gy, 1.