Structural and Functional Characterization of a Na1.5-Mitochondrial Couplon.

Rationale: The cardiac sodium channel Na1.5 has a fundamental role in excitability and conduction. Previous studies have shown that sodium channels cluster together in specific cellular subdomains.

Enhanced and Timely Investigation of ARVs for Use in Pregnant Women.

Background: Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV), and their infants.

Setting: The World Health Organization convened a Paediatric Antiretroviral Drug Optimization group meeting, December 10-12, 2018, in Geneva, Switzerland.

Methods: The group, comprised of clinicians, scientists, HIV program managers, regulators, and community representatives, were tasked to consider how ARVs are studied in PWLHIV, define alternative approaches to studying ARVs in PWLHIV, identify ways to shorten the timeline to determine safe use of new agents during pregnancy, and define strategies to collaborate with regulators and industry to change longstanding practices.

Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function.

Aims: Increasing attention is being given to patients with heart failure and 'mid-range' left ventricular ejection fraction (LVEF, ≥40% and <50%) for whom there are no approved therapies that improve prognosis. We aim to assess for the first time the effects of cardiac contractility modulation (CCM) therapy in this patient population.

Methods And Results: We assessed the effects of 6-  month CCM therapy on functional status, exercise tolerance and quality of life in a subgroup of 53 patients with a LVEF of 40-45% recruited in previous CCM studies, including 37 patients in the CCM group and 16 in the control group.

Association of Peri-ictal Brainstem Posturing With Seizure Severity and Breathing Compromise in Patients With Generalized Convulsive Seizures.

Objective: To analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).

Methods: In this prospective, multicenter analysis of GCS, ictal brainstem semiology was classified as (1) decerebration (bilateral symmetric tonic arm extension), (2) decortication (bilateral symmetric tonic arm flexion only), (3) hemi-decerebration (unilateral tonic arm extension with contralateral flexion) and (4) absence of ictal tonic phase. Postictal posturing was also assessed.

Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo.

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA).

Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m; upper bounds of the 95% confidence intervals: 0.

Low-dose dual-energy CT for stone characterization: a systematic comparison of two generations of split-filter single-source and dual-source dual-energy CT.

Purpose: To compare noise texture and accuracy to differentiate uric acid from non-uric acid urinary stones among four different single-source and dual-source DECT approaches in an ex vivo phantom study.

Methods: Thirty-two urinary stones embedded in gelatin were mounted on a Styrofoam disk and placed into a water-filled phantom. The phantom was imaged using four different DECT approaches: (A) dual-source DECT (DS-DE); (B) 1st generation split-filter single-source DECT (SF1-TB); (C) 2nd generation split-filter single-source DECT (SF2-TB) and (D) 2nd generation split-filter single-source DECT using serial acquisitions (SF2-TS).

Bi-directional association between epilepsy and dementia: The Framingham Heart Study.

Objective: To assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).

Methods: We analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case-control designs and matched each case to 3 age-, sex- and FHS cohort-matched controls.

Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection.

The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC).

International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM).

Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system.

Evaluating the clinical value of MRI multi-model diffusion-weighted imaging on liver fibrosis in chronic hepatitis B patients.

Purpose: To explore the value of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential in assessing liver fibrosis in chronic hepatitis B (CHB).

Methods: DWI and intravoxel incoherent motion (IVIM) MRI were performed prospectively on liver for 146 patients with CHB and 21 healthy volunteers. ADC values were obtained from monoexponential model imaging.

SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.

The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein show promise therapeutically and are being evaluated clinically. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies in complex with the SARS-CoV-2 spike trimer or RBD.

Treatment Response Score to Glatiramer Acetate or Interferon Beta-1a.

Objective: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments.

Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.

Results: The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10^{18} eV Using the Pierre Auger Observatory.

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18}  eV based on 215 030 events. New results are presented: at about 1.

Agricultural labor, COVID-19, and potential implications for food security and air quality in the breadbasket of India.

To contain the COVID-19 pandemic, India imposed a national lockdown at the end of March 2020, a decision that resulted in a massive reverse migration as many workers across economic sectors returned to their home regions. Migrants provide the foundations of the agricultural workforce in the 'breadbasket' states of Punjab and Haryana in Northwest India.There are mounting concerns that near and potentially longer-term reductions in labor availability may jeopardize agricultural production and consequently national food security.

Extraparenchymal human neurocysticercosis induces autoantibodies against brain tubulin and MOG35-55 in cerebral spinal fluid.

Neurocysticercosis (NC) presents two broad clinical entities: extraparenchymal (EP-NC) and parenchymal (P-NC). Using ELISA methodology, we demonstrate autoantibodies to tubulin and the Major oligodendrocyte glycoprotein (MOG) in the CSF of most, but not all, EP-NC samples. Levels of these autoantibodies were considerably reduced or absent in the P-NC samples.

Enhanced SARS-CoV-2 Neutralization by Secretory IgA in vitro.

SARS-CoV-2 primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of the illness. Although potent IgG antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might impact the initial viral spread and transmissibility from the mucosa.

Responsive neurostimulation for refractory epilepsy in the pediatric population: A single-center experience.

Drug-resistant focal epilepsy (DRFE) in children can impair cognition and behavior, and lead to premature death. Increased pediatric epilepsy surgery numbers reflect the improvements in seizure control and long-term developmental outcomes. Yet, many children with DRFE are not candidates for surgical resection due to overlap of the seizure network with eloquent cortex or multiple seizure-onset zones, making surgery dangerous or ineffective.

Risk compensation in HIV PrEP adherence among Black men who have sex with men in HPTN 073 study.

While HIV infections among men who have sex men (MSM) have started to decline in the United States, Black MSM continue to experience disproportionate rates of HIV infection. The purpose of this secondary analysis is to examine risk perception and its influence on PrEP adherence among Black MSM from HPTN 073. Risk perception was measured using the adapted Perceived Vulnerability to HIV Scale.

Indian agriculture, air pollution, and public health in the age of COVID.

Emerging evidence supports the intuitive link between chronic health conditions associated with air pollution and the vulnerability of individuals and communities to COVID-19. Poor air quality already imposes a highly significant public health burden in Northwest India, with pollution levels spiking to hazardous levels in November and early December when rice crop residues are burned. The urgency of curtailing the COVID-19 pandemic and mitigating a potential resurgence later in the year provides even more justification for accelerating efforts to dramatically reduce open agricultural burning in India.

Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic Solution 0.02% in Patients With Open-angle Glaucoma or Ocular Hypertension.

Precis: In pooled phase III analyses, once-daily netarsudil 0.02% resulted in intraocular pressure (IOP) reduction that was noninferior to twice-daily timolol 0.5%, with minimal treatment-related serious or systemic adverse events (AEs).

Probability of Major Depression Classification Based on the SCID, CIDI, and MINI Diagnostic Interviews: A Synthesis of Three Individual Participant Data Meta-Analyses.

Introduction: Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.

Objective: To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.