IRF1 cooperates with ISGF3 or GAF to form innate immune de novo enhancers in macrophages.

Macrophages exposed to immune stimuli reprogram their epigenomes to alter their subsequent functions. Exposure to bacterial lipopolysaccharide (LPS) causes widespread nucleosome remodeling and the formation of thousands of de novo enhancers. We dissected the regulatory logic by which the network of interferon regulatory factors (IRFs) induces the opening of chromatin and the formation of de novo enhancers.

Quantifying VMAT2 target occupancy at effective valbenazine doses and comparing to a novel VMAT2 inhibitor: a translational PET study.

Positron emission tomography (PET) is frequently used to obtain target occupancy (%TO) of central nervous system (CNS) drug candidates during clinical development. Obtaining %TO with PET can be particularly powerful when the %TO associated with efficacy is known for a protein target. Using the radiotracer [F]AV-133, the relationship between plasma concentration (PK) and %TO of NBI-750142, an experimental inhibitor of the vesicular monoamine transporter type 2 (VMAT2) was obtained in both nonhuman primate (NHP) and human.

A Vocal Hygiene Program for Mitigating the Effects of Occupational Vocal Demand in Primary School Teachers.

Purpose: Teachers are occupational voice users with significant vocal demand. This study examined if a vocal hygiene program could mitigate the effects of occupational vocal demand in primary school teachers across 1 month.

Method: Sixty female teachers participated, with 30 in an experimental group receiving vocal hygiene education plus daily home practice for 1 month and 30 in a control group with no intervention.

Validating real-time three-dimensional echocardiography against cardiac magnetic resonance, for the determination of ventricular mass, volume and ejection fraction: a meta-analysis.

Introduction: Real-time three-dimensional echocardiography (RT3DE) is currently being developed to overcome the challenges of two-dimensional echocardiography, as it is a much cheaper alternative to the gold standard imaging method, cardiac magnetic resonance (CMR). The aim of this meta-analysis is to validate RT3DE by comparing it to CMR, to ascertain whether it is a practical imaging method for routine clinical use.

Methods: A systematic review and meta-analysis method was used to synthesise the evidence and studies published between 2000 and 2021 were searched using a PRISMA approach.

Mapping the quality of prenatal and postnatal care and demographic differences on child mortality in 26 low to middle-income countries.

Background: Closing the gap between child mortality in low- and middle-income countries (LMICs) and high-income countries is a priority set by the WHO in sustainable development goals (SDGs). We aimed to examine poor nutrition and prenatal and postnatal care that could increase the risk of child mortality in LMICs.

Methods: The Demographic and Health Survey (DHS) was used to examine data from 26 countries to compare prenatal, postnatal, nutritional, and demographic factors across LMICs.

Effects of Polyphenol Supplementations on Improving Depression, Anxiety, and Quality of Life in Patients With Depression.

Increased prevalence of mental disorders has become a significant public health concern. Recent studies have linked nutrition to depression and anxiety, suggesting that dietary changes or nutritional supplementation may be beneficial in improving mental disorders. Polyphenols have anti-inflammatory and antioxidant properties that may counteract physiological changes in depression and anxiety.

Assessment of the Field Utility of a Rapid Point-of-Care Test for SARS-CoV-2 Antibodies in a Household Cohort.

Point-of-care (POC) tests to detect SARS-CoV-2 antibodies offer quick assessment of serostatus after natural infection or vaccination. We compared the field performance of the BioMedomics COVID-19 IgM/IgG Rapid Antibody Test against an ELISA in 303 participants enrolled in a SARS-CoV-2 household cohort study. The rapid antibody test was easily implemented with consistent interpretation across 14 users in a variety of field settings.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in the United States: Living Density, Viral Load, and Disproportionate Impact on Communities of Color.

Background: Households are hot spots for severe acute respiratory syndrome coronavirus 2 transmission.

Methods: This prospective study enrolled 100 coronavirus disease 2019 (COVID-19) cases and 208 of their household members in North Carolina though October 2020, including 44% who identified as Hispanic or non-White. Households were enrolled a median of 6 days from symptom onset in the index case.

Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings.

Alternatives to nasopharyngeal sampling are needed to increase capacity for SARS-CoV-2 testing. Among 275 participants, we piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including polyester flocked swabs as well as 3D-printed plastic lattice swabs, placed into viral transport media or an RNA stabilization agent. Flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), missing those with low viral load (<10 viral copies/mL).

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color.

Background: Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color.

Methods And Findings: This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white.

Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings.

Background: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods.

Methods: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both standard polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into either viral transport media or an RNA stabilization agent. Quantitative SARS-CoV-2 viral detection by RT-qPCR was compared to that obtained by nasopharyngeal sampling as the reference standard.

The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth of EGFRvIII-activated glioblastomas.

Purpose: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the clinic. Here, we examine the efficacy of the newly discovered ATP-competitive mTOR kinase inhibitors CC214-1 and CC214-2 in glioblastoma, identifying molecular determinants of response and mechanisms of resistance, and develop a pharmacologic strategy to overcome it.

Experimental Design: We conducted in vitro and in vivo studies in glioblastoma cell lines and an intracranial model to: determine the potential efficacy of the recently reported mTOR kinase inhibitors CC214-1 (in vitro use) and CC214-2 (in vivo use) at inhibiting rapamycin-resistant signaling and blocking glioblastoma growth and a novel single-cell technology-DNA Encoded Antibody Libraries-was used to identify mechanisms of resistance.

Perioperative, functional, and oncologic outcomes of partial adrenalectomy for multiple ipsilateral pheochromocytomas.

Objective: Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting.

Materials And Methods: We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010.

Outcomes of patients with surgically treated bilateral renal masses and a minimum of 10 years of followup.

Purpose: Nephron sparing surgery has been advocated for patients with bilateral renal masses but long-term functional and oncological outcomes are lacking. We report the outcomes of patients with bilateral renal masses and a minimum 10-year followup.

Materials And Methods: Patients with bilateral renal masses evaluated at our institution who were treated with initial surgery at least 10 years ago and underwent interventions on each renal unit were included in the analysis.

EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy.

Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma, their clinical relevance is poorly understood. Studies of tumors from patients treated with the EGFR inhibitor lapatinib revealed that EGFR induces the cleavage and nuclear translocation of the master transcriptional regulator of fatty acid synthesis, sterol regulatory element-binding protein 1 (SREBP-1).