A PAS-targeting hERG1 activator reduces arrhythmic events in Jervell and Lange-Nielsen syndrome patient-derived hiPSC-CMs.

The hERG1 potassium channel conducts the cardiac repolarizing current, IKr. hERG1 has emerged as a therapeutic target for cardiac diseases marked by prolonged actional potential duration (APD). Unfortunately, many hERG1 activators display off-target and proarrhythmic effects that limit their therapeutic potential.

FHIRing up OpenMRS: Architecture, Implementation and Real-World Use-Cases in Global Health.

HL7 FHIR was created almost a decade ago and is seeing increasingly wide use in high income settings. Although some initial work was carried out in low and middle income (LMIC) settings there has been little impact until recently. The need for reliable and easy to implement interoperability between health information systems in LMICs is growing with large scale deployments of EHRs, national reporting systems and mHealth applications.

Psychological safety and perceived organizational support in emergency medicine residencies.

Background: The clinical learning environment (CLE) is a key focus of the Accreditation Council of Graduate Medical Education. It impacts knowledge acquisition and professional development. A previous single-center study evaluated the psychological safety and perceived organizational support of the CLE across different specialties.

Connectivity and molecular profiles of Foxp2- and Dbx1-lineage neurons in the accessory olfactory bulb and medial amygdala.

In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA.

People hold mood-congruent beliefs about memory but do not use these beliefs when monitoring their learning.

Contemporary theories of metacognitive monitoring propose that beliefs play a critical role in monitoring of learning. Even so, recent evidence suggests that beliefs are not always sufficient to impact people's monitoring. In seven experiments, we explored people's beliefs about the impact of mood and item valence on memory and whether people use their beliefs about these cues when monitoring their learning.

Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Mutant Mice.

In humans, mutations in the transcription factor encoding gene, , are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care.

Calming Troubled Waters: A Narrative Review of Challenges and Potential Solutions in the Residency Interview Offer Process.

The rising numbers of residency applications along with fears of a constrained graduate medical education environment have created pressures on residency applicants. Anecdotal evidence suggests substantial challenges with the process of offering residency interviews. This narrative review is designed to identify and propose solutions for the current problems in the process of offering residency interviews.

Widespread pustular eruption following probiotic use.

A 26-year-old woman with Crohn disease and palmoplantar psoriasis on ustekinumab presented with a diffuse and intensely pruritic rash with a few pin-point pustules within days after initiation of an over-the-counter Align brand probiotic. Biopsy revealed psoriasiform and spongiotic dermatitis with spongiform subcorneal pustules and scattered eosinophils, consistent with acute generalized exanthematous pustulosis. Our case highlights a unique presentation of acute generalized exanthematous pustulosis following probiotic exposure with fewer than usual pustular lesions.

Pneumocephalus causing oculomotor nerve palsy: A case report.

Background: Pneumocephalus, the presence of gas or air within the intracranial cavity, is a common finding after cranial procedures, though patients often remain asymptomatic. Rare cases of cranial nerve palsies in patients with pneumocephalus have been previously reported. However, only two prior reports document direct unilateral compression of the third cranial nerve secondary to pneumocephalus, resulting in an isolated deficit.

Comparison of Ventricular and Lumbar Cerebrospinal Fluid Composition.

Objective Cerebrospinal fluid (CSF) analysis is a common diagnostic tool used to evaluate diseases of the central nervous system (CNS). We sought to determine whether there is a difference between the composition of CSF sampled from an external ventricular drain (EVD) and lumbar drain (LD) and whether this made a difference in guiding therapeutic decisions. Patients and Methods This study was a retrospective analysis from a single neurosurgery service between the dates of January 2011 and April 2019.

Concordance of Rural-Urban Self-identity and ZIP Code-Derived Rural-Urban Commuting Area (RUCA) Designation.

Purpose: This study examined the concordance between individuals' self-reported rural-urban category of their community and ZIP Code-derived Rural-Urban Commuting Area (RUCA) category.

Methods: An Internet-based survey, administered from August 2017 through November 2017, was used to collect participants' sociodemographic characteristics, self-reported ZIP Code of residence, and perception of which RUCA category best describes the community in which they live. We calculated weighted kappa (ĸ) coefficients (95% confidence interval [CI]) to test for concordance between participants' ZIP Code-derived RUCA category and their selection of RUCA descriptor.

PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder.

Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala.

An approach for controlling the timing and order of engineered mutations in mice.

Significant advances in our understanding of normal development and disease have been facilitated by engineered mice in which genes can be altered in a spatially, temporally, or cell type restricted manner using site specific recombinase systems like Cre-loxP or Flp-frt. In many circumstances it is important to understand how interactions between multiple genes influence a given phenotype. Robust approaches for precisely controlling multiple genetic alterations independently are limited, however, thus the impact of mutation order and timing on phenotype is generally unknown.

Multi-level Influences on Breast Cancer Screening in Primary Care.

Background: Use of breast cancer screening is influenced by factors associated with patients, primary care providers, practices, and health systems.

Objective: We examined the relative effects of these nested levels on four breast cancer screening metrics.

Design: A web-based survey was completed at 15 primary care practices within two health systems representing 306 primary care providers (PCPs) serving 46,944 women with a primary care visit between 1/2011-9/2014.

Preoperative breast MRI and mortality in older women with breast cancer.

Purpose: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial.

Methods: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data.

Communication Practices of Mammography Facilities and Timely Follow-up of a Screening Mammogram with a BI-RADS 0 Assessment.

Rationale And Objectives: The objective of this study was to evaluate the association of communication practices with timely follow-up of screening mammograms read as Breast Imaging Reporting and Data Systems (BI-RADS) 0 in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.

Materials And Methods: A radiology facility survey was conducted in 2015 with responses linked to screening mammograms obtained in 2011-2014. We considered timely follow-up to be within 15 days of the screening mammogram.

Cooperating with machines.

Since Alan Turing envisioned artificial intelligence, technical progress has often been measured by the ability to defeat humans in zero-sum encounters (e.g., Chess, Poker, or Go).

Preoperative Breast Magnetic Resonance Imaging Use by Breast Density and Family History of Breast Cancer.

Background: Use of preoperative breast magnetic resonance imaging (MRI) among women with a new breast cancer has increased over the past decade. MRI use is more frequent in younger women and those with lobular carcinoma, but associations with breast density and family history of breast cancer are unknown.

Materials And Methods: Data for 3075 women ages >65 years with stage 0-III breast cancer who underwent breast conserving surgery or mastectomy from 2005 to 2010 in the Breast Cancer Surveillance Consortium were linked to administrative claims data to assess associations of preoperative MRI use with mammographic breast density and first-degree family history of breast cancer.

Personal history of proliferative breast disease with atypia and risk of multifocal breast cancer.

Background: A history of proliferative breast disease with atypia (PBDA) may be indicative of an increased risk not just of breast cancer but also of a more aggressive form of breast cancer.

Methods: Multifocal breast cancer (MFBC), defined as 2 or more tumors in the same breast upon a diagnosis of cancer, is associated with a poorer prognosis than unifocal (single-tumor) breast cancer. PBDA, including atypical ductal hyperplasia and atypical lobular hyperplasia, is a known risk factor for breast cancer.

Correlation between obesity and fat-infiltrated axillary lymph nodes visualized on mammography.

Objective: Using screening mammography, this study investigated the association between obesity and axillary lymph node (LN) size and morphology.

Methods: We conducted a retrospective review of 188 females who underwent screening mammography at an academic medical centre. Length and width of the LN and hilum were measured in the largest, mammographically visible axillary node.

Relationship between preoperative breast MRI and surgical treatment of non-metastatic breast cancer.

Background And Objectives: More extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established.

Methods: Using Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non-metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation).

Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues.

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors.