Development of CGS-15943 Adjunctives for the Disruption of Plasmid Maintenance in Multidrug Resistant .

Carbapenemase producing (CPEs) represent a group of multidrug resistant pathogens for which few, if any, therapeutics options remain available. CPEs generally harbor plasmids that encode resistance to last resort carbapenems and many other antibiotics. We previously performed a high throughput screen to identify compounds that can disrupt the maintenance and replication of resistance conferring plasmids through use of a synthetic screening plasmid introduced into K-12 cells.

Efficacy of parenteral bronchodilators on ventilatory outcomes in pediatric critical asthma: a national cohort study.

To evaluate the association of parenteral epinephrine and terbutaline use on ventilatory support in children admitted to the intensive care unit (ICU) with critical asthma in the United States. Data were obtained from the Pediatric Health Information System data base for children ages 2 to 18 years admitted to the ICU with a diagnosis of asthma exacerbation from January 1, 2016, to December 31, 2023. The primary outcomes included noninvasive ventilation (NIV) and/or invasive mechanical ventilation (IMV) use after receipt of terbutaline and/or epinephrine.

Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.

Background: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) developed standardized variant curation guidelines for Mendelian disorders. Although these guidelines have been widely adopted, they are not gene- or disease-specific. To mitigate classification discrepancies, the Clinical Genome Resource FBN1 variant curation expert panel (VCEP) was established in 2018 to develop adaptations to the ACMG/AMP criteria for FBN1 in association with Marfan syndrome.

Deep learning enhanced transmembranous electromyography in the diagnosis of sleep apnea.

Obstructive sleep apnea (OSA) is widespread, under-recognized, and under-treated, impacting the health and quality of life for millions. The current gold standard for sleep apnea testing is based on the in-lab sleep study, which is costly, cumbersome, not readily available and represents a well-known roadblock to managing this huge societal burden. Assessment of neuromuscular function involved in the upper airway using electromyography (EMG) has shown potential to characterize and diagnose sleep apnea, while the development of transmembranous electromyography (tmEMG), a painless surface probe, has made this opportunity practical and highly feasible.

Identifying Settler Colonial Determinants of Indigenous Health Within the United States: A Discursive Paper.

Aim(s): This discursive article aims to examine how systemic factors (both) reproduce the structure of settler colonialism and influence health outcomes among Indigenous peoples in the United States through settler colonial determinants of Indigenous health (SCDoIH).

Design: Discursive paper.

Methods: This discursive paper demonstrates how settler colonialism and health relate to each other within a nursing context.

10-Year outcomes of marginal ulcer formation and impact of gastrojejunostomy technique in Roux-en-Y gastric bypass.

Background: Marginal ulcers (MUs) are potential complications following Roux-en-Y gastric bypass (RYGB) surgery. Our institution performs 3 different laparoscopic gastrojejunal anastomosis (GJA) techniques. The aim of this study was to analyze the incidence of MUs between 25-mm circular stapler (CS), linear stapler (LS), and hand-sewn (HS) GJA techniques using data collected over a 10-year period.

Re-visiting professional ethics in psychotherapy: reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis/chronic fatigue syndrome and 'medically unexplained symptoms'.

Following years of debate over the effectiveness of cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), public health bodies in the UK and beyond have determined that no psychotherapy is clinically proven for this patient group. In the field of ME/CFS and the wider arena of 'medically unexplained symptoms' (MUS), patient survey data and qualitative research capturing patient experiences and psychotherapist attitudes suggest that therapeutic practice may sometimes fall short of required ethical standards. This raises questions about how psychotherapists can safely support, as opposed to treat, people with these debilitating conditions.

Video Game Therapy in a Neurosciences Critical Care Unit: A Pilot Study.

Background: Therapeutic activity after stroke is a component of early recovery strategies. Interactive video games have been shown to be safe as an adjunct rehabilitation therapy in the medical intensive care setting, but patients with neurologic disease were often excluded from those protocols.

Objectives: To evaluate the feasibility and safety of individualized interactive video game therapy in critically ill neurologic patients.

Identification of a T2-hyperintense Perivascular Space in Brain Arteriovenous Malformations.

Background/aim: Brain arteriovenous malformations (AVMs) are vascular malformations characterized by dysmorphic, aberrant vasculature. During previous surgeries of compact nidus brain AVMs (representing the majority of cases), we have observed a "shiny" plane between nidal and perinidal AVM vessels and the surrounding grey and white matter and hypothesized that preoperative neuroimaging of brain AVMs may show a neuroradiological correlate of these intraoperative observations.

Patients And Methods: We retrospectively reviewed and analyzed multiplanar and multisequence 3-Tesla magnetic resonance (3T MR) imaging in five consecutive brain AVMs with special attention on imaging characteristics of the brain-AVM interface, i.

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Background/aim: Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation.

Patients And Methods: In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed.

Practice-pattern variation in anticoagulation intensity in acute cerebral venous thrombosis: A two-center experience.

Background And Purpose: Cerebral venous thrombosis (CVT) requires acute anticoagulation. Heparin is commonly used but specific recommendations on intensity and timing are lacking. We sought to characterize practice-pattern variation in the use of unfractionated heparin (UFH) for acute CVT treatment across multiple centers.

The Perceived Impact of Global Surgery Engagement on Career Advancement among US Medical Students.

Introduction: There is growing interest among medical institutions to formalize global surgery training. Understanding medical students' perceptions of how global surgery engagement can enhance career advancement is essential for providing appropriate guidance and support for individuals with aspirations in academic global surgery.

Methods: A cross-sectional survey study of US-based medical students from 38 participating schools was performed.

Predicting sinonasal inverted papilloma attachment using machine learning: Current lessons and future directions.

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed.

Dissolved metal concentrations in coastal seawater and groundwater in Saipan, Commonwealth of the Northern Mariana Islands, USA.

Saipan, the largest and most populated island of the Commonwealth of the Northern Mariana Islands, has coastal areas with high submarine groundwater discharge (SGD) and heavy metal pollution of sediments. Here, we measured metal concentrations in coastal Saipan groundwater and surface water and explored spatial correlations with pollution sources. Concentrations of Cd, Pb, Cu, and Zn were highest in inland wells, with 3 wells exceeding USEPA guidelines for Cu or Pb.

Subtypes of brain change in aging and their associations with cognition and Alzheimer's disease biomarkers.

Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer's disease biomarkers, and (3) the degree of overlap between clusters derived from different structural modalities in 1899 cognitively healthy older adults followed up to 16 years.

Gut-derived appetite regulating hormones across the anorexia nervosa spectrum.

Background: Appetite-regulating hormones are implicated in anorexia nervosa (AN) pathophysiology, however, data are limited for appetite-regulating hormones across the AN weight spectrum. We aimed to investigate fasting and post-prandial concentrations of appetite-regulating hormones - peptide YY (PYY), cholecystokinin (CCK), and ghrelin - among adolescent and young adult females across the AN weight spectrum, specifically those with AN and Atypical AN, and healthy controls (HC).

Methods: Participants (N = 95; ages 11-22 years) included 33 with AN, 25 with Atypical AN, and 37 HC.

Kinematic Hand Synergies Differ Between Reach-and-Grasp and Functional Object Manipulation.

Humans possess a unique ability to manipulate tools to help us navigate the world around us. This ability is facilitated by the dexterity of our hands. However, millions lose this capability annually due to conditions like limb amputation or Cerebral Vascular Accident (i.

Comparison of DIEP and PAP free flaps for breast reconstruction in the context of breast cancer: A retrospective study of 677 patients over 10 years.

Background: Profunda artery perforator (PAP) flap following cancer surgery has emerged as a relevant alternative for breast reconstruction but is mainly used in cases where the deep inferior epigastric perforator (DIEP) flap cannot be performed. The aim of this study was to compare the PAP and DIEP flaps' surgical and aesthetics outcomes in breast reconstruction.

Methods: Women who underwent breast reconstruction by DIEP or PAP flap at the Plastic Surgery Department of Georges Pompidou European University Hospital, Paris, France, between January 2012 and December 2020 were included.

Medical sovereignty in Eritrea: Reducing maternal mortality and challenging global health humanitarianism in Africa.

This article examines how Eritrea's realization of Millennium Development Goal 5 (the reduction of maternal mortality) reveals the complex workings of medical sovereignty in sub-Saharan Africa. Through the case study of Eritrea, I demonstrate how postcolonial African countries might approach structuring their healthcare systems to navigate-and challenge-the neoliberal contours of global health humanitarianism. By analyzing both Eritrea's colonial history and the liberation-era history of medicine alongside contemporary healthcare policymaking, I trace how racial and gender dynamics shape the reduction of maternal mortality and the pursuit of medical sovereignty more broadly.

Forming Connections: Functional Brain Connectivity is Associated With Executive Functioning Abilities in Early Childhood.

Functional magnetic resonance imaging (fMRI) studies with adults provide evidence that functional brain networks, including the default mode network and frontoparietal network, underlie executive functioning (EF). However, given the challenges of using fMRI with infants and young children, little work has assessed the developmental trajectories of these networks or their associations with EF at key developmental stages. More recently, functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging tool which can provide information on cortical functional networks and can be more easily implemented with young children.

MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.

Introduction: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID).

Methods: Four independent cohorts were examined.

Secondary Prophylaxis of Cirrhotic Gastric Variceal Bleeding: Addition of Non-Selective Beta-Blockers to Endoscopic Combined Treatment.

Background: It remains unclear whether the addition of non-selective beta-blockers (NSBB) provides further benefit after combined use of tissue adhesive and endoscopic variceal ligation for bleeding gastroesophageal varices.

Objective: This is the first cohort study comparing the secondary prophylactic efficacy of adding NSBB to combined endoscopic treatment in cirrhotic patients with gastric varices (without inclusion of isolated gastric varices [IGVs], which are rare in patients with cirrhosis without splanchnic thrombosis).

Methods: We retrospectively analyzed two matched large cohorts of cirrhotic patients with gastric varices who received combined endoscopic treatment and were assigned to receive NSBB treatment or not as secondary prophylaxis.

With big data comes big responsibility: Strategies for utilizing aggregated, standardized, de-identified electronic health record data for research.

Electronic health records (EHRs), though they are maintained and utilized for clinical and billing purposes, may provide a wealth of information for research. Currently, sources are available that offer insight into the health histories of well over a quarter of a billion people. Their use, however, is fraught with hazards, including introduction or reinforcement of biases, clarity of disease definitions, protection of patient privacy, definitions of covariates or confounders, accuracy of medication usage compared with prescriptions, the need to introduce other data sources such as vaccination or death records and the ensuing potential for inaccuracy, duplicative records, and understanding and interpreting the outcomes of data queries.