Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

Risks of Autologous Abdominal Free Flap Breast Reconstruction in Patients With Elevated Body Mass Index.

Background: Obesity is widely recognized as a significant risk factor for postoperative complications of breast reconstruction. Despite extensive research, there remains a lack of consensus regarding the specific complications and outcomes experienced by patients with obesity who undergo deep inferior epigastric perforator (DIEP) flap reconstruction. To provide a clearer understanding of the challenges faced by patients with obesity, we present a single-center outcome analysis of individuals who underwent DIEP flap reconstruction.

Anatomical mapping of neural lineages expressing the transient receptor potential vanilloid type 1 receptor using a modified and combined PACT and CUBIC protocol for rapid tissue clearance.

Aim: Tissue clearance is a rapidly evolving technology that allows for the three-dimensional imaging of intact biological tissues. Preexisting tissue-clearing techniques, such as Passive Clarity Technique (PACT) and Clear Unobstructed Brain Imaging Cocktails and Computational Analysis (CUBIC), clear tissues adequately but have distinct disadvantages, such as taking extensive time to clear tissues and degradation of endogenous tissue fluorescence. We developed a new tissue-clearing technique combining PACT and CUBIC protocols to map the neural lineages expressing the transient receptor potential vanilloid type 1 (TRPV1) receptor.

Demographic and Geographic Trends in First-Episode Psychosis: A Cross-Sectional Study of Hospital Discharge Data in Adolescents and Young Adults.

This cross-sectional study aimed to assess the demographic and geographic variations in the visit rate for first-episode psychosis (FEP), identify trends and diagnostic patterns, and explore factors associated with FEP visits in Nebraska. Inpatient and emergency department data spanning 2017-2021 were collected by the Nebraska Hospital Association (NHA). The study focused on Nebraska residents aged 14-35 admitted for FEP, identified through specific ICD-10 codes.

Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.

The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation.

Use of disease modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis.

Background: Biologic (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis (RA) target inflammatory pathways implicated in the pathogenesis of multiple myeloma (MM). It is unknown whether use of b/tsDMARDs affects the incidence of MM.

Methods: In this cohort study using Veterans Health Administration (VHA) data, we identified Veterans newly diagnosed with RA from 1/1/2002 to 12/31/2018 using diagnostic codes and medication fills.

Precision Medicine in Congenital Heart Disease, Rheumatic Heart Disease, and Kawasaki Disease of Children: An Overview of Literature.

Congenital heart disease and common acquired heart diseases like Kawasaki disease and rheumatic heart disease are prevalent cardiovascular conditions in children worldwide. Despite the availability of treatment options, they continue to be significant contributors to morbidity and mortality. Advancements in early diagnosis, improvements in treatment approaches, and overcoming resistance to available treatments are crucial to reduce morbidity.

Altering the redox status of directly impacts its developmental cycle progression.

is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown.

Cardiac Critical Care of the Cardio-Obstetric Patient.

Cardiovascular disease (CVD) is the leading cause of pregnancy-related mortality in the United States, with an incidence that has increased from 7.2 to 32.9 fatalities per 100,000 live births in the last 3 decades.

A preliminary analysis of teaching children with autism spectrum disorder self-protection skills for bullying situations.

Children diagnosed with autism spectrum disorder are at high risk of being bullied, but research on teaching children with autism self-protection skills for bullying situations is scant. We taught five children self-protection skills for two types of bullying (threats and unkind remarks) and consecutive bullying occurrences. We first evaluated behavioral skills training and a textual prompt to teach children to report threats of physical or material harm, provide a disapproving statement after a first unkind remark, and occupy themselves with an activity away from a bully after a second unkind remark.

Facilitators and Barriers to COVID-19 Vaccine Uptake Among Meat Processing Workers in Nebraska: A Mixed-Methods Analysis Using the COM-B Model.

The meat processing industry was significantly impacted by the COVID-19 pandemic. Deemed essential, the meat processing workforce faced the risk of exposure to the SARS-CoV-2 virus. Along with other essential workforces, meat processing workers were prioritized in the national approach to receive COVID-19 vaccines by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.

Ground Reaction Forces and Joint Moments Predict Metabolic Cost in Physical Performance: Harnessing the Power of Artificial Neural Networks.

Understanding metabolic cost through biomechanical data, including ground reaction forces (GRFs) and joint moments, is vital for health, sports, and rehabilitation. The long stabilization time (2-5 min) of indirect calorimetry poses challenges in prolonged tests. This study investigated using artificial neural networks (ANNs) to predict metabolic costs from the GRF and joint moment time series.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Blood Culture Use in Medical and Surgical Intensive Care Units and Wards.

Importance: Blood culture (BC) use benchmarks in US hospitals have not been defined.

Objective: To characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.

Design, Setting, And Participants: A retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

Health Care Resource Utilization With Dronedarone Versus Sotalol Following Catheter Ablation in Adults With Atrial Fibrillation.

Background: Clinical trials support dronedarone use for atrial fibrillation (AF) following catheter ablation (CA); however, comparative data on health care resource utilization (HCRU) with other antiarrhythmic drugs are lacking.

Methods: Retrospective analysis of Merative MarketScan databases (January 01, 2012-March 31, 2020) comparatively assessed HCRU in US adults with AF who received dronedarone or sotalol post-CA. Patients with ≥ 12-months' pre-CA data were followed from post-CA index treatment to disenrollment, death, or study end.

Break through the mold: Hyper-IgE syndrome as a vehicle for invasive aspergillosis.

Hyperimmunoglobulin E syndrome (HIGES) is a rare immunodeficiency characterized by high levels of immunoglobulin E (IgE) in the setting of various clinical features such as cutaneous candidiasis, asthma, recurrent rashes, and fungal infections. This case describes a 70-year-old male with cachexia and dyspnea found to have a cavitary lesion and aspergilloma, with remarkably high IgE and positive 1,3-β-D-glucan and Aspergillus testing. Herein, we describe the aforementioned case, review the available literature, and hypothesize the connection between invasive fungal infections and HIGES.

FOXJ3, a novel tumor suppressor in neuroblastoma.

Neuroblastoma (NB) poses a significant challenge in pediatric cancer care due to its aggressive nature and poor prognosis. While advances have been made in clinical treatments, therapy resistance remains a tough hurdle in NB treatment. While much research has focused on identifying oncogenes in NB, there has been less emphasis on understanding tumor suppressors.

Identifying Predictors of Extended Intensive Care Unit Stay Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: An Analysis of 101 ACS NSQIP Pediatric Participating Centers.

Background: While prolonged operative time and increased levels fused have been shown to increase the risk of prolonged intensive care unit (ICU) length-of-stay (LOS), studies are limited in guiding decision-making regarding the need for intensive care postoperatively. This is especially the case among the cohort of adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF); associations between comorbidities and ICU LOS are not well-delineated.

Methods: AIS patients who underwent PSF from January 1st, 2016 to December 1st, 2016 at 101 participating centers were identified using the American College of Surgeons (ACS) National Surgical Quality Im-provement Project (NSQIP) Pediatric database.

The MyLungHealth study protocol: a pragmatic patient-randomised controlled trial to evaluate a patient-centred, electronic health record-integrated intervention to enhance lung cancer screening in primary care.

Introduction: Early lung cancer screening (LCS) through low-dose CT (LDCT) is crucial but underused due to various barriers, including incomplete or inaccurate patient smoking data in the electronic health record and limited time for shared decision-making. The objective of this trial is to investigate a patient-centred intervention, MyLungHealth, delivered through the patient portal. The intervention is designed to improve LCS rates through increased identification of eligible patients and informed decision-making.

Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions.

is an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle, modifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM, manipulates the host cell to acquire lipids and nutrients necessary for its growth.