Structural and functional characterization of FabG4 from Mycolicibacterium smegmatis.

The rise in antimicrobial resistance is a global health crisis and necessitates the development of novel strategies to treat infections. For example, in 2022 tuberculosis (TB) was the second leading infectious killer after COVID-19, with multi-drug-resistant strains of TB having an ∼40% fatality rate. Targeting essential biosynthetic pathways in pathogens has proven to be successful for the development of novel antimicrobial treatments.

Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies.

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is an essential effector of B-cell receptor (BCR) signaling. Chronic activation of BTK-mediated BCR signaling is a hallmark of many hematological malignancies, which makes it an attractive therapeutic target. Pharmacological inhibition of BTK enzymatic function is now a well-proven strategy for the treatment of patients with these malignancies.

Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.

Concern over per- and polyfluoroalkyl substances (PFAS) has increased as more is learned about their environmental presence, persistence, and bioaccumulative potential. The limited monitoring, toxicokinetic (TK), and toxicologic data available are inadequate to inform risk across this diverse domain. Here, 73 PFAS were selected for in vitro TK evaluation to expand knowledge across lesser-studied PFAS alcohols, amides, and acrylates.

Successful Medical-Surgical Management of Intracardiac Thrombosis and Pulmonary Pseudoaneurysms in an Adolescent With Hughes-Stovin Syndrome.

We present an adolescent male with a single intracardiac mass and pulmonary emboli, complicated by peripheral venous thrombosis and subsequent development of pulmonary pseudoaneurysms, leading to diagnosis of Hughes-Stovin syndrome. Remission was achieved with cyclophosphamide, corticosteroids, and pseudoaneurysm resection and maintained with infliximab and methotrexate.

Evaluation of Per- and Polyfluoroalkyl Substances (PFAS) Toxicity Testing for Developmental Neurotoxicity.

Per- and polyfluoroalkyl substances (PFAS) are a diverse set of commercial chemicals widely detected in humans and the environment. However, only a limited number of PFAS are associated with epidemiological or experimental data for hazard identification. To provide developmental neurotoxicity (DNT) hazard information, the work herein employed DNT new approach methods (NAMs) to generate screening data for a set of 160 PFAS.

NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts.

Bruton tyrosine kinase (BTK) is essential for B-cell receptor (BCR) signaling, a driver of chronic lymphocytic leukemia (CLL). Covalent inhibitors bind C481 in the active site of BTK and have become a preferred CLL therapy. Disease progression on covalent BTK inhibitors is commonly associated with C481 mutations.

Dual Balloon Catheter: A Novel Laparoscopic Common Bile Duct Exploration Device.

Choledocholithiasis is a disease process that can be managed by laparoscopic common bile duct exploration at the time of cholecystectomy. However, it can be negatively perceived by surgeons as lengthening procedure time and adding technical complexity. We have created a dual balloon biliary intervention catheter designed to make common duct exploration efficient, simple, and safe.

Implementation of enhanced recovery protocols reduces opioid use in pediatric laparoscopic cholecystectomy surgery.

Purpose: Enhanced recovery protocols [ERPs] standardize care and have been demonstrated to improve surgical quality in adults. We retrospectively compared outcomes before and after implementation of ERPs in children undergoing elective laparoscopic cholecystectomy [ELC] surgery.

Methods: A pediatric-specific ERP was implemented for children undergoing ELC at one [C1] of the two Pediatric Surgical Centers in July 2016.

Impedance planimetry (EndoFLIP) assisted laparoscopic esophagomyotomy in pediatric population.

Introduction: Functional lumen imaging probe (EndoFLIP) is a diagnostic technology that assesses esophageal cross-sectional area via impedance planimetry during controlled volumetric distention. The purpose of this study is to evaluate the utility of EndoFLIP intraoperatively during laparoscopic esophagomyotomy.

Methods: We performed a retrospective cohort study reviewing all patients undergoing EndoFLIP assisted laparoscopic esophagomyotomy for achalasia between January and December 2021 (n = 10).

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B () gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness.

Broad-spectrum cyclic boronate β-lactamase inhibitors featuring an intramolecular prodrug for oral bioavailability.

Early efforts to broaden the spectrum and potency of cyclic boronic acid β-lactamase inhibitor vaborbactam included a series of 7-membered ring boronates. Exploration of stereoisomers and incorporation of heteroatoms allowed identification of the all-carbon cyclic boronate with substituents trans as the preferred core structure, showing inhibition of Class A and C enzymes. Crystal structures of one analog bound to important β-lactamase enzymes were obtained.

Utility of cephalic drains in infants receiving extracorporeal membrane oxygenation.

Introduction: The addition of cephalic drains (CDs) in extracorporeal membrane oxygenation (ECMO) to augment venous drainage may offer benefit, though their use is varied. Our objective was to describe our institution's experience with CDs including flow rates and patency. We also compared complication rates between patients with and without a CD.

Implementation of enhanced recovery protocols reduces opioid use in pediatric laparoscopic Heller myotomy surgery.

Background: Enhanced recovery protocols (ERPs) are effective means of standardizing and improving the quality of surgical care in adults. Our purpose was to retrospectively compare outcomes before and after implementation of ERPs in children undergoing laparoscopic Heller myotomy for achalasia.

Methods: A pediatric-specific ERP was used for children undergoing laparoscopic Heller myotomy starting July 2017 at two pediatric surgery centers within a single metropolitan healthcare system.

Global dissemination of knowledge through virtual platforms: Reflections and recommendations from APSA/IPEG.

Background: The COVID-19 pandemic forced the cancelation of conventional in-person academic conferences due to the risk of virus transmission and limited ability to travel. Both the American Pediatric Surgical Association (APSA) and International Pediatric Endosurgery Group (IPEG) converted to a virtual format for their 2020 annual meetings. The purpose of this article is to review the successful implementation of the APSA and IPEG virtual meetings and reflect upon lessons learned for future virtual conferences.

Minimally invasive surgery of the pancreas: a narrative review of current practice.

Minimally invasive surgery has moved from the fringe of pediatric surgery to the mainstream to address a variety of problems. Pancreatic pathology, though uncommon and complex, is frequently amenable to laparoscopic intervention. Indications for pediatric pancreatic operative intervention includes trauma, congenital hyperinsulinemia and neoplasm.

Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis.

Objectives: To advance our understanding of monogenic forms of intrahepatic cholestasis.

Methods: Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data.

Dietary Exposures and Intake Doses to Bisphenol A and Triclosan in 188 Duplicate-Single Solid Food Items Consumed by US Adults.

Few data exist on bisphenol A (BPA) or triclosan (TCS) residue levels in foods consumed by adults in everyday settings. In a further analysis of study data, the objectives were to determine BPA and TCS residue concentrations in duplicate-single solid food items consumed by adults and to estimate dietary exposure and intake doses per food item. A convenience sample of 50 adults was recruited in North Carolina (2009-2011).

Exposure to Triclosan and Bisphenol Analogues B, F, P, S and Z in Repeated Duplicate-Diet Solid Food Samples of Adults.

Triclosan (TCS) and bisphenol analogues are used in a variety of consumer goods. Few data exist on the temporal exposures of adults to these phenolic compounds in their everyday diets. The objectives were to determine the levels of TCS and five bisphenol analogues (BPB, BPF, BPP, BPS, and BPZ) in duplicate-diet solid food (DDSF) samples of adults and to estimate maximum dietary exposures and intake doses per phenol.

Biologic Mesh Underlay in Thoracoscopic Primary Repair of Congenital Diaphragmatic Hernia Confers Reduced Recurrence in Neonates: A Preliminary Report.

The purpose of this study was to determine if utilization of biologic mesh underlay during thoracoscopic congenital diaphragmatic hernia (CDH) primary repair (PR) results in reduced 5-year hernia recurrence rates. A retrospective review was completed for all primarily repaired CDH utilizing a thoracoscopic approach from January 1, 2003 to June 31, 2013. Patients were included in the study cohort if they had a thoracoscopic PR of their CDH without any mesh reinforcement or with biologic mesh underlay.