Ceftobiprole: A therapeutic update.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.

CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.

Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival.

Influence of birthplace and age at migration on cognitive aging among Hispanic/Latino populations in the U.S.: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background And Objectives: While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging.

Modeling Biases from Low-Pass Genome Sequencing to Enable Accurate Population Genetic Inferences.

Low-pass genome sequencing is cost-effective and enables analysis of large cohorts. However, it introduces biases by reducing heterozygous genotypes and low-frequency alleles, impacting subsequent analyses such as model-based demographic history inference. Several approaches exist for inferring an unbiased allele frequency spectrum (AFS) from low-pass data, but they can introduce spurious noise into the AFS.

Changes in Axial Length in Patients of Acute Retinal Necrosis Undergoing Vitrectomy.

Purpose: To observe the changes in the axial length (AL) in patients of acute retinal necrosis (ARN) undergoing vitrectomy and investigate the correlated factors.

Methods: Retrospective case series. Patients diagnosed as ARN undergoing vitrectomy with silicone oil (SO) tamponade, and with attached retina more than one year after silicone oil removal (SOR) were included.

Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research.

Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease.

Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding , a human coronary artery disease risk locus.

Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms.

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders.

Influence of Source of Origin and Region of Finishing on Growth Performance and Carcass Characteristics of Finishing Heifers Fed in the United States.

The objective was to evaluate growth performance and carcass traits of finishing beef heifers sourced and finished in different regions in the U.S. Heifers [n = 190; initial body weight (BW) 483 ± 0.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.

Background: Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells.

Through-the-sensor sub-bottom imaging using the self-noise of an autonomous underwater vehiclea).

This work demonstrates the feasibility of performing through-the-sensor (TTS) sub-bottom imaging using low-frequency ([100 Hz-1kHz]) self-noise generated by the propulsion of an autonomous underwater vehicle (AUV) acting as a source of opportunity. The self-noise was recorded by a short towed horizontal line array (11.4 m aperture) by the same AUV while it operated ∼35 m above the seabed along a range-dependent section at the New England shelf break.

A meta-analysis of genome-wide association studies to identify candidate genes associated with feed efficiency traits in pigs.

Pig production is an agricultural sector of great economic and social relevance to Brazil and global markets. Feed efficiency traits directly influence the sustainability of pig production due to the economic impact of feed costs on the production system and the environmental footprint of the industry. Therefore, breeding for improved feed efficiency has been a target of worldwide pig breeding programs.

A Pilot Trial of Nicotinamide Riboside and Coenzyme Q10 on Inflammation and Oxidative Stress in Chronic Kidney Disease.

Background: Mitochondria-driven oxidative/redox stress and inflammation play a major role in chronic kidney disease (CKD) pathophysiology. Compounds targeting mitochondrial metabolism may improve mitochondrial function, inflammation, and redox stress; however, there is limited evidence of their efficacy in CKD.

Methods: We conducted a pilot randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/day of coenzyme Q10 (CoQ10) or 1000 mg/day of nicotinamide riboside (NR) supplementation to placebo in 25 people with moderate-to-severe CKD (estimated glomerular filtration rate [eGFR] <60mL/min/1.

Using a Composite Summary of Daily Sex Hormones to Gauge Time Until Menopause: A Focus on Pregnanediol Glucuronide (PDG).

Context: The timing of a woman's final menstrual period (FMP) in relation to her age is considered a valuable indicator of overall health, being associated with cardiovascular, bone health, reproductive, and general mortality outcomes.

Objective: This work aimed to evaluate the relationship between hormones and the "time to FMP" when daily hormone trajectories are characterized by their 1) entropy, and 2) deviation from premenopausal/stable cycle patterns (representing a textbook "gold standard"; GS).

Methods: As part of the Study of Women's Health Across the Nation, urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen conjugates (E1C), and pregnanediol glucuronide (PDG) were measured daily from a multiracial sample of 549 mid-life women for the duration of one menstrual cycle.

A Pilot Intervention to Prevent Financial Exploitation.

Objectives: Based on previous empirical research on financial stressors and resources and using a prevention science framework, this pilot study examined the effect and acceptability of a three-session older adult financial exploitation prevention intervention.

Methods: Forty-five older adults participated in the study. Each participant completed three 30- to 45-minute sessions.

Noninvasive Anemia Detection and Hemoglobin Estimation from Retinal Images Using Deep Learning: A Scalable Solution for Resource-Limited Settings.

Purpose: The purpose of this study was to develop and validate a deep-learning model for noninvasive anemia detection, hemoglobin (Hb) level estimation, and identification of anemia-related retinal features using fundus images.

Methods: The dataset included 2265 participants aged 40 years and above from a population-based study in South India. The dataset included ocular and systemic clinical parameters, dilated retinal fundus images, and hematological data such as complete blood counts and Hb concentration levels.

Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.

Purpose: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells.

Concurrent Surgical Care in an Austere Military Setting: A Preparation for Mass Casualty Events.

Background: The U.S. military utilizes small, forward deployed surgical teams to provide Role 2 surgical care in austere environments.

Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.

Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE).

Pathophysiology, symptoms, outcomes, and evaluation of hyponatremia: comprehension and best clinical practice.

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar includes lively discussions based on cases, which are also partly included in this series as self-assessment questions. The first article in this series focuses on pathophysiology, symptoms, outcomes, and evaluation of hyponatremia, a common water and electrolyte disorder in clinical practice.