A Review of Initial and Ongoing Training Needs through the Alabama Regional Center for Infection Prevention and Control.

Established in 2021, the Alabama Regional Center for Infection Prevention and Control (ARC IPC) aims to address critical gaps in infection prevention and control (IPC) across Alabama's public health and healthcare systems. Through a comprehensive needs assessment, the Center identified priority areas which informed its targeted training and technical assistance programs. This paper examines the Center's multifaceted approach to addressing significant IPC challenges throughout the state, with particular emphasis on underserved areas.

Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca channel (Ca1.2) and reduce Ca-dependent inactivation.

Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship.

Evaluation and treatment of lead toxicosis in rehabilitated avian species: 95 cases (2014-2023).

Objective: To evaluate avian patients presented to a wildlife rehabilitation facility with confirmed lead toxicity for clinical signs associated with blood lead level groups, efficacy of subcutaneous chelation therapy with calcium disodium EDTA, and case outcome based on presenting blood lead levels.

Methods: A retrospective record review of 95 avian cases representing 19 species treated for lead toxicosis from a wildlife rehabilitation center in Wisconsin between 2014 and 2023 was conducted. Data were evaluated for presenting complaints, clinical signs, radiographic findings, chelation therapy protocol, clinical pathology data, and case outcome.

Liver safety of tolvaptan in patients with autosomal dominant polycystic kidney disease: interim data from a post-authorization safety study.

Background: After the risk of drug-induced liver injury was detected during tolvaptan clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), a post-marketing pharmacovigilance study was required for European Union regulatory approval.

Methods: This is an interim analysis from a prospective, observational study enrolling patients prescribed tolvaptan for ADPKD in routine clinical practice. Data were obtained through physician records collected during regular care.

Computationally accelerated identification of P-glycoprotein inhibitors.

Overexpression of the polyspecific efflux transporter, P-glycoprotein (P-gp, MDR1, ), is a major mechanism by which cancer cells acquire multidrug resistance (MDR), the resistance to diverse chemotherapeutic drugs. Inhibiting drug transport by P-gp can resensitize cancer cells to chemotherapy, but there are no P-gp inhibitors available to patients. Clinically unsuccessful P-gp inhibitors tend to bind at the pump's transmembrane drug binding domains and are often P-gp transport substrates, resulting in lowered intracellular concentration of the drug and altered pharmacokinetics.

Addressing infection prevention and control in Alabama through the long-term care strike team.

The COVID-19 pandemic exposed the lack of infection prevention and control (IPC) infrastructure among long-term care facilities (LTCFs) in the United States; the situation in Alabama is particularly dire with LTCFs receiving some of the lowest quality ratings in the country. Alabama's LTCFs continue to be challenged by frequent staff turnover, vaccine hesitancy, and reluctance to embrace new Centers for Disease Control and Prevention (CDC) recommendations such as enhanced barrier precautions. However, the made funds available to states through a CDC Epidemiology and Laboratory (ELC) Cooperative Agreement to promote IPC system improvement, including the creation of the Alabama Nursing Home and Long-Term Care Strike Team (LTC Strike Team).

Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.

SARS-CoV-2 has the capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta-the most pathogenic variant in a highly susceptible animal model.

Equipping the Public Health Workforce of the Future: Evaluation of an Evidence-Based Public Health Training Delivered Through Academic-Health Department Partnerships.

Objective: Maintaining a skilled public health workforce is essential but challenging given high turnover and that few staff hold a public health degree. Situating workforce development within existing structures leverages the strengths of different organizations and can build relationships to address public health challenges and health equity. We implemented and evaluated an innovative, sustainable model to deliver an established evidence-based public health (EBPH) training collaboratively among Prevention Research Centers (PRC), local and state health departments, and Public Health Training Centers (PHTC).

Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.

Macrocyclic drugs can address an increasing range of molecular targets but enabling central nervous system (CNS) access to these drugs has been viewed as an intractable problem. We designed and synthesized a series of quinolinium-modified cyclosporine derivatives targeted to the mitochondrial cyclophilin D protein. Modification of the cation to enable greater delocalization was confirmed by x-ray crystallography of the cations.

An analysis of ICAR recommendations for long-term care facilities in Alabama.

The Alabama Long-Term Care Strike Team was established in 2022 to help long-term care facilities build and maintain infection prevention and control (IPC) systems. Infection preventionists use CDC's Infection Control Assessment and Response (ICAR) tools to provide IPC-specific recommendations. Analysis of ICAR recommendations identified the 3 greatest training needs in Alabama: source control, hand hygiene, and environmental cleaning.

Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial.

Rationale & Objective: Body mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan.

Expanding the Public Health Pipeline Through the Public Health Influencers Summer Institute.

The need for a robust public health system in the United States is critical for safeguarding population health. However, current data suggest an insufficient number of individuals entering or staying in the governmental public health workforce. Expanding the public health pipeline requires creative thinking about recruitment and training activities.

Loss of the E3 ubiquitin ligase TRIM67 alters the post-synaptic density proteome.

The E3 ubiquitin ligase TRIM67 is enriched in the central nervous system and is required for proper neuronal development. Previously we demonstrated TRIM67 coordinates with the closely related E3 ubiquitin ligase TRIM9 to regulate cytoskeletal dynamics downstream of the netrin-1 during axon guidance and axon branching in early neuronal morphogenesis. Interestingly, loss of impacts cognitive flexibility in a spatial learning and memory task.

Uncovering Structural Plasticity of through Deep Insertional and Deletional Scanning.

Insertions and deletions (InDels) are essential sources of novelty in protein evolution. In RNA viruses, InDels cause dramatic phenotypic changes contributing to the emergence of viruses with altered immune profiles and host engagement. This work aimed to expand our current understanding of viral evolution and explore the mutational tolerance of RNA viruses to InDels, focusing on Enterovirus A71 (EV-A71) as a prototype for Enterovirus A species (EV-A).

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative (DN) mode-of-action, wherein an increased level of AFF3 resulted in pathological effects.

Methods: Evolutionary constraints suggest that other mode-of-inheritance could be at play.

Multi-monoubiquitylation controls VASP-mediated actin dynamics.

The actin cytoskeleton performs multiple cellular functions, and as such, actin polymerization must be tightly regulated. We previously demonstrated that reversible, non-degradative ubiquitylation regulates the function of the actin polymerase VASP in developing neurons. However, the underlying mechanism of how ubiquitylation impacts VASP activity was unknown.

Loss of the E3 ubiquitin ligase TRIM67 alters the post-synaptic density proteome.

The E3 ubiquitin ligase TRIM67 is enriched in the central nervous system and is required for proper neuronal development. Previously we demonstrated TRIM67 coordinates with the closely related E3 ubiquitin ligase TRIM9 to regulate cytoskeletal dynamics downstream of the netrin-1 during axon guidance and axon branching in early neuronal morphogenesis. Interestingly, loss of impacts cognitive flexibility in a spatial learning and memory task.

The E3 ubiquitin ligase TRIM9 regulates synaptic function and actin dynamics.

During neuronal development, dynamic filopodia emerge from dendrites and mature into functional dendritic spines during synaptogenesis. Dendritic filopodia and spines respond to extracellular cues, influencing dendritic spine shape and size as well as synaptic function. Previously, the E3 ubiquitin ligase TRIM9 was shown to regulate filopodia in early stages of neuronal development, including netrin-1 dependent axon guidance and branching.

Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends.

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which the bound nucleotide regulates the strength of tubulin:tubulin interactions is debated. The 'self-acting' (cis) model posits that the nucleotide (GTP or GDP) bound to a particular tubulin dictates how strongly that tubulin interacts, whereas the 'interface-acting' (trans) model posits that the nucleotide at the interface of two tubulin dimers is the determinant. We identified a testable difference between these mechanisms using mixed nucleotide simulations of microtubule elongation: with a self-acting nucleotide, plus- and minus-end growth rates decreased in the same proportion to the amount of GDP-tubulin, whereas with interface-acting nucleotide, plus-end growth rates decreased disproportionately.

Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.