Transthyretin Cardiac Amyloidosis: Current and Emerging Therapies.

Purpose Of Review: In this article, we describe current and newer TTR stabilizers, TTR silencers which include small interfering RNA agents (siRNA), antisense oligonucleotides (ASO) and CRISPR-Cas9 gene editing, and TTR depleters, which investigates the use of monoclonal antibodies to remove amyloid fibril deposits for patients with advanced disease.

Recent Findings: Once thought to be a rare and fatal condition, increased recognition, improved non-invasive diagnostic tools, and the explosive development of novel therapies, has transformed the landscape of transthyretin amyloid cardiomyopathy (ATTR-CM). Advances in cardiac imaging with respect to echocardiography, cardiac magnetic resonance imaging (CMR), and radionuclide bone scintigraphy has increased the diagnosis of ATTR-CM over the last twenty years.

Metformin use and pancreatic ductal adenocarcinoma outcomes: a narrative review.

Background: Metformin is a diabetes medication with anti-mitotic properties. A narrative review was performed to investigate people using metformin and the risk of developing pancreatic ductal adenocarcinoma (PDAC) as well as survival outcomes in established PDAC.

Methods: Relevant studies on metformin use and PDAC were retrieved from PubMed including observational studies on metformin and the risk of developing PDAC and survival outcomes in PDAC, and randomized controlled trials of metformin as a treatment in PDAC.

Vascularized composite allograft deceased donation in the United States.

Vascularized composite allograft (VCA) transplantation represents a significant advancement in reconstructive surgery and offers hope to individuals who experienced congenital disorders or severe tissue injuries to restore physical appearance, function, and enhance quality of life. VCA recovery introduces complexities to conventional solid organ recovery, and there remain concerns regarding the potential impact of VCA recovery on non-VCA organs for transplant. The current retrospective study examines deceased donor characteristics and observed-to-expected (O/E) organ yield ratios for 51 VCA donors recovered in the US between July 4, 2014 and March 31, 2024, compared with a contemporary cohort of non-VCA donors recovered in 2023.

Impact and Recovery of VHA Epilepsy Care Services During the COVID-19 Pandemic.

Background: The Epilepsy Centers of Excellence (ECoE) is a network of facilities within the Veterans Health Administration that evaluates and treats veterans with epilepsy and seizure disorders. This article outlines how the COVID-19 pandemic impacted ECoE services and recovery.

Methods: Directors of 17 ECoEs were surveyed 4 times between May 2020 and July 2022 on 5 domains: functioning of outpatient epilepsy clinics, outpatient electroencephalogram, epilepsy monitoring unit, anticipated permanent operational changes, and utility of national and local recommendations.

Age Is Just a Number? A Retrospective Review of Cause of Death in Patients 85 Years and Over Receiving Lung Stereotactic Ablative Radiotherapy.

Introduction: Patients aged > 85 years are under-represented in research that has established stereotactic body radiotherapy (SBRT) as the standard of care in early stage non-small cell lung cancer (NSCLC) not suitable for or refusing surgery. With an ageing population in Australia, it is important to assess SBRT and cause of death (COD) in elderly patients receiving curative intent lung SBRT.

Methods: This is a multi-centre retrospective review of eligible patients treated across Australia from 2016 to 2022 with curative intent lung SBRT for early stage primary NSCLC, and aged 85 years or over.

Article Retraction in Otolaryngology Journals: A Thirty Year Analysis.

Objectives: To gain insight into the integrity of research in Otolaryngology-Head & Neck Surgery (OHNS) literature through characterising retracted articles, analysing the reason for their retraction, and the trends in the collected data.

Methods: Pubmed, Embase, and Retraction Watch Database were queried for retracted articles published between the dates of 1/31/92 and 9/30/22. Articles with titles relating to OHNS subjects and published in OHNS journals, as determined by Scimago Journal and Country Ranking, were selected for further analysis.

Conformational flexibility of human ribokinase captured in seven crystal structures.

d-ribose is a critical sugar substrate involved in the biosynthesis of nucleotides, amino acids, and cofactors, with its phosphorylation to ribose-5-phosphate by ribokinase (RK) constituting the initial step in its metabolism. RK is conserved across all domains of life, and its activity is significantly enhanced by monovalent metal (M) ions, particularly K, although the precise mechanism of this activation remains unclear. In this study, we present several crystal structures of human RK in both unliganded and substrate-bound states, offering detailed insights into its substrate binding process, reaction mechanism, and conformational changes throughout the catalytic cycle.

Ternary stochastic neuron - implemented with a single strained magnetostrictive nanomagnet.

Stochastic neurons are extremely efficient hardware for solving a large class of problems and usually come in two varieties - "binary" where the neuronal state varies randomly between two values of ±1 and "analog" where the neuronal state can randomly assume any value between -1 and +1. Both have their uses in neuromorphic computing and both can be implemented with low- or zero-energy-barrier nanomagnets whose random magnetization orientations in the presence of thermal noise encode the binary or analog state variables. In between these two classes is n-ary stochastic neurons, mainly ternary stochastic neurons (TSN) whose state randomly assumes one of three values (-1, 0, +1), which have proved to be efficient in pattern classification tasks such as recognizing handwritten digits from the MNIST data set or patterns from the CIFAR-10 data set.

ENHANCEMENT OF CIRRHOSIS MORTALITY PREDICTION BY INCLUDING HEPATIC ENCEPHALOPATHY TO MELD3.0 IN A NATIONAL VETERAN COHORT.

Despite negative outcomes, hepatic encephalopathy (HE) is not included in model-for-end-stage liver disease (MELD) scores, including MELD3.0. In a national Veterans affairs (VA) database, we studied the additive mortality predictive impact of a documented inpatient overt HE diagnosis on MELD3.

Life With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Challenges and Burdens.

Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic condition requiring daily medication(s) and attention to details. In addition to daily medications and regular visits with healthcare providers, families may live with perpetual angst regarding unpredictable occurrences of acute adrenal insufficiency. Despite numerous barriers and challenges imposed by this chronic condition, caregivers and healthcare professionals can empower our patients to achieve a good quality of life.

The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1.

Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.

Australian Community Pharmacists' Preparedness to Offer and Discuss Hepatitis C Testing and Treatment With Pharmacy Clients: A Representative Cross-Sectional Survey.

The World Health Organisation (WHO) has set goals to eliminate hepatitis C (HCV) as a global health threat by 2030. To meet this goal, Australia must increase testing and diagnosis, including expanding access to care through community pharmacists. This study aims to explore community pharmacists' preparedness to discuss and offer HCV testing and treatment.

Clinical and Epidemiologic Review of Capnocytophaga Spp. Infections Identified at a Public Health Reference Laboratory-California, 2005-2021.

Introduction: Capnocytophaga is a genus of bacteria that are commensal to the oral microbiome of humans and some animals. Some Capnocytophaga species are found in the human oral cavity and rarely cause disease in people; the species found in animals are zoönotic and can be transmitted to people via saliva. This study describes the clinical and epidemiologic features of patients from whom Capnocytophaga spp.

A probabilistic approach to estimating timber harvest location.

Determining the harvest location of timber is crucial to enforcing international regulations designed to protect natural resources and to tackle illegal logging and associated trade in forest products. Stable isotope ratio analysis (SIRA) can be used to verify claims of timber harvest location by matching levels of naturally occurring stable isotopes within wood tissue to location-specific ratios predicted from reference data ("isoscapes"). However, overly simple models for predicting isoscapes have so far limited the confidence in derived predictions of timber provenance.

Strongyloides Hyperinfection Syndrome (SHS) in a Patient With Prolonged Intensive Care Unit (ICU) Exposure: A Case Report.

Strongyloides hyperinfection syndrome (SHS) is a severe manifestation of the Strongyloides parasite, often occurring in immunocompromised patients due to the inability to subdue larvae autoinfection. As the parasitic burden increases, the patient can develop worsening respiratory symptoms that mimic common pathologies such as chronic obstructive pulmonary disease (COPD). The parasite is endemic to the Appalachian region as well as subtropical and tropical areas worldwide.

Decoding the chicken gastrointestinal microbiome.

Metataxonomic studies have underpinned a vast understanding of microbial communities residing within livestock gastrointestinal tracts, albeit studies have often not been combined to provide a global census. Consequently, in this study we characterised the overall and common 'core' chicken microbiota associated with the gastrointestinal tract (GIT), whilst assessing the effects of GIT site, bird breed, age and geographical location on the GIT resident microbes using metataxonomic data compiled from studies completed across the world. Specifically, bacterial 16S ribosomal DNA sequences from GIT samples associated with various breeds, differing in age, GIT sites (caecum, faeces, ileum and jejunum) and geographical location were obtained from the Sequence Read Archive and analysed using the MGnify pipeline.

Twenty years of advances in prediction of nucleic acid-binding residues in protein sequences.

Computational prediction of nucleic acid-binding residues in protein sequences is an active field of research, with over 80 methods that were released in the past 2 decades. We identify and discuss 87 sequence-based predictors that include dozens of recently published methods that are surveyed for the first time. We overview historical progress and examine multiple practical issues that include availability and impact of predictors, key features of their predictive models, and important aspects related to their training and assessment.

Updating the kidney donor risk index: Removing donor race and hepatitis C virus status.

This study reports the results of a recalculation of the kidney donor risk index (KDRI) formula requested by the Organ Procurement and Transplantation Network's Minority Affairs Committee to remove donor race and hepatitis C virus (HCV) status variables. The updated KDRI model was fit on adult, deceased donor, solitary kidney, first-time transplants from 2018 through 2021. Deceased donors from 2018 through 2021 were included in a counterfactual analysis to evaluate how the kidney donor profile index (KDPI) would change if race and HCV seropositivity were excluded.

Modeling the Health and Economic Impact of Pharmacologic Therapies for MASLD in the United States.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition leading to chronic liver disease which generates substantial health care costs. Our aim was to model the impact on disease and economic burden of a hypothetical pharmacologic therapy which halts MASLD fibrosis progression.

Methods: The U.

Fibrotic extracellular matrix preferentially induces a partial Epithelial-Mesenchymal Transition phenotype in a 3-D agent based model of fibrosis.

One of the main drivers of fibrotic diseases is epithelial-mesenchymal transition (EMT): a transdifferentiation process in which cells undergo a phenotypic change from an epithelial state to a pro-migratory state. The cytokine transforming growth factor-β1 (TGF-β1) has been previously shown to regulate EMT. TGF-β1 binds to fibronectin (FN) fibrils, which are the primary extracellular matrix (ECM) component in renal fibrosis.

Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.

Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine.

Posttraumatic Stress Disorder Is Associated With Endothelial Dysfunction in Women With HIV.

Background: HIV induced endothelial dysfunction (ED) contributes to cardiovascular disease (CVD) in women with HIV (WWH). Although psychosocial stress has been implicated in the development of CVD in HIV, its impact on ED in WWH remains unknown.

Objectives: The authors hypothesized that posttraumatic stress disorder (PTSD) and HIV interact to contribute to ED in WWH.