Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.

Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates.

Engineering CAR-T therapies for autoimmune disease and beyond.

Chimeric antigen receptor-T cell (CAR-T) therapy has transformed the management of refractory hematological malignancies. Now that targeting pathogenic cells of interest with antigen-directed cytotoxic T lymphocytes is possible, the field is expanding the reach of CAR-T therapy beyond oncology. Recently, breakthrough progress has been made in the application of CAR-T technology to autoimmune diseases, exploiting the same validated targets that were used by pioneering CAR-T therapies in hematology.

PKMζ alters oxycodone-taking in a dose- and sex-dependent manner.

Opioid use disorder involves disruptions to glutamate homeostasis and dendritic spine density in the reward system. PKMζ is an atypical isoform of protein kinase C that is expressed exclusively in neurons and plays a role in postsynaptic glutamate signaling and dendritic spine maturation. As opioid use leads to alterations in glutamate transmission and dendritic spine density, we hypothesized that PKMζ deletion would alter opioid-taking behaviors.

Sleep loss-induced oncogenic pathways are mediated via the neuron-specific interleukin-1 receptor accessory protein (AcPb).

Interleukin-1β (IL1), a pleiotropic cytokine, is involved in sleep regulation, tumor ontogeny, and immune responses. IL1 receptor adaptor proteins, including the IL1 receptor accessory protein (AcP), and its neuron-specific isoform, AcPb, are required for IL1 signaling. The AcPb isoform is resultant from alternate splicing of the AcP transcript.

Sleeping Beauty mRNA-LNP enables stable rAAV transgene expression in mouse and NHP hepatocytes and improves vector potency.

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene.

Limitations of glycated albumin standardization when applied to the assessment of diabetes patients.

Objectives: Glycated albumin (GA) has potential value in the management of people with diabetes; however, to draw meaningful conclusions between clinical studies it is important that the GA values are comparable. This study investigates the standardization of the Norudia Glycated Albumin and Lucica Glycated Albumin-L methods.

Methods: The manufacturer reported imprecision was verified by performing CLSI-EP15-A3 protocol using manufacturer produced controls.

Efficacy and Safety of Liraglutide in Patients With an Ileal Pouch-Anal Anastomosis and Chronic High Bowel Frequency: A Placebo-Controlled, Crossover, Proof-of-Concept Study.

Introduction: After colectomy with ileoanal pouch anastomosis (IPAA), many patients develop high bowel frequency (BF) refractory to antimotility agents, despite normal IPAA morphology. Low circulating levels of glucagon-like protein-1 (GLP-1), a modulator of gastroduodenal motility, have been reported after colectomy.

Methods: Double-blind crossover study of 8 IPAA patients with refractory high BF treated with daily administration of the GLP-1 receptor agonist liraglutide or placebo.

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

Introduction: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy.

Methods: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics.

Nociceptive and Transcriptomic Responses in a Swine Diabetic Wound Model Treated With a Topical Angiotensin 1 Receptor Antagonist.

Background: Painful, treatment-resistant wounds are prevalent among diabetic patients and significantly affect health-related quality of life (HRQOL). Topical treatments may help alleviate pain without risk of dependence or side effects. However, there is a lack of topical wound compounds targeting pain-specific receptors.

Innovations in HbA analysis: finding the balance between speed and accuracy. An investigation of a potential new Secondary Reference Measurement Procedure for the IFCC.

Objectives: The escalating prevalence of diabetes worldwide has resulted in a dramatic increase in the number of people who need testing, which in turn necessitates faster HbA measurement. The Tosoh GR01 addresses the need for fast turnaround times of whilst offering pragmatic steps to maintain result accuracy in a single instrument by offering two distinct operating modes: Short Mode (SM) and Long Mode (LM). The aim of this study was to evaluate all relevant aspects of the performance of the Tosoh GR01 with a view to accepting the instrument as a future Secondary Reference Measurement Procedure (SRMP) for the IFCC.

The risk of clinical misinterpretation of HbA1c: Modelling the impact of biological variation and analytical performance on HbA1c used for diagnosis and monitoring of diabetes.

Background: The validity of clinical interpretation of HbA1c depends on the analytical performance of the method and the biological variation of HbA1c in patients. The contribution of non-glucose related factors to the biological variation of HbA1c (NGBVA1c) is not known. This paper explores the cumulative impact of analytical errors and NGBVA1c on the risk of misinterpretation.

Generation of LexA enhancer-trap lines in Drosophila by an international scholastic network.

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons.

An integrated approach to address diabetes in the context of food insecurity: Delivering health study protocol.

Background: Diabetes self-management education and support (DSMES) interventions among food insecure individuals with type 2 diabetes (T2D) have found modest improvements in nutrition and health outcomes but are limited by barriers to attendance and retention. This study applies a community-based participatory research approach, engaging community members at all levels of intervention planning, development, implementation, and dissemination, to deliver a plain-language DSMES curriculum to food insecure community members with T2D.

Methods: This is a single-arm, pre-post design assessing the efficacy of a 12-week home-delivered DSMES curriculum and T2D-appropriate food box intervention to improve the nutrition and health outcomes of food insecure individuals with T2D.

Prevalence and associations between food insecurity and overweight/obesity among native Hawaiian and Pacific Islander adolescents.

Objective: This study estimates the prevalence of, and associations between, family food insecurity and overweight/obesity among Native Hawaiian and Pacific Islander (NHPI) adolescents and explores socio-demographic factors which might have a moderation effect on the association.

Design: Cross-sectional study using 2014 NHPI-National Health Interview Survey data reported by a parent or guardian. Family-level food security was assessed by the US Department of Agriculture 10-item questionnaire.

Food Pantry Clients' Needs, Preferences, and Recommendations for Food Pantries: A Qualitative Study.

A qualitative formative approach was used to explore food pantry clients' needs, preferences, and recommendations regarding food received from food pantries. Fifty adult clients of six Arkansas food pantries were interviewed in English, Spanish, or Marshallese. Data analysis used the constant comparative qualitative methodology.

Experiences of Farmers Market Vendors in a Healthy Food Incentive Program.

Healthy food incentive programs for Supplemental Nutrition Assistance Program participants, often implemented in farmers markets, have shown promise in improving the purchase and consumption of fruits and vegetables. However, variation in program context, program strategies, and participant populations has produced gaps in knowledge about which healthy food incentive program implementation strategies are most effective, and few studies have focused on farmers market vendors' experiences. This study evaluated experiences of farmers market vendors who participated in the Northwest Arkansas Double Your Dollars (NWA DYD) healthy food incentive program intended to increase access to healthy foods for local Hispanic/Latino and Marshallese community members with low incomes.

Micropatterned fibrin scaffolds increase cardiomyocyte alignment and contractility for the fabrication of engineered myocardial tissue.

Cardiovascular disease is the leading cause of death in the United States, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI), scar tissue formation in the myocardium, and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplantation. An alternative to total-organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch.

Equipping nutrition graduates for the complex realities of practice: Using practitioner perspectives and experiences to inform authentic sustainability curriculum.

Background: Nutrition professionals function at the nexus of food, nutrition status and the myriad of determinants influencing these. However, defining our role in food system transformation requires a multifaceted and deep understanding of sustainability in the context of nutrition and dietetics (N&D). Practitioner perspectives and experiences provide a rich source of practice wisdom that can inform authentic curriculum to equip students for the complex realities of practice; however, there is limited understanding of these in the Australian higher education setting.

Hiatal failure: effects of pregnancy, delivery, and pelvic floor disorders on level III factors.

Introduction And Hypothesis: The failure of the levator hiatus (LH) and urogenital hiatus (UGH) to remain closed is not only associated with pelvic floor disorders, but also contributes to recurrence after surgical repair. Pregnancy and vaginal birth are key events affecting this closure. An understanding of normal and failed hiatal closure is necessary to understand, manage, and prevent pelvic floor disorders.

Reducing Sodium Content of Foods Served in Arkansas's Largest School District: Evaluation of the Sodium Reduction in Communities Program.

Purpose And Objectives: The Centers for Disease Control and Prevention's Sodium Reduction in Communities Program aims to reduce dietary sodium intake through policy, systems, and environmental approaches. The objective of our study was to evaluate changes in sodium levels over 5 years (2016-2021) in food served in school lunches as an outcome of a Sodium Reduction in Communities program in Arkansas's largest school district.

Intervention Approach: We collaborated with Springdale Public Schools (SPS) to reduce dietary sodium intake in school lunches through increased implementation of 1) food service guidelines, 2) procurement practices, 3) food preparation practices, and 4) environmental strategies.

Food Pantry Usage Patterns are Associated with Client Sociodemographics and Health.

Characterizing food pantry (FP) clients' FP usage patterns may provide opportunities to tailor health-related interventions. Respondents (n=245) at seven FPs reported their frequency and reliance on FPs and their sociodemographics, health status, and health-related trade-offs. Clients were categorized via latent class analysis.

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting.

Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study.

Methods: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56.