Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. T2DM increases the risk for AD by approximately twofold. Animal models provide one means of interrogating the relationship of T2DM to AD and investigating brain insulin resistance in the pathophysiology of AD.

Applying implementation science in mental health services: Technical assistance cases from the Mental Health Technology Transfer Center (MHTTC) network.

Objective: Critical gaps exist between implementation of effective interventions and the actual services delivered to people living with mental disorders. Many technical assistance (TA) efforts rely on one-time trainings of clinical staff and printed guidelines that alone are not effective in changing clinical practice. The Mental Health Technology Transfer Center (MHTTC) Network uses implementation science to accelerate the use of evidence-based practices (EBPs), improve performance, and bring about systems-level change.

ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization.

ATRX, a chromatin remodeler protein, is recurrently mutated in H3F3A-mutant pediatric glioblastoma (GBM) and isocitrate dehydrogenase (IDH)-mutant grade 2/3 adult glioma. Previous work has shown that ATRX-deficient GBM cells show enhanced sensitivity to irradiation, but the etiology remains unclear. We find that ATRX binds the regulatory elements of cell-cycle phase transition genes in GBM cells, and there is a marked reduction in Checkpoint Kinase 1 (CHEK1) expression with ATRX loss, leading to the early release of G2/M entry after irradiation.

Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer's disease.

Background: Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful.

Methods: To address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein-protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics.

Extending Expectancy Theory to Food Intake: Effect of a Simulated Fast-Food Restaurant on Highly and Minimally Processed Food Expectancies.

Unhealthy diets are widespread and linked to a number of detrimental clinical outcomes. The current preregistered experiment extended Expectancy Theory into the study of food intake; specifically, we tested whether a fast-food restaurant affects food expectancies, or the emotions one expects to feel while eating highly (e.g.

Brain Health Executives: A Transdisciplinary Workforce Innovation-A Commentary.

Given the rapidly evolving landscape of technologies, social, health, and consumer trends, the development of effective Brain Health Executives is a key workforce innovation. Convergence Brain Health involves the integration of scientists, clinicians, bioinformaticists, global health experts, social scientists, engineers, technology entrepreneurs, medical educators, caregivers, and consumers. Synergy between government, academia, and industry is also vital.

Transitioning from Intravenous to Subcutaneous Vedolizumab in Patients with Inflammatory Bowel Disease [TRAVELESS].

Background And Aims: Subcutaneous [SC] vedolizumab presents the opportunity for inflammatory bowel disease [IBD] patients to manage their treatment at home. There are currently no data on the process of transitioning patients established on intravenous [IV] to SC vedolizumab as part of routine clinical care. The aim of this programme is to evaluate the clinical and biochemical outcomes of switching a cohort of IBD patients established on IV vedolizumab to SC, at 12 weeks following the transition.

Development and assessment of a brief screening tool for psychosis in dementia.

Introduction: Hallucinations and delusions (H+D) are common in dementia, but screening for these symptoms-especially in busy clinical practices-is challenging.

Methods: Six subject matter experts developed the DRP3™ screen, a novel valid tool to detect H+D in dementia, assessed its content validity through alignment with DRP reference assessments (Scale for the Assessment of Positive Symptoms-Hallucinations + Delusions, Neuropsychiatric Inventory-Questionnaire, International Psychogeriatric Association Criteria), and retrospectively investigated its ability to detect H+D in HARMONY trial (NCT03325556) enrollees.

Results: All items from three reference assessments demonstrated significant agreement with the DRP3 screen among raters ( < .

Highly processed food intake and immediate and future emotions in everyday life.

Increased consumption of highly processed foods may result in lower diet quality, and low diet quality is associated with elevated risk of cardiovascular disease, type 2 diabetes, and cancer. One mechanism driving highly processed food intake is the expectation that eating these foods will improve emotional experiences, particularly in individuals with elevated "highly processed food addiction" symptoms. However, experimental findings about the emotional experiences following highly processed food intake are mixed.

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design.

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against , mono-resistant MTB strains, and nontuberculous strains and Mycobacterium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound ), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains.

Disease modification is not all - we need symptomatic therapies for Alzheimer disease.

A new study found methylphenidate to be effective in treating apathy in individuals with Alzheimer disease. At a time when the recent aducanumab approval is focusing attention on the promise of disease-modifying therapies, the new findings highlight the importance of developing better symptomatic treatment options for individuals with psychiatric disorders of Alzheimer disease.

The probabilistic model of Alzheimer disease: the amyloid hypothesis revised.

The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered.

Stakeholder perspectives on the advantages and challenges of expanded school mental health services for publically-insured youth.

Although partnerships between community-based mental health (MH) organizations and school systems to deliver MH services on school grounds (i.e., expanded school mental health, ESMH services) are growing, qualitative research is needed about stakeholders' perspectives on ESMH services.

The Alzheimer's disease drug development landscape.

Background: Alzheimer's disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration.

Return of individual research results from genomic research: A systematic review of stakeholder perspectives.

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders' perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them.

A Pavlovian Intervention to Condition Comforting Effects of Fruits.

Objective: Perceived stress, lower fruit intake, and comfort eating are all risk factors for chronic disease. The present pilot study aimed to simultaneously mitigate all three risk factors by applying Pavlovian conditioning to change the nature of comfort eating. Specifically, stressed participants underwent a Pavlovian conditioning intervention designed to elicit comforting effects of fruit intake and thereby reduce negative mood while promoting fruit intake.

Knowledge creation through collaboration: The role of shared institutional affiliations and physical proximity.

This paper examines how shared affiliations within an institution (e.g., same primary appointment, same secondary appointment, same research center, same laboratory/facility) and physical proximity (e.

The Unifying Hypothesis of Alzheimer's Disease: Heparan Sulfate Proteoglycans/Glycosaminoglycans Are Key as First Hypothesized Over 30 Years Ago.

The updated "Unifying Hypothesis of Alzheimer's disease" (AD) is described that links all the observed neuropathology in AD brain (i.e., plaques, tangles, and cerebrovascular amyloid deposits), as well as inflammation, genetic factors (involving ApoE), "AD-in-a-Dish" studies, beta-amyloid protein (Aβ) as a microbial peptide; and theories that bacteria, gut microflora, gingivitis and viruses all play a role in the cause of AD.

Optimization of TopoIV Potency, ADMET Properties, and hERG Inhibition of 5-Amino-1,3-dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Identification of a Lead with Efficacy against MRSA.

Novel bacterial topoisomerase inhibitors (NBTIs) are among the most promising new antibiotics in preclinical/clinical development. We previously reported dioxane-linked NBTIs with potent antistaphylococcal activity and reduced hERG inhibition, a key safety liability. Herein, polarity-focused optimization enabled the delineation of clear structure-property relationships for both microsomal metabolic stability and hERG inhibition, resulting in the identification of lead compound .

Aducanumab: Appropriate Use Recommendations.

Aducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer's disease (AD). Clinicians require guidance on the appropriate use of this new therapy. An Expert Panel was assembled to construct Appropriate Use Recommendations based on the participant populations, conduct of the pivotal trials of aducanumab, updated Prescribing Information, and expert consensus.

The costs of developing treatments for Alzheimer's disease: A retrospective exploration.

Introduction: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs-all for symptomatic treatment only-have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector.

Methods: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1-4) conducted between January 1, 1995 and June 21, 2021 from various databases.

Rational design of a new antibiotic class for drug-resistant infections.

The development of new antibiotics to treat infections caused by drug-resistant Gram-negative pathogens is of paramount importance as antibiotic resistance continues to increase worldwide. Here we describe a strategy for the rational design of diazabicyclooctane inhibitors of penicillin-binding proteins from Gram-negative bacteria to overcome multiple mechanisms of resistance, including β-lactamase enzymes, stringent response and outer membrane permeation. Diazabicyclooctane inhibitors retain activity in the presence of β-lactamases, the primary resistance mechanism associated with β-lactam therapy in Gram-negative bacteria.

There's no sugar-coating psychological distress and illness perceptions in gestational diabetes mellitus: depression and anxiety are associated with negative illness perceptions.

Objective: To gain an understanding of how women with gestational diabetes perceive their illness, and whether depressive/anxiety symptoms and/or psychological distress influence these illness perceptions.

Method: A cross-sectional study was conducted with 159 pregnant women aged 18-44 attending gestational diabetes clinics. Participants completed a questionnaire, which included the Edinburgh Depression Scale (EDS), Kessler 10-item Psychological Distress Scale (K-10), Brief Illness Perception Questionnaire (BIPQ), and psychiatric/general health items.