Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments.

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates.

Controlling the Subcellular Localization of Signaling Proteins Using Chemically Induced Dimerization and Optogenetics.

A given protein can perform numerous roles in a cell with its participation in protein complexes and distinct localization within the cell playing a critical role in its diverse functions. Thus, the ability to artificially dimerize proteins and recruit proteins to specific locations in a cell has become a powerful tool for the investigation of protein function and the understanding of cell biology. Here, we discuss two systems that have been used to activate signal transduction pathways, a chemically inducible dimerization (CID) and a light-inducible (LI) system to control signaling and cytoskeletal regulation in a spatial and temporal manner.

Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

Background And Objectives: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear.

Methods: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19).

Impairment of the Glial Phagolysosomal System Drives Prion-Like Propagation in a Model of Huntington's Disease.

Protein misfolding, aggregation, and spread through the brain are primary drivers of neurodegenerative disease pathogenesis. Phagocytic glia are responsible for regulating the load of pathological proteins in the brain, but emerging evidence suggests that glia may also act as vectors for aggregate spread. Accumulation of protein aggregates could compromise the ability of glia to eliminate toxic materials from the brain by disrupting efficient degradation in the phagolysosomal system.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy.

Promoting hands-on science learning globally with low-cost lab kits through Women Supporting Women in the Sciences.

Women Supporting Women in the Sciences (WS2)-ws2global.org-is an international initiative unifying and supporting graduate- and professional-level women and allies in science, technology, engineering, and mathematics (STEM), while providing outreach to elementary- and secondary-level students. WS2 has been involved in the development of professional development workshops intended to empower university women and promote STEM careers.

Assessing Effectiveness of Physical Therapy Clinical Education Site Visits: Clinical Instructor and Student Perspectives.

Introduction: Video, phone, or in-person site visits are used to assess clinical education in entry-level physical therapy education programs. The perspectives of students and clinical instructors (CIs) related to site visits were examined in this article using 2 consecutive surveys. The first included items related to in-person and phone call site visits.

"I go out of my way to give them an extra smile now:" A study of pharmacists who participated in Respond to Prevent, a community pharmacy intervention to accelerate provision of harm reduction materials.

Background: Community pharmacies are well-positioned to improve the health of people with opioid use disorder and who use drugs by providing naloxone and other essential public health supplies. Respond to Prevent (R2P) is a clinical trial which sought to accelerate provision of harm reduction materials through a multicomponent intervention that included in-store materials, online training, and academic detailing.

Objectives: The objective of this study was to explore pharmacists' attitudes, knowledge, and experiences in providing naloxone, dispensing buprenorphine, and selling nonprescription syringes following participation in the R2P program.

Impairment of the glial phagolysosomal system drives prion-like propagation in a model of Huntington's disease.

Protein misfolding, aggregation, and spread through the brain are primary drivers of neurodegenerative diseases pathogenesis. Phagocytic glia are responsible for regulating the load of pathogenic protein aggregates in the brain, but emerging evidence suggests that glia may also act as vectors for aggregate spread. Accumulation of protein aggregates could compromise the ability of glia to eliminate toxic materials from the brain by disrupting efficient degradation in the phagolysosomal system.

Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques.

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness.

Novel Triazolopyridine-Based BRD4 Inhibitors as Potent HIV-1 Latency Reversing Agents.

Bromodomain-containing protein 4 (BRD4) inhibitors have been proven to be a promising option for anti-HIV-1 latency therapeutics. We herein describe the design, synthesis, and anti-HIV-1 latency bioevaluation of triazolopyridine derivatives as BRD4 inhibitors. Among them, compound displayed favorable HIV-1 reactivation and prominent safety profile without triggering abnormal immune activation.

Should secondary pharmacogenomic variants be actively screened and reported when diagnostic genome-wide sequencing is performed in a child?

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over time, decision supports to assist using pharmacogenetic results in future treatment decisions, and sharing information in public databases to improve the clinical interpretation of pharmacogenetic variants identified in other children. We conclude by presenting a series of points to consider for clinicians and policymakers regarding whether, and under what circumstances, routine screening and return of pharmacogenomic variants unrelated to the indications for testing is appropriate in children who are undergoing genome-wide sequencing to assist in the diagnosis of a suspected genetic disease.

Documenting limited health literacy in a clinical setting.

Objective: Health literacy is important in lung cancer care, where treatments and symptoms are difficult to navigate. This study aims to describe how a single-item measure of health literacy can facilitate health literacy system capacity.

Methods: Data include retrospective medical records from 456 patients with lung cancer.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

Background And Objectives: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance.

Administration of β-lactam antibiotics to patients with reported penicillin allergy in the emergency department.

Background: β-lactam antibiotics are amongst the most commonly prescribed medications in the Emergency Department (ED) due to their role in empiric sepsis therapy; however, inferior therapeutic options are often utilized due to a reported allergy; penicillin (PCN) being most frequent. In the United States, 10% of the population endorses an allergic reaction to PCN while <1% experience IgE-mediated reactions. This study aimed to evaluate the frequency and outcome of patients in the ED whose PCN allergies were challenged with β-lactam antibiotics.

Commentary: When applying dietary therapies for gastrointestinal conditions, family values, culture, and social challenges matter.

Some gastrointestinal conditions now have diet as a cornerstone to therapy. Three examples include the low-fermentable, oligosaccharide, disaccharide, monosaccharide, and polyol diet for irritable bowel syndrome, a gluten-free diet for celiac disease, and a hypoallergenic diet for eosinophilic esophagitis. All have been shown to be effective in Western or highly industrialized countries.

Nail Changes during Pregnancy: A Cross-Sectional Survey of Patients at an Academic Center.

Introduction: Physiological changes in skin and hair are common during pregnancy. There are limited data on nail changes during pregnancy. Therefore, our study objectives were to determine prevalence and types of nail changes in pregnant women.

Cost-effectiveness of precision molecular diagnostic tests for stage II colorectal cancer.

Background: In colorectal cancer, inappropriate use of adjuvant chemotherapies may lead to significant increases in healthcare costs and harms to patients. Genome-based interventions are being increasingly used in the stratification of patients according to their risk profiles. However, earlier cost-effectiveness analyses of precision molecular diagnostics have indicated a paucity of data on comparative health economic outcomes.

Criteria for placental examination for obstetrical and neonatal providers.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach.

Single dose topical inserts containing tenofovir alafenamide fumarate and elvitegravir provide pre- and post-exposure protection against vaginal SHIV infection in macaques.

Background: Vaginal products for HIV prevention that can be used on-demand before or after sex may be a preferable option for women with low frequency or unplanned sexual activity or who prefer not to use daily or long-acting pre-exposure prophylaxis (PrEP). We performed dose ranging pharmacokinetics (PK) and efficacy studies of a vaginally applied insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in macaques under PrEP or post-exposure prophylaxis (PEP) modalities.

Methods: PK studies were performed in 3 groups of pigtailed macaques receiving inserts with different fixed-dose combinations of TAF and EVG (10/8, 20/16 and 40/24 mg).

Reliability and Validity Evidence for an Academic Gender Equity Questionnaire.

The majority of practicing pharmacists and student pharmacists are women. However, instruments to assess perceptions of gender equity within pharmacy academia are not available. The objective of this research was to describe the psychometric analysis of a questionnaire developed to assess gender equity by a Gender Equity Task Force and to report reliability and validity evidence.

Atomically engineered cobaltite layers for robust ferromagnetism.

Emergent phenomena at heterointerfaces are directly associated with the bonding geometry of adjacent layers. Effective control of accessible parameters, such as the bond length and bonding angles, offers an elegant method to tailor competing energies of the electronic and magnetic ground states. In this study, we construct unit-thick syntactic layers of cobaltites within a strongly tilted octahedral matrix via atomically precise synthesis.