Developing Topics.

Background: Early-onset Alzheimer's disease (EOAD) is a complex disease that occurs at an early age at onset (AAO) before 65 years, constituting 5-6% of all AD cases and remains poorly understood. Patient-derived induced pluripotent stem cells (iPSCs) have been used to model different forms of EOAD that display heterogeneous disease mechanisms.

Method: We examined iPSC-derived neurons from both familial EOAD harboring mutations in PSEN1 , PSEN2, and APP and non-familial EOAD patients at an early AAO.

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

Long-Term Functional and Clinical Outcomes in Familial Exudative Vitreoretinopathy.

Purpose: To characterize long-term functional and anatomical outcomes in patients with familial exudative vitreoretinopathy (FEVR).

Methods: A retrospective chart review was conducted of all patients with a diagnosis of FEVR at a tertiary academic institution and its affiliated children's hospital treated from January 2003 through January 2024. Demographic and clinical data were collected.

Airway macrophage glycolysis controls lung homeostasis and responses to aeroallergen.

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism.

Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation.

Throughout evolution, the placenta has diversified in both structure and cellular composition while maintaining its fundamental function. Trophoblasts are fetal-derived cells responsible for nourishing and protecting the developing fetus and are a universal component of all placentas. While primate placentas exhibit many shared morphological features, species-specific differences in gene expression remain largely unexplored, primarily due to the lack of suitable models.

MERTK Inhibitor Associated Retinal Toxicity in a Human.

Purpose: The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics.

Wet military uniforms pose low risk of hypothermia while static in mild cold air.

Wet clothing is less insulative than dry clothing and consequently increases heat loss in cold air. Tactical necessity can render removal of wet clothing impossible and/or require Warfighters to remain static to avoid detection, limiting heat production and posing a threat of hypothermia (core temperature <35 °C). This study aimed to characterize body temperatures and evaluate hypothermia risk while statically exposed to 5 °C air wearing three wet military uniforms.

Evaluation of socioecological factors on health behaviors and weight change during major life event: A cross-sectional study using data collected during the COVID-19 pandemic.

Background: Socioecological factors are associated with key health behaviors that are critical for weight management, and major life events may disrupt engagement in these behaviors. However, the influence of socioecological factors on health behaviors in the midst of major life events is not clear and is difficult to study due to the random and sporadic nature of their occurrence. The COVID-19 pandemic provided a unique opportunity to study a major life event and its impacts on diet, physical activity, and body weight.

Parent-Mediated Occupational Therapy Interventions for Children with Developmental Disabilities: A Scoping Review.

Aim: This scoping review synthesizes literature about occupational therapy parent-mediated interventions (PMIs) that target occupation-based outcomes for children with developmental disabilities (DD).

Methods: A search of PubMed, Web of Science, and CINAHL from 2010 through 2023 was performed resulting in 471 publications. Studies were included if they involved PMIs for participants with DD aged 3-12 years and were published in English.

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation.

Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches).

Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

Background: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge.

Effectiveness of preconception weight loss interventions on fertility in women: a systematic review and meta-analysis.

Importance: Weight loss before conception is recommended for women with overweight or obesity to improve fertility outcomes, but evidence supporting this recommendation is mixed.

Objective: To examine the effectiveness of weight loss interventions using lifestyle modification and/or medication in women with overweight or obesity on pregnancy, live birth, and miscarriage.

Data Sources: An electronic search of MEDLINE, Embase, Cochrane Library, including Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature was conducted through July 6, 2022, via Wiley.

Psychometric validation of four-item exercise identity and healthy-eater identity scales and applications in weight loss maintenance.

Background: Identifying as someone who engages in health promoting behaviors like healthy eating and exercising may be associated with sustained engagement in those behaviors, but reliable and valid instruments are needed to improve the rigor of this research. Two studies were conducted to (1) examine the psychometric properties of a four-item exerciser identity measure (4-EI) and an adapted healthy-eater identity measure (4-HEI) and (2) examine differences in identity strengths across categories of weight loss success.

Methods: Data from 1,709 community dwelling adults in the International Weight Control Registry (IWCR) were used.

NSAIDs do not prevent exercise-induced performance deficits or alleviate muscle soreness: A placebo-controlled randomized, double-blinded, cross-over study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently consumed by athletes to manage muscle soreness, expedite recovery, or improve performance. Despite the prevalence of NSAID use, their effects on muscle soreness and performance, particularly when administered prophylactically, remain unclear. This randomized, double-blind, counter-balanced, crossover study examined the effect of consuming a single dose of each of three NSAIDs (celecoxib, 200 mg; ibuprofen, 800 mg; flurbiprofen, 100 mg) or placebo 2 h before on muscle soreness and performance following an acute plyometric training session.

Food Waste from Campus Dining Hall as a Potential Feedstock for 2,3-Butanediol Production via Non-Sterilized Fermentation.

Food waste is a major issue that is increasingly affecting our environment. More than one-third of food is wasted, resulting in over $400 billion in losses to the U.S.

Sex Does Not Affect Changes in Body Composition and Insulin-Like Growth Factor-I During US Army Basic Combat Training.

Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US Army basic combat training. J Strength Cond Res 38(6): e304-e309, 2024-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition.

ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism.

Fatty acid β-oxidation (FAO) is a central catabolic pathway with broad implications for organismal health. However, various fatty acids are largely incompatible with standard FAO machinery until they are modified by other enzymes. Included among these are the 4-hydroxy acids (4-HAs)-fatty acids hydroxylated at the 4 (γ) position-which can be provided from dietary intake, lipid peroxidation, and certain drugs of abuse.

Relation of body surface area-to-mass ratio to risk of exertional heat stroke in healthy men and women.

Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S.