Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults.

Efficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.

The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.

Optimizing regulatory frameworks for gene therapies in rare diseases: Challenges and solutions.

The advent of genetic medicines and advanced diagnostics has revolutionized the treatment landscape for rare diseases and, with over 10,000 identified conditions affecting millions globally, has the potential to improve many lives. Despite this progress, only 5% of rare diseases have FDA-approved therapies, highlighting a significant unmet need. This article examines the critical need for optimizing the regulatory environment to support the development and approval of gene therapies for rare and ultrarare diseases, which often face unique challenges due to their complexity in the midst of a rapidly evolving field.

Hepatic artery pseudoaneurysm-the Mayo Clinic experience and literature review.

Introduction: Hepatic artery pseudoaneurysm (HAP) is a rare and potentially life-threatening condition associated with high mortality. This study aims to review the etiology, clinical manifestations, management, and outcomes of patients diagnosed and treated for HAP at the Mayo Clinic.

Methodology: This study was a retrospective chart review of medical records for patients diagnosed and treated for hepatic artery pseudoaneurysm (HAP) at the Mayo Clinic (Florida, Minnesota, and Arizona) between September 1, 1998, and June 30, 2022.

Alterations of T Cell Subsets Associated with Sickle Cell Trait.

Sickle cell trait (SCT) has been associated with alterations in various immune-related laboratory parameters including lower circulating lymphocyte counts. To further characterize the impact of SCT on the immune system, we performed flow cytometry of monocyte and lymphocyte immune cell subsets from peripheral blood mononuclear cells collected in a large, community-based cohort of SCT-positive (n = 68) and SCT-negative (n = 959) Black adults. SCT was significantly associated with lower proportions of CD8 and CD4 T cell subsets that include senescent-like markers of repeated immune system challenges.

The Use of Perampanel in the Treatment of Lance-Adams Syndrome.

Lance Adams syndrome (LAS) is characterized by chronic action or intention myoclonus resulting from cerebral hypoxia. Perampanel, a non-competitive antagonist of aamino-3-hydroxy-5methyl-4 isooxazoleproprionic acid glutamate receptor, has demonstrated some efficacy in myoclonic epilepsy and other types of myoclonus. We report significant benefit in a patient with LAS treated with add on perampanel and provide a review of the relevant literature.

MicroGlycoDB: A database of microbial glycans using Semantic Web technologies.

Glycoconjugates are present on microbial surfaces and play critical roles in modulating interactions with the environment and the host. Extensive research on microbial glycans, including elucidating the structural diversity of the glycan moieties of glycoconjugates and polysaccharides, has been carried out to investigate the function of glycans in modulating the interactions between the host and microbes, to explore their potential applications in the therapeutic targeting of pathogenic species, and in the use as probiotics in gut microbiomes. However, glycan-related information is dispersed across numerous databases and a vast amount of literature, which makes it laborious and time-consuming to identify and gather the relevant information about microbial glycosylation.

The CareVirtue Digital Journal for Family and Friend Caregivers of People Living With Alzheimer Disease and Related Dementias: Exploratory Topic Modeling and User Engagement Study.

Background: As Alzheimer disease (AD) and AD-related dementias (ADRD) progress, individuals increasingly require assistance from unpaid, informal caregivers to support them in activities of daily living. These caregivers may experience high levels of financial, mental, and physical strain associated with providing care. CareVirtue is a web-based tool created to connect and support multiple individuals across a care network to coordinate care activities and share important information, thereby reducing care burden.

The Structure, Function, and Adaptation of Lower-Limb Aponeuroses: Implications for Myo-Aponeurotic Injury.

The aponeurosis is a large fibrous connective tissue structure within and surrounding skeletal muscle and is a critical component of the muscle-tendon unit (MTU). Due to the lack of consensus on terminology and the heterogeneous nature of the aponeurosis between MTUs, there are several questions that remain unanswered. For example, the aponeurosis is often conflated with the free tendon rather than being considered an independent structure.

MRI in the evaluation of plantar plate disease: diagnostic value of the "stress test".

Introduction: The plantar plate, also called the plantar ligament, is a fibrocartilaginous structure found in the metatarsophalangeal (MTP) and interphalangeal (IP) joints. Our study aimed to evaluate the role of magnetic resonance imaging (MRI) performed with the patient in the standard position or with joint hyperextension (the "stress test", ST) in the study of plantar plate (PP) disease that involves metatarsophalangeal joints.

Materials And Methods: All patients underwent forefoot MRI (Atroscan C, Esaote, Genoa, Italy), operating at 0.

Gold nanoparticles mediate suppression of angiogenesis and breast cancer growth via MMP-9/NF-κB/mTOR and PD-L1/PD-1 signaling: integrative in vitro validation and network pharmacology insights.

Gold nanoparticles (AuNPs) have emerged as promising candidates for cancer therapy due to their unique physicochemical properties and biocompatibility. In this study, we investigate the synthesis, characterization, and therapeutic potential of AuNPs in breast cancer treatment. Further, it establishes a comprehensive understanding of the mechanisms by which AuNPs suppress angiogenesis and breast cancer growth, identifying novel targets and signaling nodes contributing to the anti-tumor effects of AuNPs.

Characterizing the Relationships Amongst Psychological Safety, the Learning Environment, and Well-Being in Surgical Faculty and Trainees.

Objective: Learning environments affect the well-being of surgical faculty and trainees. Psychological safety (PS) has been linked with learning behaviors and aspects of well-being within medicine; however, given the unique challenges inherent to the surgical learning environment, there is a need to more closely examine these concepts for surgical faculty and trainees. The objective of this study is to examine the relationships between learning environment and PS, as well as PS and well-being with surgery.

Evaluating the effectiveness of community-informed resource dissemination at increasing knowledge and testing rates among private well water owners in a statewide population.

Background: Threats to groundwater quality pose health risks to private well owners. Knowledge gaps are the main reason for low testing rates. Yet, few studies have examined the extent to which community-informed resource distribution increases knowledge and promotes private well testing.

Design, Synthesis, Biological Evaluation and Molecular Docking Study of New 1,3,4-Thiadiazole-Based Compounds as EGFR Inhibitors.

Five series of new 1,3,4-thiadiazole hybrids were designed and synthesized as promising EGFR inhibitors. Three human cancer cell lines were employed for testing each hybrid's in vitro antiproliferative efficacy; colon HCT-116, liver HepG-2 and breast MCF-7 using MTT assay. Comparing compound 9a to the reference doxorubicin, 9a shown superior activity to that of Dox with respect to MCF-7 (IC 3.

A meta-analysis highlights the idiosyncratic nature of tradeoffs in laboratory models of virus evolution.

Different theoretical frameworks have been invoked to guide the study of virus evolution. Three of the more prominent ones are (i) the evolution of virulence, (ii) life history theory, and (iii) the generalism-specialism dichotomy. All involve purported tradeoffs between traits that define the evolvability and constraint of virus-associated phenotypes.

DUAL SELF-DISTILLATION OF U-SHAPED NETWORKS FOR 3D MEDICAL IMAGE SEGMENTATION.

U-shaped networks and its variants have demonstrated exceptional results for medical image segmentation. In this paper, we propose a novel dual self-distillation (DSD) framework for U-shaped networks for 3D medical image segmentation. DSD distills knowledge from the ground-truth segmentation labels to the decoder layers and also between the encoder and decoder layers of a single U-shaped network.

Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects.

Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.

Dataset for gastrointestinal tract segmentation on serial MRIs for abdominal tumor radiotherapy.

Purpose: Integrated MRI and linear accelerator systems (MR-Linacs) provide superior soft tissue contrast, and the capability of adapting radiotherapy plans to changes in daily anatomy. In this dataset, serial MRIs of the abdomen of patients undergoing radiotherapy were collected and the luminal gastro-intestinal tract was segmented to support an online segmentation algorithm competition. This dataset may be further utilized by radiation oncologists, medical physicists, and data scientists to further improve auto segmentation algorithms.

A new approach for increasing graduate students' science communication capacity and confidence.

There is an increasing demand for emerging scientists to improve their ability to communicate with public audiences, yet little research investigates the effectiveness of science communication training for graduate students. We responded to this need by developing SciWrite@URI-an interdisciplinary model for science graduate students designed around three learning outcomes based on tenets from the field of writing and rhetoric-habitual writing, multiple genres, and frequent review. SciWrite students completed courses and a science communication internship, attended writing workshops, and became tutors at a newly established Graduate Writing Center.

A Novel Automated Method for Comprehensive Renal Cast Quantification from Rat Kidney Sections using QuPath.

The presence of tubular casts within the kidney serves as an important feature when assessing the degree of renal injury. Quantification of renal tubular casts has been historically difficult due varying cast morphologies, protein composition, and stain uptake properties, even within the same kidney. Color thresholding remains one of the most common methods of quantification in the laboratory when assessing the percentage of renal casting; however, this method is unable to account for tubule casts stained a variety of colors.

Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Pediatric Upper and Lower Limb Spasticity: Results From 2 Open-Label, Long-term Extension Trials.

Aim: To evaluate the efficacy and safety of onabotulinumtoxinA for treating upper and lower limb spasticity among pediatric patients in 2 open-label extension trials.

Methods: Patients aged <18 years received ≤5 doses of onabotulinumtoxinA (maximum: 8 U/kg [300 U], cycle 1; 10 U/kg [340 U], cycles 2-5) over 60 weeks. Week 6 efficacy endpoints included mean change from baseline in Modified Ashworth Scale-Bohannon and Modified Tardieu Scale scores, and mean Clinical Global Impression of Overall Change score.