We examined the effect of habitual pre-exercise caffeine supplementation on training-induced adaptations to exercising systolic (SBP), diastolic (DBP), pulse pressure (PP), heart rate (HR), and double product (DP). Young women (mean±SD; 24±7 y) were randomized to a caffeine (120 mg) supplement (CAF; n=17) or placebo (PLA; n=16) group, completed 6-weeks of high intensity exercise training on three non-consecutive days per week, and supplemented with CAF or PLA 30-60 minutes before exercise or else upon waking. Before (PRE) and after (POST) the intervention, SBP, DBP, and HR were measured, and PP and DP calculated, at rest and during fixed-power exercise at 50W and 75W.
View Article and Find Full Text PDFLyme disease, caused by , is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects.
View Article and Find Full Text PDFObjectives: Screening recommendations for gynecologic cancers (GC) associated with Lynch syndrome (LS) are diverse. The objectives of this study were to examine among women with LS: 1) psychosocial factors that influence thoughts and choices about GC screening, and 2) information and unmet healthcare access needs when making GC screening decisions.
Methods: This study used a qualitative design.
Objective: To assess whether the mode and formatting of invitations affect enrollment in a large, decentralized study.
Patients And Methods: Between July 1, 2022, and October 30, 2022, we prospectively compared various approaches to enroll patients in the Tapestry DNA Sequencing Research Study, a decentralized exome-sequencing study. In phase 1, patients were randomized to receive invitations via the electronic health record (EHR) patient portal or email (cohort 1, 69,852 patients).
J Neuropsychiatry Clin Neurosci
December 2024
Background: The IMPACT Survey explored the humanistic, clinical, and economic burden of osteogenesis imperfecta (OI) on individuals with OI, their families, caregivers, and wider society. Two previous publications report research methodology, initial insights of the survey, and cost of illness of OI. Here, we present data on the impact of OI on the quality of life (QoL) of adults with OI and explore potential drivers of this impact.
View Article and Find Full Text PDFBackground/objectives: Informed consent is crucial in medical practice, especially for complex treatments such as postoperative radiotherapy for patients with breast cancer. Conventional consent procedures are often based on verbal declarations with a highly condensed but nevertheless large amount of information, which can exceed the recording capacity of patients and lead to misunderstandings. The aim of this study was to develop and test an educational video on breast cancer patients to enhance the informed consent process by improving patients' understanding and reducing the duration of the subsequent consultation.
View Article and Find Full Text PDFMutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers.
View Article and Find Full Text PDFThe peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis in mouse models by signaling via the kisspeptin 1 receptor (KISS1R). However, whether kisspeptin impacts fibrogenesis in the human liver is not known. We investigated the impact of a potent kisspeptin analog (KPA) on fibrogenesis using human precision-cut liver slices (hPCLS) from fibrotic livers from male patients, in human hepatic stellate cells (HSCs), LX-2, and in primary mouse HSCs.
View Article and Find Full Text PDFJ Int Neuropsychol Soc
October 2024
The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4.
View Article and Find Full Text PDFGenomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including and in non-small cell lung cancer. Previously, we and others have identified that -mutant lung cancers are highly dependent on oxidative phosphorylation (OXPHOS). Despite initial excitements, therapeutics targeting metabolic pathways such as OXPHOS have largely been disappointing due to rapid adaptation of cancer cells to inhibition of single metabolic enzymes or pathways, suggesting novel combination strategies to overcome adaptive responses are urgently needed.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2024
Background: Synthetic lethality offers a promising strategy for cancer treatment by targeting genetic vulnerabilities unique to tumor cells, leading to selective tumor cell death. However, single-gene knockout screens often miss functional redundancy due to paralog genes. Multiplex CRISPR systems, including various Cas9 and Cas12a platforms, have been developed to assay genetic interactions, yet no systematic comparison of method to identify synthetic lethality from CRISPR screens has been conducted.
View Article and Find Full Text PDFMutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a limited range of other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad range of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers.
View Article and Find Full Text PDFLyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective.
View Article and Find Full Text PDFThe microbiome is a key factor in the health, well-being, and success of vertebrates, contributing to the adaptive capacity of the host. However, the impact of geographic and biotic factors that may affect the microbiome of wild birds in polar environments is not well defined. To address this, we determined the bacterial 16S rRNA gene sequence profiles in faecal samples from pygoscelid penguin populations in the Scotia Arc, focusing on gentoo penguins.
View Article and Find Full Text PDFBackground: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces.
Methods: Between 2017 and 2019, sexually active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling.
According to Mendel's second law, chromosomes segregate randomly in meiosis. Non-random segregation is primarily known for cases of selfish meiotic drive in females, in which particular alleles bias their own transmission into the oocyte. Here we report a rare example of unselfish meiotic drive for crossover inheritance in the clonal raider ant, Ooceraea biroi, in which both alleles are co-inherited at all loci across the entire genome.
View Article and Find Full Text PDFObjective: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g.
View Article and Find Full Text PDFVector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens.
View Article and Find Full Text PDFWhile the neural basis of age-related decline has been extensively studied, less is known about changes in neural function during the pre-senescent stages of adulthood. Adult neural plasticity is likely a key factor in social insect age polyethism, where individuals perform different tasks as they age and divide labor in an age-dependent manner. Primarily, workers transition from nursing to foraging tasks, become more aggressive, and more readily display alarm behavior as they get older.
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