Chromosomal linkages formed through crossover recombination are essential for accurate segregation of homologous chromosomes during meiosis. DNA events of recombination are spatially and functionally linked to structural components of meiotic chromosomes. Imperatively, biased resolution of double-Holliday junction (dHJ) intermediates into crossovers occurs within the synaptonemal complex (SC), the meiosis-specific structure that mediates homolog synapsis during the pachytene stage.
View Article and Find Full Text PDFBackground: Evidence-based practice (EBP) is crucial to high-quality health care, yet nurse practitioner graduates report low levels of confidence in their EBP abilities. This may be because of limited incorporation of EBP learning opportunities outside of foundational course-work.
Method: Family nurse practitioner (FNP) program faculty incorporated EBP learning activities across the three-semester clinical year curriculum, and the activities scaffolded in complexity.
Nuclear envelope proteins have recently gained traction as novel regulators of endothelial and vascular function. Nuclear pore complexes (NPCs) stand as one of the largest protein complexes found at the nuclear envelope yet the role of component NPC proteins (i.e.
View Article and Find Full Text PDFtoxicology research has accelerated with the use of , computational approaches and human tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches.
View Article and Find Full Text PDFAs the innermost lining of the vasculature, endothelial cells (ECs) are constantly subjected to systemic inflammation and particularly vulnerable to aging. Endothelial health is hence vital to prevent age-related vascular disease. Healthy ECs rely on the proper localization of transcription factors via nuclear pore complexes (NPCs) to govern cellular behavior.
View Article and Find Full Text PDFBlood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known.
View Article and Find Full Text PDFObjective: We have previously demonstrated the importance of the Akt-eNOS substrate-kinase relationship, as defective postnatal angiogenesis characteristic of global Akt1-null mice is rescued when bred to 'gain-of-function' eNOS S1176D mutant mice. While multiple studies support the vascular protective role of endothelial NO generation, the causal role of Akt1-dependent eNOS S1176 phosphorylation during atherosclerotic plaque formation is not yet clear.
Approach And Results: We herein bred congenic 'loss-of-function' eNOS S1176A and 'gain-of-function' eNOS S1176D mutant mice to the exacerbated atherogenic Akt1; ApoE double knockout mice to definitively test the importance of Akt-mediated eNOS S1176 phosphorylation during atherogenesis.
Endothelial cells (ECs) form the innermost lining of the vasculature and serve a pivotal role in preventing age-related vascular disease. Endothelial health relies on the proper nucleocytoplasmic shuttling of transcription factors via nuclear pore complexes (NPCs). Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-related EC dysfunction.
View Article and Find Full Text PDFThe COVID-19 pandemic's impact on preschool children's school readiness skills remains understudied. This research investigates Head Start preschool children's early numeracy, literacy, and executive function outcomes during a pandemic-affected school year. Study children ( = 336 assessed at fall baseline; = 237-250 assessed in spring depending on outcome; fall baseline sample: mean age = 51 months; 46% Hispanic; 36% Black Non-Hispanic; 52% female) in a network of Head Start centers in four states (Nevada, New Jersey, Pennsylvania, and Wisconsin) experienced low in-person preschool exposure compared to national pre-pandemic norms.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic brought significant disruptions to pharmacy experiential education. To ensure the safety of students and staff, university and rotation site educators needed to make changes rapidly to adapt to the dynamic environment.
Objectives: To explore the impact of the COVID-19 pandemic on pharmacy students and their preceptors during experiential rotations and to identify any barriers to learning that arose and opportunities for improvement.
Background: COVID-19, a novel respiratory illness caused by SARS-CoV-2, has become a global pandemic. As of December 2020, 4.8% of the 941 people living with HIV in our Ryan White clinic have tested polymerase chain reaction positive for SARS-CoV-2.
View Article and Find Full Text PDFmethods offer opportunities to provide mechanistic insight into bioactivity as well as human-relevant toxicological assessments compared to animal testing. One of the challenges for this task is putting bioactivity data in an exposure context, for which to extrapolation (IVIVE) translates bioactivity to clinically relevant exposure metrics using reverse dosimetry. This study applies an IVIVE approach to the toxicity assessment of ingredients and their mixtures in e-cigarette (EC) aerosols as a case study.
View Article and Find Full Text PDFWorldviews Evid Based Nurs
February 2022
Background: Cardiac rehabilitation programs (CRP) are effective evidence-based secondary prevention programs that reduce morbidity and mortality in patients with cardiovascular disease (CVD). However, participation remains suboptimal, resulting in under-treatment and greater risk for recurrent cardiac events. Understanding the reasons behind CRP dropout is urgently needed to inform the development of programs that best meet patient needs and support sustained engagement.
View Article and Find Full Text PDFHere we genetically and functionally addressed potential pathways of Notch signalling in mediating vascular regeneration in mouse models. We first used transgenic adult mice with either gain- or loss-of-function Notch signalling in vascular endothelial cells and monitored perfusion in the hindlimb following ischaemia induced by femoral artery ligation. Mice deficient in Notch signalling showed defective perfusion recovery and expansion of collateral arteries.
View Article and Find Full Text PDFBackground: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR).
Objective: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality.
Genetic diseases involving overactivation of the mechanistic target of rapamycin (mTOR) pathway, so-called "mTORopathies," often manifest with malformations of cortical development (MCDs), epilepsy, and cognitive impairment. How mTOR pathway hyperactivation results in abnormal human cortical development is poorly understood. To study the effect of mTOR hyperactivity on early stages of cortical development, we focused on Pretzel Syndrome (polyhydramnios, megalencephaly, symptomatic epilepsy; PMSE syndrome), a rare mTORopathy caused by homozygous germline mutations in the STRADA gene.
View Article and Find Full Text PDFIn vitro to in vivo extrapolation (IVIVE) leverages in vitro biological activities to predict corresponding in vivo exposures, therefore potentially reducing the need for animal safety testing that are traditionally performed to support the hazard and risk assessment. Interpretation of IVIVE predictions are affected by various factors including the model type, exposure route and kinetic assumptions for the test article, and choice of in vitro assay(s) that are relevant to clinical outcomes. Exposure scenarios are further complicated for mixtures where the in vitro activity may stem from one or more components in the mixture.
View Article and Find Full Text PDFLeishmaniasis is a neglected tropical disease with two main clinical forms: cutaneous and visceral leishmaniasis. Diagnosis of leishmaniasis is still a challenge, concerning the detection and correct identification of the species of the parasite, mainly in endemic areas where the absence of appropriate resources is still a problem. Most accessible methods for diagnosis, particularly in these areas, do not include the identification of each one of more than 20 species responsible for the disease.
View Article and Find Full Text PDFPurpose: In order to minimize the risk of transmission of coronavirus disease 2019 (COVID-19), many clinic appointments were postponed to lower patient attendance. Actively calling patients to postpone appointments is a labour-intensive process. We were the first ophthalmic clinics in Hong Kong to use short message service (SMS) to dispatch messages simultaneously to a large number of patients to offer postponement of appointments.
View Article and Find Full Text PDFBackground: Multiple exercise modalities and mindfulness activities are beneficial in Parkinson's Disease (PD). Karate is a martial art that combines aerobic and large-amplitude movements, balance and core training, and mindfulness, suggesting a potential benefit for individuals with PD from multiple perspectives.
Objective: To evaluate the feasibility of community-based Shotokan karate classes involving physical activity and mindfulness among individuals with mild- to moderate-stage PD, and to explore the effects of karate on objective and patient-reported outcomes.
Cigarette smoke (CS) exposure is one of the leading risk factors for human health. Nicotine-containing inhalable products, such as e-cigarettes, can effectively support tobacco harm reduction approaches. However, there are limited comparative data on the effects of the aerosols generated from electronic vapor products (e-vapor) and CS on bone.
View Article and Find Full Text PDFAccurately determining the delivered dose is critical to understanding biological response due to cell exposure to chemical constituents in aerosols. Deposition efficiency and uniformity of deposition was measured experimentally using monodisperse solid fluorescent particles with mass median aerodynamic diameters (MMAD) of 0.51, 1.
View Article and Find Full Text PDFJ Clin Aesthet Dermatol
November 2019
Dermatomyositis is a disease of inflammation and vasculopathy, characterized by proximal muscle weakness and classic cutaneous eruptions. Often, patients show signs of lung, esophageal, and cardiac involvement. Cardiac involvement in dermatomyositis and other inflammatory myosidities can result in conduction abnormalities, ventricular dysfunction, and hypertrophy.
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