Identification and validation of G protein-coupled receptors modulating flow-dependent signaling pathways in vascular endothelial cells.

Vascular endothelial cells are exposed to mechanical forces due to their presence at the interface between the vessel wall and flowing blood. The patterns of these mechanical forces (laminar vs. turbulent) regulate endothelial cell function and play an important role in determining endothelial phenotype and ultimately cardiovascular health.

Probabilistic evaluation of plan quality for time-dependent anatomical deformations in head and neck cancer patients.

Purpose: In addition to patient set-up uncertainties, anatomical deformations, e.g., weight loss, lead to time-dependent differences between the planned and delivered dose in a radiotherapy course that currently cannot easily be predicted.

Evaluating principal component analysis models for representing anatomical changes in head and neck radiotherapy.

Background And Purpose: Anatomical changes during radiotherapy pose a challenge to robustness of plans. Principal component analysis (PCA) is commonly used to model such changes. We propose a toolbox to evaluate how closely a given PCA model can represent actual deformations seen in the patient and highlight regions where the model struggles to capture these changes.

Skeletal muscle capillary density is related to anaerobic threshold and claudication in peripheral artery disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. Exercise intolerance may result from reduced skeletal muscle capillary density and impaired muscle oxygen delivery. This cross-sectional study tested the hypothesis that capillary density is related to claudication times and anaerobic threshold (AT) in patients with PAD.

Update on childhood/adolescent obesity and its sequela.

Purpose Of Review: We aim to describe current concepts on childhood and adolescent obesity with a strong focus on its sequela. Childhood obesity is a national epidemic with increasing prevalence over the past three decades placing children at increased risk for many serious comorbidities, previously felt to be only adult-specific diseases, making this topic both timely and relevant for general pediatricians as well as for subspecialists.

Recent Findings: Childhood obesity develops through an interplay of genetics, environment, and behavior.

Listeria monocytogenes InlP interacts with afadin and facilitates basement membrane crossing.

During pregnancy, the placenta protects the fetus against the maternal immune response, as well as bacterial and viral pathogens. Bacterial pathogens that have evolved specific mechanisms of breaching this barrier, such as Listeria monocytogenes, present a unique opportunity for learning how the placenta carries out its protective function. We previously identified the L.

Impact of Psychosocial Risk on Outcomes among Families Seeking Treatment for Obesity.

Objectives: To test the hypothesis that children with elevated psychosocial risk would have increased attrition and worse weight outcomes in weight management treatment.

Study Design: This was a prospective cohort study of 100 new patients, aged 4-12 years, in a weight management clinic. Parents completed the Psychosocial Assessment Tool.

Animal and Human Tissue Models of Vertical Listeria monocytogenes Transmission and Implications for Other Pregnancy-Associated Infections.

Intrauterine infections lead to serious complications for mother and fetus, including preterm birth, maternal and fetal death, and neurological sequelae in the surviving offspring. Improving maternal and child heath is a global priority. Yet, the development of strategies to prevent and treat pregnancy-related diseases has lagged behind progress made in other medical fields.

PRIME: A Novel Low-Mass, High-Repetition Approach to Improve Function in Older Adults.

Introduction: The ability to maintain functional independence in a rapidly aging population results in an increased life expectancy without corresponding increases in health care costs. The accelerated decline in V˙O2peak after the age of 65 yr is primarily due to peripheral tissue changes rather than centrally mediated factors. The purpose of this study was to determine whether the Peripheral Remodeling through Intermittent Muscular Exercise (PRIME) approach, consisting of a low-mass, high-repetition/duration skeletal muscle focused training regimen would provide superior functional benefits in participants older than 70 yr old and at risk for losing functional independence.

Beyond race and place: distal sociological determinants of HIV disparities.

Informed behavior change as an HIV prevention tool has yielded unequal successes across populations. Despite decades of HIV education, some individuals remain at high risk. The mainstream media often portrays these risk factors as products of race and national borders; however, a rich body of recent literature proposes a host of complex social factors that influence behavior, including, but not limited to: poverty, income inequality, stigmatizing social institutions and health care access.

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training.

Aims: To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET).

Methods: In subjects with T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT).

Placental syncytium forms a biophysical barrier against pathogen invasion.

Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is bathed in maternal blood, and constitutes the main interface between fetus and mother. Syncytiotrophoblasts are exposed to pathogens circulating in maternal blood, and appear to have unique resistance mechanisms against microbial invasion. These are due in part to the lack of intercellular junctions and their receptors, the Achilles heel of polarized mononuclear epithelia.

Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial".

Advancing age is associated with an increase in physical impairment, functional limitations, disability, and loss of independence. Regular physical activity conveys health benefits, but the yield on physical function in the elderly, is less clear. Current exercise guidelines are focused predominantly on aerobic programs despite evidence that age-associated declines are mediated by peripheral tissue changes.

Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts.

During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis.

Pathogens and the placental fortress.

Placental infections are major causes of maternal and fetal disease. This review introduces a new paradigm for placental infections based on current knowledge of placental defenses and how this barrier can be breached. Transmission of pathogens from mother to fetus can occur at two sites of direct contact between maternal cells and specialized fetal cells (trophoblasts) in the human placenta: firstly, maternal immune and endothelial cells juxtaposed to extravillous trophoblasts in the uterine implantation site and secondly, maternal blood surrounding the syncytiotrophoblast (SYN).

Tissue barriers of the human placenta to infection with Toxoplasma gondii.

Toxoplasma gondii is a ubiquitous, obligate intracellular parasite capable of crossing the placenta to cause spontaneous abortion, preterm labor, or significant disease in the surviving neonate. Exploration of the cellular and histological components of the placental barrier is in its infancy, and both how and where T. gondii breaches it are unknown.

Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients.

Objective: Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. The mechanism(s) by which exercise training improves functional capacity is not understood. This study tested the hypothesis that in PAD patients who undergo supervised exercise training, increases in capillary density (CD) in calf muscle take place before improvements in peak oxygen uptake (VO(2)).

Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease.

The aim of this study was to determine if skeletal muscle capillary density is lower in patients with peripheral artery disease (PAD) and if capillary density relates to functional limitations. PAD patients with intermittent claudication (IC) have a decreased exercise tolerance due to exercise-induced muscle ischemia. Despite the apparent role diminished arterial flow has in this population, the degree of walking pain and functional limitation is not entirely explained by altered hemodynamics of the affected limbs.

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease.

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion.

Invasive extravillous trophoblasts restrict intracellular growth and spread of Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that can infect the placenta, a chimeric organ made of maternal and fetal cells. Extravillous trophoblasts (EVT) are specialized fetal cells that invade the uterine implantation site, where they come into direct contact with maternal cells. We have shown previously that EVT are the preferred site of initial placental infection.

Plasma nitrite flux predicts exercise performance in peripheral arterial disease after 3months of exercise training.

Plasma nitrite is a major oxidation product of nitric oxide. It has also recently been suggested to perform an endocrine-like function as a nitric oxide donor in hypoxic tissues, allowing vasodilation. Exercise performance is limited in peripheral arterial disease because of an inadequate blood supply to working tissues.

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread.

Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection.

Background: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.

Methodology/principal Findings: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5-/-). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L.