Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.

Polycystic ovary syndrome (PCOS) is among the most common disorders affecting up to 15% of the menstruating population globally. It is the leading cause of anovulatory infertility and a major risk factor for type 2 diabetes. Elevated testosterone levels are a core endophenotype.

The Ontogeny of Distinct Reproductive Phenotypes in Girls at Risk for PCOS During the Postmenarchal Transition.

Context: Daughters of women with PCOS (PCOS-d) and girls with overweight/obesity (OW-g) have hyperandrogenemia (HA) beginning in childhood. However, other features of their early reproductive phenotypes differ, suggesting that there are distinct mechanisms conferring increased risk for PCOS.

Objective: We performed a cross sectional study of adolescent girls during the early postmenarchal transition.

Clustering Identifies Subtypes With Different Phenotypic Characteristics in Women With Polycystic Ovary Syndrome.

Context: Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS).

Objective: This work aimed to identify clinically significant subtypes in a PCOS cohort diagnosed with the Rotterdam criteria and to further characterize the distinct subtypes.

Methods: Clustering was performed using the variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose.

Evaluation of a specialist antenatal nutrition clinic for women with a body mass index ≥ 40kg/m: A qualitative study.

Objective: To explore the views of women who attended a specialist antenatal nutrition clinic that was specifically developed and piloted for pregnant women with a BMI ≥ 40 kg/m.

Design: A phenomenological approach, using individual interviews, was employed. Discussions were audio recorded, transcribed verbatim and scrutinised using Interpretive Phenomenological Analysis.

Binocular Alignment Changes Between Sitting and Supine Positions in Patients with Dizziness.

Vertical and torsional ocular misalignment can occur from mild traumatic brain injury or inner ear pathology, which may vary depending on head position. Here, we evaluate differences in a behavioral measure of binocular alignment in both upright and supine head position. Ocular perception of vertical and torsional alignment was measured using the torsional and vertical alignment nulling (TAN, VAN) task in N = 52 veterans with dizziness (N = 38 with traumatic brain injury), N = 41 civilians with vestibular schwannoma resection (UVD), and N = 33 healthy controls for both positions.

The Instrumented Timed "Up & Go" Test Distinguishes Turning Characteristics in Vestibular Hypofunction.

Objective: Deficits in vestibular function increase the risk for falls while turning. However, the clinical assessment of turning in patients with vestibular dysfunction is lacking, and evidence is limited that identifies the effectiveness of vestibular physical therapy in improving turning performance. The purpose of this study was to quantify walking and turning performance during the instrumented Timed "Up & Go" (TUG) test using body-worn inertial measurement units (IMUs).

Molecular analysis of cyclin D1 modulators PRKN and FBX4 as candidate tumor suppressors in sporadic parathyroid adenomas.

Objective: Primary hyperparathyroidism is most often caused by a sporadic single-gland parathyroid adenoma (PTA), a tumor type for which cyclin D1 is the only known and experimentally validated oncoprotein. However, the molecular origins of its frequent overexpression have remained mostly elusive. In this study, we explored a potential tumorigenic mechanism that could increase cyclin D1 stability through a defect in molecules responsible for its degradation.

Veterans with dizziness recruit compensatory saccades in each semicircular canal plane although VOR gain is normal.

Background: Exposure to brain injury via blast or blunt mechanisms disrupts multiple sensorimotor systems simultaneously. Large numbers of US Gulf War era and Operation Iraqi/Enduring Freedom veterans with traumatic brain injury (TBI) are suffering the symptom of dizziness - presumed due to "Multi-Sensory Impairment", a clinical pattern of damage to the auditory, visual and vestibular sensorimotor systems.

Objective: To describe the oculomotor response to rapid head rotation in a population of veterans with dizziness.

Veterans have greater variability in their perception of binocular alignment.

Introduction: A significant population of our wounded veterans suffer long-term functional consequences of visual deficit, disorientation, dizziness, and an impaired ability to read. These symptoms may be related to damage within the otolith pathways that contribute to ocular alignment. The purpose of this study was to compare perception of vertical and torsional ocular alignment between veterans and healthy controls in an upright and supine test position.

Molecular genetic insights into sporadic primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are attributable to sporadic, single-gland parathyroid adenoma, in which MEN1 and CCND1/cyclin D1 are the most well-established drivers of tumorigenesis. Sporadic parathyroid carcinoma, which appears to mostly arise through molecular pathways distinct from those causing benign parathyroid tumors, is rare and is most frequently driven by mutational inactivation of the CDC73 (HRPT2) tumor suppressor gene.

Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases.

Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis.

Addressing the challenges of collaborative goal setting with children and their families.

Collaborative goal setting between clinicians and clients/families is considered a fundamental component of the pediatric rehabilitation process. However, truly client-centered goal setting is not without its challenges. The purpose of this paper is to highlight theoretical concepts relevant to rehabilitation goal setting, review clinical studies directly evaluating relationships between goal setting and pediatric rehabilitation outcomes, and provide recommendations to facilitate collaborative goal processes.

Role of membrane oxidation in controlling the activity of human group IIa secretory phospholipase A(2) toward apoptotic lymphoma cells.

The membranes of healthy lymphocytes normally resist hydrolysis by secretory phospholipase A(2). However, they become susceptible during the process of apoptosis. Previous experiments have demonstrated the importance of certain physical changes to the membrane during cell death such as a reduction in membrane lipid order and exposure of phosphatidylserine on the membrane surface.

Reliability of the Community Balance and Mobility Scale (CB&M) in high-functioning school-aged children and adolescents who have an acquired brain injury.

Primary Objective: To examine inter-rater, intra-rater and test-re-test reliability of the Community Balance and Mobility Scale (CB&M) and compare reliability in live vs videotape rating contexts for children with acquired brain injury (ABI).

Research Design: Repeated measures design.

Methods And Procedures: Seven physiotherapists (PTs) were trained as assessors.

Closed neural tube defects: neurologic, orthopedic, and gait outcomes.

Purpose: The purpose of our study was to obtain a clear understanding of the various diagnoses within the closed neural tube defect (NTD) groups included in the large database of clients in our Spina Bifida Clinic and a clear picture of the outcomes for the various NTD groups.

Methods: One hundred and four clients with closed NTD were categorized using a classification system devised by Tortori-Donati et al. Various clinical markers were investigated, including ambulation and the need for orthoses and wheelchairs.

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage.

This study evaluated the utility of human blood micronucleated reticulocyte (MNCD71+) frequency measurement as a cytogenetic damage biomarker. The analytical methodology was flow cytometry in conjunction with a previously described three color fluorescence labeling technique that includes anti-CD71 to focus analyses on the most immature fraction of reticulocytes [S.D.

Effects of elastase on the mechanical and failure properties of engineered elastin-rich matrices.

Pulmonary emphysema and vessel wall aneurysms are diseases characterized by elastolytic damage to elastin fibers that leads to mechanical failure. To model this, neonatal rat aortic smooth muscle cells were cultured, accumulating an extracellular matrix rich in elastin, and mechanical measurements were made before and during enzymatic digestion of elastin. Specifically, the cells in the cultures were killed with sodium azide, the cultures were lifted from the flask, cut into small strips, and fixed to a computer-controlled lever arm and a force transducer.

Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling.

Enlargement of the respiratory air spaces is associated with the breakdown and reorganization of the connective tissue fiber network during the development of pulmonary emphysema. In this study, a mouse (C57BL/6) model of emphysema was developed by direct instillation of 1.2 IU of porcine pancreatic elastase (PPE) and compared with control mice treated with saline.

Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue.

Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers.

Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic damage in humans.

The frequency of micronuclei (also known as Howell-Jolly bodies) in peripheral blood erythrocytes of humans is extremely low due to the efficiency with which the spleen sequesters and destroys these aberrant cells. In the past, this has precluded erythrocyte-based analyses from effectively measuring chromosome damage. In this report, we describe a high-throughput, single-laser flow cytometric system for scoring the incidence of micronucleated reticulocytes (MN-RET) in human blood.

Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment.

We investigated the relationship between the microscopic elastic and hysteretic behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo elastase-treated rat model of emphysema. We measured the input impedance of isolated lungs at three levels of transpulmonary pressure (Ptp) and used a linear model to estimate the dynamic elastance and hysteresivity of the lungs. The elastance of the normal lungs increased steeply with Ptp, whereas this dependence diminished in the treated lungs.