A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers.

Background: Tenapanor (RDX5791, AZD1722), a small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor acts locally in the gut to reduce absorption of sodium and phosphate. It is being developed for the treatment of patients with hyperphosphatemia in CKD requiring dialysis and patients with constipation-predominant irritable bowel syndrome.

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis.

Background And Objectives: Interdialytic weight gain in patients on hemodialysis is associated with adverse cardiovascular outcomes and increased mortality. The degree of interdialytic weight gain is influenced by sodium intake. We evaluated the effects of tenapanor (AZD1722 and RDX5791), a minimally systemically available inhibitor of the sodium/hydrogen exchanger isoform 3, on interdialytic weight gain in patients with CKD stage 5D treated with hemodialysis.

Haptic feedback helps bipedal coordination.

The present study investigated whether special haptic or visual feedback would facilitate the coordination of in-phase, cyclical feet movements of different amplitudes. Seventeen healthy participants sat with their feet on sliding panels that were moved externally over the same or different amplitudes. The participants were asked to generate simultaneous knee flexion-extension movements, or to let their feet be dragged, resulting in reference foot displacements of 150 mm and experimental foot displacements of 150, 120, or 90 mm.

Retinal arteriolar remodeling evaluated with adaptive optics camera: Relationship with blood pressure levels.

Aim: To research a retinal arterioles wall-to-lumen ratio or lumen diameter cut-off that would discriminate hypertensive from normal subjects using adaptive optics camera.

Patients And Methods: One thousand and five hundred subjects were consecutively recruited and Adaptive Optics Camera rtx1™ (Imagine-Eyes, Orsay, France) was used to measure wall thickness, internal diameter, to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. Sitting office blood pressure was measured once, just before retinal measurements and office blood pressure was defined as systolic blood pressure>=140mmHg and diastolic blood pressure>=90mmHg.

Crystal structure of the human sterol transporter ABCG5/ABCG8.

ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis.

In-shoe plantar pressure distribution and lower extremity muscle activity patterns of backward compared to forward running on a treadmill.

Objective: Backward locomotion in humans occurs during leisure, rehabilitation, and competitive sports. Little is known about its general biomechanical characteristics and how it affects lower extremity loading as well as muscle coordination. Thus, the purpose of this research was to analyze in-shoe plantar pressure patterns and lower extremity muscle activity patterns for backward compared to forward running.

Fatty liver is an independent predictor of early carotid atherosclerosis.

Background & Aims: Whether steatosis is incidentally or causally associated with carotid atherosclerosis is debated, and long-term follow-up data are missing. This study aims to examine the impact of steatosis on the presence and progression of carotid intima-media thickness (C-IMT) and carotid plaques (CP) in a large cohort with longitudinal follow-up.

Methods: A retrospective single-center study between 1995 and 2012.

Does cognitive avoidance mediate the relation of anxiety and binge eating?

Purpose: Theory suggests that binge eating symptoms may develop in an attempt to avoid distressing states that arise in the context of negative affect. In light of its theoretical significance, including the "escape from awareness" model of binge eating, surprisingly few empirical evaluations have examined the empirical evidence for this variable in relation to anxiety and binge eating symptoms. In addition, although it is understood that anxiety is more prevalent among women than men, empirical investigations of gender differences in cognitive avoidance in binge eating are thus far absent from the published literature.

Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS.

Cholesterol homeostasis is mediated by Scap, a polytopic endoplasmic reticulum (ER) protein that transports sterol regulatory element-binding proteins from the ER to Golgi, where they are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. We earlier provided indirect evidence that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles.

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics.

Background: In humans, adaptive optics camera enables precise large-scale noninvasive retinal microcirculation evaluation to assess ageing, blood pressure and antihypertensive treatments respective roles on retinal arterioles anatomy.

Method: We used adaptive optics camera rtx1 (Imagine-Eyes, Orsay, France) to measure wall thickness, internal diameter and to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. This assessment was repeated within a short period in two subgroups of hypertensive individuals without or with a drug-induced blood pressure drop.

Physical activity and health-related quality of life in pediatric cancer patients following a 4-week inpatient rehabilitation program.

Purpose: Chronic health conditions and impaired quality of life are commonly experienced in childhood cancer survivors. While rehabilitation clinics support patients in coping with the disease, studies evaluating an inpatient rehabilitation program on promoting physical activity (PA) and health-related quality of life (HRQoL) are missing.

Methods: A 4-week inpatient rehabilitation program was prospectively evaluated.

Abnormalities in Diffusional Kurtosis Metrics Related to Head Impact Exposure in a Season of High School Varsity Football.

The purpose of this study was to determine whether the effects of cumulative head impacts during a season of high school football produce changes in diffusional kurtosis imaging (DKI) metrics in the absence of clinically diagnosed concussion. Subjects were recruited from a high school football team and were outfitted with the Head Impact Telemetry System (HITS) during all practices and games. Biomechanical head impact exposure metrics were calculated, including: total impacts, summed acceleration, and Risk Weighted Cumulative Exposure (RWE).

MR Imaging in Postreduction Assessment of Developmental Dysplasia of the Hip: Goals and Obstacles.

Developmental dysplasia of the hip is a spectrum disorder of hip development that ranges in severity from abnormal acetabular morphology to complete hip dislocation. While treatment with a Pavlik harness is highly effective in infants younger than 6 months, older infants and children and those with orthotic failure often warrant surgical reduction and placement of a spica cast, which limits subsequent imaging evaluation. Magnetic resonance (MR) imaging has been described in the evaluation of the adequacy of hip reduction for more than 2 decades, but the practice is still not widespread and is performed routinely at relatively few centers.

Energy intake highs and lows: how much does consistency matter in weight control?

Behavioural weight control programmes recommend adherence to daily energy intake goals, yet also allow for flexibility in intake across days. Evidence is lacking as to whether intake consistency is important for weight control. The current study explored the relation between day-to-day intake consistency and weight loss in the context of behavioural weight loss treatment and examined the relationship between variability in intake and several factors known to be associated with weight control success.

Relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance in hypertensives.

Microvascular remodeling and large artery stiffness are key determinants of cardiovascular hemodynamics and can now be studied with new non-invasive methods. Our objective was to study the relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance (total peripheral resistance (TPR)) in hypertensives. In 80 subjects (age 52±13 years; 53% males; including 23 normotensives and 57 hypertensives, among which 29 were uncontrolled hypertensives), we used: (1) the new non-invasive RTX1 adaptive optics (AO) camera (Imagine Eyes, Orsay, France) to measure the wall-to-lumen ratio (WLR) on retinal microvasculature; (2) cardiovascular magnetic resonance (CMR) imaging to assess aortic stiffness, geometry and cardiac output; and (3) the validated SphymoCor Xcel device to measure central blood pressure (BP) and carotido-femoral pulse wave velocity (Cf-PWV).

Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls.

Binge Eating among Women Veterans in Primary Care: Comorbidities and Treatment Priorities.

Background: Little is known about the clinical profile and treatment priorities of women with binge eating disorder (BED), a diagnosis new to the fifth edition of Diagnostic and Statistical Manual of Mental Disorders. We identified comorbidities and patients' treatment priorities, because these may inform implementation of clinical services.

Methods: Data were collected from women veteran primary care patients.

Cognitive framing in action.

Cognitive framing effects have been widely reported in higher-level decision-making and have been ascribed to rules of thumb for quick thinking. No such demonstrations have been reported for physical action, as far as we know, but they would be expected if cognition for physical action is fundamentally similar to cognition for higher-level decision-making. To test for such effects, we asked participants to reach for a horizontally-oriented pipe to move it from one height to another while turning the pipe 180° to bring one end (the "business end") to a target on the left or right.

Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors.

The orexin (also known as hypocretin) G protein-coupled receptors (GPCRs) regulate sleep and other behavioral functions in mammals, and are therapeutic targets for sleep and wake disorders. The human receptors hOX1R and hOX2R, which are 64% identical in sequence, have overlapping but distinct physiological functions and potential therapeutic profiles. We determined structures of hOX1R bound to the OX1R-selective antagonist SB-674042 and the dual antagonist suvorexant at 2.

Prevalence and factors associated with cognitive deficit in women with gynecologic malignancies.

Objective: Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate the prevalence and risk factors associated with cognition in women with gynecologic malignancies.

Methods: After Institutional Review Board approval, 165 women at an urban ambulatory gynecologic oncology facility were queried using a Montreal Cognitive Assessment (MoCA), Wong-Baker pain scale, neuropathy scale, Patient Health Questionnaire 9 (PHQ-9) Depression Scale, and Generalized Anxiety Disorder Scale (GAD 7).

State-dependent altered connectivity in late-life depression: a functional near-infrared spectroscopy study.

There is a large body of evidence showing a substantial relationship between depression and deficits in cognitive functioning. Especially in late-life depression, cognitive impairments are associated with worse treatment progress and are considered a risk factor for neurodegenerative disorders. However, little is known about the differences in neural processing and coupling during rest and cognitive functions in patients with late-life depression compared to healthy elderly individuals.

The role of negative reinforcement eating expectancies in the relation between experiential avoidance and disinhibition.

Objectives: Eating-related disinhibition (i.e., a tendency to overeat in response to various stimuli) is associated with weight gain and poorer long-term weight loss success.

Four questions for passive frame theory.

Four questions are raised about the passive frame theory of Morsella et al.: (1) What is the relation of the theory to the response-selection-bottleneck view of attention? (2) Does the theory accommodate the contents of consciousness? (3) What about animals without skeletal muscles? (4) How do the contents of consciousness change with the development of automaticity?

One in Four Questioned Children Faces Problems Regarding Reintegration Into Physical Education at School After Treatment for Pediatric Cancer.

Resumption of physical activity and reintegration into social surroundings after treatment for pediatric cancer is of high importance to recover from the burden of disease and treatment and to positively influence long-term health outcomes. Eighty-three children who had completed intensive treatment for pediatric cancer were surveyed regarding their participation in physical education at school (PES). The results show a concerning low rate of participation, particularly in children treated for pediatric bone tumors, and associated barriers.