Novel Video Imaging to Examine Cardiac Function in Xenopus Embryos

Congenital heart defects (CHDs) occur in approximately 1% of live births and the etiology has been associated with disturbances in cardiogenesis. However, the majority of research examining CHDs relies on static morphological data, which does not elucidate how defects alter cardiac function. I used Xenopus laevis embryos to examine the association between CHDs and functional alterations using a novel imaging system that can obtain high- resolution images through a non-invasive procedure. A high-speed video camera and software were used to assess cardiac function, permitting functional characterization of late Xenopus cardiogenesis. Verification of the imaging system’s ability to detect changes in function was confirmed by exposing embryos to well-established agents that alter heart rate. Additionally, significant functional changes were detected following exposure of embryos to small molecules known to disrupt morphogenesis. The imaging system will be a useful alternative to current imaging modalities for elucidating mechanisms underlying CHDs in optically transparent embryos

Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1-/- mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r-/- mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence

Resilience of health-care workers in the UK; a cross-sectional survey

Background Working for the UK National Health Service (NHS) requires working for organisations under financial pressures and frequent restructures, which can lead to anxiety over continuing employment and income. There are currently no studies to date that have examined the influence of personal resilience across all professions and demographics in the NHS. This study aims to quantify resilience within an NHS trust and explore the contribution of demographic variables of gender, age, years of service, pay grade, hours worked, job role, and division worked to the resilience response of employees. The study also explores the relationship between resilience levels and absence rates, as a marker for health and well-being amongst NHS staff. Methods This study consists of a cross-sectional on-line survey of staff employed in an NHS Trust. All trust employees were asked to complete a Resilience Scale (RS-25), and demographic questions including age, sex, length of service, NHS pay grade (banding), division, job role and number of hours worked per week. Trust level sickness absence rates were also collected during this period. Results were analysed using descriptive statistics, bivariate comparisons and chi-squared tests. Results Data was gained from 845 employees; a significant association between gender and resilience found females scoring higher on the resilience scale; x 2(5) =18.30, p < 0.05. A weak positive correlation between age and resilience found older employees displaying a higher level of resilience; r = 0.11, p <0.05. Results also suggest employees working between 18.75-37.5 hours a week have higher levels of resilience. Ancillary staff scored low on resilience compared to all other staff groups which showed moderate resilience. Clinical staff scored lower on resilience compared to both administrative staff and clinical staff with line management responsibilities. No correlations were found between absence rates and resilience. Conclusion This study gives a snapshot of the resilience of employees in a NHS trust. It is the first of its kind to take into consideration all job roles, divisions and the banding system within a trust. The results also indicate that resilience levels may not be a mediating factor for the health and well-being of NHS staff

Life satisfaction and mortality in elderly people: The Kangwha Cohort Study

<p>Abstract</p> <p>Background</p> <p>As well as biomedical risk factors, psychological factors have been reported to be related to mortality rate. The purpose of this study was to examine the relationship between life satisfaction and mortality in elderly people through an 11.8-year follow-up study of a prospective cohort.</p> <p>Methods</p> <p>Among 3,600 participants of the Kangwha Cohort Study who survived in 1994, 1,939 respondents of the Life Satisfaction Index (LSI)-A questionnaire were included (men, 821; women, 1118). The mortality risk for the period up to December 2005 was measured using the Cox Proportional Hazard Model.</p> <p>Results</p> <p>When the relationship between LSI and mortality was evaluated in men, the unsatisfied group with lower LSI scores showed a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.83) than the satisfied group with higher LSI scores. In women, the unsatisfied group showed a significantly higher risk of all-cause mortality (HR, 1.51; 95% CI, 1.18-1.92) and cardiovascular mortality (HR, 2.23; 95% CI, 1.30-3.85) than the satisfied group.</p> <p>Conclusion</p> <p>We found that elderly people with a lower LSI score, regardless of gender, were at risk of increased mortality from all causes, and low LSI score was also associated with cardiovascular mortality.</p

Assessment of Artifacts and Reproducibility across Spectral- and Time-Domain Optical Coherence Tomography Devices

Purpose To report the frequency of optical coherence tomography (OCT) scan artifacts and to compare macular thickness measurements, interscan reproducibility, and interdevice agreeability across 3 spectral-domain (SD) OCT (also known as Fourier domain; Cirrus HD-OCT, RTVue-100, and Topcon 3D-OCT 1000) devices and 1 time-domain (TD) OCT (Stratus OCT) device. Design Prospective, noncomparative, noninterventional case series. Participants Fifty-two patients seen at the New England Eye Center, Tufts Medical Center Retina Service, between February and August 2008. Methods Two scans were performed for each of the SD OCT protocols: Cirrus macular cube 512×128 (software version 3.0; Carl Zeiss Meditec, Inc., Dublin, CA), RTVue (E)MM5 and MM6 (software version 3.5; Optovue, Inc., Fremont, CA), Topcon 3D Macular and Radial (software version 2.12; Topcon, Inc., Paramus, NJ), in addition to 1 TD OCT scan via Stratus macular thickness protocol (software version 4.0; Carl Zeiss Meditec, Inc.). Scans were inspected for 6 types of OCT scan artifacts and were analyzed. Interscan reproducibility and interdevice agreeability were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots, respectively. Main Outcome Measures Optical coherence tomography image artifacts, macular thickness, reproducibility, and agreeability. Results Time-domain OCT scans contained a significantly higher percentage of clinically significant improper central foveal thickness (IFT) after manual correction (11-μm change or more) compared with SD OCT scans. Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT (11.1%) compared with the other SD OCT devices (Topcon 3D, 20.4%; Topcon Radial, 29.6%; RTVue (E)MM5, 42.6%; RTVue MM6, 24.1%; P = 0.001). All 3 SD OCT devices had central foveal subfield thicknesses that were significantly more than that of TD OCT after manual correction (P<0.0001). All 3 SD OCT devices demonstrated a high degree of reproducibility in the central foveal region (ICCs, 0.92–0.97). Bland-Altman plots showed low agreeability between TD and SD OCT scans. Conclusions Out of all OCT devices analyzed, cirrus HD-OCT scans exhibited the lowest occurrence of any artifacts (68.5%), IFT (40.7%), and clinically significant IFT (11.1%), whereas Stratus OCT scans exhibited the highest occurrence of clinically significant IFT. Further work on improving segmentation algorithm to decrease artifacts is warranted.Research to Prevent Blindness, Inc. (United States) (Challenge Grant)National Institutes of Health (U.S.) (Grant R01-EY11289-23)National Institutes of Health (U.S.) (Grant R01-EY13178-07)National Institutes of Health (U.S.) (Grant P30-EY008098)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0101)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0014

Developmental origins for kidney disease due to Shroom3 deficiency

CKD is a significant health concern with an underlying genetic component. Multiple genome-wide association studies (GWASs) strongly associated CKD with the shroomfamilymember 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman\u27s capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho-kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease

Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1(-/-) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(-/-) mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence