Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels

Mechanically Induced Chromatin Condensation Requires Cellular Contractility in Mesenchymal Stem Cells

This work was supported by the National Institutes of Health (R01 AR056624, R01 EB02425, T32 AR007132, and P30 AR050950). Additional support was provided by a Montague Research Award from the Perelman School of Medicine and a University of Pennsylvania University Research Foundation Award

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The Diabetic Program Evaluation for a Peer Educator Model in Takeo, Cambodia from 2007 to 2013

Thesis (Master's)--University of Washington, 2015University of Washington Abstract The Diabetic Program Evaluation for a Peer Educator Model in Takeo, Cambodia from 2007 to 2013 Dawn Taniguchi Chair of the Supervisory Committee: Professor, James LoGerfo M.D., M.P.H., F.A.C.P. Department of Global Health Background: Early detection and treatment for diabetes (DM) are essential for reducing disability and death from the disease. Finding effective ways of improving affordable screening, access, and quality of care for diabetic patients living in developing countries is a challenge. MoPoTsyo, a Cambodian non-governmental organization, was established to help address this lack of DM care in Cambodia utilizing a peer educator model. This study aimed to describe the outcomes of MoPoTsyo’s diabetic program in Takeo Province by assessing glycemic and blood pressure outcomes over 5 years of follow up. Methods: We calculated the mean fasting blood glucose (FBG) and blood pressure (BP) at regular intervals of follow up. The proportion of patients reaching recommended treatment targets for FBG and BP were assessed for each interval. The paired t-test was used to compare baseline and follow up at one year. Results: Of 3411 patients enrolled, 2230 were included in the study. The cohort was predominantly female (68.9%) with a median age of 54 years. Median follow up time in the program was 16 months (4.9-38.4 months). There was a significant decrease (p<0.001) of 63.9 mg/dl in mean FBG (95% CI 58.5 to 69.3) at one year of follow up when compared to enrollment FBG. After one year, 45% (321/708) of patients achieved this goal. By year five, 41% (108/259) were within target FBG < 126. When assessing goal FBG < 150, 60% and 59% were within goal at one year and five years of follow up respectively. Systolic and diastolic BP levels significantly (p<0.001) decreased by 10.9 mmHg (95% CI 8.9 to 12.9) and 7.7 mm Hg (95% CI 6.4 to 8.8) respectively between enrollment and one year of follow up. Of the 65% with elevated BP at enrollment, 30% (163/529) of them reach the BP goal at one year of follow up and 34.4% (78/227) reach goal at 5 years. When accounting for all patients, 44.4% (156/351) had target BP at 5 years of follow up. When using the BP goal of less than 140/90 mmHg, 70% were within goal at 5 years of follow up (248/351). Conclusion: The outcome indicators of DM care for MoPoTsyo’s Takeo program evaluation are promising. This illustrates a reasonable approach to delivering effective quality DM care to a large number of patients in rural parts of LMIC

Evaluation of a multi-faceted diabetes care program including community-based peer educators in Takeo province, Cambodia, 2007-2013.

Early detection and treatment for diabetes are essential for reducing disability and death from the disease. Finding effective screening and treatment for individuals living with diabetes in resource-limited countries is a challenge. MoPoTsyo, a Cambodian non-governmental organization, addressed this gap by utilizing a multi-pronged approach with community-based peer educators, access to laboratory procedures, local outpatient medical consultation, and a revolving drug fund. This study evaluated outcomes of MoPoTsyo's diabetes program in Takeo Province by assessing glycemic and blood pressure outcomes for individuals diagnosed with diabetes over a 24-month follow-up period between 2007-2013.This is a retrospective cohort analysis of records without a comparison group. We calculated the mean fasting blood glucose (FBG) and blood pressure (BP) at regular intervals of follow-up. The proportion of patients reaching recommended treatment targets for FBG and BP was assessed.Of the 3411 patients enrolled in the program, 2230 were included in the study. The cohort was predominantly female (68.9%) with a median age of 54 years. Median follow-up time in the program was 16 months (4.9-38.4 months). Mean FBG decreased 63.9 mg/dl in mean FBG (95% CI 58.5 to 69.3) at one year of follow-up (p<0.001). After one year, 45% (321/708) of patients achieved goal FBG < 126. Of the 41.6% (927/2230) with elevated BP at enrollment, systolic and diastolic BP levels significantly decreased (p<0.001) by 16.9 mmHg (95% CI 1.2 to 22.9) and 10 mm Hg (95% CI 0.7 to 12.9) respectively between enrollment and one year of follow-up. At one year of follow-up, 51.1%% (183/355) of these patients reached the BP goal < 140/90.The improved outcome indicators of diabetes care for MoPoTsyo's Takeo program evaluation showed promise. The program demonstrated a reasonable and practical approach to delivering effective diabetes care in a rural area and may serve as a model for other low-income communities. Future prospective evaluations with more complete data are necessary for longer-term outcomes

Correction: Evaluation of a multi-faceted diabetes care program including community-based peer educators in Takeo province, Cambodia, 2007-2013.

[This corrects the article DOI: 10.1371/journal.pone.0181582.]

Gravimetry, altimetry and mean sea level in North Africa

Comunicación presntada a la 3ª Asamblea Hispano-Portuguesa de Geodesia y Geofísica = 3ª Assembleia Luso-Espanhola de Geodesia e Geofisica, celebrada en Valencia entre el 4 y el 8 de febrero de 2002.The North Africa region has a great geodetic and geophysical interest. In order to obtain an enough infrastructure of data for diverse applications, we have proceeded to gather information about gravimetric data, digital terrain models and mean sea surfaces models in this region, including the Atlantic and Mediterranean areas. The data of different sources has been transformed to the same reference system, fundamentally the WGS84, in forecast of future applications with GPS. The different sets of data have been analyzed and validated, trying to eliminate gross errors that surpass some certain appropriate limits of tolerance previously assigned to each category. As a result we have obtained: a) A database of validated gravimetric data with terrestrial measures and marine ones with gravimeters, and obtained by satellites, b) Gravimetric data coming from a geopotential model, c) A digital terrain model including bathymetry in marine areas, d) Data of free air anomalies, and e) Data of the mean sea surface, obtained from satellite altimetry. The results are presented in gridded form, with an interval of 2x2 arc minutes, in geodetic coordinated. A set of images and graphics is presented to illustrate the results.La región del Norte de África tiene un gran interés tanto geodésico como geofisico. A fin de obtener una infraestructura suficiente de datos para diversas aplicaciones, hemos procedido a recopilar información sobre datos gravimétricos, modelos digitales del terreno y modelos de superficies medias del mar en esta región, incluyendo las áreas atlántica y mediterránea. Los datos de diferente procedencia han sido transformados a un mismo sistema de referencia, fundamentalmente el WGS84, en previsión de futuras aplicaciones con GPS. Los diferentes conjuntos de datos han sido analizados y validados, tratando de eliminar en lo posible errores groseros que sobrepasen unos ciertos límites de tolerancia adecuados a cada categoría. Como resultado hemos obtenido: a) Un banco de datos gravimétricos validados, tanto de medidas terrestres como marinas con gravímetros, junto a datos gravimétricos obtenidos por satélites, b) Datos gravimétricos procedentes de un modelo de geopotencial, e) Un modelo digital del terreno incluyendo batimetría en zonas marinas, d) Datos de anomalías aire libre, y e) Datos de la superficie media del mar, obtenidos a partir de altimetría por satélites. Los resultados se presentan en forma de mallas, con un intervalo de 2x2 minutos de arco, en coordenadas geodésicas. Se presenta también un conjunto de imágenes y gráficos para ilustrar los resultados.Peer reviewe

Mean fasting blood glucose level over time.

<p>Mean fasting blood glucose level over time.</p

Evaluation of a multi-faceted diabetes care program including community-based peer educators in Takeo province, Cambodia, 2007-2013

<div><p>Introduction</p><p>Early detection and treatment for diabetes are essential for reducing disability and death from the disease. Finding effective screening and treatment for individuals living with diabetes in resource-limited countries is a challenge. MoPoTsyo, a Cambodian non-governmental organization, addressed this gap by utilizing a multi-pronged approach with community-based peer educators, access to laboratory procedures, local outpatient medical consultation, and a revolving drug fund. This study evaluated outcomes of MoPoTsyo’s diabetes program in Takeo Province by assessing glycemic and blood pressure outcomes for individuals diagnosed with diabetes over a 24-month follow-up period between 2007–2013.</p><p>Methods</p><p>This is a retrospective cohort analysis of records without a comparison group. We calculated the mean fasting blood glucose (FBG) and blood pressure (BP) at regular intervals of follow-up. The proportion of patients reaching recommended treatment targets for FBG and BP was assessed.</p><p>Results</p><p>Of the 3411 patients enrolled in the program, 2230 were included in the study. The cohort was predominantly female (68.9%) with a median age of 54 years. Median follow-up time in the program was 16 months (4.9–38.4 months). Mean FBG decreased 63.9 mg/dl in mean FBG (95% CI 58.5 to 69.3) at one year of follow-up (p<0.001). After one year, 45% (321/708) of patients achieved goal FBG < 126. Of the 41.6% (927/2230) with elevated BP at enrollment, systolic and diastolic BP levels significantly decreased (p<0.001) by 16.9 mmHg (95% CI 1.2 to 22.9) and 10 mm Hg (95% CI 0.7 to 12.9) respectively between enrollment and one year of follow-up. At one year of follow-up, 51.1%% (183/355) of these patients reached the BP goal < 140/90.</p><p>Conclusion</p><p>The improved outcome indicators of diabetes care for MoPoTsyo’s Takeo program evaluation showed promise. The program demonstrated a reasonable and practical approach to delivering effective diabetes care in a rural area and may serve as a model for other low-income communities. Future prospective evaluations with more complete data are necessary for longer-term outcomes.</p></div