The decrease in growth hormone (GH) response after repeated stimulation with GH-Releasing hormone is partly caused by an elevation of somatostatin tonus.

Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Organic Micropollutants from an Agricultural Drainage Ditch Contaminate a Shrimp Farm in Sinaloa (Mexico)

Among nutrients and pesticides, agricultural draining ditches also transport pollutants discharged with untreated wastewater from the municipalities adjoining the ditch. When the ditch water is used for irrigation and aquaculture, risks for the environment and food production are suggested. For the conducted field study, a shrimp farm in Sinaloa (Mexico) was used to trace organic pollutants (pesticides and pharmaceutical residues) on their way from an agricultural draining ditch to a shrimp farm fed partially by the drain water. The concentrations of pollutants in the drain water ranged from 10 ng L-1 to 453 ng L-1. The pond water of the shrimp farm contained concentrations between &lt;10 ng L-1 and 177 ng L-1. The shrimps were contaminated by pollutants at concentrations between 40 μg kg-1 d.w. (dry weight) to 3.3 mg kg-1 d.w. (fungicide Metalaxyl). Health risks for the cultivated shrimps cannot be excluded because some pesticides are known for their toxic effects to crustaceans. The concentrations of selected antibiotics in the shrimps were low and comparable with those found in the shrimps declared as seawater shrimps from a German supermarket. The incorporation of the antibiotics was probably caused by contact to the wastewater in the shrimp ponds and/or by contaminated shrimp feed. Additionally to the anthropogenic chemicals, coliforms were determined in the water (total coliforms: 30-50 CFU 100 mL-1; fecal coliforms: 0-20 CFU 100 mL-1). These values agree with the Mexican Norm NOM-242-SSA1-2009 representing a microbiological quality of water adequate for aquaculture. The number of coliforms measured in shrimp was higher than in pond water, suggesting bioaccumulation and a potential health risk for consumers

Organic Micropollutants from an Agricultural Drainage Ditch Contaminate a Shrimp Farm in Sinaloa (Mexico)

Agricultural draining ditches transport among nutrients and pesticides also pollutants discharged with untreated wastewater from the municipalities adjoining the ditch. When the ditch water is used for irrigation and aquaculture, risks for the environment and food production are suggested. For our field study, a shrimp farm in Sinaloa (Mexico) was used to trace organic pollutants (pesticides and pharmaceutical residues) on their way from an agricultural draining ditch to a shrimp farm feed partially by the drain water. The concentrations of pollutants in the drain water ranged from 10 ng L-1 to 453 ng L-1 . The pond water of the shrimp farm contained concentrations between <10 ng L-1 and 177 ng L-1. The shrimps were contaminated by pollutants at concentrations between 40 µg kg-1 d.w. (dry weight) to 3.3 mg kg-1 d.w. (fungicide Metalaxyl). Health risks for the cultivated shrimps cannot be excluded because some pesticides are known for their toxic effects to crustaceans. The concentrations of selected antibiotics in the shrimps were low and comparable with those found in shrimps declared as seawater shrimps from a German supermarket. The incorporation of the antibiotics was probably caused by contact to the wastewater in the shrimp ponds and/or by contaminated shrimp feed. Additionally to the anthropogenic chemicals, coliforms were determined in the water (total coliforms: 30-50 CFU 100 mL-1; fecal coliforms: 0-20 CFU 100 mL-1). These values agree with the Mexican Norm NOM-242-SSA1-2009 representing a microbiological quality of water adequate for aquaculture. The number of coliforms measured in shrimp was higher than in pond water, suggesting bioaccumulation and a potential health risk for consumers