Measuring the repertoire of age-related behavioral changes in Drosophila melanogaster

Aging affects almost all aspects of an organism -- its morphology, its physiology, its behavior. Isolating which biological mechanisms are regulating these changes, however, has proven difficult, potentially due to our inability to characterize the full repertoire of an animal's behavior across the lifespan. Using data from fruit flies (D. melanogaster) we measure the full repertoire of behaviors as a function of age. We observe a sexually dimorphic pattern of changes in the behavioral repertoire during aging. Although the stereotypy of the behaviors and the complexity of the repertoire overall remains relatively unchanged, we find evidence that the observed alterations in behavior can be explained by changing the fly's overall energy budget, suggesting potential connections between metabolism, aging, and behavior

Association between First Trimester Pregnancy Associated Plasma Protein–A and the Development of Gestational Diabetes Mellitus

Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism. Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk. Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM. Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile. Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis

Association between First Trimester Pregnancy Associated Plasma Protein–A (PAPP-A) and Gestational Diabetes Mellitus Development

Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism. Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk. Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM. Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile. Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis

The Accuracy of Recalled versus Measured Pre-Pregnancy Weight for the Calculation of Pre-Pregnancy Body Mass Index

Background: In 2009, the Institute of Medicine (IOM) published gestational weight gain (GWG) guidelines with the goal of optimizing maternal and fetal outcomes. GWG recommendations are specific to pre-pregnancy body mass index (BMI): 28-40 lbs for underweight (UW; BMI2), 25-35 lbs for normal weight (NW; 18.5≤BMI/m2), 15-25 lbs for overweight (OW; 25 ≤BMI/m2), and 11-20 lbs for obese (OB; BMI≥30 kg/m2) women. With upwards of 50% of pregnancies in the U.S. unplanned, measured pre-pregnancy weight is often unavailable in clinical and research settings. Evaluating the accuracy of recalled pre-pregnancy weight early in prenatal care is important in order to establish accuracy of pre-pregnancy BMI calculations in order to counsel about GWG accurately. Objective: To examine differences in recalled versus measured pre-pregnancy weight and to examine factors associated with accuracy of recalled weights. Methods: Medical record review of 1,998 randomly selected pregnancies. Eligible women received prenatal care in faculty and resident clinics at UMass Memorial Health Care (UMMHC), delivered between January 2007 and December 2012, and had available both: (1) a measured weight within one year of conception and (2) a pre-pregnancy weight self-reported at first prenatal visit. Data were obtained from the UMMHC paper or electronic prenatal record and the Allscripts EMR. We calculated the difference in weights as recalled pre-pregnancy weight minus most recent measured weight within one year of conception. Subjects were excluded if they received care at a non-faculty or non-resident practice, charts not available after three separate retrieval attempts, both weights of interest not available, or if measured weight occurred at a prenatal visit for a prior pregnancy. For women with more than one pregnancy during the study time frame, one was randomly selected for inclusion in the analytic data set. Results: Of the 1,998 pregnancy charts reviewed, 400 records met eligibility criteria and were included in this analysis. Women were mean age 29.7 (SD: 6.2) years, 69.3% multigravida, 64.4% non-Hispanic white, 65.2% married, and 62.4% had a college or greater education. Based on recalled weight, 3.3% of women were underweight, 46.6% were normal weight, 25.9% overweight, and 24.2% obese. 63% received care in the faculty obstetric clinic. Recorded recalled weights were mean 2.4 (SD: 11.1) pounds lower than measured pre-pregnancy weight. This difference did not differ by age, location of care, pre-pregnancy BMI, marital status, race/ethnicity, primary language, gravity, education, or time between measured weight and conception, in unadjusted and adjusted models. For 88.7% of women, calculating pre-pregnancy BMI based on weight measured up to a year prior to conception or based on recalled pre-pregnancy weight reported at the first prenatal visit resulted in the same classification of pre-pregnancy BMI. Conclusion: Prenatal care providers may calculate pre-pregnancy BMIs using recalled pre-pregnancy weights early in prenatal care and use such calculated BMIs to accurately provide GWG recommendations regardless of demographic variables, gravity, or location of care

Demographic Characteristics Associated with the Presence of Recalled and Measured Prepregnancy Weights

Background: Gestational weight gain within prepregnancy BMI-specific Institute of Medicine (IOM) recommended ranges are associated with good outcomes for both mother and baby. Availability of measured prepregnancy weight, recalled prepregnancy weight or measured weight at first prenatal visit if the former two weights are not available, influences the accuracy of provider recommendations for gestational weight gain. Objective: The purpose of this study is to examine demographic characteristics associated with the presence of recalled prepregnancy weight and measured prepregnancy weight in the prenatal care medical record. Methods: Medical record review of 1,998 randomly selected pregnancies, of which 1,911 met inclusion criteria of delivery between January 2007 and December 2012 and receipt of prenatal care in faculty and resident clinic sites at UMass Memorial Health Care (UMMHC). Subjects\u27 paper prenatal chart and electronic record (AllScripts and QS prenatal EMR) were fully abstracted if available and contained both: (1) a recorded measured weight within one year of conception, and (2) a self-reported prepregnancy weight obtained at first prenatal visit. Additionally, exclusion criteria included those pregnancies with only prenatal weights recorded one year prior to conception for index pregnancy. For women with multiple pregnancies during the study time period, one pregnancy was randomly selected for inclusion in study analyses. Demographic data was abstracted for all available charts regardless of presence or absence of weights of interest. Demographic characteristics considered were age (15-29, 20-24, 25-29, 30-34, 35+ years), prepregnancy BMI calculated based on recalled height and weight (underweight: BMI2, normal weight: 18.5≤ BMI/m2, overweight: 25≤BMI/m2, and obese: 30 kg/m2≤BMI), race/ethnicity (non-Hispanic white vs. other race/ethnicity), marital status (not married vs. married), primary language (non-English vs. English), gravidity (1, 2, 3+), education (high school diploma or less, some college, 4 year college or more) and prenatal care site (faculty vs. resident obstetric clinic). Logistic regressions were performed to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) and adjusted analyses controlled for demographics. Results: Of the 1911 pregnancies meeting initial inclusion criteria, 1711 (89.5%) had charts available for abstraction; fifty-three subjects had multiple pregnancies of which only one was included in analyses resulting in an analytic sample of 1656 pregnancies. Of these, 511 (30.9%) were missing a recalled prepregnancy weight at first prenatal visit, 711 (42.9%) had the recalled prepregnancy weight but did not have a measured weight; and only 434 (26.2%) had both weights of interest. Overweight women had decreased odds of having a recalled weight compared to women of normal weight (aOR 0.75; 95% CI 0.56-1.00). Additionally, women with ≥4 years of college compared to those with ≤ high school diploma (aOR 0.54; 95% CI 0.40-0.73), and those receiving care in the faculty compared to the resident clinics (aOR 0.48; 95% CI 0.35-0.65) had decreased odds of having a recalled weight available in the chart. Among women with available recalled prepregnancy weight (n=1101), 390 (35.4%) also had a documented measured weight within one year of conception and 711 (64.6%) did not. Women who were not married (aOR 0.54; 95% 0.39-0.76) had decreased odds of having a measured weight, whereas those receiving care in the faculty compared to resident clinics had greater odds (aOR 1.79; 95% CI 1.26-2.53) of having a measured weight within one year of conception available in their charts. Conclusions: Our results suggest that approximately 25% of women have both recalled weight at first prenatal visit and at least one weight measured within one year of conception in their medical records. Prepregnancy BMI, education, and prenatal care site were associated with presence or absence of recalled weight. Similarly, amongst those with recalled weight, martial status and prenatal care in faculty practice where associated with decreased and increased odds respectively of having a measured weight within one year of conception. We can use this information to help practitioners target women for which greater efforts are needed to provide accurate IOM-recommended BMI-specific gestational weight gain guidelines. This may be utilized to discern patterns of health care access in this patient population

The genetic basis of variation in clean lineages of Saccharomyces cerevisiae in response to stresses encountered during bioethanol fermentations.

Saccharomyces cerevisiae is the micro-organism of choice for the conversion of monomeric sugars into bioethanol. Industrial bioethanol fermentations are intrinsically stressful environments for yeast and the adaptive protective response varies between strain backgrounds. With the aim of identifying quantitative trait loci (QTL's) that regulate phenotypic variation, linkage analysis on six F1 crosses from four highly divergent clean lineages of S. cerevisiae was performed. Segregants from each cross were assessed for tolerance to a range of stresses encountered during industrial bioethanol fermentations. Tolerance levels within populations of F1 segregants to stress conditions differed and displayed transgressive variation. Linkage analysis resulted in the identification of QTL's for tolerance to weak acid and osmotic stress. We tested candidate genes within loci identified by QTL using reciprocal hemizygosity analysis to ascertain their contribution to the observed phenotypic variation; this approach validated a gene (COX20) for weak acid stress and a gene (RCK2) for osmotic stress. Hemizygous transformants with a sensitive phenotype carried a COX20 allele from a weak acid sensitive parent with an alteration in its protein coding compared with other S. cerevisiae strains. RCK2 alleles reveal peptide differences between parental strains and the importance of these changes is currently being ascertained

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women

Background: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 μg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. Methods: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 μg/L. Results: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 μg/L, 3.1 μg/L, and 514 μg/L, respectively. One-third of women had UIC <100 μg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 μg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. Conclusion: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 μg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants

Damage costs from invasive species exceed management expenditure in nations experiencing lower economic activity

Financial disclosure The InvaCost project was funded by the French National Research Agency (ANR-14-CE02-0021), the BNP-Paribas Foundation Climate Initiative, the AXA Research Fund Chair of Invasion Biology of University Paris Saclay and by the BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios (AlienScenarios; BMBF/PT DLR 01LC1807C). M.K. received funding from the European Union's Horizon 2020 research programme under a Marie Skłodowska-Curie grant agreement 899546. C.J.A.B. acknowledges the Australian Research Council (CE170100015) for support. A.B. acknowledges Azim Premji University's grants programme (UNIV-RC00326) for support.Peer reviewe

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB