Elevated Medical Costs for Obese Fifth Graders in California and Texas

Finkelstein et al. (2014) estimated that an obese ten-year-old, typically in the fifth grade, will incur between $12,660 and$19,630 in direct medical costs beyond those of a normal-weight ten-year-old over a lifetime. PURPOSE: The purpose was to estimate the lifetime direct medical costs attributable to obesity for fifth graders in the two most populous states, Texas and California. METHODS: Body composition data from the Presidential Youth Fitness Program’s FITNESSGRAM® administered in California and Texas each school year from 2010 – 2011 to 2012 – 2013 were used. Data included information on 447,619 – 456,409 fifth graders each year in California and 296,887 – 337,514 fifth graders in Texas. The number and percentage of students in each of the FITNESSGRAM® body composition categories was calculated and those in the Needs Improvement – High Risk (NI – HR) were used for cost estimation. The number of students in the NI – HR category for each year in each state was multiplied by the recommended cost estimate of $19,000 to project the elevated lifetime medical costs attributable to obesity for each group of fifth graders in each state. RESULTS: More than 33$3 billion for each group of fifth graders in California and more than $2 billion for each group of fifth graders in Texas. CONCLUSIONS: When the percentage of obese fifth graders is extrapolated to the entire United States’ 4 million 10-year-olds, this results in more than$25 billion in elevated direct lifetime medical costs attributable to obesity for this 1-year age cohort. These estimates are for obesity and do not include the additional costs associated with overweight (i.e., FITNESSGRAM® Needs Improvement – Some Risk category). This information should be used to influence spending decisions and resource allocation to obesity reduction and prevention efforts

An Analysis of the Medical Costs of Obesity for Fifth Graders in California and Texas

International Journal of Exercise Science 9(1): 26-33, 2016. The prevalence of childhood obesity in the United States increased more than three-fold from 1976 – 1980 to 2007 – 2008. The Presidential Youth Fitness Program’s FitnessGram® is the current method recommended by the President’s Council on Fitness, Sports & Nutrition for assessing health-related fitness factors, including body composition. FitnessGram® data from California and Texas, the two most populous states, over a three-year time span indicate that more than one-third of fifth grade students, typically ten-year-olds, are obese. Previous studies report that an obese ten-year-old child who remains obese into adulthood will incur elevated direct medical costs beyond his or her normal-weight peers over a lifetime. The recommended elevated cost estimates are approximately $12,660 when comparing against a normal-weight child who gains weight as an adult and approximately$19,000 compared to a child who remains at normal weight as an adult. By applying these figures to FitnessGram® results from California and Texas, each group of fifth grade students in each of the two states will incur between $1.4 and$3.0 billion in direct medical costs over a lifetime. When the percentage of obese fifth graders is extrapolated to the rest of the United States’ 4 million ten-year-olds, this results in more than $17 billion (accounting for adulthood weight gain) or$25 billion (not accounting for adulthood weight gain) in added direct lifetime medical costs attributable to obesity for this single-year age cohort. This information should be used to influence spending decisions and resource allocation to obesity reduction and prevention efforts

Meeting USDHHS Physical Activity Guidelines and Health Outcomes

International Journal of Exercise Science 10(1): 121-127, 2017 Current public health physical activity (PA) guidelines suggest ≥500 METmin/week of PA, with additional benefits beyond 1000 METmin/week (i.e., a dose response). Revised U.S. PA guidelines are scheduled for 2018. The purpose was to relate health markers (blood pressure, percent fat, BMI, blood glucose, cholesterol, and cardiorespiratory fitness) to verify the dose response for PA guidelines revision. 505 non-smoking participants self-reported PA behaviors and completed medical screening. MANCOVA controlling for age and gender determined the relation between health markers and PA. MANCOVA indicated significantly (P\u3c.001) different health markers of percent fat, BMI, glucose, and treadmill time as a function of PA. Post-hoc Helmert contrasts (1] \u3c500 METmin/week vs. ≥500 METmin/week and 2] 500 to \u3c1000 METmin/week vs. ≥1000 METmin/week) indicated that meeting the PA guidelines was associated with better health markers and higher cardiorespiratory fitness. Effect sizes were greater for contrast 1 than for contrast 2, suggesting a plateauing effect. Revised public health guidelines should consider achievement of ≥500 METmin/week to be most important, with additional modest gain thereafter. Revised PA guidelines should stress the importance of achieving 500-1000 METmin/week

Volume 17. Article 1. Oceanography of Long Island Sound.

https://elischolar.library.yale.edu/bulletin_yale_bingham_oceanographic_collection/1157/thumbnail.jp

Muscular Fitness and All-Cause Mortality: Prospective Observations

Background: The beneficial effects of cardiorespiratory fitness on mortality are well known; however, the relation of muscular fitness, specifically muscular strength and endurance, to mortality risk has not been thoroughly examined. The purpose of the current study is to determine if a dose-response relation exists between muscular fitness and mortality after controlling for factors such as age and cardiorespiratory fitness. Methods: The study included 9105 men and women, 20-82 years of age, in the Aerobics Center Longitudinal Study who have completed at least one medical examination at the Cooper Clinic in Dallas, TX between 1981 and 1989. The exam included a muscular fitness assessment, based on 1-min sit-up and 1-repetition maximal leg and bench press scores, and a maximal treadmill test. We conducted mortality follow-up through 1996 primarily using the National Death Index, with a total follow-up of 106,046 person-years. All-cause mortality rates were examined across low, moderate, and high muscular fitness strata. Results: Mortality was confirmed in 194 of 9105 participants (2.1%). The age- and sex-adjusted mortality rate of those in the lowest muscular fitness category was higher than that of those in the moderate fitness category (26.8 v. 15.3 per 10,000 persons-years, respectively). Those in the high fitness category had a mortality rate of 20.6 per 10,000 persons-years. The moderate and high muscular fitness groups had relative risks of 0.64 (95% CI = 0.44-0.93) and 0.80 (95% CI = 0.49-1.31), adjusting for age, health status, body mass index, cigarette smoking, and cardiorespiratory fitness when compared with the low muscular fitness group. Conclusions: Mortality rates were lower for individuals with moderate/high muscular fitness compared to individuals with low muscular fitness. These findings warrant further research to confirm the apparent threshold effect between low and moderate/high muscular fitness and all-cause mortality

Characteristics of HIV-1 Discordant Couples Enrolled in a Trial of HSV-2 Suppression to Reduce HIV-1 Transmission: The Partners Study

Background: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort. Methods: HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count ≥250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed. Results: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2–9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001). Conclusions: The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission. Trial Registration ClinicalTrials.gov NCT0019451

A Microhomology-Mediated Break-Induced Replication Model for the Origin of Human Copy Number Variation

Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV). A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2–5 base pairs (bp). Third, endpoints occur near pre-existing low copy repeats (LCRs). Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR) for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR). Under these circumstances, single-strand 3′ tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

A Deviation from the Bipolar-Tetrapolar Mating Paradigm in an Early Diverged Basidiomycete

In fungi, sexual identity is determined by specialized genomic regions called MAT loci which are the equivalent to sex chromosomes in some animals and plants. Usually, only two sexes or mating types exist, which are determined by two alternate sets of genes (or alleles) at the MAT locus (bipolar system). However, in the phylum Basidiomycota, a unique tetrapolar system emerged in which four different mating types are generated per meiosis. This occurs because two functionally distinct molecular recognition systems, each encoded by one MAT region, constrain the selection of sexual partners. Heterozygosity at both MAT regions is a pre-requisite for mating in both bipolar and tetrapolar basidiomycetes. Tetrapolar mating behaviour results from the absence of genetic linkage between the two regions bringing forth up to thousands of mating types. The subphylum Pucciniomycotina, an early diverged lineage of basidiomycetes encompassing important plant pathogens such as the rusts and saprobes like Rhodosporidium and Sporidiobolus, has been so far poorly explored concerning the content and organization of MAT loci. Here we show that the red yeast Sporidiobolus salmonicolor has a mating system unlike any previously described because occasional disruptions of the genetic cohesion of the bipolar MAT locus originate new mating types. We confirmed that mating is normally bipolar and that heterozygosity at both MAT regions is required for mating. However, a laboratory cross showed that meiotic recombination may occur within the bipolar MAT locus, explaining tetrapolar features like increased allele number and evolution rates of some MAT genes. This pseudo-bipolar system deviates from the classical bipolar–tetrapolar paradigm and, to our knowledge, has never been observed before. We propose a model for MAT evolution in the Basidiomycota in which the pseudo-bipolar system may represent a hitherto unforeseen gradual form of transition from an ancestral tetrapolar system to bipolarity