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Introduction To compare outcomes in patients hospitalized with coronavirus (COVID-19) receiving famotidine therapy with those not receiving famotidine. Methods Retrospective, propensity-matched observational study of consecutive COVID-19-positive patients between February 24, 2020, and May 13, 2020. Results Of 878 patients in the analysis, 83 (9.5%) received famotidine. In comparison to patients not treated with famotidine, patients treated with famotidine were younger (63.5 ± 15.0 vs 67.5 ± 15.8 years, P = 0.021), but did not differ with respect to baseline demographics or preexisting comorbidities. Use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio 0.37, 95% confidence interval 0.16-0.86, P = 0.021) and combined death or intubation (odds ratio 0.47, 95% confidence interval 0.23-0.96, P = 0.040). Propensity score matching to adjust for age difference between groups did not alter the effect on either outcome. In addition, patients receiving famotidine displayed lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs 12.7 mg/dL, P = 0.002), lower median procalcitonin levels (0.16 vs 0.30 ng/mL, P = 0.004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs 964.0 ng/mL, P = 0.076). Logistic regression analysis demonstrated that famotidine was an independent predictor of both lower mortality and combined death/intubation, whereas older age, body mass index >30 kg/m, chronic kidney disease, National Early Warning Score, and higher neutrophil-lymphocyte ratio were all predictors of both adverse outcomes. Discussion Famotidine use in hospitalized patients with COVID-19 is associated with a lower risk of mortality, lower risk of combined outcome of mortality and intubation, and lower levels of serum markers for severe disease in hospitalized patients with COVID-19.(Equation is included in full-text article.).

The safe release of a patient from hospital care after bariatric surgery depends upon the achievement of satisfactory health status. Here, we describe a new objective scale (the Readiness for Discharge, RFD Scale) to measure the patient’s suitability for hospital discharge after bariatric surgery. We conducted a retrospective, observational analysis of data collected in a randomized clinical trial of an enhanced recovery after surgery protocol for laparoscopic sleeve gastrectomy from 3/15/2018 to 1/12/2019. Nursing staff assessed 122 patients every 4–8 h after surgery using a checklist to document 5 components: ambulation, vital signs, pain, nausea, and oral intake of clear fluid. Satisfaction of each component was scored as “1” (satisfactory) or “0” (not satisfactory). Scores were summed and analyzed for patterns. RFD = 5 marked the patient as ready for discharge. Sufficient intake of clear liquid was the last RFD component satisfied in 87% of patients. Two overall response patterns emerged: “Steady Progressors” (n = 51) whose RFD score rose steadily from 0 to 5 without reversion to a lower score; and “Oscillators” (n = 71) who had at least one temporary decrease in RFD score on the way to attaining 5, or showed a simultaneous oscillation of components without change in RFD. The RFD checklist allows objective scoring of medical readiness for discharge after LSG and has the potential to improve clinical communication.

Management of staple line dehiscence following laparoscopic sleeve gastrectomy (LSG) varies based on local expertise and timing of presentation. We present our experience with an endoscopic suturing platform to treat patients with staple line dehiscence following LSG. We included all patients who presented to our institution with a staple line dehiscence following LSG from 2005 through November 2017. All endoscopic suturing procedures were performed by a single interventional endoscopist. Five patients, ages 25–69 years, received treatment of staple line dehiscence at a median time of 22 days following LSG (range 13–335 days). Four out of the five patients received a stent at some point during their treatment. One patient with a chronic leak required gastrectomy and esophago-jejunostomy as a definitive treatment. The remaining four patients experienced resolution of the leak at a median of 48 days post-operatively (range 21–82 days). Endoscopic suturing may have a role in the management of leaks following LSG, as a primary treatment or as an adjunct to treatment with a stent. However, given that the technique requires considerable endoscopic expertise and in light of a number of other available therapeutic choices, further studies are required to better define the role of this technology in the algorithm of LSG-related leak management.

Patients undergoing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have different healthcare needs after surgery. Our aim was to quantify non-routine healthcare utilization after RYGB vs. SG. We compared non-routine (NR) visits made and associated services provided up to 2 years post-surgery for patients undergoing RYGB or SG at a Bariatric Surgery Comprehensive Center between March 2013 and April 2015. A total of 258 and 461 patients had primary RYGB and SG, respectively. Successful follow-up rates at one (76.2%) and 2 years post-surgery (52.6%) did not differ between groups. Rates for all NR visits, expressed as the number per 100 patients, were 68.6 in RYGB vs. 35.4 in SG patients (p

FDA approved anti-obesity medications may not be cost effective for patients struggling with pre-operative weight loss prior to bariatric surgery. Metformin, a biguanide, and Topiramate, a carbonic anhydrase inhibitor, both cost effective medications, have demonstrated weight loss when used for the treatment of type 2 diabetes or seizures, respectively. The aim of the three cases is to demonstrate the clinical utility of topiramate and metformin for preoperative weight loss in patients with a body mass index (BMI) ≥ 50 kg/m2 prior to bariatric surgery who are unable to follow the bariatric nutritional prescription due to a dysregulated appetite system Each patient was prescribed metformin and/or topiramate in an off-label manner in conjunction with lifestyle modifications and achieved >8% total body weight loss during the preoperative period.

We evaluated the utility of C peptide as an addition to the DiaRem score for predicting type 2 diabetes (T2D) remission 1 year after bariatric surgery in 175 patients. DiaRem score was significantly correlated with C peptide (r = − .43; p < .001). Both DiaRem and C peptide were significant predictors of remission of T2D (OR (95% CI) = .81 (.75–.86); p < 0001 and OR (95% CI) = 1.35 (1.15–1.60); p < .001, respectively). ROC analysis indicated that DiaRem was a significantly stronger predictor than C peptide (p < .001). Hierarchical regression indicated that C peptide failed to significantly improve the prediction of diabetes remission after accounting for DiaRem (OR (95% CI) = 1.079 (.87–1.26); p = .406). This study does not support the inclusion of C peptide in the DiaRem algorithm.

Background and aims GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. Methods Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions. Results Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10−6) reduced plasma GlycA (−8.26 ± 1.8 μmol/L). This reduction remained significant (−9.12 ± 1.9 μmol/L, p = 1.22 × 10−6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21–0.38, p Conclusions Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.

A stronger evidence base is needed to more fully understand the precise role that robot-assisted (RA) approaches may play in bariatrics.To investigate the utilization and safety of RA-sleeve gastrectomy (RA-SG) and RA-Roux-en-Y gastric bypass (RA-RYGB) using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) registry.National Database.We queried the MBSAQIP 2015 through 2016 registry for patients who underwent primary conventional laparoscopic or RA-SG and RA-RYGB. We compared pre- and perioperative characteristics and 30-day outcomes using logistic regression where number of events met statistical guidelines.We included 126,987 cases: conventional laparoscopic SG (n = 83,940), RA-SG (n = 6,780), conventional laparoscopic RYGB (n = 33,525), and RA-RYGB (n = 2,742). The RA significantly lengthened operation time by 24 and 23 minutes for SG and RYGB, respectively. Mortality and serious adverse events were similar for the 2 techniques. RA-SG was associated with higher rates of 30-day intervention (1.3% versus .8%, OR: 1.38, P.05) and hospital stay2 days (12.1% versus 9.3%, OR: 1.30, P.001). RA-RYGB was associated with higher 30-day rates of reoperation (2.6% versus 2.0%, OR: 1.37, P.05) and readmission (7.0% versus 5.8%, OR:1.21, P.05) and lower rates of transfusion (0.62% versus 1.12%, OR: .54, P.05) and hospital stay2 days (15.7% versus 17%, OR: .89, P.05).RA is as safe as the conventional laparoscopic approach in terms of mortality and serious adverse events.

Background: Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. The CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C) and VKORC1 -1639 G>A polymorphisms affect warfarin dose through altered metabolism (CYP2C9) and sensitivity (VKORC1). Objective: We determined the frequencies of SNPs in the CYP2C9 and VKORC1 genes in a clinical outpatient population and the carrier prevalences for a variety of genotype combinations to gauge the impact of these polymorphisms on warfarin dosage using published algorithms. Method: A total of 127 patients from an outpatient clinic at Hartford Hospital (Hartford, CT, USA) were genotyped for five SNPs in the CYP2C9 gene and seven SNPs in the VKORC1 gene using Luminex® technology. Results: The polymorphism frequencies were 10.2, 7.9 and 37.4% for the functionally deficient CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms, respectively. Combining prevalence of combinatorial genotypes, 18% were carriers of both CYP2C9 and VKORC1 polymorphisms, 13% were CYP2C9 polymorphism carriers only, 42.5% were VKORC1 carriers only, and the remaining 27% were noncarriers for either gene. Based on published warfarin dosing algorithms, carriers of 1, 2, 3 and 4 functionally deficient polymorphisms predict reductions of 1.0 to 1.6, 2.0 to 2.9, 2.9 to 3.7, and 3.6 to 4.4 mg/day, respectively, in warfarin dose. Conclusion: Overall, 73% of the population carried at least one polymorphism predicting deficient warfarin metabolism or responsiveness and 18% were carriers for polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin amongst patients with gene polymorphisms potentially reducing the risk of accentuated responses and bleeding.

Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk.

Background Demographic factors such as ethnicity may affect bariatric surgery outcomes. We examined weight loss and co-morbidities outcomes in African American, Caucasian, and Hispanic patients who underwent laparoscopic gastric banding (LAGB) and Roux-en-Y gastric bypass (RYGB). The primary aim was to investigate demographic differences in weight loss and co-morbidities outcomes. Methods We retrospectively examined weight change and co-morbidities outcomes in our prospective database. A total of 1,903 patients underwent LAGB or RYGB between January 1, 2005 and March 31, 2012. Of those, 1828 completed their 1-year follow-up visit (9–15 mo) and had complete data. We excluded patients who were missing ethnicity information, resulting in a final cohort of 1,684 patients. Multivariate analyses and χ 2 tests were used to examine demographic variables in body mass index (BMI) change, percent excess weight loss (%EWL), and remission of co-morbidities. We also examined weight loss outcomes at 2- and 3-year follow-up. Results Overall, those who underwent RYGB had a lower BMI and greater %EWL at 1, 2, and 3 years compared to those who had undergone LAGB. Overall, African American patients had a higher postoperative BMI than either Caucasian or Hispanic patients. African American patients also showed less %EWL than Caucasian and Hispanic patients. When we examined within surgery type, ethnic differences between African American and Caucasian patients were present across all 3 years in RYGB, but there were no ethnic differences by year 3 in LAGB. Additionally, African American and Hispanic patients no longer differed by year 3 in RYGB and by year 2 in LAGB. There were no significant ethnic differences in remission of diabetes, hyperlipidemia, hypertension, and sleep apnea at 1 year. Conclusion Our study found significant ethnic differences in the postoperative BMI and %EWL, which were more pronounced in patients undergoing RYGB than LAGB at the 3-year time point. These weight loss differences did not translate to a lower rate of co-morbidities remission.

Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (

Objective: Our goal was to examine the effects of regular endurance exercise on plasma GlycA levels, a novel NMR-derived biomarker of systemic inflammation. Methods: We examined NMR-derived plasma GlycA levels before and after 5-6 months of exercise training in 1,194 adults from four studies: APOE (N=104), DREW (N=298), GERS (N=78), HERITAGE (N=714). We used unadjusted and adjusted general linear models to evaluate changes in GlycA with regular exercise across sex-specific quartiles of baseline GlycA in all studies combined. Results: At baseline, the combined participants (69% white, 66% female) were an average of 42.5 (15.4) years old with a mean BMI of 28.1 (5.8) kg/m 2 . Exercise training resulted in a decrease in GlycA of 5.6 (42.0) μmol/L (PFigure 1 ). In both models, Q4 showed the greatest decrease in GlycA. Conclusions: Regular exercise tended to decrease GlycA levels across four diverse, standardized exercise training studies. Our results suggest that the individuals at highest risk appear to benefit the most from regular exercise in terms of GlycA. Figure 1. Mean change in GlycA after exercise training by baseline GlycA quartile in four exercise studies combined . P2 max, baseline GlycA quartile, and three study group dummy variables as covariates. Sex-specific baseline GlycA quartiles in combined group (M/F): Q1: 370/>395

Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (Psem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (PP∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.

The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI). Thirteen candidate genes from previous studies of the same phenotypes in non-psychiatric populations were tested for association. We confirmed 8 of the 13 candidate genes at the 95% confidence level. An increased genetic effect size was observed for triglycerides in the psychiatric population compared to that in the cardiovascular population.

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p

Admixture is of great relevance to the clinical application of pharmacogenetics and personalized medicine, but unfortunately these studies have been scarce in Puerto Ricans. Besides, allele frequencies for clinically relevant genetic markers in warfarin response (i.e., CYP2C9 and VKORC1) have not yet been fully characterized in this population. Accordingly, this study is aimed at investigating whether a correlation between overall genetic similarity and CYP2C9 and/or VKORC1 genotypes could be established.98 DNA samples from Puerto Ricans were genotyped for major CYP2C9 and VKORC1 polymorphisms and tested on a physiogenomic (PG)-array to infer population structure and admixture pattern.Analysis affirmed that Puerto Ricans are broadly admixed. A genetic distance dendrogram was constructed by clustering those subjects with similar genetic profiles. Individual VKORC1 and CYP2C9 genotypes were visually overlaid atop the three dendrogram sectors. Sector-1, representing Amerindian ancestry, showed higher VKORC1 -1639GA variant frequency than the rest of the population (p=0.051). Although CYP2C9*3 allele frequencies matched the expected HapMap values, admixture may explain deviations from published findings regarding VKORC1 -1639GA and CYP2C9*2 allele frequencies in sector-3.Results suggest that the observed inter-individual variations in ancestral contributions have significant implications for the way each Puerto Rican responds to warfarin therapy. Our findings provide valuable evidence on the importance of controlling for admixture in pharmacogenetic studies of Puerto Rican Hispanics.

Aim: Administered at maximal dosages, the most common statins – atorvastatin, simvastatin and rosuvastatin – lower low-density lipoprotein cholesterol (LDLC) by an average of 37–57% in patients with primary hypercholesterolemia. We hypothesized novel genetic underpinnings for variation in LDLC levels in the context of statin therapy. Materials & methods: Genotyping of 384 SNPs in 202 volunteers from a lipid outpatient clinic was accomplished and LDLC levels obtained from chart records. The SNPs were distributed across 222 genes representing physiological pathways such as general metabolism, cholesterol biochemistry, cardiovascular function, inflammation, neurobiology and cell proliferation. We discovered significant associations with LDLC levels for the rs34274 SNP (p < 0.0002) and for rs2241220 (p < 0.008) in the acetyl-coenzyme A carboxylase β (ACACB) gene. When corrected for multiple testing, the false-discovery rate associated with rs34274 was 0.076 (significance threshold: 0.10) and for rs2241220 the false-discovery rate was 0.93 (not significant). The acetyl coenzyme A carboxylase β enzyme synthesizes malonyl coenzyme A, an essential substrate for hepatic fatty acid synthesis and an inhibitor of fatty acid oxidation. Results: The SNPs were in weak linkage disequilibrium (D´ = 0.302). Minor alleles at these sites demonstrate opposing influences on LDLC; the C>T substitution at rs34724 is a risk marker and the C>T substitution at rs2241220 a protective marker for LDLC levels. These SNPs hypothetically influence enzymatic activity through different mechanisms, rs34274 through the PII promoter and rs2241220 via alteration of the protein’s responsiveness to allosteric influence. Conclusion: Physiogenomic evidence suggests a novel link between LDLC levels and the regulation of fatty acid metabolism. The findings complement previously discovered novel SNP relationships to myalgia (pain) and myositis (serum creatine kinase activity). By genotyping for myositis, myalgia and LDLC levels, a physiogenomic model may be developed to help clinicians maximize effectiveness and minimize side effects in prescribing statins.

Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1–10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C19*2 and *3 alleles (cumulative frequency: 20–50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel.

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P

The present study examined associations between the ciliary neurotrophic factor (CNTF) 1357 G → A polymorphism and the muscle strength response to a unilateral, upper arm resistance-training (RT) program among healthy, young adults. Subjects were 754 Caucasian men (40%) and women (60%) who were genotyped and performed a training program of the nondominant (trained) arm with the dominant (untrained) arm as a comparison. Peak elbow flexor strength was measured with one repetition maximum, isometric strength with maximum voluntary contraction, and bicep cross-sectional area with MRI in the trained and untrained arms before and after training. Women with the CNTF GG genotype gained more absolute isometric strength, as measured by MVC (6.5 ± 0.3 vs. 5.2 ± 0.5 kg), than carriers of the CNTF A1357 allele in the trained arm pre- to posttraining ( P < 0.05). No significant associations were seen in men. Women with the CNTF GG genotype gained more absolute dynamic (1.0 ± 0.1 vs. 0.6 ± 0.1 kg) and allometric (0.022 ± 0.0 vs. 0.015 ± 0.0 kg/kg−0.67) strength, as measured by 1 RM, than carriers of the CNTF A1357 allele in the untrained arm pre- to posttraining ( P < 0.05). No significant associations were seen in men. No significant associations, as measured by cross-sectional area, were seen in men or women. The CNTF 1357 G → A polymorphism explains only a small portion of the variability in the muscle strength response to training in women.

The purpose of this study was to assess the association of age with muscle mass and strength in a group of young adults before and after 12 weeks of progressive resistance training. Eight hundred twenty-six young males and females (age 24.34 +/- 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral resistance training program of the nondominant arm. Isometric (maximal voluntary contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic resonance imaging (MRI) scans were measured before and after training. Pearson correlation coefficients were calculated for size and strength variables and age. In addition, the cohort was divided into groups according to decade of life and differences assessed by analysis of variance. Age correlated significantly and positively with all pretraining measures of muscle size and strength (CSA: r = 0.191, p < 0.001; MVC: r = 0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was not related to the training-induced changes in CSA or MVC but was negatively associated with the change in 1RM (r = -0.217, p < 0.001). The study indicates that age does have a significant positive relationship with muscle size and strength in untrained young adults. Although age was negatively associated with improvements in 1RM, the effect of age was small relative to the improvements induced through resistance training, thus suggesting age does not limit response to training in any practical way during early adulthood.

KOSTEK, M. A., T. J. ANGELOPOULOS, P. M. CLARKSON, P. M. GORDON, N. M. MOYNA, P. S. VISICH, R. F. ZOELLER, T. B. PRICE, R. L. SEIP, P. D. THOMPSON, J. M. DEVANEY, H. GORDISH-DRESSMAN, E. P. HOFFMAN, and L. S. PESCATELLO. Myostatin and Follistatin Polymorphisms Interact with Muscle Phenotypes and Ethnicity. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 1063–1071, 2009. Purpose: We examined associations among myostatin (MSTN) 2379 A 9 G and 163 G 9 A and follistatin (FST) j5003 A 9 T and j833 G 9 T single nucleotide polymorphisms (SNP) on the muscle size and the strength response to resistance training (RT). Methods: Subjects (n = 645, age = 24.1 T 0.2 yr, body mass index [BMI] = 24.2 T 0.2 kgIm j2 ) self-disclosed themselves as Caucasian (78.9%), African American (3.6%), Asian (8.4%), Hispanic (5.0%), or Other (4.2%). They were genotyped for MSTN 2379 A 9 G( n = 645), MSTN 163 G 9 A( n = 639), FST j5003 A 9 T( n = 580), and FST j833 G 9 T( n = 603). We assessed dynamic (one repetition maximum [1RM]) and isometric (maximum voluntary contraction [MVC]) muscle strength and size (crosssectional area [CSA]) of the elbow flexors before and after 12 wk of unilateral upper-arm RT. Repeated-measures ANCOVA tested associations among genetic variants and muscle phenotypes with age and BMI as covariates. Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G 2379 allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 T 6.8 vs 49.8 T 8.7 kg). African Americans who were carriers of the FST T j5003 allele (n = 12) had greater baseline 1RM (11.9 T 0.7 vs 8.8 T 0.5 kg) and CSA (24.4 T 1.3 vs 19.1 T 1.2 cm 2 ) than African Americans with the A-5003A genotype (n = 14; P G 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P Q 0.05). Conclusion: MSTN 2379 A 9 G and FST j5003 A 9 T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

The purposes of this study were to (1) derive and test allometric scaling models of biceps isometric strength using body mass (BM) and muscle cross-sectional area (CSA) as the scaling variables, (2) assess the influence of body mass index (BMI) by separating the cohort by BMI (normal25 kg/m(2) vs. overweight/obeseor =25 kg/m(2)) and repeating step 1, and (3) assess the effect of BMI on isometric strength allometrically adjusted for differences in CSA by comparing scaled strength between normal weight versus overweight/obese women. The participants were 183 women (18-39 years old) who reported no strength training in the prior year. Isometric strength and CSA of the biceps were assessed on the non-dominant arm. The CSA allometric model met all statistical criteria and produced a scaling exponent of 0.44. The BM model did not meet these criteria until the entire cohort was separated by BMI. The scaling exponents for normal weight and overweight/obese women were 1.48 and 0.35, respectively. These data suggest that BMI exerted an influence on the relationship between BM and allometrically scaled isometric strength and may be explained by previous studies demonstrating greater contribution of fat mass (FM) versus fat-free mass (FFM) to BMI in overweight/obese women. As such, allometric scaling models of isometric strength, especially in populations that are heterogeneous with regard to body composition, must be carefully tested and examined across the range of BMI. Isometric strength relative to CSA was not significantly different between groups. However, allometrically scaled strength, using CSA as the criterion variable, was significantly greater in overweight/obese women compared to those of normal weight. These data suggest that isometric strength in women is not completely determined by CSA and other factors such as intramuscular fat and muscle fiber type may be confounding or contributing factors.

Apolipoprotein B (apoB) concentration and age are independently associated with an increased risk for cardiovascular disease. Age is also associated with increased apoB concentration. The purpose of this study was to determine the effects of exercise on apoB and examine the association between age and lipoproteins. Forty-one sedentary individuals exercised for 6 months, four times/week for 40 min between 60 and 85% of their maximal heart rate. Lipids were determined three times: before training, 24 and 72 h after the last training session. Exercise did not alter apoB (1.2+/-0.05 g/l vs. 1.2+/-0.05 g/l; P0.05), or other lipids or lipoproteins. When participants were sequestered by baseline low density lipoprotein cholesterol (LDLc), total cholesterol (TC) was decreased at 24 h post (6.3+/-0.2 mmol/l vs. 6.0+/-0.2 mmol/l, P0.05) and LDLc after 24 and 48 h post (4.3+/-0.1 mg/dl vs. 3.9+/-0.1 and 4.1+/-0.2 mg/dl, P0.05) in the high LDLc group. In the low LDLc group both TC (4.4+/-0.2 mmol/l vs. 4.6+/-0.2 and 4.6+/-0.2 mmol/l, P0.05) and LDLc (2.6+/-0.1 mmol/l vs. 2.8+/-0.1 and 2.8+/-0.2 mmol/l, P0.05) were elevated at 24 h and remained elevated at 72 h post compared to baseline. Age does not affect apoB or lipoproteins in response to exercise. Individuals with high baseline LDLc experienced acute reduction in TC and LDLc produced by each exercise session.

Precision medicine, a recently popularized term, aims to use patient-specific information to improve clinical practice [1]. A major part of precision medicine that has attracted particular attention involves use of genetic information for patient care. Genetic and genomics data are becoming more cost-effective and readily available. In this context, Seip et al. have performed a timely “physiogenomic” analysis of patients with different extremes of weight loss outcomes after bariatric surgery. The study focused on patients in the top and bottom quartiles of weight loss after 2 different types of surgery: laparoscopic adjustable gastric banding (LAGB) and Roux-en-Y gastric bypass (RYGB). The study tested the association of 384 single nucleotide polymorphisms (SNP) with 1-year weight loss outcomes. The authors tested the association of select variants in or close to several genes with lowest and highest quartiles of weight loss outcome. Many of the selected genes play critical roles in either the metabolic or neuropsychiatric pathways contributing to obesity. Genetics play a role in both obesity [2] and weight loss after surgery [3]. Previous studies on genetics of postsurgery weight loss have looked at both common [4,5], typically defined as >1% to 5% frequency, and rare genetic variants [6–8] but are limited to RYGB weight loss outcomes. The Seip et al. study did not discover any variants that are significantly associated with differential weight loss among the RYGB subgroup. This is not surprising because previously identified genetic variants that contribute to weight loss outcomes were not included in the SNP panel used in the study. In addition, the study likely was underpowered to find such differences. So far, most genetic analyses have found limited effect size for specific genetic factors [4–6,9] with regard to weight loss, limiting their utility in predicting outcomes or in patient selection. A major value of studies on genetic association with weight loss outcomes after bariatric surgery is in identification of biologic targets and pathways that may be critical for weight loss. For example, a very common variant close to MC4R is associated with obesity and predicts slightly poorer RYGB outcomes [4], and a coding variant in MC4R is negatively associated with obesity and predicts slightly better RYGB outcomes [9]. These findings do not warrant genetic testing for MC4R before surgery, per se; however, they point to the critical role of the MC4R physiologic pathway in weight loss [7,8] and the potential for targeting MC4R for pharmacotherapy in improving weight loss outcomes. The authors’ findings in the LAGB cohort did reach significance for 1 SNP in apolipoprotein E (APOE) after Bonferroni correction for multiple testing. The APOE findings and clarification of a role for genes in the neuropsychiatric and cardiometabolic pathways in LAGB are important. However, LAGB surgeries are performed less frequently, possibly limiting the clinical value of these findings. Seip et al. found different genetic contributors to weight loss after RYGB and LAGB. A next obvious step is to compare genetic contributors to outcomes after the 2 most common bariatric procedures, RYGB and laparoscopic sleeve gastrectomy. Comprehensive approaches using the latest available data, from whole exome and genome sequencing and other “omics” approaches (including proteomic, transcriptomic, epigenomic, metabolomic, and microbiome analyses), will continue to identify critical “players” in bariatric surgery outcomes. Clinical predictors of weight loss after surgery have been reported [10] and will continue to improve with larger and new studies. Combining the “omics” data with clinical predictors promises to further improve our ability to more accurately forecast surgical weight loss outcomes and resolution of co-morbidities, which, as the authors point out, may improve patient selection and allocation of resources. Finally, although these “omics” findings may not always lead to new predictive tests for bariatric outcomes, they do provide a clearer picture for the physiologic basis of surgical outcomes.

OBJECTIVES Genetic variants in pharmacokinetic genes can alter the effectiveness and increase the risks of using analgesics to treat pain. The purpose of this retrospective study is to describe the clinical experiences that led to pharmacogenetic testing of pediatric pain management program patients for alterations in the CYP2D6, CYP2C19, and CYP2C9 genes and correlate the analgesic efficacy and adverse analgesic effects with the gene-specific findings and Metabolic Reserve (MR) index. MATERIALS AND METHODS Nineteen patients were referred for pharmacogenetic testing between February 2010 and December 2013 due to analgesic ineffectiveness or adverse analgesic effects. CYP2D6, CYP2C19, and CYP2C9 functional status was inferred from genotyping; and MR calculated. Data from the available inpatient and outpatient medical records from January 2007 to May 2014 for these patients were reviewed and extracted to characterize patient analgesic response phenotype. RESULTS Significant CYP2D6 genetic variants were identified in 16 of the 19 (84%) patients: 4 were ultra-rapid metabolizers, 8 were deficient, 3 were poor metabolizers, and 1 was CYP2D6 null metabolizer. Of the 3 patients with functional CYP2D6 status, 2 were CYP2C19 null metabolizers. The MR scores ranged from 3.0 to 7.0, with a bimodal distribution with high frequencies corresponding to 4.0/4.5 and 7.0. DISCUSSION Clinical evaluation of analgesic ineffectiveness and adverse effects led to the high likelihood of identifying patients with CYP2D6, CYP2C19, and CYP2C9 alleles associated with alterations in analgesic metabolism. Further research is needed to integrate pharmacogenetic and clinical information into anticipatory guidance for pharmacogenetic testing and analgesic prescribing to children with pain.

Exercise affects lipoprotein metabolism and apolipoprotein E (Apo E) genotype may alter changes in lipoprotein subclasses that occur with exercise. The present study examined the effects of Apo E genotype (APOE) on the response of lipoprotein subclass concentrations to long-term exercise. A prospective longitudinal study, conducted at seven centers, genetically screened 566 individuals to create three cohorts of healthy adults, equal for gender and the most common APOE variants: E2/3 (n = 35), E3/3 (n = 40), and E3/4 (n = 31). Subjects with body mass index (BMI) > or = 31 or evidence of dyslipidemia or metabolic disease were excluded. All subjects exercised aerobically at 75% of maximal heart rate for 40 min, four times weekly for 6 months. Fasting lipoprotein subpopulations were measured before and after exercise training using proton nuclear magnetic resonance spectroscopy. Serum lipids for the entire cohort did not change with exercise training, but the LDL subpopulation response varied by APOE. Small-sized LDL particles decreased only in the APOE3 homozygotes whereas medium-sized LDL particles increased only in this group. These changes were directionally different from the responses in the E2/3 and E3/4 subjects (p < 0.05). Neither exercise nor APOE variant affected overall LDL or HDL size or cholesterol concentration, but exercise decreased VLDL diameter by 3.5 nm (p < 0.001) attributable to decreases in large VLDL in each APOE group. In conclusion, APOE variants influence the serum LDL subpopulation response to exercise training in normolipidemic subjects. Subjects homozygous for APOE3 experienced the most beneficial lipid effects from exercise training.

OBJECTIVE To determine the impact of energy restriction (ER) upon the previously reported increased resting and exercise-related oxygen utilization, reduced body temperature, increased serum TSH, and reduced serum free T3 concentrations found during Antarctic residence (AR). DESIGN Prospective, intervention with both paired controls and a similar reference control group (RG). PATIENTS AND MEASUREMENTS Seven subjects were assessed before and after a 50% ER period of 60 h. This ER was carried out within 30 days of arriving in Antarctica in October (OCT) and again after 10 months AR in August (AUG). During the periods of ER, mean energy consumption was 5662 +/- 1344 kJ/day in OCT and 5529 +/- 967 kJ/day in AUG. Resting metabolic rate (RMR), a calculated resting metabolic rate (RMR(reg)) using a submaximal work regression, serum TSH, FT3 and tympanic temperature (Tty) were measured. These values were compared with a similar RG of 12 subjects reported previously who were studied in California, USA before and then again during AR. RESULTS Weight declined by 1.1 +/- 0.1 kg/day (OCT) and 0.92 +/- 0.2 kg/day (AUG) with ER, resulting in a reduction of body weight by 3.1 +/- 0.4% in OCT (P = 0.0001) and 2.5 +/- 0.4% in AUG (P = 0.0015) during AR. The RMR before ER did not change with AR and it was not significantly different from the RG studied in California. With ER the RMR tended to decline in both OCT (132 +/- 5 to 122 +/- 4 mlO2/min/m2) and AUG (134 +/- 5 to 126 +/- 5 mlO2/min/m2), but these were not significant. By contrast, RMR(reg) obtained before ER was increased with AR by 22.5 +/- 7.8% (P = 0.01) in OCT and by 28.1 +/- 7.0% (P = 0.0008) in AUG over the RG values obtained in California. RMR(reg) did not decrease with ER in either OCT or AUG. The total energy expenditure derived from these measures of weight loss suggests that 24-h energy requirements are 74.4%[95% confidence interval (CI) 2.6-146.3; P < 0.05] more than those expected in temperate climates. Tty declined by 0.6 +/- 0.2 degrees C (P < 0.01) with AR compared with the RG measured in California, but was not affected by either period of ER. ER had no effect on FT3 but tended to decrease serum TSH in AUG (P = 0.06). CONCLUSIONS Exercise-related energy requirements are increased with AR. Moderate ER may reduce resting but not exercise-related energy expenditure and it is associated with a weight loss exceeding expectations for 50% restriction of temperate climate energy predictions.

Purpose: To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d·wk-1) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Methods: Subjects were 631 (mean ± SEM, 24.2 ± 0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (?2 = 1.688, P = 0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Results: Baseline muscle strength and size were greater in UT than T (P < 0.001) and did not differ among ACE ID genotype in either arm (P = 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P < 0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P = 0.05). In UT, MVC increased among ACE II/ID (7%) (P < 0.001) but was similar among ACE DD (2%) pre- to post-RT (P = 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P < 0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P < 0.05). Conclusion: ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.