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This paper reveals secrets. Like their Renaissance counterparts, pedagogical alchemists often work in secret networks as they struggle against dominant forces. Pedagogical alchemists seek to transform assemblages of neoliberal education policies, shifting enactments of such policies from replication of systemic hierarchies and oppressions towards teacher and student experiences of joy, hope, and resistance. The secret art of pedagogical alchemy adopts critical praxis research method that amplifies epistemological insights arising from teacher experience. This paper utilizes performative autoethnography and social fiction to interrogate the influence of socio-political context on the labour of an 8th grade school-teacher. The secret art of pedagogical alchemy locates the experiences of a pedagogical alchemist whose 8th grade history class includes a unit of work on Renaissance alchemist Isabella Cortese. The experiences are framed by globalised, neo-liberal education policy assemblage. Like the writings of Renaissance alchemist, Isabella Cortese, the voice of the 8th grade history pedagogical alchemist is performed in quatrains that are written in iambic pentameter.

Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p0.0001). WLM with the greatest weight loss (15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (7%) (p0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss.

This study examined the associations between overall diet quality and the risk of dementia in a rural cohort among the oldest old. Included in this prospective cohort study were 2232 participants aged ≥ 80 years and dementia-free at the baseline according to the Geisinger Rural Aging Study (GRAS), a longitudinal cohort in rural Pennsylvania. In 2009, diet quality was assessed by a validated dietary screening tool (DST). Incident cases of dementia during 2009–2021 were identified using diagnosis codes. This approach was validated by a review of electronic health records. Associations between diet quality scores and the incidence of dementia were estimated using the Cox proportional hazards models, adjusted for potential confounders. Across a mean of 6.90 years of follow-up, we identified 408 incident cases of all-cause dementia. Having a higher diet quality was not significantly associated with a lower risk for incidents of all-cause dementia (adjusted HR for the highest compared with the lowest tertile: 1.01, 95% CI: 0.79, 1.29, P-trend = 0.95). Similarly, we did not observe a significant association between diet quality and altered risks of Alzheimer’s disease and other forms of dementia. Overall, having a higher diet quality was not significantly associated with a lower risk of dementia among the oldest old during the full follow-up.

Background: Adipokines mediate many metabolic effects of adipose tissue. While regional body composition is associated with metabolic risk, it is unclear if metabolic risk associations differ for adipokine expression in visceral and subcutaneous tissue and adipokine concentrations in the circulation. Methods: We obtained visceral and subcutaneous fat samples, and pre-surgical serum samples from Geisinger Obesity Registry patients undergoing bariatric surgery. We used real-time PCR to quantify mRNA expression of adipokines (adiponectin, leptin, leptin/adiponectin ratio) in fat samples, and targeted assays (ELISA) to measure serum adipokines. Using multivariable linear regression, we evaluated the individual and combined associations of visceral, subcutaneous and serum adipokines (per-1-SD and tertiles) with a metabolic syndrome (MetS) severity Z-score. Results: 181 participants (mean age 45 years, mean BMI 47 kg/m 2 , 85% female) with available fat and serum samples were included. Visceral, subcutaneous and serum adipokines were all weakly correlated (all ρ Conclusion: Visceral, but not subcutaneous, adipokine expression provides complementary information to serum adipokines on metabolic risk. This indicates significant differences in the physiologic impact of regional adipose tissue and highlights adipokines as a potential target for modifying cardiometabolic risk.

A long-held goal of synthetic biology has been the transfer of a bacterial nitrogen-fixation pathway into plants to reduce the use of chemical fertiliser on crops such as rice, wheat and maize. There are three classes of bacterial nitrogenases, named after their unique metalloclusters containing either Mo-, V- or Fe, that convert N2 gas to ammonia. Relative to the Mo-nitrogenase the Fe-nitrogenase is not as efficient for catalysis but has less complex genetic and metallocluster requirements, features that may be preferable for engineering into crops. Here we report the successful targeting of bacterial Fe-nitrogenase proteins, AnfD, AnfK, AnfG and AnfH, to plant mitochondria. When expressed as a single protein AnfD was mostly insoluble in plant mitochondria, but coexpression of AnfD with AnfK greatly improved its solubility. Using affinity-based purification of mitochondrially expressed AnfK or AnfG we were able to demonstrate a strong interaction of AnfD with AnfK and a weaker interaction of AnfG with AnfDK. This work establishes that the structural components of the Fe-nitrogenase can be engineered into plant mitochondria and form a complex, which will be a requirement for function. This report outlines the first use of Fe-nitrogenase genes within a plant as a preliminary step towards engineering an alternative nitrogenase into crops.

Background Patients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data has shown that age, gender and obesity are strongly correlated with poor outcomes in COVID-19 positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese. Objectives Examine if prior bariatric surgery correlates with increased risk of hospitalization and outcome severity after COVID-19 infection. Setting University Hospital Methods A cross-sectional retrospective analysis of a COVID-19 database from a single, NYC-based, academic institution was conducted. A cohort of COVID-19 positive patients with a history of bariatric surgery (n=124) were matched in a 1:4 ratio to a control cohort of COVID-19 positive patients who were eligible for bariatric surgery (BMI >40 kg/m2 or BMI >35 kg/m2 with a comorbidity at the time of COVID-19 diagnosis) (n=496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using Chi-square test or Fisher’s exact test. Additionally, overall length of stay and duration of time in ICU were compared using Wilcoxon Rank Sum test. Conditional logistic regression analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR). Results A total of 620 COVID-19 positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y Gastric Bypass (RYGB, n=45), 35% laparoscopic adjustable gastric banding (LAGB, n=44), and 28% laparoscopic sleeve gastrectomy (LSG, n=35). The body mass index (BMI) for the bariatric group was 36.1 kg/m2 (SD=8.3), which was significantly lower than the control group, 41.4 kg/m2 (SD=6.5) (p

Patient reported outcome measures (PROM) can engage patients and clinicians to improve health outcomes. Their population health impact may be limited by systematic barriers inhibiting access to completion. In this analysis we evaluated the association between individual parent/child characteristics and clinic factors with parental completion of a locally developed PROM, the Early Healthy Lifestyles (EHL) questionnaire. Participants included parent-child dyads who presented at 14 pediatric clinics for regularly scheduled well-child visits (WCV) prior to age 26 months. EHL items include feeding practices, diet, play time, screen exposure, and sleep. Completion was categorized at patient- (i.e., parent-child dyad) and clinic-levels. Parents completed the 15-item EHL in the patient portal before arrival or in the clinic; ninety-three percent of EHL questionnaires were completed in the clinic vs. 7% in the patient portal. High-completers completed EHL for half of WCVs; low-completers completed at least once; and non-completers never completed. Clinics were classified by EHL adoption level (% high completion): High-adoption: >50%; Moderate-adoption: 10%–50%; and Low-adoption: p 1 clinic site for WCV (OR = 1.83 [1.34, 2.50]), non-White birth mother (OR = 1.78 [1.28, 2.47]), and body weight

Background: With the increasing focus of metabolomic methods on obesityrelated diseases, it is important to consider how sample handling may need to be adapted for the high compositions of lipids that can occur in such subjects. Introduction: High-lipid (cloudy, milky appearances; a.k.a. lipemic) biofluids are common in very high BMI subjects. Organic extractions of biofluids are useful for removing protein backgrounds, inactivating capsid viruses, and yielding relatively stable samples with excellent spectroscopic characteristics. This work considered how acetonitrile extractions, which are widely used, perform on lipemic sera. Results: In this technical note, we report the observation and remediation of a liquid-liquid phase separation in acetonitrile extractions of many lipemic sera. This unexpected behavior can be challenging to identify, especially if working with small volumes. The liquid-liquid separation shows a high miscibility of proteins in both liquid phases that impairs NMR data quality. We also report a simple temperature-based adaption of the acetonitrile extraction procedure that consistently results in a single aqueous phase and eliminates unwanted constituents. Conclusion: A robust approach to achieving reproducible, high quality samples of aqueous metabolites from lipemic sera from very high BMI subjects should be of utility in expanding metabolomics applications to lipemic biofluids.

More perceived physical fatigability and poor diet quality are associated with impairments in physical function in older adults. However, the degree to which more perceived fatigability explains the association between poor diet quality and low physical function is unknown. We examined this relationship in 122 (66F, 56M) of the oldest-old participants from the Geisinger Rural Aging Study (GRAS). We used 24-h dietary recalls to assess the Healthy Eating Index (HEI), the Pittsburgh Fatigability Scale (PFS, 0–50) to assess perceived physical fatigability, and the PROMIS Physical Function 20a* to assess physical function. We grouped participants into three age categories: 80–84 (n = 51), 85–89 (n = 51), and 90+ (n = 20) years. Multiple linear regression revealed that a lower HEI was associated with higher PFS Physical score after adjusting for age group, sex, body mass index, and the number of medical conditions (p = 0.001). Several macro- and micro-nutrient intakes were also lower in those reporting more (≥15) compared to less (&lt, 15) perceived physical fatigability. Mediation analysis revealed that PFS Physical scores explained ~65% (p = 0.001) of the association between HEI total score and PROMIS19 Physical Function score. Poor diet quality may contribute to more perceived physical fatigability, which could exacerbate impairments in the oldest-old’s physical function.

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)—resolvins (Rv), protectins (PD) and maresins (MaR)—actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs—RvD3, RvD4 and PD1—and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation.

The near universal presence of chronic low-grade systemic inflammation among patients with severe obesity disrupts iron homeostasis and underlies the association between obesity and iron deficiency. Immune activation and inflammation results in a reduction in circulating iron and diminished iron bioavailability for erythropoiesis. Inflammation also alters blood levels of commonly measured markers of iron nutrition status, which makes the diagnosis of iron deficiency difficult and has led to new recommendations regarding laboratory markers for the diagnosis. Recent evidence utilizing these newly recommended laboratory markers which include levels of ferritin, C Reactive Protein, and Transferrin Saturation suggests that the actual prevalence of iron deficiency among candidates for metabolic surgery may be double or triple the prevalence identified by low levels of ferritin alone. Thus, large numbers of surgical candidates have iron deficiency which has been heretofore largely unrecognized and inadequately treated. The assessment of iron status utilizing the currently recommended markers in the presence of chronic inflammatory diseases, and repletion of depleted stores for surgical candidates with deficiency during the pre-operative period presents an important opportunity for mitigating this condition in post-operative patients.

This critical reflective practice article juxtaposes the temporal relationship between lived experiences in my past, with my present actions as a schoolteacher. Presented in the style of a dwam—the state of semiconsciousness that precedes sleep—I uncover dominant colonial narratives that continue to inscribe racialized power relations in school curriculum and pedagogy, and that have done so throughout my experiences as a child–student and an adult–teacher. Drawing from Albert Memmi's “colonizer who refuses,” my dwam demonstrates critical awakening as a white teacher through six scenes that span four decades.

IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.

The objective of this study was to determine whether the DiaRem, a score that predicts type 2 diabetes (T2D) remission following roux-en-y gastric bariatric surgery (RYGB), also predicts remission following laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in white and Hispanic patients.While bariatric surgery is highly effective in reversing insulin resistance, there are patients for whom surgery will not lead to remission. To date, there is no score for predicting remission following LAGB or LSG surgery. Additionally, there is little known about how to predict whether Hispanic patients will experience remission.We conducted a retrospective cohort study of white and Hispanic patients with T2D who received bariatric surgery. There were 361 white and 130 Hispanic patients among whom 328 had RYGB surgery, 107 had LSG surgery, and 56 had LAGB surgery. We used age, diabetes treatment, and hemoglobin A1c to calculate DiaRem scores. Mann-Whitney U test was used to determine the association between DiaRem scores and remission. Area under the receiver operant curve (AUC) was used to assess the ability of the DiaRem to discriminate between patients who did and did not remit.The DiaRem was associated with partial remission in all surgery types for white and Hispanic patients (Mann-Whitney, p 0.001). The DiaRem had moderate to high discriminant ability (AUC 0.70) for all surgical and racial/ethnic groups.The DiaRem distinguishes between patients likely and unlikely to experience remission, informing expectations of patients making T2D treatment decisions.

OBJECTIVE This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Objective To examine the risk factors of developing functional decline and make probabilistic predictions by using a tree-based method that allows higher order polynomials and interactions of the risk factors. Methods The conditional inference tree analysis, a data mining approach, was used to construct a risk stratification algorithm for developing functional limitation based on BMI and other potential risk factors for disability in 1,951 older adults without functional limitations at baseline (baseline age 73.1 ± 4.2 y). We also analyzed the data with multivariate stepwise logistic regression and compared the two approaches (e.g., cross-validation). Over a mean of 9.2 ± 1.7 years of follow-up, 221 individuals developed functional limitation. Results Higher BMI, age, and comorbidity were consistently identified as significant risk factors for functional decline using both methods. Based on these factors, individuals were stratified into four risk groups via the conditional inference tree analysis. Compared to the low-risk group, all other groups had a significantly higher risk of developing functional limitation. The odds ratio comparing two extreme categories was 9.09 (95% confidence interval: 4.68, 17.6). Conclusions Higher BMI, age, and comorbid disease were consistently identified as significant risk factors for functional decline among older individuals across all approaches and analyses.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue. METHODS: Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record. RESULTS: The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples. CONCLUSION: Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.

Background Formal psychosocial support programs after weight-loss surgery are limited in scope and availability. Objective This randomized pilot study evaluated the feasibility of a postoperative behavioral intervention program. Materials and methods Postoperative weight-loss surgery patients (N = 50) were recruited from February 2017–July 2017 and randomized to a four-month behavioral program or usual care wait-list. Outcomes evaluated in addition to feasibility included health-related quality of life (Short Form -36), psychosocial functioning and adherence. Secondary outcomes included within-group changes for each outcome. Results Out of eight possible sessions, intervention participants attended a mean of 4.2 sessions. Intervention group participants experienced greater improvements in the social functioning domain of health-related quality of life compared to usual care. Self-reported dietary adherence in the intervention group remained stable, while usual care group dietary adherence declined. Within the intervention group, participants also reported gains in the physical function, pain and general health aspects of quality life from baseline to post-treatment. No differences in weight, mood or other eating behaviors (e.g., loss of control, emotional eating) were evident between groups. Conclusion Though participation in a postoperative behavioral intervention varied, the program helped participants to maintain aspects of quality of life and self-reported adherence to dietary recommendations. Trial registration ClinicalTrials.gov NCT03092479

OBJECTIVE: We sought to validate an algorithm designed to identify patients with post-gastric bypass hypoglycemia (PGBH) using clinician chart review. METHODS: We conducted a chart review study of nondiabetic patients who underwent Roux-en-Y gastric bypass (RYGB) at our institution from 2004 to 2013. The EMR algorithm was based on any post-operative glucose

OBJECTIVES: Little is known regarding dietary patterns and diet composition for the oldest old (defined as adults ≥ 80 years old) who usually have compromised diet quality due to age-related decline. We examined overall dietary patterns and further related the patterns to consumption of selected nutrients as well as perceived physical and mental fatigue. We hypothesized that those that had a healthy dietary pattern would have better nutrient intake profiles and reduced perceived fatigue. METHODS: We studied a cross-section of the Geisinger Rural Aging Study (GRAS) longitudinal cohort in rural Pennsylvania that included 122 participants (56 men and 66 women) aged from 82 to 97 years old. Average daily nutrient and food group intake were calculated from the average of three dietary recalls (1 weekend and 2 weekdays) by telephone. Dietary patterns were characterized using cluster analysis of 34 food groups. Mean nutrient intake and standard errors across dietary patterns were calculated after adjusting for age, sex, and energy consumption. Mean Pittsburgh fatigability questionnaire score examining physical and mental fatigue were calculated after adjusting for age, sex, and body mass index. RESULTS: Two dietary patterns were defined: one pattern (n = 53) characterized by its higher consumption of fruits, vegetables, seafood, and whole grains, and another pattern (n = 69), with higher intake of fats and oil, refined grains, and cheese. After adjusting for potential confounders, participants in the healthier pattern had significantly higher consumption of carbohydrate, protein, fiber, vitamin A, E, K, C, B6, B12, iron, zinc, and potassium with lower intakes of fat and sodium compared with those in the less healthy pattern (P

OBJECTIVE To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice. RESEARCH DESIGN AND METHODS Outcomes of 736 patients with T2DM who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at an academic center (2004–2012) and had ≥5 years’ glycemic follow-up were assessed. Of 736 patients, 425 (58%) experienced diabetes remission (HbA1c RESULTS In 136 (32%) patients who experienced late relapse, a statistically significant improvement in glycemic control, number of diabetes medications including insulin use, blood pressure, and lipid profile was still observed at long-term. Independent baseline predictors of late relapse were preoperative number of diabetes medications, duration of T2DM before surgery, and SG versus RYGB. Furthermore, patients who relapsed lost less weight during the 1st year after surgery and regained more weight afterward. Prediction models were constructed and externally validated. CONCLUSIONS While late relapse of T2DM is a real phenomenon (one-third of our cohort), it should not be considered a failure, as the trajectory of the disease and its related cardiometabolic risk factors is changed favorably after bariatric surgery. Earlier surgical intervention, RYGB (compared with SG) and more weight loss (less late weight regain) are associated with less diabetes relapse in the long-term.

The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis. To test this, we genotyped rs58542926 in 983 bariatric surgery patients from the Geisinger Medical Center for Nutrition and Weight Management, Geisinger Health System, in Pennsylvania and from 3,556 study participants enrolled in the Amish Complex Disease Research Program. Although these two cohorts have different metabolic profiles, carriers in both cohorts had improved fasting lipid profiles. Importantly, following a high-fat challenge, carriers in the Amish Complex Disease Research Program cohort exhibited significantly lower postprandial serum triglycerides, suggestive of a role for TM6SF2 in the small intestine. To gain further insight into this putative role, effects of TM6SF2 deficiency were studied in a zebrafish model and in cultured human Caco-2 enterocytes. In both systems TM6SF2 deficiency resulted in defects in small intestine metabolism in response to dietary lipids, including significantly increased lipid accumulation, decreased lipid clearance, and increased endoplasmic reticulum stress. CONCLUSIONS These data strongly support a role of TM6SF2 in the regulation of postprandial lipemia, potentially through a similar function for TM6SF2 in the lipidation and/or export of both hepatically and intestinally derived triglyceride-rich lipoproteins. (Hepatology 2017;65:1526-1542).

Objective The epidemiology of post-gastric bypass surgery hypoglycemia (PGBH) is incompletely understood. This study aimed to evaluate the risk of PGBH among nondiabetic patients and associated factors. Methods A cohort study of nondiabetic patients who underwent Roux-en-Y gastric bypass (RYGB) was conducted. PGBH was defined by any postoperative record of glucose

This cohort study examines the association of bariatric surgery with rates of kidney function decline.

OBJECTIVES Diet quality has been associated with health outcomes and quality of life. However, the association between diet quality and mortality in older people, those aged 80 years and older, is understudied. Therefore, we conducted a prospective study to examine whether better diet quality, assessed by a validated dietary screening tool (DST), was associated with lower mortality in those aged 80 years and older. METHODS Our study included 1990 participants (812 men and 1178 women), with a mean age of 84.1 years at baseline (ranging from 80 to 102 years old), from the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Baseline descriptive information was obtained in 2009, and the DST was administered via mailed survey. The DST is composed of 25 food- and behavior-specific questions associated with dietary intake that generate a diet quality score ranging from 0 (lowest) to 100 (highest). Death was identified using electronic medical record and the Social Security Death Index data. Hazard ratios (HRs) and 95% confidence intervals (CIs) across three diet quality categories were calculated by using Cox proportional hazards models after adjusting for potential confounders. RESULTS Over 8 years of follow-up (October 2009-February 2018), 931 deaths were documented. Higher diet quality was associated with lower mortality risk (P-trend = .04). Participants with high diet quality (defined as DST scores >75) had significantly lower risk of mortality compared with those with low diet quality (defined as DST scores

BACKGROUND: History of abuse may impact weight loss (WL) following bariatric surgery. Some investigations have indicated slower WL rates among patients reporting abuse; however, among studies with multiple assessments, significant differences in WL are not evidenced at later measurement. Few investigations have extended follow-up beyond 18 months, limiting understanding of the impact of abuse on weight trajectory over time. Furthermore, existing research has insufficiently accounted for forms of interpersonal trauma beyond sexual abuse (i.e., emotional, physical) that may impact WL and other health outcomes. OBJECTIVES: To determine whether post-surgical percent total WL (%TWL) and specific clinical outcomes are differentially impacted by history of interpersonal abuse. SETTING: Large, comprehensive medical center. METHODS: Retrospective data was collected from patients who underwent bariatric surgery at a single center (N = 433). Based on pre-surgical interview, patients were grouped according to reported history of interpersonal abuse (Y/N). Nonlinear repeated measures regression examined impact of abuse history on %TWL, and clinical selequae. RESULTS: Differences in %TWL at 6, 12, 18, 24 and 36 months post-surgically did not differ significantly. Further, %TWL did not differ across time, according to group. A significantly greater number of those with history of interpersonal abuse had a clinical diagnosis of depression as compared with those not reporting interpersonal abuse (38% vs. 22% respectively), p < .001. CONCLUSIONS: Interpersonal abuse history does not negatively impact %TWL post-surgically but is associated with diagnosis of depression, indicating depressive symptoms may be a viable clinical intervention target for surgery patients with interpersonal trauma history.

Background DiaRem is a validated tool for predicting the likelihood of type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery. Objectives The objective of this study was to determine if the addition of duration of T2D to DiaRem improves its ability to discriminate between patients with or without T2D remission and/or to reclassify presurgery patients into accurate risk groups. Setting Academic Medical Center. Methods This study included patients consented into a prospective registry of Roux-en-Y gastric bypass between July 2009 and November 2015 with known duration of T2D (n = 307). Electronic health record–derived duration of T2D was compared with patient reported duration of T2D in a subset of patients (n = 48). DiaRem2 was created using clinical variables from DiaRem and duration of T2D. Area under the curve and the net reclassification index were used to assess increased performance of DiaRem2. Results Self-reported duration of T2D was highly concordant with electronic health record–derived T2D duration (96% agreement). Early T2D remission occurred in 44% of patients. DiaRem2 included age, hemoglobin A1C, insulin medication use, and duration of T2D. DiaRem2 had a higher area under the curve than DiaRem (.876 versus .850, P = .026), reduced the number of remission risk groups from 5 down to 3, and reclassified patients from intermediate to either high or low remission groups (net reclassification index, P Conclusions DiaRem2 simplifies and improves the accuracy of assessing probability of T2M remission after Roux-en-Y gastric bypass. Self-reported duration of T2D is an acceptable surrogate for T2D duration derived from clinical data.

PURPOSE: The objective of this descriptive study was to identify clinical characteristics of Roux-en-Y Gastric Bypass (RYGB) patients who died from intentional self-harm or accidental overdose postoperatively. MATERIALS AND METHODS: This retrospective, descriptive study included RYGB patients from a large rural medical center that completed surgery between January 2004 and December 2014 and died from intentional self-harm or accidental overdose through December 2015. Specific causes of death were obtained from the National Death Index and clinical data from electronic health records. Clinical characteristics explored were age, sex, time to surgery, weight loss expectations, postoperative weight loss, medication, diagnoses, psychiatric histories (diagnoses, self-harm, suicidal ideation and behaviors, medications, substance use, preoperative Beck Depression Inventory-II scores), pain, social support and reported life stressors. RESULTS: Overall, twenty-two patients of 146 total deceased patients died from intention self-harm (n = 6) or accidental overdose (n = 16) over the study period (77.3% female, mean age at time of surgery = 38.4±9.1 years). Younger age (< 40 years), history of self-harm or depression, preoperative pain and use of opioids at the time of surgery emerged as common characteristics in weight-loss surgery patients who died from intentional self-harm or accidental overdose. No trends regarding social support, life stressors, or actual or expected weight loss were identified. CONCLUSION: Certain weight-loss surgery patients may be at risk for death from self-harm or overdose and may benefit from greater surveillance postoperatively.

Objective Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. Methods Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. Results The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. Conclusions OSA severity and its accompanying hypoxia are associated with the severity of NAFLD.

BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples. RESULTS: A splice variant (rs72613567:TA) in HSD17B13, encoding the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, was found to be associated with reduced levels of ALT (P=4.20×10(−12)) and AST (P=6.2×10(−10)). Among DiscovEHR study participants, this variant was found to be associated with a reduced risk of alcoholic liver disease (by 42% [95% confidence interval {CI}, 20 to 58] among heterozygotes and by 53% [95% CI, 3 to 77] among homozygotes), nonalcoholic liver disease (by 17% [95% CI, 8 to 25] among heterozygotes and by 30% [95% CI, 13 to 43] among homozygotes), alcoholic cirrhosis (by 42% [95% CI, 14 to 61] among heterozygotes and by 73% [95% CI, 15 to 91] among homozygotes), and nonalcoholic cirrhosis (by 26% [95% CI, 7 to 40] among heterozygotes and by 49% [95% CI, 15 to 69] among homozygotes). Associations were confirmed in two independent cohorts. The rs72613567:TA variant was associated with a reduced risk of nonalcoholic steatohepatitis, but not steatosis, in human liver samples. The rs72613567:TA variant mitigated liver injury associated with the risk-increasing PNPLA3 p.I148M allele and resulted in an unstable and truncated protein with reduced enzymatic activity. CONCLUSIONS: A loss-of-function variant in HSD17B13 is associated with a reduced risk of chronic liver disease and of progression from steatosis to steatohepatitis. (Funded by Regeneron Pharmaceuticals and others.)

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. Methods Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. Results Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p

This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status.RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes.Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Background Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long‐term cardiovascular events. Methods and Results A cohort of Roux‐en‐Y gastric bypass surgery ( RYGB ) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated‐measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan–Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI =0.42–0.82). Improvements of cardiovascular risk factors (eg, 10‐year cardiovascular risk score, total cholesterol, high‐density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Conclusions Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure.

Health care resource consumption is a growing concern. The aim of this study was to examine the associations between diet quality and body mass index with health care resource use (HRU) in a cohort of advanced age. Participants in the Geisinger Rural Aging Study (n=5,993) were mailed demographic and dietary questionnaires in 2009. Of those eligible, 2,995 (50%; 1,267 male, 1,728 female; mean age 81.4±4.4 years) provided completed surveys. Multivariate negative binomial models were used to estimate relative risk and 95% CI of HRU outcomes with diet quality as assessed by the Dietary Screening Tool score and body mass index determined from self-reported height and weight. Poor diet quality was associated with a 20% increased risk for emergency room (ER) visits. Fruit and vegetable consumption was grouped into quintiles of intake, with the highest quintile serving as the reference group in analyses. The three lowest fruit and vegetable quintiles were associated with increased risk for ER visits (23% to 31%); the lowest quintile increased risk for inpatient visits (27%). Obesity increased risk of outpatient visits; however, individuals with class I obesity were less likely than normal-weight individuals to have ER visits (relative risk=0.84; 95% CI 0.70 to 0.99). Diets of greater quality, particularly with greater fruit and vegetable intake, are associated with favorable effects on HRU outcomes among older adults. Overweight and obesity are associated with increased outpatient HRU and, among obese individuals, with decreased ER visits. These findings suggest that BMI and diet quality beyond age 74 years continue to affect HRU measures.

Objective To evaluate the impact of adult bariatric surgery on the body mass index (BMI) of children living in the same household. Methods A retrospective case-control study. Case dyads (n = 128) were composed of one adult who had bariatric surgery and one child at the same address. Control dyads (n = 384) were composed of an adult with obesity but no bariatric surgery and a child at the same address. Two-sample t-test was used to determine whether the differences between actual and expected BMI at follow-up (post-surgery) differed between children in the case and control dyads. Results Among boys who were overweight, boys who lived with a surgery patient had a lower than expected BMI post-surgery, while boys who did not live with a surgery patient had a higher than expected BMI at follow-up (P = 0.045). Differences between actual and expected BMIs of children were not significantly different between cases and controls in girls or in children in other weight classes. Conclusions Overweight boys who lived with an adult bariatric surgery patient had a lower than expected BMI after surgery as compared to controls. Future studies may be warranted to determine the mechanisms by which these children experience collateral weight loss.