John G Kral

State University of New York Downstate Medical Center, Brooklyn, New York, United States

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Publications (93)480.72 Total impact

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    ABSTRACT: The double burden of under- and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity and diabetes rates have almost doubled worldwide since 1980, and, in 2011, more than 40 million children under 5 years of age were overweight. Ecologic factors, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines the effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life-in particular, diabesity and its comorbidities. © 2015 New York Academy of Sciences.
    Annals of the New York Academy of Sciences 05/2015; DOI:10.1111/nyas.12778 · 4.31 Impact Factor
  • Journal of the American Society of Hypertension 04/2015; 9(4):e86-e87. DOI:10.1016/j.jash.2015.03.206 · 2.68 Impact Factor
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    ABSTRACT: This study investigated the possible influence of the Subdural Pharmacotherapy Device (SPD) on spatial memory in 3 adult, male bonnet macaques (Macaca radiata). The device was implanted in and above the subdural/subarachnoid space and cranium overlaying the right parietal/frontal cortex: a circuitry involved in spatial memory processing. A large test chamber, equipped with 4 baited and 4 non-baited food-ports at different locations, was used: reaches into empty food ports were counted as spatial memory errors. In this study of within-subject design, before SPD implantation (control) the animals made mean 373.3±114.9 (mean±SEM) errors in the first spatial memory test session. This value dropped to 47.7±18.4 by the 8(th) session. After SPD implantation and alternating cycles of transmeningeal saline delivery and local cerebrospinal fluid (CSF) drainage in the implanted cortex the spatial memory error count, with the same port locations, was 33.0±12.2 during the first spatial memory test session, further decreasing to 5.7±3.5 by the 8(th) post-implantation session (P<0.001 for trend). Replacing transmeningeal saline delivery with similar delivery of the GABAA receptor agonist muscimol (1.0mM) by the SPD did not affect the animals' spatial memory performance, which in fact included at least one completely error-free session per animal over time. The study showed that complication-free implantation and use of the SPD over the parietal and frontal cortices for months leave spatial memory processes intact in nonhuman primates. Copyright © 2015. Published by Elsevier B.V.
    Behavioural Brain Research 03/2015; 286. DOI:10.1016/j.bbr.2015.03.014 · 3.39 Impact Factor
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    ABSTRACT: Biliopancreatic diversion (BPD) is a complex bariatric operation requiring meticulous surveillance which has impeded its broad adoption. Improvements in surgical care and technique, better teaching programs, and stringent norms for follow-up have contributed to increased safety of BPD for patients with BMI <50, achieving better long-term results than other bariatric operations. Here we report 20-year outcomes of 2615 consecutive patients (median 8) having open BPD with duodenal switch (DS) between 1992 and 2010. Chart of 92 % of patients with complete clinical, biochemical, and physical examinations completed before 2013 was reviewed. The research was conducted at Academic Medical Center, Quebec City. There was total mortality of 4.7 %, equivalent to that of the general population of Quebec. Incident diabetes (38.8 %) was cured in 93.4 % (blood glucose <6 mmol/l; HbA1c <6.5 %) with 4 % relapse rate after mean 9.6 years with no new cases. Dyslipidemia (24.2 %) was cured in 80 %. Hypertension (60 %) was cured in 64 % and improved in 31 %. Mean weight loss of 55.3 kg (71 % excess weight loss (EWL); 20 BMI units) was maintained for 5 to 20 years. Operative mortality was reduced from 1.3 % in 1992 to 0.2 % during 2005-2010, with cumulated rate surgical mortality of 0.5, revision rate 3, and reoperations in 13 %. Nutritional deficiencies were present in 2 % for calcium, iron, and vitamin A. Side effects were considered minor by the great majority of patients, rating global satisfaction as 4.5/5 (91 % "satisfied"). BPD deserves more consideration as a primary procedure for eligible patients in experienced centers with sufficient resources for delivering high-quality care and long-term follow-up.
    Obesity Surgery 02/2015; DOI:10.1007/s11695-015-1599-5 · 3.74 Impact Factor
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    ABSTRACT: Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis. Significant interactions (p ≤ 1.22x10-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways. We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.
    PLoS ONE 01/2015; 10(1):e0117011. DOI:10.1371/journal.pone.0117011 · 3.53 Impact Factor
  • The Journal of Strength and Conditioning Research 08/2014; DOI:10.1519/JSC.0000000000000562 · 1.86 Impact Factor
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    ABSTRACT: The wide-ranging manipulations to the cardiovascular system that frequently occur during cardiac surgery can expose the brain to variations in its blood supply that could prove deleterious. As a first step to developing a resource suitable for monitoring such changes, we detected the hemodynamic events induced in the brain of a primate model, using high-density near-infrared spectroscopy combined with tomographic reconstruction methods and validated the findings using established radiologic and histologic techniques. Continuous monitoring of the relative changes in the components of the cerebral hemoglobin signal was performed using high-density near-infrared spectroscopy (270 source-detector channel array) in anesthetized bonnet macaques with the brain exposed to induced ischemia and other acute events. A comparative analysis (exact binomial test) applied to reconstructed 3-dimensional images before and after the events and between cerebral hemispheres, combined with postprocedure magnetic resonance imaging, and postmortem histopathologic examination of the macaques' brains was performed to document and validate the spatial features revealed by the optical findings. Relative changes in the measured and calculated components of the hemoglobin signal, in response to the performed manipulations, revealed substantial concurrence among the reconstructed 3-dimensional images, magnetic resonance imaging of the macaques' brains, and postmortem histopathologic examination findings. Concurrence was seen when the manipulated hemoglobin concentration and associated oxygenation levels were either increased or decreased, and whether they were bilateral or restricted to a specified hemisphere. Continuous near-infrared spectroscopy tomography has been shown to accurately capture and localize cerebral ischemia, vasodilatation, and hemorrhage in primates in real time. These findings are directly applicable to clinical intraoperative functional cerebral monitoring. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    Journal of Thoracic and Cardiovascular Surgery 07/2014; 148(6):3204-3210.e2. DOI:10.1016/j.jtcvs.2014.07.041 · 3.99 Impact Factor
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    ABSTRACT: The choice of first-stage operation in bilio-pancreatic diversion with duodenal switch (BPD-DS) is controversial. There are no published long-term comparisons of one- and two-stage BPD-DS outcomes. During 2001-2009, among 1,762 patients scheduled for BPD-DS 48 had duodenal switch (DS) and 53 sleeve gastrectomy (SG) as first-stage procedures. We compared prospectively updated outcomes of 42 DS (100 % open) and 49 SG (88 % laparoscopic), 13 of whom completed their second stage, to a control group of 91 patients with open one-stage BPD-DS. One-year mean percent excess weight loss (%EWL) was greater after SG than DS (47 +/- 19 vs. 39 +/- 13 SD; p = 0.01) with earlier nadir (16 +/- 10 vs. 45 +/- 30 months; p < 0.0001) but more rapid significant weight regain. After 5 years, %EWL was 12 +/- 35 for 9 SG, 45 +/- 19 for 30 DS (p < 0.0006), and 70 +/- 18 for the first-stage BPD-DS (p < 0.0001). Weight loss was less after two- than one-stage procedures (p < 0.02). Comorbidities improved progressively between SG, DS and BPD-DS (p < 0.001 for trend). HbA1C decreased by 10, 19, and 31 %, respectively (p < 0.0001). Dyslipidemia was cured in 41, 82, and 100 %, respectively. Systolic and diastolic blood pressure decreased only after DS (12 %; p < 0.0002). Patient satisfaction was similar for SG and DS but greater after BPD-DS overall (p = 0.04). SG and DS independently contribute to beneficial metabolic outcomes after BPD-DS. Long-term weight loss and correction of metabolic abnormalities were better after DS favoring its use as first stage in BPD-DS; one-stage BPD-DS outcomes were superior to two-staged.
    Obesity Surgery 05/2014; 24(11). DOI:10.1007/s11695-014-1284-0 · 3.74 Impact Factor
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    ABSTRACT: The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 kg/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.International Journal of Obesity accepted article peview online, 15 April 2014. doi:10.1038/ijo.2014.59.
    International journal of obesity (2005) 04/2014; 39(1). DOI:10.1038/ijo.2014.59 · 5.39 Impact Factor
  • John B Dixon, John G Kral
    New England Journal of Medicine 04/2014; 370(14):1362-3. DOI:10.1056/NEJMc1401876#SA4 · 54.42 Impact Factor
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    ABSTRACT: Body weight support (WS) during treadmill exercise is used to rehabilitate orthopedic/neurological patients. WS lowers musculoskeletal strain and load. It compresses the lower body and increases intrathoracic volume. We studied short-term effects of WS on wave reflection indices using applanation tonometry during progressive WS of 25%, 50%, and 75% of body weight in 25 healthy men. WS decreased mean heart rate from 79 to 69 beats/min (P < .001). Peripheral and central mean arterial, systolic, and pulse pressures (PP) remained unchanged. There was a trend toward lower peripheral and central diastolic pressure. PP amplification ratio decreased significantly (P = .005). Reflected wave characteristics: Augmented pressure and index increased in a stepwise manner with WS (both P < .001). Both ejection duration and systolic duration of the reflected pressure wave (Ätr) increased progressively (both P < .001). The round-trip travel time (Δtp) was unchanged. Left ventricular workload and oxygen demand: Left ventricular wasted pressure energy increased (P < .001), and the subendocardial viability ratio decreased (P = .005), whereas the tension time index remained unchanged. In normal men, WS acutely decreases the PP amplification ratio, increases the amplitude and duration of the reflected aortic pressure wave, and increases measures of wasted left ventricular pressure energy and oxygen demand.
    Journal of the American Society of Hypertension (JASH) 03/2014; 8(6). DOI:10.1016/j.jash.2014.03.004 · 2.68 Impact Factor
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    ABSTRACT: We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS). We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables. Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA. Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
    01/2014; 4:326-35. DOI:10.1016/j.nicl.2013.12.014
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.
    01/2014; 2014(9). DOI:10.1155/2014/917981
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    ABSTRACT: Background. Maternal obesity, excess weight gain and overnutrition during pregnancy increase risks of obesity, type 2 diabetes mellitus, and cardiovascular disease in the offspring. Maternal biliopancreatic diversion is an effective treatment for severe obesity and is beneficial for offspring born after maternal surgery (AMS). These offspring exhibit lower severe obesity prevalence and improved cardiometabolic risk factors including inflammatory marker compared to siblings born before maternal surgery (BMS). Objective. To assess relationships between maternal bariatric surgery and the methylation/expression of genes involved in the immune and inflammatory pathways. Methods. A differential gene methylation analysis was conducted in a sibling cohort of 25 BMS and 25 AMS offspring from 20 mothers. Following differential gene expression analysis (23 BMS and 23 AMS), pathway analysis was conducted. Correlations between gene methylation/expression and circulating inflammatory markers were computed. Results. Five immune and inflammatory pathways with significant overrepresentation of both differential gene methylation and expression were identified. In the IL-8 pathway, gene methylation correlated with both gene expression and plasma C-reactive protein levels. Conclusion. These results suggest that improvements in cardiometabolic risk markers in AMS compared to BMS offspring may be mediated through differential methylation of genes involved in immune and inflammatory pathways.
    Journal of obesity 06/2013; 2013:492170. DOI:10.1155/2013/492170
  • American Journal of Clinical Nutrition 06/2013; 97(6):1413-1415. DOI:10.3945/ajcn.113.062125 · 6.92 Impact Factor
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    ABSTRACT: Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.
    Proceedings of the National Academy of Sciences 05/2013; DOI:10.1073/pnas.1216959110 · 9.81 Impact Factor
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    ABSTRACT: Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.
    Annals of the New York Academy of Sciences 05/2013; DOI:10.1111/nyas.12138 · 4.31 Impact Factor
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    John G Kral
    Diabetes care 04/2013; 36(4):e58. DOI:10.2337/dc12-1843 · 8.57 Impact Factor
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    ABSTRACT: Objective: To investigate the metabolic effects of open Roux-en Y gastric bypass (RYGB) on pancreatic endocrine reserve in overweight/obese Chinese patients with type 2 diabetes during postoperative year 1. Methods: Retrospective analysis comparing pre- and postoperative results of oral glucose tolerance tests (OGTT) with determinations of insulin and C-peptide, glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), and BMI at 1, 3, 6, and 12 months in 99 overweight patients (BMI 26.3 ± 4.0 kg/m(2); 59 men) with type 2 diabetes at the General Hospital of Chengdu Military Region. Results: 79 patients (80%) achieved complete remission (maintaining random blood glucose levels < 11.1 mmol/l, fasting blood glucose levels < 7.0 mmol/l, 2-hour OGTT blood glucose levels < 11.1 mmol/l, and glycated hemoglobin < 6.5%). Nine cases (9%) were 'improved' (reduced medication or diet controlled blood sugar), and 11 cases did not meet either criterion ('unchanged'). Patients in complete remission were younger and heavier, more often men, had significantly shorter history of diabetes (4.3 ± 3.8 years vs. 7.6 ± 3.8 years, p < 0.05), and exhibited significantly higher fasting and OGTT levels of C-peptide and insulin, and HOMA-IR than the other 2 groups (p < 0.05-0.01). Conclusion: Open gastric bypass achieved complete remission of type 2 diabetes in Chinese overweight/obese, heavier, younger, predominantly male patients with shorter duration of disease exhibiting greater pancreatic endocrine reserve. Copyright © 2013 S. Karger GmbH, Freiburg.
    Obesity Facts 04/2013; 6(2):176-84. DOI:10.1159/000351018 · 1.71 Impact Factor
  • John G. Kral
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    ABSTRACT: This opinionated evidence-based selective review addresses flawed concepts related to “obesity”, bariatric surgery and approaches to treatment and prevention of a dysmetabolic syndrome of overnutrition and underactivity from the perspective of developmental origins of diseases prevalent in mid-life and beyond. Innovations focus on methods affecting appetite regulation and energy expenditure applicable throughout the life-cycle on the individual level but with transgenerational population-wide implications. Readers can expect new knowledge and enhanced understanding of a global health problem: “diabesity”.
    Maturitas 01/2013; 77(3). DOI:10.1016/j.maturitas.2013.12.004 · 2.86 Impact Factor

Publication Stats

3k Citations
480.72 Total Impact Points

Institutions

  • 2001–2015
    • State University of New York Downstate Medical Center
      • • Department of Surgery
      • • Department of Psychiatry (LICH)
      Brooklyn, New York, United States
  • 1999–2013
    • Laval University
      • Department of Surgery
      Québec, Quebec, Canada
  • 2009
    • University of Chicago
      • Department of Surgery
      Chicago, Illinois, United States
  • 2006
    • Boston University
      • Department of Pediatrics
      Boston, Massachusetts, United States
  • 2005
    • Virginia Commonwealth University
      • Department of Surgery
      Ричмонд, Virginia, United States
  • 2003
    • Klinik Hirslanden
      Zürich, Zurich, Switzerland
  • 2000–2001
    • State University of New York
      New York City, New York, United States
  • 1987–1990
    • Columbia University
      • Department of Surgery
      New York City, New York, United States