John G Kral

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

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Publications (74)390.86 Total impact

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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. · 3.53 Impact Factor
  • The Journal of Strength and Conditioning Research 08/2014; · 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. · 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.
    Obesity Surgery 05/2014; 24(11). · 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; · 5.22 Impact Factor
  • John B Dixon, John G Kral
    New England Journal of Medicine 04/2014; 370(14):1362-3. · 54.42 Impact Factor
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    PLoS ONE 03/2014; 9(3):e93324. · 3.53 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;
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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.
    NeuroImage. Clinical. 01/2014; 4:326-35.
  • American Journal of Clinical Nutrition 06/2013; 97(6):1413-1415. · 6.50 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; · 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; · 4.38 Impact Factor
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    John G Kral
    Diabetes care 04/2013; 36(4):e58. · 7.74 Impact Factor
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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 01/2013; 2013:492170.
  • 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; · 2.84 Impact Factor
  • John G Kral, Nandor Ludvig
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    ABSTRACT: We postulate that alternating use of microcontroller-regulated delivery and drain pumps connected to one or more sealed subarachnoid fluid exchange ports can maintain localized bi-directional molecular fluxes across pia mater covering multiple diseased areas of the cerebral cortex or spinal cord. This system enables local irrigation with drugs and drainage of endogenous neurotoxic molecules normalizing regional neurochemistry and restoring physiological function. Viewing the pia mater as an endogenous dialysis membrane, testing this hypothesis requires demonstrating: (a) benefits of removing neurotoxic molecules from diseased cerebral cortical or spinal areas via subarachnoid dialysis, (b) neuropharmacological effects of subarachnoid drug delivery and (c) evaluating additive effects of combining the two, as a novel, "pharmacodialysis" procedure. Our supporting experimental data show that this procedure can drain proinflammatory cytokines from the neocortex to the subarachnoid cerebrospinal fluid in rats and can prevent focal seizures in monkeys through subarachnoid delivery of muscimol to their neocortex. Subarachnoid pharmacodialysis allows effective site-specific treatment and microcontroller-regulated timing responsive to the evolving course of a disease and can be performed with bedside systems or fully implanted devices. The procedure provides a two-pronged, combined therapy for traumatic brain and spinal cord injuries, cortically localized epilepsy, stroke and tumors as well as psychiatric disorders such as Alzheimer's disease with pathology of the association cortex. Therapeutic subarachnoid pharmacodialysis drainage of endogenous molecules from the neocortical interstitial space offers unprecedented opportunities to gain new insights into the neurochemistry of the human neocortex in real-life conditions over months or even years.
    Medical Hypotheses 11/2012; · 1.15 Impact Factor
  • Medical care 05/2012; 50(5):460; author reply 460-1. · 2.94 Impact Factor
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    ABSTRACT: Severe obesity (SO) is increasing faster than obesity in adults and in children. Because it is associated with numerous comorbidities, SO accounts for more health care expenditures than any other medical condition. Furthermore, it is associated with poor pregnancy outcomes for mother, fetus, and infant and a high risk of offspring obesity carried into adulthood. Bariatric surgery is the treatment of choice for SO because nonoperative methods fail to provide medically significant durable weight loss and because it is both preventive and therapeutic. The number of operations has sharply increased globally, yet only a small fraction of eligible patients are referred for surgical treatment demonstrating the need for improved access, especially for those disproportionately affected by SO. The risks of surgery mandate careful postoperative long-term multidisciplinary follow-up care. Education is critical for truly informed consent and must continue postoperatively, especially for women with reproductive potential. Even so, surgical treatment of SO remains cost-effective compared to conventional nonoperative treatment, which also requires long-term care. Just as obesity affects all medical disciplines (from allergology and immunology to oncology, urology and women's health), so does postoperative management of bariatric surgery patients. We offer wide-ranging recommendations for policymakers and others to consider in addressing SO. Copyright © 2012 S. Karger GmbH, Freiburg.
    Obesity Facts 04/2012; 5(2):254-269. · 1.58 Impact Factor
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    ABSTRACT: Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts. This strip can be positioned between the dura and pia maters. The second novel component is an implantable dual minipump that directs fluid movement to and from the silicone strip and is accessible for refilling and emptying the drug and CSF reservoirs, respectively. This minipump is regulated by a battery-powered microcontroller integrating a bi-directional radiofrequency (RF) communication module. The entire apparatus was implanted in 5 macaque monkeys, with the subdural strip positioned over the frontal cortex and the minipump assembly secured to the cranium under a protective cap. The system was successfully tested for up to 8 months for (1) transmeningeal drug delivery using acetylcholine (ACh) and muscimol as test compounds, (2) RF-transmission of neocortical EEG data to assess the efficacy of drug delivery, and (3) local CSF removal for subsequent diagnostic analyses. The device can be used for (a) monitoring neocortical electrophysiology and neurochemistry in freely behaving nonhuman primates for more than 6 months, (b) determining the neurobiological impact of subdural/subarachnoid drug delivery interfaces, (c) obtaining novel neuropharmacological data on the effects of central nervous system (CNS) drugs, and (d) performing translational studies to develop subdural pharmacotherapy devices.
    Journal of neuroscience methods 01/2012; 203(2):275-83. · 2.30 Impact Factor
  • Laura Dhariwal, John G Kral
    Surgery for Obesity and Related Diseases 12/2011; 8(4):391-2. · 4.94 Impact Factor

Publication Stats

2k Citations
390.86 Total Impact Points

Institutions

  • 2001–2014
    • State University of New York Downstate Medical Center
      • • Department of Psychiatry (LICH)
      • • Department of Surgery
      Brooklyn, New York, United States
    • Saint Agnes Hospital
      Baltimore, Maryland, United States
  • 2000–2014
    • State University of New York
      New York City, New York, United States
  • 1999–2013
    • Laval University
      • Department of Surgery
      Québec, Quebec, Canada
  • 2007–2009
    • University of Minnesota Twin Cities
      • Department of Integrative Biology and Physiology
      Minneapolis, MN, United States
  • 2005
    • Virginia Commonwealth University
      • Department of Surgery
      Richmond, Virginia, United States
  • 2003–2005
    • Klinik Hirslanden
      Zürich, Zurich, Switzerland
  • 2001–2005
    • Karolinska Institutet
      • Department of Surgery
      Solna, Stockholm, Sweden