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1.  Clinical Management of Patients Presenting with Non-Adjustable Gastric Band (NAGB) Complications 
Background: A number of bariatric surgical procedures have been developed to manage morbid obesity and related co-morbidities. The non-adjustable gastric band (NAGB) was one such procedure that created restriction to food intake by gastric segmentation. Benefits of the procedure included a low risk of perioperative complications and substantial early weight loss. Unfortunately, the long term results of NAGB include a high incidence of complications and failure to maintain weight loss. The purpose of this study was to examine the presentation, workup, and treatment of patients presenting with complications following NAGB placement.
Methods: A retrospective review of the diagnosis and management of 11 patients who presented with complications related to NAGB placement.
Results: All patients presented with some degree of proximal gastric outlet obstruction. The majority of patients (8/11) presented with vomiting as the main complaint. Other complaints included intolerance to solids, liquids, and reflux. Only 2/11 patients presented with weight loss since undergoing NAGB placement, while the remainder had weight regain to their pre-NAGB level and above. Depending on clinical presentation, desire for additional weight loss and co-morbid conditions, patients underwent a variety of treatments. This included NAGB removal (endoscopic, laparo-endoscopic, and laparoscopic) as well as conversion to another bariatric procedure (sleeve gastrectomy, Roux-en-Y gastric bypass).
Conclusion: Patients with NAGB complications present with symptoms related to a proximal gastric outlet obstruction, related to constriction imposed by the band. This may result in severe food and liquid intolerance and subsequent weight loss, but more likely results in maladaptive eating and subsequent weight gain. Optimal therapy involves removal of the NAGB. Laparoscopic conversion to another bariatric procedure, optimally a Roux-en-Y gastric bypass, is warranted to treat morbid obesity and associated co-morbidities.
PMCID: PMC4031789  PMID: 24910561
bariatric; complications; revision; laparoscopic; non-adjustable gastric band
2.  The Pathogenesis of Obesity from a Genomic and Systems Biology Perspective 
The recent obesity epidemic has imposed significant health, economical, and societal concerns. However, effective preventive and therapeutic strategies are currently lacking, primarily due to a lack of comprehensive understanding of the underlying molecular mechanisms. Recent genome-wide scans of genetic variants, transcriptome, and epigenome have uncovered >50 genetic loci that predispose individuals to obesity and revealed hundreds of genes with altered transcriptional activity and/or epigenetic variations in obesity-related tissues upon various environmental challenges such as high caloric diets, lack of physical activity, and environmental chemicals. These discoveries highlight the importance of genes involved in the control of energy homeostasis and food intake by the central nervous system, as well as genes contributing to lipid metabolism, adipogenesis, fat cell differentiation, and immune response in peripheral tissues, in obesity development. Future studies that are directed to obtain a more comprehensive, systems-level understanding of disease mechanisms and that test novel therapeutic strategies aiming at systems-level normalization of the obesity-related molecular alterations are warranted.
PMCID: PMC4031785  PMID: 24910557
obesity; genomics; genetic risks; environmental risks; high caloric diets; exercise; obesogen; transcriptome; epigenome; integrative genomics; systems biology
3.  A Dangerous Duo in Adipose Tissue: High-Mobility Group Box 1 Protein and Macrophages 
High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a non-histone nuclear protein that regulates gene expression. Not so long ago, it was also shown that HMGB1 has an additional surprising function. When released into the extracellular milieu, HMGB1 triggers an inflammatory response by serving as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well-established and has been associated with several diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. Yet very little is known about its role in obesity, wherein adipose tissue is typified by a persistent, smoldering inflammatory response instigated by high macrophage infiltrate that potentiates the risk of obesity-associated comorbidities. This mini-review focuses on the putative causal relationship between HMGB1 and macrophage pro-inflammatory activation in pathologically altered adipose tissue associated with obesity.
PMCID: PMC4031786  PMID: 24910558
adipose tissue; adipocyte; obesity; insulin resistance; diabetes mellitus type 2; inflammation; macrophage; phagocytosis; cell death; apoptosis; necrosis; danger signals; damage-associated molecular patterns; pattern-recognition receptors; high-mobility group box 1 protein; crown-like structure; interleukin-6; tumor-necrosis factor-α; lipolysis; lipid droplets; free fatty acids
4.  Effects of Dairy on Metabolic Syndrome Parameters: A Review 
Metabolic syndrome (MetS), characterized by central obesity, dyslipidemias, hypertension, and hyperglycemia, impacts 34 percent of the U.S. adult population. MetS has been demonstrated to be affected by dietary components. Data from epidemiological studies and clinical interventions suggest that one or more dairy components might directly affect MetS parameters. For example, calcium has been postulated to reduce body weight by modulating vitamin D concentrations in plasma and therefore attenuating intracellular calcium effects in activating genes involved in fatty acid synthesis and reducing those involved in lipolysis. Peptides present in milk have been associated with the inhibition of angiotensin converting enzyme and, therefore, with blood pressure reductions. Branched chain amino acids may increase post-prandial insulin secretion and regulate plasma glucose levels, and leucine, an abundant amino acid in milk, may be responsible for decreased plasma glucose through modulation of mTOR. Through different proposed mechanisms, dairy nutrients may target all components of MetS.
PMCID: PMC4031787  PMID: 24910559
metabolic syndrome; dairy; calcium; leucine; body weight
5.  A Temperature Hypothesis of Hypothalamus-Driven Obesity 
Obesity is a metabolic state in which excess fat is accumulated in peripheral tissues, including the white adipose tissue, muscle, and liver. Sustained obesity has profound consequences on one’s life, which can span from superficial psychological symptoms to serious co-morbidities that may dramatically diminish both the quality and length of life. Obesity and related metabolic disorders account for the largest financial burden on the health care system. Together, these issues make it imperative that obesity be cured or prevented. Despite the increasing wealth of knowledge on the etiology of obesity (see below), there is no successful medical strategy that is available for the vast majority of patients. We suggest that brain temperature control may be a crucial component in obesity development and that shortcutting the brain metabolic centers by hypothalamic temperature alterations in a non-invasive remote manner will provide a revolutionary approach to the treatment of obesity.
PMCID: PMC4031788  PMID: 24910560
hypothalamus; obesity; temperature regulation; circuit activity
6.  Obesity: From Public Health to Public Policy 
PMCID: PMC4031790  PMID: 24910562
childhood obesity; soda tax; Yale Rudd Center; food addiction
7.  Genetic and Epigenetic Regulation of the Brain-Derived Neurotrophic Factor in the Central Nervous System 
The BDNF is required for the development and proper function of the central nervous system, where it is involved in a variety of neural and molecular events relevant to cognition, learning, and memory processes. Although only a functional mature protein is synthesized, the human BDNF gene possesses an extensive structural complexity, including the presence of multiple promoters, splicing events, and 3´UTR poly-adenylation sites, resulting in an intricate transcriptional regulation and numerous messengers RNA. Recent data support specific cellular roles of these transcripts. Moreover, a central role of epigenetic modifications on the regulation of BDNF gene transcription is also emerging. The present essay aims to summarize the published information on the matter, emphasizing their possible implications in health and disease or in the treatment of different neurologic and psychiatric disorders.
PMCID: PMC4031791  PMID: 24910563
BDNF; alternative promoters; transcripts; epigenetic; psychiatric and neurological disorders
8.  Clinical Decision Support: Effectiveness in Improving Quality Processes and Clinical Outcomes and Factors That May Influence Success 
The use of electronic health records has skyrocketed following the 2009 HITECH Act, which provides financial incentives to health care providers for the “meaningful use” of electronic medical record systems. An important component of the “Meaningful Use” legislation is the integration of Clinical Decision Support Systems (CDSS) into the computerized record, providing up-to-date medical knowledge and evidence-based guidance to the physician at the point of care. As reimbursement is increasingly tied to process and clinical outcomes, CDSS will be integral to future medical practice. Studies of CDSS indicate improvement in preventive services, appropriate care, and clinical and cost outcomes with strong evidence for CDSS effectiveness in process measures. Increasing provider adherence to CDSS recommendations is essential in improving CDSS effectiveness, and factors that influence adherence are currently under study.
PMCID: PMC4031792  PMID: 24910564
electronic health record; electronic medical records; clinical decision support systems; computerized provider order entry; quality process measure; quality outcomes; meta-analysis of randomized controlled trials; clinical practice guidelines; preventive services guidelines
9.  Anticoagulation for the Acute Management of Ischemic Stroke 
Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others.
PMCID: PMC4031793  PMID: 24910565
ischemic stroke; anticoagulation; cardioembolism; left ventricular thrombus; intracardiac thrombus; hemorrhagic transformation
10.  How to Learn Effectively in Medical School: Test Yourself, Learn Actively, and Repeat in Intervals 
Students in medical school often feel overwhelmed by the excessive amount of factual knowledge they are obliged to learn. Although a large body of research on effective learning methods is published, scientifically based learning strategies are not a standard part of the curriculum in medical school. Students are largely unaware of how to learn successfully and improve memory. This review outlines three fundamental methods that benefit learning: the testing effect, active recall, and spaced repetition. The review summarizes practical learning strategies to learn effectively and optimize long-term retention of factual knowledge.
PMCID: PMC4031794  PMID: 24910566
learning; testing effect; active recall; spaced repetition; medical curriculum
11.  On the Outcome Project 
Background: In 2001, graduate medical education in the United States was renovated to better complement 21st century developments in American medicine, society, and culture. As in 1910, when Abraham Flexner was charged to address a relatively non-standardized system that lacked accountability and threatened credibility of the profession, Dr. David Leach led the Accreditation Council of Graduate Medical Education (ACGME) Outcome Project in a process that has substantially changed medical pedagogy in the United States.
Methods: Brief review of the Flexner Report of 1910 and 6 hours of interviews with leaders of the Outcome Project (4 hours with Dr. David Leach and 1-hour interviews with Drs. Paul Batalden and Susan Swing).
Results: Medical educational leaders and the ACGME concluded in the late 1990s that medical education was not preparing clinicians sufficiently for lifelong learning in the 21st century. A confluence of medical, social, and historic factors required definitions and a common vocabulary for teaching and evaluating medical competency. After a deliberate consensus-driven process, the ACGME and its leaders produced a system requiring greater accountability of learners and teachers, in six explicitly defined domains of medical “competence.” While imperfect, this construct has started to take hold, creating a common vocabulary for longitudinal learning, from undergraduate to post-graduate (residency) education and in the assessment of performance following graduate training.
PMCID: PMC4031795  PMID: 24910567
medical education; Outcome Project; ACGME; Flexner
12.  Introduction 
PMCID: PMC4031801  PMID: 24910555
13.  Thinking Evolutionarily About Obesity 
Obesity, diabetes, and metabolic syndrome are growing worldwide health concerns, yet their causes are not fully understood. Research into the etiology of the obesity epidemic is highly influenced by our understanding of the evolutionary roots of metabolic control. For half a century, the thrifty gene hypothesis, which argues that obesity is an evolutionary adaptation for surviving periods of famine, has dominated the thinking on this topic. Obesity researchers are often not aware that there is, in fact, limited evidence to support the thrifty gene hypothesis and that alternative hypotheses have been suggested. This review presents evidence for and against the thrifty gene hypothesis and introduces readers to additional hypotheses for the evolutionary origins of the obesity epidemic. Because these alternate hypotheses imply significantly different strategies for research and clinical management of obesity, their consideration is critical to halting the spread of this epidemic.
PMCID: PMC4031802  PMID: 24910556
review; obesity; diabetes; metabolic syndrome; evolution; thrifty gene hypothesis
14.  Pushing the Boundaries: The Development of Super-Resolution Microscopy at Yale and Beyond 
PMCID: PMC3941448  PMID: 24600336
TIRF; microscopy; super-resolution microscopy
17.  Family Presence During Resuscitation: Attitudes of Yale-New Haven Hospital Staff 
Introduction: A novel paradigm of patient- and family-centered care has been promoted and adopted by many parties in the United States. This new attitude emphasizes the role of the family in the care of the patient. One topic that should be affected by the new paradigm is family presence during resuscitation, which continues to be a highly debatable topic with no widespread implementation. The objective of this study was to assess the attitudes of Yale Emergency Department (ED) health care personnel toward Family Presence during Resuscitation (FPDR).
Materials and Methods: In 2012, we surveyed 100 health care professionals in the Yale-New Haven Hospital ED, including physicians, nurses, technicians, social workers, and chaplains. One researcher analyzed the qualitative data, and both researchers reviewed the results to increase internal validity.
Results: Seventy-seven percent of staff members favored allowing the option of FPDR. Seventy-six percent of staff members believed that family members would want to be present during their loved one’s resuscitation.
Conclusion: Given scientific evidence to support FPDR and the staff’s wide acceptance of it, we recommend drafting and implementing a protocol for allowing FPDR. The protocol should be individualized to the Yale-New Haven Hospital ED setting.
PMCID: PMC3941452  PMID: 24600337
family presence during cardiopulmonary resuscitation; family-centered approach, emergency department
19.  The Importance of Student Initiative Both In and Out of The Lab 
In September 2013, graduate students from the Yale Immunobiology Department hosted the second Yale Immunobiology Student Symposium. It was an eclectic and thought-provoking event that encouraged scientists to think outside the box both in their research and in their endeavors outside of the laboratory. The speakers ranged from a government representative to a New York Times science journalist and included four research scientists at the cutting-edge in their field. Speakers discussed their current research, from the role of our gut microbiota in causing colorectal cancers to the biochemical modifications in histone tails that give rise to our unique human biology. The overarching message was to let scientists, especially those of the younger generation, know how to approach, think, and talk about science.
PMCID: PMC3941454  PMID: 24600338
student symposium; science policy; student involvement; government; autoimmunity; microbiome; histone modifications; cancer; science writing
21.  Fluorescence Microscopy Gets Faster and Clearer: Roles of Photochemistry and Selective Illumination 
Significant advances in fluorescence microscopy tend be a balance between two competing qualities wherein improvements in resolution and low light detection are typically accompanied by losses in acquisition rate and signal-to-noise, respectively. These trade-offs are becoming less of a barrier to biomedical research as recent advances in optoelectronic microscopy and developments in fluorophore chemistry have enabled scientists to see beyond the diffraction barrier, image deeper into live specimens, and acquire images at unprecedented speed. Selective plane illumination microscopy has provided significant gains in the spatial and temporal acquisition of fluorescence specimens several mm in thickness. With commercial systems now available, this method promises to expand on recent advances in 2-photon deep-tissue imaging with improved speed and reduced photobleaching compared to laser scanning confocal microscopy. Superresolution microscopes are also available in several modalities and can be coupled with selective plane illumination techniques. The combination of methods to increase resolution, acquisition speed, and depth of collection are now being married to common microscope systems, enabling scientists to make significant advances in live cell and in situ imaging in real time. We show that light sheet microscopy provides significant advantages for imaging live zebrafish embryos compared to laser scanning confocal microscopy.
PMCID: PMC3941456  PMID: 24600334
confocal microscopy; photoactivatable GFP; 2-photon microscopy; superresolution microscopy; selective plane illumination microscopy; light sheet microscopy
23.  What Ticks Do Under Your Skin: Two-Photon Intravital Imaging of Ixodes Scapularis Feeding in the Presence of the Lyme Disease Spirochete 
Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding.
PMCID: PMC3941458  PMID: 24600332
Ixodes scapularis ticks; two-photon intravital microscopy; Borrelia burgdorferi; Lyme disease
24.  Introduction 
PMCID: PMC3941459  PMID: 24741749

Results 1-25 (7338)