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Title:
Metabolism and epilepsy: Ketogenic diets as a homeostatic link
Authors:
Masino, Susan A.; Rho, Jong M.
Abstract:
Metabolic dysfunction can underlie seizure disorders, and metabolism-based treatments can afford seizure control and promote homeostasis. This relationship between metabolism and the risk of sporadic seizures was observed historically with the clinical success of a low-carbohydrate, high-fat, ketosis-inducing ketogenic diet – a treatment that remains relevant today, and one that has been shown to be effective against medically refractory epilepsy. Mechanisms underlying the success of the ketogenic diet are a topic of intense research efforts – not only because of proven success in arresting treatment-resistant seizures, but also because recent evidence suggests that altering metabolism with a ketogenic diet enables a homeostatic state in the brain that is less excitable, and hence raises the threshold for seizure genesis. Metabolic therapy with a ketogenic diet has been shown to normalize a range of abnormal physiological and behavioral parameters and may also make the central nervous system more resilient to other insults or physiological stresses. Because the therapeutic ability of such a diet may be more limited than a drug because of a dose “ceiling” investigations are underway to develop and test analogous or supplemental approaches. In addition, significant efforts have been made to demonstrate broader applications of metabolic therapy in promoting health and preventing disease, including conditions where epileptic seizures manifest in a comorbid fashion.
Published:
2019-06
Title:
The Philosophy of Evidence-Based Principles and Practice in Nutrition
Authors:
Johnston, Bradley C.; Seivenpiper, John L.; Vernooij, Robin W.M.; de Souza, Russell J.; Jenkins, David J.A.; Zeraatkar, Dena; Bier, Dennis M.; Guyatt, Gordon H.
Abstract:
The practice of evidence-based nutrition involves using the best available nutrition evidence, together with clinical experience, to conscientiously work with patients' values and preferences to help them prevent (sometimes), resolve (sometimes), or cope with (often) problems related to their physical, mental, and social health. This article outlines the 3 fundamental principles of evidence-based practice as applied to the field of clinical nutrition. First, optimal clinical decision making requires awareness of the best available evidence, which ideally will come from unbiased systematic summaries of that evidence. Second, evidence-based nutrition provides guidance on how to decide which evidence is more or less trustworthy-that is, how certain can we be of our patients' prognosis, diagnosis, or of our therapeutic options? Third, evidence alone is never sufficient to make a clinical decision. Decision makers must always trade off the benefits with the risks, burden, and costs associated with alternative management strategies, and, in so doing, consider their patients' unique predicament, including their values and preferences.
Published:
2019-06
Title:
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans
Authors:
Andreux, Pénélope A.; Blanco-Bose, William; Ryu, Dongryeol; Burdet, Frédéric; Ibberson, Mark; Aebischer, Patrick; Auwerx, Johan; Singh, Anurag; Rinsch, Chris
Abstract:
Here the authors report the results of a first-in-human trial with urolithin A in healthy elderly individuals, demonstrating that the compound is well tolerated and bioavailable after oral administration. They also provide clinical data indicating that urolithin A may improve mitochondrial and cellular health in human muscle.
Published:
2019-06
Title:
A bioinformatics workflow to decipher transcriptomic data from vitamin D studies
Authors:
Muñoz García, Amadeo; Eijssen, Lars M.; Kutmon, Martina; Sarathy, Chaitra; Cengo, Ardi; Hewison, Martin; Evelo, Chris T.; Lenz, Michael; Coort, Susan L.
Abstract:
The link between the experimental laboratory studies and bioinformatic approaches aims to find procedures to connect tools from both branches producing workflows that bring together different techniques that are capable of exploiting data at many levels. Thanks to the open access sources and the numerous tools available, it is possible to create various pipelines capable of solving specific problems. Nevertheless the lack of connectivity between them that interconnect different approaches complicates the exploitation of these workflows. Here, we present a detailed description of a workflow composed of different bioinformatics tools that exploits data from large-scale gene expression experiments, contextualizing them at many biological levels. To illustrate the relevance of our workflow for the vitamin D community we applied it to data from myeloid cell models treated with the hormonally active form of vitamin. From raw files of functional genomic studies it is possible to utilize the whole information to obtain a biological insight. Different software and algorithms are included to analyse at pathway, metabolic, ontology and molecular biology level the effects on gene expression. The usage of different databases to analyse gene expression data allows to perform a complete interpretation of functional genomic studies and the implementation of analysis and visualization software tools gives a better understanding of the biological meaning of the results. This review is an example of how to select and bring together several software modules to create one pipeline that processes and analyses genomic data at many biological levels making it open, reproducible and user friendly. Finally, the application of our bioinformatic pipeline revealed that vitamin D modulates crucial metabolic pathways in different myeloid cells that may play an important role in their immune function.
Published:
2019-05
Title:
Brief cognitive behavioral therapy reduces suicidal ideation in veterans with chronic illnesses
Authors:
Ecker, Anthony H.; Johnson, Adrienne L.; Sansgiry, Shubhada; Fletcher, Terri L.; Hundt, Natalie; Petersen, Nancy J.; Sweeney, Alison C.; Chaison, Angelic D.; York-Ward, Kaki M.; Kauth, Michael R.; Kunik, Mark E.; Cully, Jeffrey A.
Abstract:
Objective: We evaluated the effect of brief cognitive behavioral therapy (bCBT) on suicidal ideation among medically ill veterans receiving mental health treatment in primary care. Methods: Secondary analysis was conducted on data collected during a multisite, patient-randomized trial investigating the impact of bCBT (n = 180) on depression and anxiety symptoms, relative to enhanced usual care (EUC; n = 122), in patients with congestive heart failure and/or chronic obstructive pulmonary disease. BCBT was delivered by primary care mental health providers over 4 months, with follow-up posttreatment assessments of suicidal ideation, measured by the Patient Health Questionnaire-9 (item 9) at 4, 8, and 12 months. Suicidal ideation was the primary outcome examined in the current analysis. Generalized estimating equations modeling suicidal ideation were used to compare the study arms. Results: Participants receiving bCBT were less likely to have high suicidal ideation than participants receiving EUC posttreatment and at 8-month follow-up after accounting for baseline suicidal ideation. Within-group comparisons suggest participants receiving bCBT were less likely to have high suicidal ideation at 4, 8, and 12 months when compared with baseline. High suicidal ideation for EUC participants did not differ at 4, or 8 months, but they were less likely to have high suicidal ideation at 12 months. Conclusion: bCBT in primary care reduces suicidal ideation and may help prevent future suicidal ideation. 1. Introduction Suicide in the United States is a significant public health concern, with suicide rates increasing 24% from 1999 to 2016 [1]. Engaging individuals in mental health care in the primary care setting is one potential avenue to reduce suicide by reducing stigma and increasing access to critical mental health services [2]. At particular risk for suicide in primary care settings are those with chronic medical illness and comorbid mental health disorders. Over 70% of patients in primary care have a chronic health condition [3], including chronic obstructive pulmonary disease (COPD) and cardiovascular conditions such as heart failure (HF). These conditions are associated with negative effects,
Published:
2019-05
Title:
Development of Alzheimer disease in old major depressive patients based upon their health status: A retrospective study in Taiwan.
Authors:
Tao, Ping; Yang, Szu-Nian; Tung, Yu-Chi; Yang, Ming-Chin
Abstract:
This study is conducted to investigate the association between major depressive disorder and the subsequent development of Alzheimer disease (AD) in elderly patients with different health statuses using Taiwan's National Health Insurance Research Database (NHIRD).A retrospective cohort study was performed on subjects over 65 years old from 2002 to 2006 using a random sampling from the 1 million beneficiaries enrolled in the NHI. Patients who were diagnosed with major depressive disorder were selected as the case group. Subjects in the control group were selected from elderly patients who did not have depression during the study period by matching age, sex, and index date of depression with subjects in the case group using a ratio of 1:4 (case:control). Both groups of patients were checked annually over a period of 7 years to observe whether they subsequently developed AD.A total of 1776 subjects were included in the case group while 7104 subjects were in the control group. After the follow-up period, 59 patients (3.3%) with depression developed AD while 96 patients (1.4%) without depression developed AD. The Kaplan-Meier curves showed that the incidence rate of AD in both groups varied significantly depending on different health statuses (log-rank P
Published:
2019-05
Title:
Dietary protein source and butyrylated high-amylose maize starch included in a high-protein diet determines the urinary metabolome of rats
Authors:
Sattari Najafabadi, Zahra; Skau Nielsen, Tina; Skou Hedemann, Mette
Abstract:
Intake of red and processed meat increases the risk of colorectal cancer (CRC), whereas dairy product consumption and the intake of dietary fibre are negatively associated with this risk. We investigated the effect of (i) low-protein diets with either whey or cooked meat (beef) as the protein source and (ii) high-protein diets with cooked meat (beef) either without or with the inclusion of 10% butyrylated high-amylose maize starch (HAMSB), on the urinary metabolome of rats. Urine samples from rats were analysed using untargeted LC-MS metabolomics. The level and source of the dietary protein affected the urinary excretion of numerous metabolites indicating that several metabolic pathways were changed. The inclusion of HAMSB in a high-protein diet caused significant alterations in the excretion of several metabolites. HAMSB reduced urinary excretion of potentially harmful metabolites resulting from a high level of meat consumption.
Published:
2019-05
Title:
Effectiveness of suicide prevention interventions: A systematic review and meta-analysis
Authors:
Hofstra, Emma; van Nieuwenhuizen, Chijs; Bakker, Marjan; Özgül, Dilana; Elfeddali, Iman; de Jong, Sjakko J.; van der Feltz-Cornelis, Christina M.
Abstract:
Objective: This study provides an estimate of the effect size of suicide prevention interventions and evaluates the possible synergistic effects of multilevel interventions. Method: A systematic review and meta-analysis were conducted of controlled studies evaluating suicide prevention interventions versus control published between 2011 and 2017 in PubMed, PsycINFO, and Cochrane databases. Data extraction and risk of bias assessment according to ROBINS criteria were performed by independent assessors. Cohen's delta was calculated by a random meta-analysis on completed and attempted suicides as outcomes. Meta-regression explored a possible synergistic effect in multilevel interventions. PROSPERO ID number: CRD42018094373. Results: The search yielded 16 controlled studies with a total of 252,932 participants. The meta-analysis was performed in 15 studies with 29,071 participants. A significant effect was found for suicide prevention interventions on completed suicides (d = −0.535, 95% CI −0.898; −0.171, p = .004) and on suicide attempts (d = −0.449, 95% CI −0.618; −0.280, p
Published:
2019-05
Title:
Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors
Authors:
Ministrini, Stefano; Calzini, Lucia; Nulli Migliola, Elisa; Ricci, Maria Anastasia; Roscini, Anna Rita; Siepi, Donatella; Tozzi, Giulia; Daviddi, Giulia; Martorelli, Eva-Edvige; Paganelli, Maria Teresa; Lupattelli, Graziana
Abstract:
A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.
Published:
2019-05
Title:
National study of emergency department disposition for high suicide risk geriatric patients
Authors:
Schmutte, Timothy; Olfson, Mark; Xie, Ming; Marcus, Steven C.
Abstract:
Objective: To examine predictors of hospitalization among older adults at high risk for suicide treated in emergency departments (EDs). Methods: This retrospective cohort analysis used national 2015 Medicare claims for adults ≥65 years with ED visits for suicide ideation or deliberate self-harm (N = 50,472) merged with data from the Area Health Resource File. Rates and adjusted risk ratios (ARR) of hospital admission were assessed. Results: A majority of ED episodes resulted in hospital admission (81.9%) with most being admitted to a psychiatric unit (62.8%). Visits for self-harm with suicide ideation were most likely to result in hospitalization (94.7%) compared to suicide ideation alone (84.0%) or self-harm alone (73.1%). Current diagnosis of depression, bipolar, anxiety, cognitive, and personality disorder were associated with hospitalization. Co-occurring mental and substance use disorders were the most predictive mental health condition of admission. Overall, severity of current medical comorbidity was the strongest predictor of hospital admission. Conclusions: Most older adults treated in EDs for suicide ideation or self-harm are hospitalized. Medical morbidity plays a more prominent role than other patient factors in admission status.
Published:
2019-05
Title:
Nutrition and its role in human evolution
Authors:
James, W. P. T.; Johnson, R. J.; Speakman, J. R.; Wallace, D. C.; Frühbeck, G.; Iversen, P. O.; Stover, P. J.
Abstract:
Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9 million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300 000 years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50 000-100 000 years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.
Published:
2019-05
Title:
O-GlcNAcylation, a sweet link to the pathology of diseases
Authors:
Nie, Hao; Yi, Wen
Abstract:
O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus, cytoplasm, and mitochondria. The donor sugar for O-GlcNAcylation, uridine-diphosphate N-acetylglucosamine (UDP-GlcNAc), is synthesized from glucose through the hexosamine biosynthetic pathway (HBP). The recycling of O-GlcNAc on proteins is mediated by two enzymes in cells-O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which catalyze the addition and removal of O-GlcNAc, respectively. O-GlcNAcylation is involved in a number of important cell processes including transcription, translation, metabolism, signal transduction, and apoptosis. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular diseases. A better understanding of the roles of O-GlcNAcylation in physiopathological processes would help to uncover novel avenues for therapeutic intervention. The aim of this review is to discuss the recent updates on the mechanisms and impacts of O-GlcNAcylation on these diseases, and its potential as a new clinical target.
Published:
2019-05
Title:
Omega-3 index in the Czech Republic: No difference between urban and rural populations
Authors:
Oseeva, Marina; Paluchova, Veronika; Zacek, Petr; Janovska, Petra; Mracek, Tomas; Rossmeisl, Martin; Hamplova, Dana; Cadova, Nadezda; Stohanzlova, Iva; Flachs, Pavel; Kopecky, Jan; Kuda, Ondrej
Abstract:
Naturally occurring long-chain omega-3 PUFA such as eicosapentaenoic acid (EPA; 20:5 ω-3) and docosahexaenoic acid (DHA; 22:6 ω-3) exert multiple effects on health, which are related to the intake of these lipids in the diet and correlate with the levels of omega-3 PUFA in the body. These levels are reflected by the omega-3 PUFA index, i.e. the EPA and DHA content as % of all fatty acids in red blood cells. The aim of this study was to evaluate omega-3 index in the Czech Republic, using blood samples collected from the capital city (n = 476) and the rural region (n = 388). The mean omega-3 index was 3.56 mol % with a maximal value of 8.10% and a minimal value of 1.12%. There was no difference in the index value between rural and urban / industrial regions, but this value was higher in subjects who reported eating fish or omega-3 PUFA supplements. In conclusion, the results indicated suboptimal values of the omega-3 index in the Czech population independent of the sampling region.
Published:
2019-05
Title:
Vitamin D and testosterone co-ordinately modulate intracellular zinc levels and energy metabolism in prostate cancer cells
Authors:
Zhang, Polly; Schatz, Adam; Adeyemi, Babatunde; Kozminski, David; Welsh, JoEllen; Tenniswood, Martin; Wang, Wei-Lin Winnie
Abstract:
Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early, and late invasive PCa were investigated. BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), and retinoid X receptor (RXR). In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, T, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism. 1,25(OH)2D3, T, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, T, and 9-cis RA is preserved in all in vitro cell lines investigated. These data suggest that 1,25(OH)2D3 and T are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.
Published:
2019-05
Title:
Western diet consumption through early life induces microvesicular hepatic steatosis in association with an altered metabolome in low birth weight Guinea pigs
Authors:
Sarr, Ousseynou; Mathers, Katherine E.; Zhao, Lin; Dunlop, Kristyn; Chiu, Jacky; Guglielmo, Christopher G.; Bureau, Yves; Cheung, Anson; Raha, Sandeep; Lee, Ting-Yim; Regnault, Timothy R.H.
Abstract:
Uteroplacental insufficiency-induced low birth weight (LBW) and postnatal high saturated fat/high sucrose-fructose diet (Western Diet, WD) consumption have been independently associated with the development of hepatic steatosis, while their additive effect on fatty acid, acylcarnitine and amino acid profiles in early adulthood have not been widely reported. We employed LBW, generated via uterine artery ablation, and normal birth weight (NBW) male guinea pigs fed either a WD or control diet (CD) from weaning to postnatal day 150 (early adulthood). Hepatic steatosis was absent in CD-fed offspring, while NBW/WD offspring displayed macrovesicular steatosis and LBW/WD offspring exhibited microvesicular steatosis, both occurring in a lean phenotype. Life-long consumption of the WD, irrespective of birth weight, was associated with an increase in hepatic medium- and long-chain saturated fatty acids, monounsaturated fatty acids, acylcarnitines, reduced oxidative phosphorylation complex III activity and polyunsaturated fatty acids, and molecular evidence of disrupted hepatic insulin signaling. In NBW/WD, hepatic C15:1 and C16:1n-6 fatty acids in phospholipids, C16, C18 and C18:1 acylcarnitines, concentrations of aspartate, phenylalanine, tyrosine and tryptophan and expression of carnitine palmitoyltransferase 1 alpha (CPT1α) and uncoupling protein 2 (UCP2) genes were elevated compared to LBW/WD livers. Our results suggest that LBW and life-long WD combined are influential in promoting hepatic microvesicular steatosis in conjunction with a specific mitochondrial gene expression and metabolomic profile in early adulthood.
Published:
2019-05
Title:
Association of soft tissue infection in the extremity with glucose and lipid metabolism and inflammatory factors
Authors:
Sun, Haijun; Zhang, Xiuyun; Shi, Wei; Fang, Bo
Abstract:
Association of soft tissue infection in the extremity with glucose and lipid metabolism as well as inflammatory factors was investigated. One hundred and twenty-six patients with diabetes mellitus (DM) complicated with soft tissue infection in the lower extremity admitted and treated in Dongying People's Hospital from March 2016 to February 2017 were selected and divided into mild (n=46), moderate (n=43) and severe group (n=37) according to the severity of the soft tissue infection in the lower extremity. The glucose and lipid metabolism, inflammatory factors and influencing factors were compared among different groups of patients before treatment, and the changes in glucose and lipid metabolism as well as inflammatory factors were observed after treatment. Before treatment, the levels of free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in mild group were remarkably lower than those in moderate and severe groups, while the serum adiponectin (APN) level was obviously higher (P<0.05). Logistic regression analysis indicated that FFA, FPG, FINS, APN, VCAM-1, CRP, TNF-α and IL-6 were risk factors influencing soft tissue infection in the extremity (P<0.05). After treatment, among the 126 patients, the levels of FFA, FPG, FINS, VCAM-1, CRP, TNF-α and IL-6 were decreased markedly, while the APN level was increased evidently (P<0.05). Compared with patients innon-toe/extremity amputation group, patients in toe/extremity amputation group had elevated levels of FFA, FPG, FINS, VCAM-1, CRP, TNF-α and IL-6 as well as declined APN level (P
Published:
2019-04
Title:
Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression
Authors:
Dunlop, Boadie W.; LoParo, Devon; Kinkead, Becky; Mletzko-Crowe, Tanja; Cole, Steven P.; Nemeroff, Charles B.; Mayberg, Helen S.; Craighead, W. Edward
Abstract:
Published:
2019-04
Title:
Core Clerkship Grading: The Illusion of Objectivity
Authors:
Hauer, Karen E.; Lucey, Catherine R.
Abstract:
Core clerkship grading creates multiple challenges that produce high stress for medical students, interfere with learning, and create inequitable learning environments. Students and faculty alike succumb to the illusion of objectivity-that quantitative ratings converted to grades convey accurate measures of the complexity of clinical performance.Clerkship grading is the first high-stakes assessment within medical school and occurs just as students are newly immersed full-time in an environment in which patient care supersedes their needs as learners. Students earning high marks situate themselves to earn entry into competitive residency programs and selective specialties. However, there is no commonly accepted standard for how to assign clerkship grades, and the process is vulnerable to imprecision and bias. Rewarding learners for the speed with which they adapt inherently favors students who bring advantages acquired before medical school and discounts the goal of all learners achieving competence.The authors propose that, rather than focusing on assigning core clerkship grades, assessment of student performance should incorporate expert judgment of learning progress. Competency-based medical education is predicated on the articulation of stepwise expectations for learners, with the support and time allocated for each learner to meet those expectations. Concurrently, students should ideally review their own performance data with coaches to self-assess areas of relative strength and areas for further growth. Eliminating grades in favor of competency-based assessment for learning holds promise to engage learners in developing essential patient care and teamwork skills and to foster their development of lifelong learning habits.
Published:
2019-04
Title:
Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder
Authors:
Narendran, Rajesh; Tollefson, Savannah; Fasenmyer, Kelli; Paris, Jennifer; Himes, Michael L.; Lopresti, Brian; Ciccocioppo, Roberto; Mason, N. Scott
Abstract:
BACKGROUND: Posttraumatic stress disorder (PTSD) is a stress disorder that develops in only some individuals following a traumatic event. Data suggest that a substantial fraction of women recover after sexual violence. Thus, the investigation of stress and antistress neuropeptides in this sample has the potential to inform the neurochemistry of resilience following trauma. Nociceptin is an antistress neuropeptide in the brain that promotes resilience in animal models of PTSD. METHODS: [11C]NOP-1A positron emission tomography was used to measure the in vivo binding to nociceptin receptors in 18 college women who had experienced sexual violence irrespective of whether they met DSM-5 diagnostic criteria for PTSD. [11C]NOP-1A data from 18 healthy control subjects were also included to provide a contrast with the sexual violence group. [11C]NOP-1A total distribution volume (VT) in the regions of interest were measured with kinetic analysis using the arterial input function. The relationships between regional VT and Clinician-Administered PTSD Scale for DSM-5 total symptom and subscale severity were examined using correlational analyses. RESULTS: No differences in [11C]NOP-1A VT were noted between the sexual violence and control groups. VT in the midbrain and cerebellum were positively correlated with PTSD total symptom severity in the past month before positron emission tomography. Intrusion/re-experiencing and avoidance subscale symptoms drove this relationship. Stratification of subjects by a DSM-5 PTSD diagnosis and contrasting their VT with that in control subjects showed no group differences. CONCLUSIONS: Decreased midbrain and cerebellum nociceptin receptors are associated with less severe PTSD symptoms. Medications that target nociceptin should be explored to prevent and treat PTSD.
Published:
2019-04
Title:
Dietary Energy Restriction Ameliorates Cognitive Impairment in a Mouse Model of Traumatic Brain Injury
Authors:
Rubovitch, V.; Pharayra, A.; Har-Even, M.; Dvir, O.; Mattson, M. P.; Pick, C. G.
Abstract:
Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young people. It was previously reported that dietary restriction, by either intermittent fasting (IF) or daily caloric restriction (CR), could protect neurons against dysfunction and degeneration in animal models of stroke and Parkinson's disease. Recently, several studies have shown that the protein Sirtuin 1 (SIRT1) plays a significant role in the induced neuroprotection following dietary restriction. In the present study, we found a significant reduction of SIRT1 levels in the cortex and hippocampus in a mouse model of mild weight-drop closed head TBI. This reduction was prevented in mice maintained on IF (alternate day fasting) and CR initiated after the head trauma. Hippocampus-dependent learning and memory (measured using a novel object recognition test) was impaired 30 days post-injury in mice fed ad libitum, but not in mice in the IF and CR groups. These results suggest a clinical potential for IF and/or CR as an intervention to reduce brain damage and improve functional outcome in TBI patients.
Published:
2019-04
Title:
Dietary carbohydrate rather than protein intake drives colonic microbial fermentation during weight loss
Authors:
Gratz, S. W.; Hazim, S.; Richardson, A. J.; Scobbie, L.; Johnstone, A. M.; Fyfe, C.; Lobley, G. E.; Russell, W. R.; Holtrop, G.
Abstract:
Purpose: High protein weight loss diets are effective in aiding body weight management. However, high protein and low carbohydrate intakes can alter colonic fermentation profiles in humans and may impact on colonic health. This study aims to identify the most important dietary contributors to colonic fermentation during diet-controlled weight loss. Methods: Overweight or obese male volunteers (n = 18) consumed a body weight maintenance diet (fed at 1.5× basic metabolic rate, BMR) followed by three weight loss diets (fed at 1× BMR) for 10 days each in a cross-over design. Weight loss diets were designed as normal protein (NPWL, 15% of energy from protein, 55% from carbohydrate), normal protein enriched with free amino acids and moderate amounts of carbohydrate (NPAAWL, 15% of energy from protein, 15% from free AA, 40% from carbohydrate) or high protein containing moderate amounts of carbohydrate (HPWL, 30% of energy from protein, 40% from carbohydrate). Faecal samples collected at the end of each diet period were profiled for dietary metabolites using LC–MS/MS. Results: This study shows that the NPWL diet only induced very minor changes in the faecal metabolome, whereas NPAAWL and HPWL diets decreased carbohydrate-related metabolites (butyrate, ferulic acid) and increased protein-related metabolites. Most faecal metabolites were correlated with dietary carbohydrate and not protein intake. Conclusion: This study demonstrates that dietary carbohydrate is the main driver of colonic fermentation in humans and that a balance between dietary carbohydrate and protein should be maintained when designing safe, effective and healthy weight loss diets.
Published:
2019-04
Title:
Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study
Authors:
Vitellio, Paola; Celano, Giuseppe; Bonfrate, Leonilde; Gobbetti, Marco; Portincasa, Piero; De Angelis, Maria
Abstract:
Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.
Published:
2019-04
Title:
Epidemiology of Prostate Cancer
Authors:
Rawla, Prashanth
Abstract:
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Prostate cancer may be asymptomatic at the early stage and often has an indolent course that may require only active surveillance. Based on GLOBOCAN 2018 estimates, 1,276,106 new cases of prostate cancer were reported worldwide in 2018, with higher prevalence in the developed countries. Differences in the incidence rates worldwide reflect differences in the use of diagnostic testing. Prostate cancer incidence and mortality rates are strongly related to the age with the highest incidence being seen in elderly men (> 65 years of age). African-American men have the highest incidence rates and more aggressive type of prostate cancer compared to White men. There is no evidence yet on how to prevent prostate cancer; however, it is possible to lower the risk by limiting high-fat foods, increasing the intake of vegetables and fruits and performing more exercise. Screening is highly recommended at age 45 for men with familial history and African-American men. Up-to-date statistics on prostate cancer occurrence and outcomes along with a better understanding of the etiology and causative risk factors are essential for the primary prevention of this disease.
Published:
2019-04
Title:
Faculty Development for Teaching Faculty in Psychiatry: Where We Are and What We Need
Authors:
De Golia, Sallie G.; Cagande, Consuelo C.; Ahn, Mary S.; Cullins, Lisa M.; Walaszek, Art; Cowley, Deborah S.
Abstract:
Objective A Faculty Development Task Force surveyed the American Association of Directors of Psychiatric Residency Training membership to assess faculty development for graduate medical education faculty in psychiatry departments and barriers to seeking graduate medical education careers. Methods An anonymous Survey Monkey survey was emailed to 722 American Association of Directors of Psychiatric Residency Training members. The survey included questions about demographics, the current state of faculty development offerings within the respondent’s psychiatry department and institution, and potential American Association of Directors of Psychiatric Residency Training faculty development programming. Two open-response questions targeted unmet faculty development needs and barriers to seeking a career in graduate medical education. Results were analyzed as frequencies and openended questions were coded by two independent coders. We limited our analysis to general psychiatry program director responses for questions regarding faculty development activities in an attempt to avoid multiple responses from a single department. Results Response rates were 21.0% overall and 30.4% for general program directors. General program directors reported that the most common existing departmental faculty development activities were educational grand rounds (58.7%), teaching workshops (55.6%), and funding for external conference attendance (52.4%). Of all survey respondents, 48.1% expressed the need for more protected time, 37.5% teaching skills workshops, and 16.3% mentorship. Lack of funding (56.9%) and time (53.9%) as well as excessive clinical demands (28.4%) were identified as the main barriers to seeking a career in graduate medical education. Conclusions Despite increasing faculty development efforts in psychiatry departments and institutions, real and significant unmet faculty development needs remain. Protected time remains a significant unmet need of teaching faculty which requires careful attention by departmental leadership.
Published:
2019-04
Title:
Is orthorexic behavior common in the general public? A large representative study in Germany
Authors:
Luck-Sikorski, Claudia; Jung, Franziska; Schlosser, Katharina; Riedel-Heller, Steffi G.
Abstract:
PURPOSE: Orthorexia is described as a strict, health-oriented eating pattern with clinically significant impairment in everyday life. Its prevalence varied widely in previous studies due to heterogenous assessment procedures. Determinants for the eating pattern and its prevalence have not been investigated in larger representative studies. METHODS: A population-based telephone survey in Germany was conducted in n = 1007 participants. The Dusseldorf Orthorexia Scale with a cut-off of 30 was used to assess orthorexic behavior. Determinants of orthorexia, including personal BMI, depressive symptoms Patient Health Questionnaire and socio-demographic variables were analyzed in multivariate regression. RESULTS: The prevalence of orthorexic behavior was 6.9%. A higher rate of orthorexic behavior was observed in heavier, less educated, vegetarian and more depressed participants; in multivariate analysis only associations to lower educational attainment, a vegetarian diet and depressive symptoms remained. No gender or age differences were observed. CONCLUSIONS: The study results show that orthorexic behavior may indeed by associated with significant strain and psychological distress. Current debates on the criteria of clinical significance of orthorexic behavior call for new instruments and further investigations, to elicit the prevalence of people with orthorexic behavior that classifies as a pathological eating disorder. LEVEL OF EVIDENCE: Level V: descriptive study.
Published:
2019-04
Title:
Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. [Review]
Authors:
Bolla, Andrea Mario; Caretto, Amelia; Laurenzi, Andrea; Scavini, Marina; Piemonti, Lorenzo
Abstract:
Low-carb and ketogenic diets are popular among clinicians and patients, but the appropriateness of reducing carbohydrates intake in obese patients and in patients with diabetes is still debated. Studies in the literature are indeed controversial, possibly because these diets are generally poorly defined; this, together with the intrinsic complexity of dietary interventions, makes it difficult to compare results from different studies. Despite the evidence that reducing carbohydrates intake lowers body weight and, in patients with type 2 diabetes, improves glucose control, few data are available about sustainability, safety and efficacy in the long-term. In this review we explored the possible role of low-carb and ketogenic diets in the pathogenesis and management of type 2 diabetes and obesity. Furthermore, we also reviewed evidence of carbohydrates restriction in both pathogenesis of type 1 diabetes, through gut microbiota modification, and treatment of type 1 diabetes, addressing the legitimate concerns about the use of such diets in patients who are ketosis-prone and often have not completed their growth.
Published:
2019-04
Title:
Major Depressive Disorder in Medical Illness: A Review of Assessment, Prevalence, and Treatment Options
Authors:
Thom, Robyn; Silbersweig, David A.; Boland, Robert J.
Abstract:
Major depression, as well as other depressive disorders, is commonly comorbid with other medical illnesses, particularly chronic and systemic medical illnesses. The co-occurrence of the disorders is so common that it challenges our notions of the meaning of comorbidity and our desire to neatly separate psychiatric and medical illnesses. The overlap between symptoms of physical illness and the neurovegetative symptoms of major depression and the initial normative emotional response to physical illness add to the challenge of accurate diagnosis and timely treatment of depression in the medically ill. We review the literature on the comorbidity of depression and the various medical illnesses, including diagnostic and treatment approaches. The differential diagnosis for major depression among medically ill patients should include delirium and medication-induced symptoms. We suggest that major depression itself may be best conceptualized as a systemic illness whose pathophysiology overlaps with other systemic medical illnesses. The initial treatment strategies for major depression in medical illness are like those for the general population; however, the comorbid medical illnesses may interfere with remission. To illustrate these points, we describe a patient with clinical characteristics covered in this review who experienced major depression as well as several chronic illnesses, including hypersensitivity pneumonitis, multiple sclerosis, chronic pain due to degenerative joint disease, and diabetes mellitus.
Published:
2019-04
Title:
Mandible strength and geometry in relation to bite force: a study in three caviomorph rodents
Authors:
Buezas, Guido N.; Becerra, Federico; Echeverria, Alejandra I.; Cisilino, Adrian; Vassallo, Aldo I.
Abstract:
The monophyletic group Caviomorpha constitutes the most diverse rodent clade in terms of locomotion, ecology and diet. Caviomorph species show considerable variation in cranio-mandibular morphology that has been linked to the differences in toughness of dietary items and other behaviors, such as chisel-tooth digging. This work assesses the structural strength of the mandible of three caviomorph species that show remarkable differences in ecology, behavior and bite force: Chinchilla lanigera (a surface-dwelling species), Octodon degus (a semi-fossorial species) and Ctenomys talarum (a subterranean species). Finite element (FE) models of the mandibles are used to predict the stresses they withstand during incisor biting; the results are related to in vivo bite forces and interspecific variations in the mandibular geometries. The study concludes that the mandible of C. talarum is better able to withstand strong incisor bites. Its powerful adducting musculature is consistent with the notorious lateral expansion of the angular process and the masseteric crest, and the enhanced cortical bone thickness. Although it has a relatively low bite force, the mandible of O. degus also shows a good performance for mid-to-strong incisor biting, in contrast to that of C. lanigera, which exhibits, from a mechanical point of view, the worst performance. The mandibles of C. talarum and O. degus appear to be better suited to withstand stronger reaction forces from incisor biting, which is consistent with their closer phylogenetic affinity and shared digging behaviors. The contrast between the low in vivo bite force of C. lanigera and the relatively high estimations that result from the models suggests that its adductor musculature could play significant roles in functions other than incisor biting.
Published:
2019-04
Title:
New windows into the brain: Central nervous system-derived extracellular vesicles in blood
Authors:
Shi, Min; Sheng, Lifu; Stewart, Tessandra; Zabetian, Cyrus P.; Zhang, Jing
Abstract:
Extracellular vesicles (EVs), including exosomes and (shedding) microvesicles, are released by nearly all cell types and carry a cargo of proteins and nucleic acids that varies by the cell of origin. They are thought to play critical roles in normal central nervous system (CNS) function and neurological disorders. A recently revealed key characteristic of EVs is that they may travel between the CNS and peripheral circulation. This property has led to intense interest in how EVs might serve as a vehicle for toxic protein clearance and as a readily accessible source of biomarkers for CNS disorders. Furthermore, by bypassing the blood-brain barrier, modified EVs could serve as a unique drug delivery system that targets specific neuronal populations. Further work is necessary to develop and optimize techniques that enable high-yield capture of relevant EV populations, analyze individual EVs and their cargos, and validate preliminary results of EV-derived biomarkers in independent cohorts.
Published:
2019-04
Title:
Redox Systems Biology of Nutrition and Oxidative Stress
Authors:
Dennis, Kristine K; Go, Young-Mi; Jones, Dean P
Abstract:
Diet and nutrition contribute to both beneficial and harmful aspects of oxidative processes. The harmful processes, termed oxidative stress, occur with many human diseases. Major advances in understanding oxidative stress and nutrition have occurred with broad characterization of dietary oxidants and antioxidants, and with mechanistic studies showing antioxidant efficacy. However, randomized controlled trials in humans with free-radical-scavenging antioxidants and the glutathione precursor N-acetylcysteine have provided limited or inconsistent evidence for health benefits. This, combined with emerging redox theory, indicates that holistic models are needed to understand the interplay of nutrition and oxidative stress. The purpose of this article is to highlight how recent advances in redox theory and the development of new omics tools and data-driven approaches provide a framework for future nutrition and oxidative stress research. Here we describe why a holistic approach is needed to understand the impact of nutrition on oxidative stress and how recent advances in omics and data analysis methods are viable tools for systems nutrition approaches. Based on the extensive research on glutathione and related thiol antioxidant systems, we summarize the advancing framework for diet and oxidative stress in which antioxidant systems are a component of a larger redox network that serves as a responsive interface between the environment and an individual. The feasibility for redox network analysis has been established by experimental models in which dietary factors are systematically varied and oxidative stress markers are linked through integrated omics (metabolome, transcriptome, proteome). With this framework, integrated redox network models will support optimization of diet to protect against oxidative stress and disease.
Published:
2019-04
Title:
The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease
Authors:
Rebholz, Casey M; Surapaneni, Aditya; Levey, Andrew S; Sarnak, Mark J; Inker, Lesley A; Appel, Lawrence J; Coresh, Josef; Grams, Morgan E
Abstract:
Background: Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables.Methods: We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease (MDRD, n = 356) study. Multivariable linear regression was used to assess the cross-sectional association between serum metabolites whose identity was known (outcome) and dietary acid load (exposure), estimated with net endogenous acid production (NEAP) based on 24-h urine urea nitrogen and potassium, and adjusted for age, sex, race, randomization group, measured glomerular filtration rate, log-transformed urine protein-to-creatinine ratio, history of cardiovascular disease, BMI, and smoking status.Results: Out of the 757 known, nondrug metabolites identified in AASK, 26 were significantly associated with NEAP at the Bonferroni threshold for significance (P < 6.6 × 10-5). Twenty-three of the 26 metabolites were also identified in the MDRD study, and 13 of the 23 (57%) were significantly associated with NEAP (P
Published:
2019-04
Title:
The brown adipose tissue glucagon receptor is functional but not essential for control of energy homeostasis in mice
Authors:
Beaudry, Jacqueline L.; Kaur, Kiran Deep; Varin, Elodie M.; Baggio, Laurie L.; Cao, Xiemin; Mulvihill, Erin E.; Stern, Jennifer H.; Campbell, Jonathan E.; Scherer, Phillip E.; Drucker, Daniel J.
Abstract:
Published:
2019-04
Title:
Vascular Endothelial Growth Factor–D (VEGF-D) Overexpression and Lymphatic Expansion in Murine Adipose Tissue Improves Metabolism in Obesity
Authors:
Chakraborty, Adri; Barajas, Sheridan; Lammoglia, Gabriela M.; Reyna, Andrea J.; Morley, Thomas S.; Johnson, Joshua A.; Scherer, Philipp E.; Rutkowski, Joseph M.
Abstract:
Published:
2019-04
Title:
An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition
Authors:
Mattson, Mark P.
Abstract:
Brain structures and neuronal networks that mediate spatial navigation, decision-making, sociality, and creativity evolved, in part, to enable success in food acquisition. Here, I discuss evidence suggesting that the reason that overconsumption of energy-rich foods negatively impacts cognition is that signaling pathways that evolved to respond adaptively to food scarcity are relatively disengaged in the setting of continuous food availability. Obesity impairs cognition and increases the risk for some psychiatric disorders and dementias. Moreover, maternal and paternal obesity predispose offspring to poor cognitive outcomes by epigenetic molecular mechanisms. Neural signaling pathways that evolved to bolster cognition in settings of food insecurity can be stimulated by intermittent fasting and exercise to support the cognitive health of current and future generations.
Published:
2019-03
Title:
Clinical Practice Recommendations for Continuation and Maintenance Electroconvulsive Therapy for Depression: Outcomes From a Review of the Evidence and a Consensus Workshop Held in Australia in May 2017
Authors:
Gill, Shane P.; Kellner, Charles H.
Abstract:
Objectives: Continuation or maintenance electroconvulsive therapy (ECT) is often provided as a strategy for post-ECT relapse prevention. However, the evidence has been insufficient until recently to produce clear consensus on what best practice maintenance ECT (mECT) should be like in a real world ECT clinical service. The aims of this article are to help fill this gap and to provide a comprehensive set of practical, clinically-based recommendations for ECT clinicians and services. Methods: Aworkshop was held at the Royal Australian and New Zealand College of Psychiatry Congress in Adelaide on April 30, 2017. This workshop was hosted by the authors. After a presentation on the state of the evidence, the 30 participants were asked to work in small groups to develop consensus recommendations on different aspects of mECT. These were then collated into one comprehensive set of clinical recommendations for the practice of mECT. Results: These best practice recommendations are set out below. Conclusions: These recommendations will assist ECT services and clinicians to provide best practice mECT according to currently available evidence.
Published:
2019-03
Title:
Editorial Commentary: There's More Meat on That Bone! Labral Hypertrophy Normalizes Femoral Head Coverage in Dysplastic Hips
Authors:
Petersen, Brian D
Abstract:
The size of the acetabular labrum has been shown to be larger in patients with acetabular hip dysplasia and smaller in patients with acetabular overcoverage. Compensatory morphologic changes to the acetabular labrum are potentially useful as an imaging biomarker of hip stability, and with additional future outcomes investigation, imaging measures may be used to guide the type and extent of hip preservation surgery.
Published:
2019-03
Title:
Effect of metformin treatment in patients with type 2 diabetes with respect to glyoxalase 1 activity in atherosclerotic lesions
Authors:
Peters, Andreas S.; Wortmann, Markus; Fleming, Thomas H.; Nawroth, Peter P.; Bruckner, Thomas; Böckler, Dittmar; Hakimi, Maani
Abstract:
BACKGROUND: The enzyme glyoxalase1 (GLO1) is the main opponent in the degradation of the reactive metabolite methylglyoxal (MG), which by glycation of macromolecules is involved in atherogenesis. Reduced GLO1-activity in atherosclerotic tissue is known to be associated with diabetes. It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells. The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes. PATIENTS AND METHODS: Patients with type 2 diabetes and carotid artery disease were included into the study prospectively. Type of diabetes-medication was documented upon admission along with demographic and clinical history. Using shock frozen endarterectomy-derived carotid artery plaques, GLO1-activity as well as protein expression was measured by a spectophotometric assay and western-blotting respectively. RESULTS: 33 patients (76 % male, mean age 71 years) were included into the study and were divided according to treatment with metformin or not (15 vs. 18 patients). GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056). Normalisation of GLO1-activity onto GLO1-expression level lead to a significant increase by more than twofold (8.48 vs. 3.85, p = 0.044) while GLO1-protein levels did not differ significantly. GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment. CONCLUSIONS: Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions. Regarding the macro- and microvascular complications in these patients further studies are needed to gain more insight into the effect of metformin on the GLO/MG system.
Published:
2019-03
Title:
Effectiveness and Cognitive Changes With Ultrabrief Right Unilateral and Other Forms of Electroconvulsive Therapy in the Treatment of Mania:
Authors:
Wong, Vincent Khung Hoon; Tor, Phern Chern; Martin, Donel M.; Mok, Yee Ming; Loo, Colleen
Abstract:
Objective: Electroconvulsive therapy (ECT) is an effective treatment in mania. However, there is little evidence regarding the use of ultrabrief right unilateral (RUL-UB) ECT in treatment of acute manic episodes. The aim of this study was to report on the effectiveness and cognitive profile of ECT in bipolar mania, including a sample who received RUL-UB ECT. Methods: This naturalistic study retrospectively collected data in 33 patients who received ECT with concurrent antipsychotics for mania between October 1, 2014, and July 30, 2016. Electroconvulsive therapy was given using RUL-UB, brief-pulse right unilateral, or brief-pulse bitemporal approaches, dosed according to the patient's seizure threshold. The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS) score, and the Montreal Cognitive Assessment (MoCA) were administered to patients before and after the ECT course. Results: For the whole sample, there was a significant improvement in BPRS (total score and manic subscale), YMRS, and MoCA total scores across the ECT treatment course. The overall BPRS response rate was 84%, and mean scores decreased from 42.1 (SD, 12.0) to 26.0 (SD, 4.0). The 13 patients who received RUL-UB ECT also showed significant improvement in BPRS, YMRS, and MoCA scores over the treatment course. Conclusions: Electroconvulsive therapy in general and also specifically RUL-UB ECT were effective in treating mania and also led to global cognitive improvement.
Published:
2019-03
Title:
Effectiveness of Electroconvulsive Therapy in Patients With Major Depressive Disorder and Comorbid Borderline Personality Disorder:
Authors:
Lee, James H.; Kung, Simon; Rasmussen, Keith G.; Palmer, Brian A.
Abstract:
Objective: Previous research suggests that electroconvulsive therapy (ECT)—the criterion standard for the treatment of severe depression—is not as effective when the patient has comorbid borderline personality disorder (BPD). The ECT outcomes of patients with and without BPD were compared in a retrospective chart review to test this claim. Methods: We enrolled 137 patients with a diagnosis of major depressive disorder who completed the McLean Screening Instrument for Borderline Personality Disorder. Twenty-nine patients had positive screening scores for BPD. The difference in Patient Health Questionnaire (PHQ-9) scores before and after ECT was compared between patients with and without BPD. Follow-up PHQ-9 scores determined after treatment were collected and analyzed. Results: Electroconvulsive therapy equally improved symptoms of depression as measured by PHQ-9 score in both patients who screened positive and patients who screened negative for BPD. No difference in the increase in PHQ-9 scores between these 2 groups was noted 1 month after treatment (P = 0.19). Conclusions: These data showed that a positive BPD screen does not necessarily predict a poorer response to ECT, nor does it predict greater symptom recurrence after ECT. This does not suggest that ECT is necessarily an appropriate treatment for major depressive disorder in patients with a comorbid BPD, given the limitations of screening instruments.
Published:
2019-03
Title:
Electroconvulsive therapy and later stroke in patients with affective disorders
Authors:
Rozing, Maarten Pieter; Jørgensen, Martin Balslev; Osler, Merete
Abstract:
The long-term effects of electroconvulsive therapy (ECT) on the risk of stroke are unknown. We examined the association between ECT and risk of incident or recurrent stroke. A cohort of 174 534 patients diagnosed with affective disorder between 2005 and 2016 in the Danish National Patient Registry were followed for stroke until November 2016. The association between ECT and stroke was analysed using Cox regression with multiple adjustment and propensity-score matching on sociodemographic and clinical variables. In 162 595 patients without previous stroke, 5781 (3.6%) were treated with ECT. The total number of patients developing stroke during follow-up was 3665, of whom 165 had been treated with ECT. In patients
Published:
2019-03
Title:
Food fortification and biofortification as potential strategies for prevention of vitamin D deficiency
Authors:
Guo, J.; Lovegrove, J. A.; Givens, D. I.
Abstract:
Hypovitaminosis D (vitamin D deficiency) is widespread throughout the world. The cutaneous production of vitamin D through sunlight can be limited by several factors (e.g. skin pigmentation, sunscreen usage and, increasingly, indoor lifestyle). Thus, diet has become an important strategy to increase vitamin D intake and status {blood 25‐hydroxyvitamin D [25(OH)D]}. However, there are a limited number of foods that naturally contain vitamin D, and concentrations can vary significantly between and within species. The need for vitamin D‐fortified foods (including via direct fortification and biofortification) to support the adequacy of vitamin D status is a corollary of several limitations to synthesise vitamin D from sunlight. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) can be found in some mushrooms and animal‐derived foods, respectively. Evidence has shown vitamin D3 is more effective than vitamin D2 at raising 25(OH)D blood concentrations. The vitamin D metabolite, 25(OH)D3, is present in animal‐derived foods (e.g. meat, eggs and fish), and several intervention trials have shown 25(OH)D3 to be more effective at raising blood 25(OH)D concentrations than vitamin D3. In addition, 25(OH)D3 supplements may prove to be preferable to vitamin D3 for patients with certain clinical conditions. However, there is limited evidence on the effects of 25(OH)D3‐fortified foods on human vitamin D status and health, both in the general population and patients with certain conditions, and long‐term randomised controlled trials are needed in this area.
Published:
2019-03
Title:
Genetics of Anxiety Disorders
Authors:
Meier, Sandra M.; Deckert, Jürgen
Abstract:
Purpose of Review Anxiety disorders are among the most common mental disorders with a lifetime prevalence of over 20%. Clinically, anxiety is not thought of as a homogenous disorder, but is subclassified in generalized, panic, and phobic anxiety disorder. Anxiety disorders are moderately heritable. This review will explore recent genetic and epigenetic approaches to anxiety disorders explaining differential susceptibility risk.
Published:
2019-03
Title:
Inter-relationship between diet, lifestyle habits, gut microflora, and the equol-producer phenotype: baseline findings from a placebo-controlled intervention trial
Authors:
Yoshikata, Remi; Myint, Khin Z.; Ohta, Hiroaki; Ishigaki, Yoko
Abstract:
Objective: Equol is an active metabolite of isoflavones produced by gut microbiota. It is beneficial to health; however, equol-producing ability varies greatly among individuals. These variations depend on the host's gut microbiota and lifestyle habits including diet. We investigated the relationship between the gut microbiota, lifestyle habits including diet, and equol-producing ability in postmenopausal Japanese women.Methods: We studied 58 postmenopausal Japanese women aged 48 to 69 years who visited the Sendai Medical Center in January, 2018. Self-administered questionnaires assessed their recent and remote food intake histories and lifestyle habits. Fecal microbiome analysis was performed using a next-generation sequencer. Urinary equol was measured using an immunochromatographic strip test. Women with urinary equol concentration >1.0 μM were defined as equol producers.Results: Equol-producing bacteria were identified in 97% (56) of women; however, only 13 (22%) were equol producers. Equol producers showed significantly higher microflora diversity (P = 0.002), and significantly different recent and remote food intake patterns compared with equol nonproducers. Higher consumption of foods such as meat, fish, soy, vegetables, and Japanese snacks positively affected microbial diversity and equol production, whereas a high intake of Ramen and smoking showed negative effects.Conclusion: Equol production might not depend on the quantity, but on the quality of equol-producing bacteria. High microbial diversity might enhance equol production. Increasing microbial diversity through healthy lifestyle habits and habitual consumption of a wide variety of foods might be useful to maintain a healthy gut environment for equol production.
Published:
2019-03
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