Metabolic Irregularities Research Articles

Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats

Hepatocellular carcinoma (HCC) is one of the world’s most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.

Immunometabolism: An Emerging Target for Immunotherapies to Treat Rheumatoid Arthritis

Abstract An increasing number of findings highlight the fundamental role of metabolism in autoimmunity. This growing recognition of metabolic irregularities being a factor of immune dysregulation in autoimmunity has provided novel therapeutic opportunities. Although there have been advancements in the field of immunometabolism, it is important to note that strategies to engineer the immune system can also be utilized to modulate immunometabolism of specific immune cells that are involved in autoimmune rheumatoid arthritis (RA). Herein, we review the metabolic heterogeneity within RA, and discuss the potential therapies based on immunometabolism and immunoengineering concepts that may reinstate immune tolerance by targeting the metabolic irregularity within specific immune cells involved in the pathogenesis of RA.

Development and organoleptic evaluation of herbal mixture for prevention of Metabolic Syndrome

Metabolic syndrome describes a group of metabolic irregularities that occur together in an individual. The number of individuals diagnosed with metabolic syndrome has risen dramatically in recent years. Metabolic syndrome significantly raises the risk of developing cardiovascular disease and type2 diabetes mellitus, obesity, and hypertension. Hence, the prevention of metabolic syndrome is need of the time. Therefore, it is seen that people are looking forward for herbal and natural products to overcome this syndrome, in this regard herbal mixture was developed with natural herbs namely tulsi, ginger, cinnamon, stevia, cardamom, black peeper etc. Trend panel members on 9-point hedonic scale standardized the herbal mixture through sensory evaluation. The best-selected herbal mixture was on twenty percent.

The Potential Benefit of Monitoring Oxidative Stress and Inflammation in the Prevention of Non-Communicable Diseases (NCDs).

The significant increase in worldwide morbidity and mortality from non-communicable diseases (NCDs) indicates that the efficacy of existing strategies addressing this crisis may need improvement. Early identification of the metabolic irregularities associated with the disease process may be a key to developing early intervention strategies. Unhealthy lifestyle behaviours are well established drivers of the development of several NCDs, but the impact of such behaviours on health can vary considerably between individuals. How can it be determined if an individual’s unique set of lifestyle behaviours is producing disease? Accumulating evidence suggests that lifestyle-associated activation of oxidative and inflammatory processes is primary driver of the cell and tissue damage which underpins the development of NCDs. However, the benefit of monitoring subclinical inflammation and oxidative activity has not yet been established. After reviewing relevant studies in this context, we suggest that quantification of oxidative stress and inflammatory biomarkers during the disease-free prodromal stage of NCD development may have clinical relevance as a timely indicator of the presence of subclinical metabolic changes, in the individual, portending the development of disease. Monitoring markers of oxidative and inflammatory activity may therefore enable earlier and more efficient strategies to both prevent NCD development and/or monitor the effectiveness of treatment.

MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model

The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P<0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P<0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P<0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.

Implantable anti-angiogenic scaffolds for treatment of neovascular ocular pathologies.

The retinal physiology can accrue oxidative damage and inflammatory insults due to age and metabolic irregularities. Two notable diseases that involve retinal and choroidal neovascularization are proliferative diabetic retinopathy and wet age-related macular degeneration. Currently, these diseases are mainly treated with anti-VEGF drugs (VEGF = vascular endothelial growth factor), generally on a monthly dosage scheme. We discuss recent developments for the treatment of these diseases, including bioactive tissue-engineered materials, which may reduce frequency of dosage and propose a path forward for improving patient outcomes. Graphical abstract Development of materials for long-term intravitreal delivery for management of posterior segment diseases.

Programmed increases in LXRα induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity

ObjectivesPaternally inherited alterations in epigenetic programming are emerging as relevant factors in numerous disease states, including the growth and metabolic defects observed in fetal alcohol spectrum disorders. In rodents, chronic paternal alcohol use induces fetal growth restriction, as well as sex-specific alterations in insulin signaling and lipid homeostasis in the offspring. Based on previous studies, we hypothesized that the observed metabolic irregularities are the consequence of paternally inherited alterations liver x receptor (LXR) activity. MethodsMale offspring of alcohol-exposed sires were challenged with a high-fat diet and the molecular pathways controlling glucose and lipid homeostasis assayed for LXR-induced alterations. ResultsSimilar to findings in studies employing LXR agonists we found that the male offspring of alcohol-exposed sires display resistance to diet-induced obesity and improved glucose homeostasis when challenged with a high-fat diet. This improved metabolic adaptation is mediated by LXRα trans-repression of inflammatory cytokines, releasing IKKβ inhibition of the insulin signaling pathway. Interestingly, paternally programmed increases in LXRα expression are liver-specific and do not manifest in the pancreas or visceral fat. ConclusionsThese studies identify LXRα as a key mediator of the long-term metabolic alterations induced by preconception paternal alcohol use.

Tributyltin impacts in metabolic syndrome development through disruption of angiotensin II receptor signaling pathways in white adipose tissue from adult female rats

White adipose tissue (WAT) dysfunction and obesity are a consequence of a low-grade inflammation state. These WAT irregularities could result from abnormal metabolic renin-angiotensin system (RAS) control. Recently, tributyltin (TBT) has been found to play a critical role in these metabolic irregularities. However, TBT actions on the WAT-RAS functions are not currently well understood. In this study, we assessed whether TBT exposure resulted in metabolic syndrome (MetS) development and other metabolic complications as a result of abnormal modulation of WAT-RAS pathways. TBT (100 ng/kg/day) was administered to adult female Wistar rats, and their WAT morphophysiology and adipokine profiles were assessed. We further assessed the expression of Angiotensin-II receptor proteins (AT1R and AT2R) and proteins involved in downstream pathways mediating inflammation and adipogenesis modulation. TBT-exposed rats exhibited increases in body weight and adiposity. TBT rats present dyslipidemia and insulin resistance, suggesting MetS development. TBT promoted WAT inflammatory infiltration, AT1R protein overexpression and reduced Angiotensin-(1–7) expression. These TBT WAT abnormalities are reflected by NFκB activation, with higher adipokine levels (leptin, TNF-α and IL-6) and overexpression of AKT, ERK, P38, FAS and PPARγ protein. In vitro, TBT exposure stimulates lipid accumulation, reduces AT2R protein expression, and increases leptin, AKT and ERK protein expression in 3T3L1 cells. These findings suggest that TBT exposure participates in MetS development via the improper function of WAT-RAS metabolic control.

The impact of a therapeutic exercise intervention on depression and body self-image in HIV-positive women in sub-Saharan Africa.

IntroductionAttitudes, responses, and reactions of HIV-positive women in three sub-Saharan African regions toward a therapeutic exercise intervention, aimed to determine the presence of depression and low body self-image, were captured. This provided insight into body satisfaction and desire to exercise (Stage 1, n=60), body self-image and depression (Stage 2, n=60), and overall concerns around the often adverse side effects of antiretroviral treatment (ART). A program of therapeutic (specialty) exercise was developed for the experimental design (Stage 2), to quantify the psychological side effects of these variables.MethodologyStage 1 constituted a qualitative exploration into attitudes and perceptions around ART, toxicity, health concerns, metabolic irregularities (lipodystrophy), body shape and size dissatisfaction, and cultural attitudes toward exercise. This stage deployed brief informal face-to-face interviews, based on the World Health Organization (WHO)/United Nations Fund for Population Activities (UNFPA) AIDS Inventory, in three sub-Saharan African regions (including provincial and district hospitals, nongovernmental organizations, voluntary counseling and testing/HIV and testing centers, and primary care outpatient clinics). Stage 2 of the study comprised a quantitative experimental design, conducted on a sample of HIV-positive women (mean age=39.0 years; mean years on ART=5.5; 86% black) in three selected HIV outpatient clinics in Johannesburg, South Africa.Data analysisThe collated data sets from both stages of the research were presented, analyzed, and interpreted (thematic analyses [Stage 1] and statistical analyses [Stage 2]) using the body self-image questionnaire and Beck’s depression inventory.ResultsStage 1 outlined participants’ concerns and reports around 1) body shape and size, including long-term effects of ART and 2) attitudes toward exercise, as a function of HIV status. Stage 2 represented pre- and posttest statistics, showing low statistical means for both the experiment and the control groups, with statistical significance for four out of nine items of subscales of body self-image questionnaire.

Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiological functions, including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with Streptococcus pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AMs) from LysM-LepRb-KO mice in vitro and were associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results confirm our previous observations in leptin-deficient ( ob/ob) and fasted mice and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, is responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro 1 H-MRS study.

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy (1 H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.

Effect of rosuvastatin on dyslipidemia and other parameters associated with metabolic syndrome in Saudi patients.

Metabolic syndrome (MS) is a constellation of metabolic irregularities consisting of dyslipidemia, hypertension, hyperglycemia, chronic inflammatory, and hypercoagulable state predisposing to diabetes and cardiovascular events. Statins are first-line drugs to treat the associated atherogenic dyslipidemia. Effect of rosuvastatin on MS in Saudi patients was studied. Prospective, open label, randomized clinical study. Patients of either sex ≥18 years (n = 153) having MS as per modified National Cholesterol Education Program Adult Treatment Panel III criteria were prescribed rosuvastatin 10 mg OD for 24 weeks. Serum lipids, biochemical, clinical, and anthropometric parameters were studied before and after treatment. Statistical Package for Social Sciences version17 was used. Descriptive analysis was used for all variables and documented as mean ± SD. Normality checked by Shapiro-Wilk test, Kurtosis and Skewness Z-score, and visualization of histograms. Lipid levels and other parameters before and after treatment were evaluated by paired t-test for parametric data and Wilcoxon signed rank test for nonparametric data. Pre- and post-test values were correlated by Pearson's correlation coefficient. Multiple regression analysis was performed to see effect of other variables. Highly significant reduction was observed in low density lipoprotein cholesterol, total cholesterol, triglycerides; very low density lipoprotein cholesterol, non-high density lipoprotein cholesterol and atherosclerotic index with an elevation in high density lipoprotein cholesterol. A total of 86% patients reached low density lipoprotein cholesterol goal of ≤ 100 mg/dL. Beneficial response was observed on other associated parameters. There was strong correlation between pre- and post values. No significant effect was observed for any of the variables on cholesterol reduction. No serious/severe adverse effect was observed. Rosuvastatin markedly improved atherogenic dyslipidemia of MS.

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in the Diagnosis of Insulin Resistance and Prediabetes

Type 2 diabetes mellitus consists of metabolic disturbances characterised mainly characterized by hyperglycemia which usually result from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. In clinical practice its very difficult to establish how much part of this metabolic disturbances is due to lack of insulin and how much it is due to peripheral resistance to insulin. In many of the cases of type 2 diabetes mellitus metabolic syndrome is present for many years before development of full blown type 2 diabetes mellitus. Metabolic syndrome is a cluster of biochemical and physiological abnormalities associated with the development of cardiovascular disease and type 2 diabetes. Insulin resistance is one of the important determinants of development of metabolic syndrome and then type 2 diabetes mellitus. Insulin resistance is increasing in many parts of the world due to sedentary lifestyle, substance abuse, obesity and harmful food habits. Several methods including estimation of blood glucose and insulin levels during fasting or after oral or intravenous glucose overload, have been used. But due to the simplicity of its determination and calculation, insulin resistance assessment by the homeostatic assay (HOMA-IR) is becoming more popular technique in clinical practice as well as in various epidemiological studies. Unlike type 1 diabetes, type 2 diabetes mellitus is gradual in onset and its diagnosis is usually delayed for many years. Early treatment of hyperglycaemia, hyperlipidemia and other metabolic irregularities reduces the cardiovascular risk in these patients. But these benefits are usually denied to patients mainly due to delay in diagnosis. In fact many of the patients admitted with myocardial infarction are diagnosed with type 2 diabetes while in intensive care units for myocardial infarction. Unlike in type I diabetes mellitus where insulin is deficient consequent to immune mediated destruction of B cells in type 2 diabetes there is Insulin resistance. Insulin resistance in pre diabetic stages can be diagnosed by using various methods. Some simple methods, from which indices can be derived, have been validated. These indices are used depending upon whether they are to be used for epidemiological or clinical purposes. For clinical purposes Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment- insulin resistance (HOMA-IR) are most commonly used while for epidemiological purposes indices like Belfiore, Cederholm and Stumvoll index are suitable. This review explains the utility of homeostasis model assessment- insulin resistance (HOMA-IR) for the diagnosis of insulin resistance which is hallmark of pre diabetic state. The purpose of this paper was to review the current information

On-column trypsin digestion coupled with LC-MS/MS for quantification of apolipoproteins

Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application. SignificanceCurrently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins.

A Review of Sleep and Its Disorders in Patients with Parkinson's Disease in Relation to Various Brain Structures.

Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinson's disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease.

What Are the Potential Sites of Protein Arylation by N-Acetyl-p-benzoquinone Imine (NAPQI)?

Acetaminophen (paracetamol, APAP) is a safe and widely used analgesic medication when taken at therapeutic doses. However, APAP can cause potentially fatal hepatotoxicity when taken in overdose or in patients with metabolic irregularities. The production of the electrophilic and putatively toxic compound N-acetyl-p-benzoquinone imine (NAPQI), which cannot be efficiently detoxicated at high doses, is implicated in APAP toxicity. Numerous studies have identified that excess NAPQI can form covalent linkages to the thiol side chains of cysteine residues in proteins; however, the reactivity of NAPQI toward other amino acid side chains is largely unexplored. Here, we report a survey of the reactivity of NAPQI toward 11 N-acetyl amino acid methyl esters and four peptides. (1)H NMR analysis reveals that NAPQI forms covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. Analogous reaction products were observed when NAPQI was reacted with synthetic model peptides GAIL-X-GAILR for X = Cys, Met, Tyr, and Trp. Tandem mass spectrometry peptide sequencing showed that the NAPQI modification sites are located on the "X" residue in each case. However, when APAP and the GAIL-X-GAILR peptide were incubated with rat liver microsomes that contain many metabolic enzymes, NAPQI formed by oxidative metabolism reacted with GAIL-C-GAILR exclusively. For the peptides where X = Met, Tyr, and Trp, competing reactions between NAPQI and alternative nucleophiles precluded arylation of the target peptide by NAPQI. Although Cys residues are favorably targeted under these conditions, these data suggest that NAPQI can, in principle, also damage proteins at Met, Tyr, and Trp residues.

Serum metabolic profile predicts adverse central haemodynamics in patients with type 2 diabetes mellitus.

People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise. Serum samples from 39 participants with T2DM (62±9years; 46% male) and 39 controls (52±10years; 51% male) were analysed by liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis. Scores on principal components (PC) were used to assess relationships with haemodynamics including peripheral and central BP, central augmentation index (AIx) and central augmentation pressure (AP). Participants with T2DM had higher resting and exercise haemodynamics (peripheral and central BP, central AIx and central AP) compared to controls (p<0.05). PC that comprised of a signature metabolic pattern of T2DM was independently associated with resting and exercise central AIx and central AP (p<0.05). Serum metabolic profile was associated with central, but not peripheral, haemodynamics in T2DM participants, suggesting that metabolic irregularities may explain abnormal central haemodynamics in T2DM patients.

Description and pilot evaluation of the Metabolic Irregularities Narrowing down Device software: a case analysis of physician programming

BackgroundThere is a gap between the abilities and the everyday applications of Computerized Decision Support Systems (CDSSs). This gap is further exacerbated by the different ‘worlds’ between the software designers and the clinician end-users. Software programmers often lack clinical experience whereas practicing physicians lack skills in design and engineering.ObjectiveOur primary objective was to evaluate the performance of Metabolic Irregularities Narrowing down Device (MIND) intelligent medical calculator and differential diagnosis software through end-user surveys and discuss the roles of CDSS in the inpatient setting.SettingA tertiary care, teaching community hospital.Study participantsThirty-one responders answered the survey. Responders consisted of medical students, 24%; attending physicians, 16%, and residents, 60%.ResultsAbout 62.5% of the responders reported that MIND has the ability to potentially improve the quality of care, 20.8% were sure that MIND improves the quality of care, and only 4.2% of the responders felt that it does not improve the quality of care. Ninety-six percent of the responders felt that MIND definitely serves or has the potential to serve as a useful tool for medical students, and only 4% of the responders felt otherwise. Thirty-five percent of the responders rated the differential diagnosis list as excellent, 56% as good, 4% as fair, and 4% as poor.DiscussionMIND is a suggesting, interpreting, alerting, and diagnosing CDSS with good performance and end-user satisfaction. In the era of the electronic medical record, the ongoing development of efficient CDSS platforms should be carefully considered by practicing physicians and institutions.

Body composition, energy metabolism and endocrine variables in weight stable gastric‐bypass patients

BackgroundDespite the vast number of weight reducing operations performed, knowledge is still scarce regarding more long term metabolic alterations caused by the operations.Aim of the studyTo investigate the relationships between various body composition as well as endocrine variables in weight stable GBP operated patients.&gt;;Subjects and methodsFormerly GBP‐operated but weight stable women (16) and men (4)(Age 48.9 ± 8.1 y; BMI 33.1 ± 1.9 kg/m2) were admitted to the laboratory after an overnight fast. Respiratory exchange ratio (RER), body composition and several endocrine variables were analyzed. RER, waist circumference, DXA % fat, and insulin were used as main variables, and correlations were calculated with all other variables.ResultsMean fasting RER was high (0.88±0.07) and did not correlate with any other measured variable. Waist circumference was large (109±9 cm) and correlated only with BMI, RMR and fat mass. DXA % fat was high (43.8±5.6%) and correlated only with body composition values from BodPod, as well as RMR. Insulin was in the normal range (9.4±3.0 pU/L) and correlated with age, height/waist ratio, BMC, glucose and ApoB/ApoA1‐ratio.ConclusionThe correlations observed, or sometimes lack of correlation, also shows that despite being weight stable for at least three years, the GBP‐subjects still show some metabolic irregularities.

Proline Content in Rice Seedlings Grown Under Saline Conditions

Severe salinity stress induces numerous metabolic irregularities in plants. Researchers have assumed that a large (up to 100 times the normal) accumulation of free-proline is one of the most dramatic characteristics of the stress.