Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL.

OBJECTIVES: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. METHODS: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing. Analysis of covariances considering the covariates age, body mass index, sex, smoking, lithium and anticonvulsant intake were performed to test methylation differences between BD and controls. RESULTS: Methylation at cg05733463 of ARNTL was significantly higher in BD than in controls (F(1,209) = 44.500, P < .001). In contrast, methylation was significantly lower in BD at PS2_POS1 compared to controls (F(1,128) = 5.787, P = .018) and by trend at PS2_POS2 (F(1,128) = 3.033, P = .084) and POS7 (F(1,34) = 3.425, P = .073). CONCLUSIONS: Methylation of ARNTL differed significantly between BD and controls. Thus, our study suggests that altered epigenetic regulation of ARNTL might provide a mechanistic basis for better understanding circadian rhythms and mood swings in BD.

Dissimilar Pain of Primary Epiploic Appendagitis and Malabsorption.

Primary Epiploic Appendagitis (PEA) is a rare cause of acute or subacute abdominal complaints and non-migratory pain. Usually the diagnosis of PEA is made when Computed Tomography (CT) reveals characteristic figures. Nonspecific abdominal complaints including diffuse abdominal pain may be caused by carbohydrate and/or protein malabsorption. We report a case of a patient with PEA who recovered without medication or surgical treatment within a few days. Eight months later, he was diagnosed with lactose- and histamine malabsorption and Helicobacter pylori infection. The malabsorption was treated successfully with an individually-tailored diet free of culprit triggers and the Helicobacter pylori infection was eradicated. A localized non-migratory abdominal pain caused by PEA needs to be differentiated from nonspecific abdominal complaints due to malabsorption and Helicobacter pylori infection.

Mood Stabilizers, Oxidative Stress and Antioxidative Defense in Euthymia of Bipolar Disorder.

BACKGROUND: Hitherto literature indicates that mood stabilizers exert variable effects on oxidative and antioxidative systems, which are involved in the pathogenesis of Bipolar Disorder. Herein we primarily sought to characterize markers of peripheral oxidative stress during euthymia in adults with Bipolar Disorder under current intake of different mood stabilizers (lithium, anticonvulsants and atypical antipsychotics/AAPs). METHODS: Peripheral oxidative stress parameters (TBARS/Thiobarbituric acid-reactive-substances, MDA/ malondialdehyde and carbonyl proteins) and antioxidative markers (SOD/Cu/Zn superoxide dismutase, GST/glutathione Stransferase and TAC/total antioxidative capacity) were measured in serum of 115 euthymic bipolar individuals (50 females, 65 males; HAMD<11 and YMRS<8). Differences in (anti)oxidative markers between bipolar participants treated with different mood stabilizing medication were tested with MANCOVAS and ANCOVAS with SPSS.21. RESULTS: Bipolar individuals taking lithium had significantly lower oxidative parameters than test persons without lithium (multivariate effect for MDA and TBARS: F(2/182)= 3.956, p= 0.021; univariate effect for MDA: F(2/182)= 7.880, p= 0.006, Partial η2= 0.041). Subjects with AAPs had significantly higher MDA and TBARS levels compared to participants without AAPs (multivariate effect F(2/182)= 3.122, p= 0.046, Partial η2= 0.033). Patients taking anticonvulsants had significantly lower GST levels than patients without antiepileptic medication (F(1/165)= 4.501, p= 0.035, Partial η2= 0.027). CONCLUSION: Lithium taking participants had the lowest MDA and TBARS levels, while AAP taking test persons had high oxidative stress markers. The observed effects on oxidative markers may provide a mechanistic basis for understanding lithium's neuroprotective effects.

Significant decrease of subcutaneous body fat during tube-weaning from enteral feeding.

BACKGROUND: The aim of this paper was to evaluate anthropometry and subcutaneous body fat on long-term enterally-fed children during tube weaning through a prospective cohort study with a pre-post-test design. METHODS: The LIPOMETER, an optical device, was used to measure the thickness of subcutaneous adipose tissue (SAT) layers (in mm). The specification of 15 evenly-distributed body sites allows for a precise measurement of subcutaneous body fat distribution, known as subcutaneous adipose tissue topography (SAT-Top). Anthropometry and SAT-Top were determined in long-term enterally fed children in the pre- and post-tube weaning phase of a 3-week tube weaning program. The results of the SAT-Top measurements are presented on three levels: 15 body sites, four body regions and SAT-total. RESULTS: The sample size consisted of 30 long-term tube-fed children (13 girls and 17 boys). Both sexes demonstrated a clear decrease of anthropometry and subcutaneous body fat during tube weaning. Girls lost -26.1 mm, -30.7%, (P=0.002) of their initial fat mass and boys -12.5 mm, -18.4%, (P<0.001). In general, girls had thicker SAT layers in all SAT-Top measurements and a higher reduction of subcutaneous body fat during the intervention. At the end of the tube weaning program girls and boys demonstrated similar results of subcutaneous body fat on the three observed levels: 15 body sites, four body regions and SAT-total. Upon discharge, total subcutaneous body fat of girls and boys was 58.9 mm and 55.5 mm, respectively. CONCLUSION: This study presents a basic documentation of changes in anthropometry and subcutaneous body fat during tube weaning and could potentially be used to help create guidelines for safe tube weaning.

The Effectiveness of Visual Short-Time Neurofeedback on Brain Activity and Clinical Characteristics in Alcohol Use Disorders: Practical Issues and Results.

The present study was carried out to examine the efficacy of alpha/theta neurofeedback (NF) with a new visual paradigm in a cohort of alcohol use disordered (AUD) patients (n = 25) treated in an Austrian therapeutic community center. The experimental study design focused on changes in absolute and relative resting EEG band power as well as in clinical variables, including depression (Beck Depresion Inventory [BDI-V]), psychiatric symptoms (Brief Symptom Inventory [BSI], coping (Freiburg Questionnaire on Coping with Illness [FKV-lis]), psychotherapy motivation (Therapy Motivation Questionnaire [FPTM-23]), sense of coherence (Sense of Coherence Scale [SOC-13]), posttraumatic growth (Posttraumatic Growth Inventory [PPR]), and alcohol cravings (Alcohol Craving Questionnaire [ACQ]). For measuring training effects, participants were randomly allocated to 2 groups: an experimental group (EG, n = 13) and a control group (CG, n = 12). Patients in EG received 12 sessions of visual NF training over a period of 6 weeks to enhance alpha (8-12 Hz) and theta (4-7 Hz) frequency band power in addition to the standard treatment program of the rehabilitation center. Participants in CG received no additional NF intervention. The multivariate analysis of covariance (MANCOVA) showed a change by trend in absolute alpha and theta power in the EG. Even though no MANCOVA effects were found in the clinical scales, AUD patients reported increasing control of their brain activity during the course of NF. However, changes in several clinical scales (BDI-V, BSI, FKV-lis, PPR) from pre- to posttest were observed only in the EG contrary to the CG. The findings of this pilot study provide first evidence for the practicality and effectiveness of visual short-term NF as an additive intervention in the therapeutic community.

Co-occurrence of carbohydrate malabsorption and primary epiploic appendagitis.

Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen (H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis (PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with co-occurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA.

Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals.

Overweight and obesity differentially affect bipolar disorder (BD) and are associated with a poorer prognosis. Herein, we sought to evaluate body fat distribution in a well-characterized BD sample. Anthropometric measures (i.e., body mass index, waist-to-hip ratio, waist-to-height ratio, waist circumference, hip circumference, and lipometry) of 100 BD individuals were compared with data of 57 matched mentally healthy controls. Additionally, fasting serum parameters including metabolic parameters and monoamines were analyzed. Findings indicate that similar to US BD cohorts, Austrian patients exhibit an increased central body fat accumulation (i.e., higher subcutaneous adipose tissue at upper abdomen) accompanying with the harmful IDF-defined metabolic syndrome. In addition, positive associations between epinephrine as well as staging and fat parameters were detected.

Weight cycling in bipolar disorder.

BACKGROUND: An association between excess weight and/or weight fluctuations and cardiovascular morbidity and mortality is amply documented. Individuals with bipolar disorder (BD) are differentially affected by overweight/obesity, chaotic eating patterns (e.g., binge eating), as well as cardiovascular morbidity and mortality. Weight cycling (WCYC) is defined as a pattern of repetitive weight loss and gain. METHODS: We sought to determine the relationship between course of illness and BD and WCYC retrospectively as well whether these co-occurring phenotypes identify a biologically distinct subpopulation on the basis of having a unique inflammatory biomarker/biosignature profile. Sociodemographic, clinical, and inflammatory markers were gathered from a well-characterized cohort of actual euthymic adults with BD (n=101) and a healthy control group (n=48). RESULTS: Individuals with BD with a history of WCYC were provided evidence of a greater frequency of prior episodes (i.e., both manic and depressed), as well as of significantly higher levels of circulating IL-6 concentrations when compared to non-WCYC individuals with BD. The association persisted after adjusting for relevant covariates (e.g., BMI, age, number of prior episodes). LIMITATIONS: Include the small control group, differing medication status and that all data relies on personal information. Nevertheless we tried to verify all data as far as clinical disclosure was available. CONCLUSION: The results of this study indicate that adults with BD excessive in weight are not only more susceptible to a relapse-prone course of illness, but also are more likely to present with WCYC. The finding of elevated pro-inflammatory cytokines in this subpopulation may identify a separate subpopulation with greater susceptibility to cardiovascular disease. The overarching aim of personalized treatment and preventive strategies in BD begins with appropriate, empirically supported patient stratification. Our results provide preliminary support for stratifying BD cardiovascular risk on the basis of anthropometrics and WCYC.

Detecting body fat-A weighty problem BMI versus subcutaneous fat patterns in athletes and non-athletes.

We aimed to describe the relationship between BMI and the subcutaneous adipose tissue topography within young athletes and non-athletic controls, to comparatively evaluate the diagnostic powers of subcutaneous adipose tissue thicknesses at different body sites, furthermore to explore appropriate cut-offs to discriminate between athletes and controls. Measurements were determined in 64 males and 42 females, who were subsequently separated into two even groups (athletes and non-athletes). The optical device LIPOMETER was applied at standardised body sites to measure the thickness of subcutaneous adipose tissue layers. To calculate the power of the different body sites and the BMI to discriminate between athletes and non-athletes, receiver operating characteristic curve analysis was performed. In men, the neck (optimal cut-off value 2.3 mm) and trunk (optimal cut-off value 15.5 mm) provided the strongest discrimination power: with 90.6% (58 of 64) of the subjects being correctly classified into athletes or non-athletes. Discrimination power of the BMI values was 64.1% (41 of 64 were correctly classified). In women, the upper back (optimal cut-off value 3.3 mm) and arms (optimal cut-off value 15.9 mm) provided the strongest discrimination power with 88.1% (37 of 42 being correctly classified). When using BMI to discriminate between athletes and non-athletes only 52.4% (22 of 42) were correctly classified. These results suggest that compared to BMI levels, subcutaneous fat patterns are a more accurate way of discriminating between athletes and non-athletes. In particular the neck and the trunk compartment in men and the upper back and arms compartment in women, were the best sites to discriminate between young athletes and non-athletes on the basis of their fat patterns.

Normal weight estonian prepubertal boys show a more cardiovascular-risk-associated adipose tissue distribution than austrian counterparts.

Objective. Risk phenotypes for cardiovascular disease (CVD) differ markedly between countries, like the reported high difference in CVD mortality in Austria and Estonia. Hitherto, the goal of this study was to find out risk profiles in body fat distribution yet present in childhood, paving the way for later clinical end points. Methods. he subcutaneous adipose tissue (SAT) distribution patterns in 553 Austrian (A) and Estonian (E) clinically healthy normal weight boys aged 11.1 (±0.8) years were analysed. We applied the patented optical device Lipometer which determines the individual subcutaneous adipose tissue topography (SAT-Top). Results. Total body fat did not differ significantly between E and A boys. A discriminant analysis using all Lipometer data, BMI, and the total body fat (TBF) yielded 84.6% of the boys correctly classified in Estonians and Austrians by 9 body sites. A factor analysis identified the SAT distribution of E as critically similar to male adult patients with coronary heart disease (CHD). Conclusions. We show in normal weight Estonian boys a highly significant decreased fat accumulation on the lower body site compared to age matched Austrian males. This SAT-Top phenotype may play an important role for the increased cardiovascular risk seen in the Estonian population.

Improvement of Cerebral Hypoperfusion with Levothyroxine Therapy in Hashimoto's Encephalopathy Demonstrated by (99m)Tc-HMPAO-SPECT.

BACKGROUND: Hashimoto's encephalopathy (HE) is a rare immune-mediated encephalopathy associated with autoimmune Hashimoto's thyroiditis. OBJECTIVES AND METHODS: We report on a patient with HE and significant clinical improvement correlating with an increase in cerebral blood flow demonstrated by hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). HMPAO-SPECT was performed with 740 MBq of technetium-99m-HMPAO. To demonstrate the improvement in regional cerebral blood flow, individual regions of interest were drawn around visually diminished HMPAO uptake, the lesion to reference region ratio was calculated and transverse section images and semi-quantitative measurements were performed. RESULTS: We show a 5-year follow-up with significant clinical improvement, a 10-fold reduction in autoantibodies to thyroid peroxidase and an approximately 20% improvement in cerebral blood flow with HMPAO-SPECT. CONCLUSION: Adequate levothyroxine treatment achieving and maintaining euthyroidism should be considered as therapy to lower autoantibodies and improve clinical outcome in patients with Hashimoto's thyroiditis and encephalopathy.

Primary epiploic appendagitis and successful outpatient management.

BACKGROUND: Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or subacute complaints. Diagnosis of PEA is made with ultrasonography (US) or when computed tomography (CT) reveals a characteristic lesion. CASE REPORT: We report on two patients with PEA. In one patient PEA was first seen with US and confirmed with contrast enhanced CT, and in the second patient CT without contrast enhancement demonstrated PEA. In both patients an outpatient recovery with conservative non-surgical treatment is described. CONCLUSIONS: Medical personnel should be aware of this rare disease, which mimics many other intra-abdominal acute and subacute conditions. A correct diagnosis of PEA with imaging procedures enables conservative and successful outpatient management avoiding unnecessary surgical intervention and additional costs.

Variance in the acute inflammatory response to prolonged cycling is linked to exercise intensity.

This study investigated the influence of age, body composition, physical fitness, training volume and intensity, and underlying systemic inflammation on exercise-induced inflammation and innate immune function in a heterogeneous group of cyclists. Subjects included 31 male cyclists (mean ± standard deviation, age 38.8 ± 10.6 years, body fat 17.8%± 5.6%, VO(2max) 55.8 ± 8.4 mL kg(-1) min(-1)) who cycled for 1.75 h at 60% watts(max) followed by a 10-km time trial (18.3 ± 0.3 min). Blood samples were collected pre-, post-, and 1-h-postexercise, and analyzed for WBCs, 9 cytokines [interleukin (IL)-6, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1ß, IL-2, IL-8, IL-10, and IL-12p70], and granulocyte and monocyte phagocytosis (GR-PHAG and MO-PHAG) and oxidative burst activity (GR-OBA and MO-OBA). Exercise-induced changes varied widely, with significant increases measured for 8 of 9 cytokines, GR-PHAG (mean change 99%) (95% confidence limits, 69%, 128%) and MO-PHAG (43%) (28%, 58%), and WBC (160%) (133%, 187%), and decreases for GR-OBA (-30%) (-43%,-16%) and MO-OBA (-23%) (-36%,-10%). Correlation and stepwise regression analysis revealed that changes in these variables were not related to age, body fat percentage, VO(2max), training volume, or pre-exercise C-reactive protein. Performance measures, specifically the average heart rate and rating of perceived exertion, were correlated with changes in several variables, including IL-8 (r=0.68 and 0.67, respectively, P<0.001) and IL-6 (r=0.51, P=0.004, and r=0.46, P=0.011, respectively). In summary, variance in exercise-induced inflammation and innate immunity in male cyclists in response to 2 h of endurance exercise is best explained by exercise intensity.

The acute effect of ingesting a quercetin-based supplement on exercise-induced inflammation and immune changes in runners.

This study tested the acute anti-inflammatory and immune-modulating influence of a quercetin-based supplement consumed by endurance athletes 15 min before an intense 2-hr run. In this randomized, crossover study, 20 runners (11 men, 9 women, age 38.4 ± 2.1 yr) completed two 2-hr treadmill runs at 70% VO(2max) (3 wk apart). Subjects ingested either 4 quercetin-based chews (Q-chew) or placebo chews (PL) 15 min before the runs. The 4 Q-chews provided 1,000 mg quercetin, 120 mg epigallocatechin 3-gallate, 400 mg isoquercetin, 400 mg each eicosapentaenoic acid and docosahexaenoic acid, 1,000 mg vitamin C, and 40 mg niacinamide. Subjects provided blood samples 30 min before, immediately after, and 1 hr postexercise and were analyzed for plasma quercetin, total blood leukocytes (WBC), C-reactive protein (CRP), 9 cytokines (IL-6, TNFα, GM-CSF, IFNγ, IL-1ß, IL-2, IL-8, IL-10, and IL-12p70), granulocyte (GR) and monocyte (MO) phagocytosis (PHAG), and oxidative-burst activity (OBA). Plasma quercetin increased from 80.0 ± 26.0 µg/L to 6,337 ± 414 µg/L immediately postexercise and 4,324 ± 310 µg/L 1 hr postexercise after ingestion of Q-chews, compared with no change in PL (p < .001). Exercise caused significant increases in, CRP, GM-CSF, IL-10, IL-1ß, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG and decreases in GR-OBA and MO-OBA, but no differences in the pattern of change were measured between Q-chew and PL trials. Acute ingestion of Q-chews 15 min before heavy exertion caused a strong increase in plasma quercetin levels but did not counter postexercise inflammation or immune changes relative to placebo.

Decrease of total subcutaneous adipose tissue from infancy to childhood.

OBJECTIVES: The observation and research of body composition is a topic of present interest. For the assessment of health and variables influencing growth and nutrition, it is of utmost interest to focus on the population of young children. SUBJECTS AND METHODS: The measurements of subcutaneous body fat distribution in a sample of clinically healthy children ages 0 to 7 years were examined. The optical device LIPOMETER was applied to measure the thickness of subcutaneous adipose tissue layers (in millimeters) at 15 well-defined body sites. This set of measurement points defines the subcutaneous adipose tissue topography. In the present study, subcutaneous adipose tissue topography was determined in 275 healthy children (128 girls and 147 boys) divided into 3 age groups. RESULTS: The results of the measurements are presented in 3 levels: total subcutaneous adipose tissue, 4 body regions, and 15 body sites. Our results show a clear physiological decrease in subcutaneous body fat in boys (-43.8%) and girls (-39.8%). One interesting finding was that the decrease occurs mainly in the trunk, abdomen, and lower extremities, whereas the body fat distribution of the upper extremities did not differ. Furthermore, slight subcutaneous adipose tissue topography differences between both sexes were found. CONCLUSIONS: The present study provides basic documentation of subcutaneous adipose tissue topography in healthy children ages 0 to 7 years. An accurate description of subcutaneous adipose tissue topography in healthy subjects could help to characterize various diseases in relation to overnutrition and malnutrition throughout childhood.

Insights into epiploic appendagitis.

Epiploic appendagitis is a rare cause of abdominal pain. Diagnosis of epiploic appendagitis, although infrequent, is easily made with CT or ultrasonography in experienced hands. As reported in the literature, most patients with primary epiploic appendagitis are treated conservatively without surgery, with or without anti-inflammatory drugs. A small number of patients are treated with antibiotics and some patients require surgical intervention to ensure therapeutic success. Symptoms of primary epiploic appendagitis usually resolve with or without treatment within a few days. A correct diagnosis of epiploic appendagitis with imaging procedures enables conservative and successful outpatient management of the condition and avoids unnecessary surgical intervention and associated additional health-care costs. Gastroenterologists and all medical personnel should be aware of this rare disease, which mimics many other intra-abdominal acute and subacute conditions, such as diverticulitis, cholecystitis and appendicitis. This article reviews epiploic appendagitis and includes discussion of clinical findings, pathophysiology, diagnosis and therapeutic possibilities.

Patent abdominal subcutaneous veins caused by congenital absence of the inferior vena cava: a case report.

INTRODUCTION: Patent paraumbilical and abdominal subcutaneous veins are found frequently as collaterals in patients due to portal hypertension mainly in liver cirrhosis. CASE PRESENTATION: For evaluation of portal hypertension in a 72-year-old Caucasian man without liver cirrhosis, magnetic resonance imaging with gadolinium contrast-enhancement was performed and demonstrated a missing inferior vena cava. A blood return from the lower extremities was shown through enlarged collateral veins of the abdominal wall, vena azygos and hemiazygos continuation, and multiple liver veins emptying into the right cardiac atrium. We describe a rare case of abdominal subcutaneous wall veins as collaterals caused by a congenitally absent infrarenal inferior vena cava with preservation of a hypoplastic suprarenal segment. CONCLUSION: Knowledge of these congenital variations can be of clinical importance and it is imperative for the reporting radiologist to identify these anomalies as they can have a significant impact on the clinical management of the patient.