Publications by authors named "Sandra Holasek"

36 Publications

Free threonine in human breast milk is related to infant intestinal microbiota composition.

Amino Acids 2021 Sep 3. Epub 2021 Sep 3.

Institute of Midwifery, University of Applied Sciences JOANNEUM, Graz, Austria.

Background: Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in human milk is still poorly characterized with respect to its correlation to maternal serum levels and its physiological significance for the infant. Studies addressing the relation of human milk FAA to the infants' intestinal microbiota are still missing.

Methods: As part of a pilot study, maternal serum and breast milk FAA concentrations as well as infant intestinal microbiota (16S rRNA) were determined 2 months after birth. The study cohort consisted of 41 healthy mothers and their term delivered, healthy infants with normal birthweight. The relationship between maternal serum and milk FAA was determined by correlation analyses. Associations between (highly correlated) milk FAA and infant intestinal beta diversity were tested using PERMANOVA, LefSe and multivariate regression models adjusted for common confounders.

Results: Seven breast milk FAA correlated significantly with serum concentrations. One of these, threonine showed a negative association with abundance of members of the class Gammaproteobacteria (Radj = 17.1%, p = 0.006; β= - 0.441). In addition, on the level of families and genera, threonine explained 23.2% of variation of the relative abundance of Enterobacteriaceae (Radj; p = 0.001; β = - 0.504) and 11.1% of variability in the abundance of Escherichia/Shigella (Radj, p = 0.025; β  = - 0.368), when adjusted for confounders.

Conclusion: Our study is the first to suggest potential interactions between breast milk FAA and infant gut microbiota composition during early lactation. The results might be indicative of a potential protective role of threonine against members of the Enterobacteriaceae family in breast-fed infants. Still, results are based on correlation analyses and larger cohorts are needed to support the findings and elucidate possible underlying mechanisms to assess the complex interplay between breast milk FAA and infant intestinal microbiota in detail.
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http://dx.doi.org/10.1007/s00726-021-03057-wDOI Listing
September 2021

Bile acid-induced tissue factor activity in hepatocytes correlates with activation of farnesoid X receptor.

Lab Invest 2021 Oct 18;101(10):1394-1402. Epub 2021 Jun 18.

Division of General Paediatrics, Department of Paediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Bile acids (BA) have been found to promote coagulation by increasing tissue factor (TF) activity. The contribution of elevated BA levels and cholestasis to TF decryption within the liver parenchyma and the role of farnesoid X receptor (FXR) in this process remain unclear. We investigated the effects of BA on TF activity and thrombin generation in hepatocytes and correlated these effects with activation of FXR-dependent signaling and apoptosis. HepG2 cells and primary hepatocytes were incubated with chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), ursodeoxycholic acid (UCDA), or the synthetic FXR agonist GW4064 for 24 h. MTT tests demonstrated cell viability throughout experiments. TF activity was tested via factor Xa generation and thrombin generation was measured by calibrated automated thrombography. Increased TF activity alongside enhanced thrombin generation was observed with CDCA and GW4064 but not with GCDCA and UDCA. TF activity was substantially reduced when FXR activation was blocked with the antagonist DY 268. Quantitative polymerase chain reaction revealed upregulation of FXR target genes only by CDCA and GW4064. Western blot analysis and fluorescence microscopy showed no TF overexpression arguing for TF decryption. Caspase 3 activity measurements and flow cytometric analysis of Annexin V binding showed no signs of apoptosis. Long-term exposure of hepatocytes to nontoxic BA may cause intracellular FXR overstimulation, triggering TF decryption irrespective of the amphiphilic properties of BA. The effect of BA on TF activation correlates with the molecule's ability to enter the cells and activate FXR. TF decryption occurs independently of apoptotic mechanisms.
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http://dx.doi.org/10.1038/s41374-021-00628-zDOI Listing
October 2021

'An Apple a Day'?: Psychiatrists, Psychologists and Psychotherapists Report Poor Literacy for Nutritional Medicine: International Survey Spanning 52 Countries.

Nutrients 2021 Mar 2;13(3). Epub 2021 Mar 2.

Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Division of Immunology and Pathophysiology, Medical University of Graz, 8036 Graz, Austria.

Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the across 52 countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or prescribe specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population ( < 0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as 'very good.' Almost all (92.9%) stated they would like to expand their knowledge regarding 'Nutritional Psychiatry.' There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.
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http://dx.doi.org/10.3390/nu13030822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000813PMC
March 2021

Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

Biomedicines 2021 Feb 27;9(3). Epub 2021 Feb 27.

Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight ( = 26), overweight ( = 22), and obese ( = 20) women.

Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women.

Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.
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http://dx.doi.org/10.3390/biomedicines9030242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997277PMC
February 2021

Branched-chain amino acids are linked with iron metabolism.

Ann Transl Med 2020 Dec;8(23):1569

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Background: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are reported to influence erythropoiesis and the human iron status. Large study cohorts encompassing biomarkers of iron metabolism and BCAAs are still lacking.

Methods: We investigated potential interactions between blood concentrations of all three BCAAs valine, leucine and isoleucine and biomarkers of iron metabolism [i.e., hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), iron, transferrin, ferritin, transferrin saturation, soluble transferrin receptor (sTfR)] in 430 outpatients referred for a medical health check-up. Linear regression models were performed to assess possible associations between variables.

Results: All three BCAAs were positively correlated with Hb, ferritin and the sTfR (r-values: 0.145-0.382; P values: <0.001-0.003). The strongest correlation was observed between valine and Hb (r=0.382; P value <0.001). Linear regression models showed a statistically significant influence of all three BCAAs on Hb and ferritin (β-coefficients: 0.173-0.351; all P values: <0.001). Seventeen patients with anemia (4%) were found with significantly lower serum BCAA concentrations compared to 413 non-anemic individuals (P<0.05).

Conclusions: These data indicate a pathophysiological link between the three BCAAs valine, leucine and isoleucine and the human iron indicators Hb and ferritin. Further studies are needed to clarify the exact causal mechanisms of these findings.
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http://dx.doi.org/10.21037/atm-20-624aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791222PMC
December 2020

Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

EXCLI J 2020 28;19:1414-1422. Epub 2020 Oct 28.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values < 0.05, ρ = 0.176 and 0.136). Ninety-five individuals with a BDI score > 13 showed significantly higher IL-6 serum levels (1.7 [1.0 - 2.8] vs. 1.1 [0.8 - 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms.
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http://dx.doi.org/10.17179/excli2020-2940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726491PMC
October 2020

Distinct maternal amino acids and oxylipins predict infant fat mass and fat-free mass indices.

Arch Physiol Biochem 2020 Dec 7:1-12. Epub 2020 Dec 7.

Institute of Midwifery, University of Applied Sciences JOANNEUM, Graz, Austria.

Interested in maternal determinants of infant fat mass index (FMI) and fat-free mass index (FFMI), considered as predictors for later development of obesity, we analysed amino acids (AA) and oxylipins in maternal serum and breast milk (BM). FMI and FFMI were calculated in 47 term infants aged 4 months (T4). Serum AA were analysed in pregnancy (T1, T2) and 6-8 weeks postpartum (T3). At T3, AA and oxylipins were analysed in BM. Biomarker-index-associations were identified by regression analysis. Infant FMI (4.1 ± 1.31 kg/m; MW ± SD) was predicted by T2 proline ( adj.: 7.6%,  = .036) and T3 BM 11-hydroxy-eicosatetraenoic-acid (11-HETE) and 13-hydroxy-docosahexaenoic-acid (13-HDHA; together:35.5% adj.,  < .001). Maternal peripartum antibiotics (AB) emerged as confounders (+AB: 23.5% higher FMI;  = .025). Infant FFMI (12.1 ± 1.19 kg/m; MW ± SD) was predicted by histidine ( adj.: 14.5%,  < .001) and 17-HDHA (BM, adj.:19.3%,  < .001), determined at T3. Confirmed in a larger cohort, the parameters could elucidate connections between maternal metabolic status, nutrition, and infant body development.
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http://dx.doi.org/10.1080/13813455.2020.1846204DOI Listing
December 2020

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption.

Nutrients 2020 Nov 30;12(12). Epub 2020 Nov 30.

Division of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, A-8010 Graz, Austria.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal-Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption ( < 0.004 and < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal-Wallis test AUCs demonstrated a significant difference between all three groups ( = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.
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http://dx.doi.org/10.3390/nu12123690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761160PMC
November 2020

Diagnosis of hepatic nuclear factor 1A monogenic diabetes mellitus (HNF1A-MODY) impacts antihyperglycemic treatment.

Wien Klin Wochenschr 2021 Mar 27;133(5-6):241-244. Epub 2020 Nov 27.

Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, 8036, Graz, Austria.

Monogenic mutations of the hepatocyte nuclear factor 1 homeobox A maturity onset diabetes of the young (HNF1A-MODY) is characterized by early onset, typically before the age of 25 years. Patients are often not clinically recognized; however, the identification of HNF1A-MODY patients is crucial because they require different antihyperglycemic medical treatment than patients with type 1 or type 2 diabetes mellitus. We describe two adult patients with monogenic diabetes, both identified as HNF1A-MODY, genetically c.815G>A, p.Arg272His and c675delC, p.Ser225Argfs*8, respectively. They were misdiagnosed as having type 1 diabetes mellitus, and consequently, initiating insulin therapy led to hypoglycemia and unstable blood glucose control. Usually, sulfonylureas represent the basis of antidiabetic treatment in patients with HNF1A-MODY; however, all medical personnel involved in diabetes care should be aware of monogenic diabetes mellitus and the possibilities for genetic testing. The patients observed have shown the necessity of the identification and appropriate genetic diagnosis of HNF1A-MODY in order to discontinue insulin therapy and to initiate adjusted diabetes management.
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http://dx.doi.org/10.1007/s00508-020-01770-2DOI Listing
March 2021

Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures.

EXCLI J 2020 9;19:1275-1281. Epub 2020 Sep 9.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (Q) and TMAO (Q) quotient and evaluating Q values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with Q and Q determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The Q was significantly associated with the Q (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 - Q3) Q values (4.7 (2.8 - 7.5) vs. 3.8 (2.5 - 5.7) x 10, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. Q showed a relevant influence on Q. Present results indicate that TMAO may cross the blood-CSF barrier.
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http://dx.doi.org/10.17179/excli2020-2763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590830PMC
September 2020

General and Disease-Specific Health Indicator Changes Associated with Inpatient Rehabilitation.

J Am Med Dir Assoc 2020 12 28;21(12):2017.e10-2017.e27. Epub 2020 Jul 28.

Division of Physiology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria; Human Research Institute, Weiz, Austria.

Objectives: Rehabilitation plays a vital role in the mitigation and improvement of functional limitations associated with aging and chronic conditions. Moderating factors such as sex, age, the medical diagnosis, and rehabilitation timing for admission status, as well as the expected change related to inpatient rehabilitation, are examined to provide a valid basis for the routine assessment of the quality of medical outcomes.

Design: An observational study was carried out, placing a focus on general and disease-specific health measurements, to assess representative results of multidisciplinary inpatient rehabilitation. Aspects that were possibly confounding and introduced bias were controlled based on data from a quasi-experimental (waiting) control group.

Measures: Existing data or general health indicators were extracted from medical records. The indicators included blood pressure, resting heart rate, self-assessed health, and pain, as well as more disease-specific indicators of physical function and performance (eg, activities of daily living, walking tests, blood lipids). These are used to identify moderating factors related to health outcomes.

Setting And Participants: A standardized collection of routine data from 16,966 patients [61.5 ± 12.5 years; 7871 (46%) women, 9095 (54%) men] with different medical diagnoses before and after rehabilitation were summarized using a descriptive evaluation in terms of a content and factor analysis.

Results: Without rehabilitation, general health indicators did not improve independently and remained stable at best [odds ratio (OR) = 0.74], whereas disease-specific indicators improved noticeably after surgery (OR = 3.20). Inpatient rehabilitation was shown to reduce the risk factors associated with certain lifestyles, optimize organ function, and improve well-being in most patients (>70%; cutoff: z-difference >0.20), with a standardized mean difference (SMD) seen in overall medical quality outcome of -0.48 ± 0.37 [pre- vs post-rehabilitation: η = 0.622; d = -1.22; 95% confidence interval (95% CI) -1.24 to -1.19]. The baseline medical values obtained at the beginning of rehabilitation were influenced by indication, age, and sex (all P < .001); however, these factors have less significant effects on improvements in general health indicators (η < 0.01). According to the disease-specific results, the greatest improvements were found in older patients (SMD for patients >60 vs ≤60 years: 95% CI 0.08-0.11) and during the early rehabilitation stage (η = 0.063).

Conclusions And Implications: Compared with those who received no inpatient rehabilitation, patients who received rehabilitation showed greater improvements in 2 independent areas, general and disease-specific health measures, regardless of their diagnosis, age, and sex. Due to the study design and the use of a nonrandomized waiting group, causal conclusions must be drawn with caution. However, the comparability and stability of the presented results strongly support the validity of the observed improvements associated with inpatient rehabilitation.
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http://dx.doi.org/10.1016/j.jamda.2020.05.034DOI Listing
December 2020

Feasibility of the ultrasound-guided supraclavicular cannulation of the brachiocephalic vein in very small weight infants: A case series.

Paediatr Anaesth 2020 08 25;30(8):928-933. Epub 2020 Jun 25.

Department of Anesthesia, Klinikum Klagenfurt, Klagenfurt, Austria.

Background: The aim of this retrospective analysis was to evaluate the clinical feasibility of the supraclavicular ultrasound-guided cannulation of the brachiocephalic vein in infants weighing less than 1500 g.

Methods: The ultrasound probe was placed in the supraclavicular region so as to obtain the optimum sonographic long-axis view of the brachiocephalic vein. By using an in-plane approach the brachiocephalic vein was cannulated by using a 24-gauge intravenous cannula under real-time ultrasound guidance into the vein followed by the insertion of a 2-French single lumen catheter using the Seldinger technique.

Results: Forty-six brachiocephalic vein cannulations in infants weighing between 0.55 and 1.5 kg (Median: 1.2; 95%-CI: 0.9-1.2) were included. Ultimate success rate was 89.1% (41 out of 46). One cannulation attempt was required in 30 (65.2%) patients, 2 in 6 (13%) and 3 in 5 (10.8%), respectively. Smaller weight babies did not require significantly more cannulation attempts. The probability of successful cannulation on the first attempt increased significantly from 40% (2010) to more than 80% (2019) over the time course of this series. Median catheter dwell time was 15 days (95%-CI: 9-20) with one catheter being removed prematurely after 8 days due to obstruction.

Conclusion: Supracalvicular in-plane real-time ultrasound-guided cannulation of the brachiocephalic vein seems to be a convenient and feasible option to provide large-bore central venous access for very small and sick babies.
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http://dx.doi.org/10.1111/pan.13928DOI Listing
August 2020

Extremely Preterm Infants Have a Higher Fat Mass Percentage in Comparison to Very Preterm Infants at Term-Equivalent Age.

Front Pediatr 2020 10;8:61. Epub 2020 Mar 10.

Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.

Early nutritional support of preterm infants is important because it influences long-term health and development. Body composition has an influence on cardiovascular disease, metabolic syndrome, and neurocognitive outcome in the long term. To assess body composition in preterm infants <32 weeks of gestation at term-equivalent age and to analyze the influence of an optimized nutritional approach. This is a prespecified secondary outcome analysis of a prospective observational study comparing the body composition in regard to gestational age. The preterm infants were classified according to gestational age as extremely preterm infants (<28 weeks gestation at birth) and very preterm infants (≥28 weeks gestation at birth) and according to weight percentile as appropriate for gestational age and small for gestational age. Body composition was determined by air displacement plethysmography using the PEA POD. The preterm infants obtained nutrition according to the ESPGHAN 2010 Guidelines. Seventy-four preterm infants were analyzed. The mean (SD) gestational age was 28.7 (2.4) weeks, and birth weight was 1,162 (372) g. Fat mass percentage was significantly higher in extremely preterm infants in comparison to very preterm infants [17.0, 95% confidence interval (CI) 15.9-18.1 vs. 15.5, 95% CI 14.7-16.2]. There was no significant difference of fat mass percentage according to weight percentiles. Extremely preterm infants had a significantly higher fat mass percentage compared to very preterm infants at term-equivalent age. There was no significant difference of fat mass percentage according to weight percentiles.
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http://dx.doi.org/10.3389/fped.2020.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078645PMC
March 2020

Effects of a plant-based fatty acid supplement and a powdered fruit, vegetable and berry juice concentrate on omega-3-indices and serum micronutrient concentrations in healthy subjects.

Int J Food Sci Nutr 2020 Sep 17;71(6):769-780. Epub 2020 Feb 17.

Green Beat - Institute of Nutrient Research and Sport Nutrition, Graz, Austria.

The major aim of this controlled, randomised, open-labelled, parallel-grouped, clinical trial was to investigate whether supplementation with different dosages of omega-3 fatty acids (0.5 g/d and 1 g/d) from a plant-based fatty acid supplement affected omega-3-indices (O3I) in well-nourished, healthy people. In addition, the combined ingestion of the plant-based fatty acid supplement, together with an encapsulated fruit, vegetable and berry (FVB) juice powder concentrate, was applied in order to observe the absorption of certain micronutrients and to examine some aspects related to the safe consumption of the products. The data demonstrate that the intake of only 0.5 g/day of omega-3 fatty acids from of a vegan supplement was able to increase the O3I significantly after 8 and 16 weeks. The combined ingestion with the FVB supplement concurrently increased serum concentrations of specific vitamins and carotenoids without effects on hepatic, kidney and thyroid function or changes in blood lipids.
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http://dx.doi.org/10.1080/09637486.2020.1725960DOI Listing
September 2020

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers.

Dis Markers 2020 6;2020:7897240. Epub 2020 Jan 6.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.

Background: The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA.

Methods: Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T polymorphism genotyping and fructose H/CH breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire.

Results: The median TMAO and zonulin serum concentrations were 2.66 (1.93-4.14) mol/L and 40.83 (34.73-47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms ( = 0.011, = 0.160). The strongest correlations were observed in 87 females ( = 0.010, = 0.274) and 49 males ( = 0.027, = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA ( = 0.062, = -0.269).

Conclusion: This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.
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http://dx.doi.org/10.1155/2020/7897240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969987PMC
September 2020

A Micromethod for Polyphenol High-Throughput Screening Saves 90 Percent Reagents and Sample Volume.

Antioxidants (Basel) 2019 Dec 21;9(1). Epub 2019 Dec 21.

Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Devision of Physiological Medicine, Medical University of Graz, Graz 8010, Austria.

There is ample evidence that polyphenols are important natural substances with pronounced antioxidative properties. This study aimed to develop a fast and reliable method to determine total polyphenol content (TPC) in foodstuffs and human samples. The microtitration format offers the advantage of low sample volumes in the microlitre range, facilitating high-throughput screening with 40 samples simultaneously. We accordingly adjusted the so-called Folin-Ciocalteu method to a microtitre format (polyphenols microtitre-PPm) with 90% reduction of reagents. The assay was standardized with gallic acid in the range between 0.1 and 3 mM, using a 20 µL sample volume. The intra-assay coefficient of variation (CV) was less than 5%, and inter-assay CV was in the range of 10%. Wavelength was measured at 766 nm after two hours of incubation. This micromethod correlates significantly with both the classical Folin-Ciocalteu method and High-Performance Thin-Layer Chromatography (HPTLC) (r = 0.9829). We further observed a significant correlation between PPm and total antioxidants (r = 0.918). The highest polyphenol concentrations were obtained for red, blue, and black fruits, vegetables, and juices. Extracts of red grapes could be harvested almost sugar free and might serve as a basis for polyphenol supplementation. Beer, flour, and bread contained polyphenol concentrations sufficient to meet the minimal daily requirement. We conclude that PPm is a sensitive and reliable method that detects polyphenols even in samples diluted 10-fold. The literature strongly recommends further investigations on the effects of polyphenol uptake on human and animal health.
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http://dx.doi.org/10.3390/antiox9010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023636PMC
December 2019

An encapsulated fruit, vegetable and berry juice powder concentrate increases plasma values of specific carotenoids and vitamins.

Int J Vitam Nutr Res 2021 Jan 15;91(1-2):77-86. Epub 2019 Nov 15.

Green Beat - Institute of Nutrient Research and Sport Nutrition, Graz, Austria.

Vitamins and carotenoids are organic compounds that are important for vital functions of the human organism. Since the human body is not able to synthesize most of these micronutrients, they need to be supplied by the intake of food or supplements. The aim of this study was to analyze whether a whole food based, encapsulated fruit, berry, and vegetable juice powder concentrate provides bioavailable carotenoids and vitamins A (all-trans retinol), E and C. Eighteen healthy subjects received 6 capsules a day for 8 weeks, which provided 2.91 mg β-carotene, 490 μg vitamin A, 18.7 mg vitamin E, 159 mg vitamin C, 6.1 mg lutein and 1 mg lycopene. Plasma concentrations of several carotenoids and vitamins before and after supplementation were measured. After 8 weeks of supplementation, the plasma concentration of the following carotenoids increased significantly: α-carotene increased from 59.6 ± 22.4 nmol/L to 85.7 ± 24.2 nmol/L (p = 0.002), β-cryptoxanthin from 106.7 ± 39.8 nmol/L to 151.9 ± 57.9 nmol/L (p = 0.017), and lycopene from 1.2 ± 0.5 μmol/L to 1.7 ± 0.5 μmol/L (p = 0.005). Significant increases were also observed for plasma concentrations of vitamin C from 70 ± 20 μmol/L to 90 ± 10 μmol/L (p < 0.001), all-trans retinol from 1.99 ± 0.24 μmol/L to 2.30 ± 0.66 μmol/L (p = 0.015), and α-tocopherol from 27 ± 6 μmol/L to 32 ± 6 μmol/L (p = 0.008). For those micronutrients with accepted plasma reference ranges, all observed increases levelled off around the upper limit of the individual reference range. The data demonstrate that the investigated supplement is able to increase plasma concentrations of certain carotenoids and vitamins of healthy subjects within 8 weeks.
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http://dx.doi.org/10.1024/0300-9831/a000609DOI Listing
January 2021

Associations between tryptophan and iron metabolism observed in individuals with and without iron deficiency.

Sci Rep 2019 10 10;9(1):14548. Epub 2019 Oct 10.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Current literature proposes associations between tryptophan metabolism and anaemia. However, study cohorts are rather small and final conclusions are still lacking. Here, we evaluated potential associations of tryptophan, kynurenine, and kynurenic acid with indicators of iron metabolism (i.e., mean corpuscular volume, mean corpuscular haemoglobin, ferritin, transferrin saturation, serum iron, transferrin, soluble transferrin receptor, reticulocyte haemoglobin) and haemoglobin in 430 individuals grouped by the presence or absence of iron deficiency or anaemia. Indicators of tryptophan metabolism were positively correlated with haemoglobin and markers of iron metabolism (p-values: <0.001-0.038; r-values: 0.100-0.305). The strongest correlation was observed between tryptophan and haemoglobin (p < 0.001, r = 0.305). The cubic regression model yielded the highest R-square values between haemoglobin and tryptophan markers. Overall, 115 patients with iron deficiency showed lower tryptophan and kynurenic acid concentrations compared to 315 individuals without iron deficiency. Six patients with anaemia of chronic disease were observed with the lowest serum tryptophan levels and the highest kynurenine/tryptophan ratio compared to 11 individuals with iron deficiency anaemia and 413 non-anaemic patients. This study showed little/moderate associations between haemoglobin, biomarkers of iron metabolism and tryptophan markers. Further studies are needed to get better insight in the causality of these findings.
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http://dx.doi.org/10.1038/s41598-019-51215-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787180PMC
October 2019

Dietary intake in patients with peripheral arterial disease and concomitant periodontal disease.

Br J Nutr 2019 07 2;122(1):78-85. Epub 2019 Jul 2.

Medical University of Graz, Department of Internal Medicine, Division of Angiology, Auenbruggerplatz 15, 8036 Graz, Austria.

Nutrition plays a crucial role in the pathophysiology and management of peripheral arterial disease (PAD) and periodontal disease (PD). As PD can have profound effects on an individual's functional ability to eat and can affect nutrient intake, we aimed to evaluate the role of PD severity on dietary intake (DI) and quality in PAD patients and compare it with current dietary recommendations for CVD. PD stages of 421 consecutive PAD patients were determined according to a standardised basic periodontal examination (Periodontal Screening and Recording Index) ('healthy', 'gingivitis', 'moderate periodontitis' and 'severe periodontitis'). Dietary intake (24-h recall), dietary quality (food frequency index (FFI)) and anthropometrical data were assessed. Nutritional intake was stratified according to the severity of PD. No significant differences in DI of macronutrients, nutrients relevant for CVD and FFI were seen between the PD stages. Only median alcohol intake was significantly different between gingivitis and severe periodontitis (P = 0·001), and positively correlated with PD severity (P = 0·001; r 0·159). PD severity and the patient's number of teeth showed no correlation with investigated nutritional parameters and FFI. Few subjects met the recommended daily intakes for fibre (5 %), SFA (10 %), Na (40 %) and sugar (26 %). Macronutrient intake differed from reference values. In our sample of patients with PAD and concomitant PD, we found no differences in DI of macronutrients, nutrients relevant for CVD and diet quality depending on PD severity. The patients' nutrition was, however, poor, deviating seriously from dietary guidelines and recommendations.
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http://dx.doi.org/10.1017/S0007114519000850DOI Listing
July 2019

Evaluation of symptoms and symptom combinations in histamine intolerance.

Intest Res 2019 Jul 7;17(3):427-433. Epub 2019 Mar 7.

Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Graz, Austria.

Background/aims: Food intolerance/malabsorption, particularly histamine intolerance (HIT), may cause nonspecific functional gastrointestinal and extraintestinal symptoms. We evaluated gastrointestinal and extraintestinal symptoms in patients with HIT.

Methods: In an analysis of outpatients' charts we identified 133 patients, who presented with recurring nonspecific functional gastrointestinal, extraintestinal symptoms, and a diamine oxidase value <10 U/mL, indicative of HIT. A standardized anonymous questionnaire with symptoms of HIT based on known symptoms and the 4 histamine receptors including gastrointestinal, cardiovascular, respiratory and skin complaints was developed, and sent by mail to the patients.

Results: In the 62 patients that completed the questionnaire bloating was the most common and most serious symptom. Other commonly reported gastrointestinal symptoms were postprandial fullness, diarrhea, abdominal pain, and constipation. The presence of 2 from a list of 24 symptoms resulted in 276 various symptom combinations. From calculated 2.024 possible combinations of 3 symptoms the patients with HIT presented 1.975 combinations.

Conclusions: The knowledge of this wide variability of symptoms and complex symptom combinations in patients with HIT may help to clinically recognize and diagnose HIT.
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http://dx.doi.org/10.5217/ir.2018.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667364PMC
July 2019

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

Clin Nutr 2019 12 10;38(6):2913-2921. Epub 2019 Jan 10.

Department of Immunology and Pathophysiology, Medical University of Graz, Otto Loewi Research Center, Heinrichstraße, Graz, Austria.

Background & Aims: Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches.

Methods: The SAT of AN patients (n = 18, body mass index (BMI) 15.3 ± 1.3 kg/m) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (D) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined.

Results: The mean MI was 15.7 ± 1.4 kg/m. The D considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low D: 1.3-28.4 mm, and Group 2 showed values up to 58.2 mm (corresponding to approximately 6 kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2 at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level.

Conclusion: Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.
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http://dx.doi.org/10.1016/j.clnu.2018.12.031DOI Listing
December 2019

Measurement of mean subcutaneous fat thickness: eight standardised ultrasound sites compared to 216 randomly selected sites.

Sci Rep 2018 11 2;8(1):16268. Epub 2018 Nov 2.

Medical University of Graz, Institute of Biophysics, Graz, Austria.

Ultrasound (US) provides the most accurate technique for thickness measurements of subcutaneous adipose tissue (SAT) layers. This US method was recently standardised using eight sites to capture SAT patterning and allows distinguishing between fat and embedded fibrous structures. These eight sites chosen for fat patterning studies do not represent the mean SAT thickness measured all over the body that is necessary for determining subcutaneous fat mass. This was obtained by SAT measurements at 216 sites distributed randomly all over the body. Ten participants with BMI below 28.5kgm and SAT means (from eight sites) ranging from 3 mm to 10 mm were selected. The means from eight sites overestimated the means obtained from 216 sites (i.e. 2160 US measurements in the ten participants); the calibration factor of 0.65 corrects this; standard deviation (SD) was 0.05, i.e. 8%. The SD of the calibration factor transforms linearly when estimating the error range of the whole body's SAT volume (body surface area times the calibrated mean SAT thickness). The SAT masses ranged from 3.2 to 12.4 kg in this group. The standard deviations resulting from solely the calibration factor uncertainty were ±0.3 and ±1.0 kg, respectively. For these examples, the SAT percentages were 4.9(±0.4)% and 13.3(±1.0)%.
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http://dx.doi.org/10.1038/s41598-018-34213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214952PMC
November 2018

Response to Letter to the Editor to Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women.

Eur J Nutr 2018 12;57(8):3001-3002

Division of Immunology and Pathophysiology, Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1007/s00394-018-1836-5DOI Listing
December 2018

The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature.

Neuropsychobiology 2018 Sep 17:1-9. Epub 2018 Sep 17.

Department for Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Introduction: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders.

Aim: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics.

Results: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders.

Conclusion: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.
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http://dx.doi.org/10.1159/000492834DOI Listing
September 2018

[Pilot study: Gut microbiome and intestinal barrier in anorexia nervosa].

Fortschr Neurol Psychiatr 2019 02 26;87(1):39-45. Epub 2018 Jul 26.

Introduction: Recent research has shown changes of the intestinal flora in anorexia nervosa (AN) patients. Alpha diversity (AD) represents the number of different bacterial species in the gut. Reduced AD and a leaky gut (zonulin) lead to inflammation and changes in nutrient absorption.

Methods: AD was calculated from stool samples of 18 AN patients and 20 normal weight controls (NC) after 16S ribosomal RNA sequencing. Furthermore, Zonulin as an indicator of gut barrier function and inflammation parameters were investigated.

Results: AN patients had significantly lower AD compared to NC (number of observed species p=0.042, Chao1 Diversity Index p=0.043). Zonulin was not significantly altered in AN patients compared to NC. There were no significant correlations of serum parameters and AD.

Discussion: Regardless of gut permeability, AN patients showed significantly decreased AD compared to NC. Decreased AD can have an additional negative impact on calorie intake in AN. These results contribute to a better understanding of the illness and the development of new therapeutic options.
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http://dx.doi.org/10.1055/s-0043-123826DOI Listing
February 2019

Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance.

Eur J Clin Nutr 2019 01 18;73(1):102-104. Epub 2018 Jul 18.

Practice for General Internal Medicine, Dr. Theodor Körnerstrasse 19b, A-8600, Bruck, Austria.

Diagnosis of histamine intolerance (HIT) has been based on low serum diamine oxidase (DAO) values, functional gastrointestinal disorders and improvement of symptoms with a histamine-reduced diet (HRD). In a retrospective analysis of outpatients' charts we identified 101 patients with HIT. After a median of 13 months, a questionnaire was distributed to the patients so that they could be classified into four diet-compliance groups. Calculated with all 101 patients we found an increase of serum DAO values due to a HRD. In the 63 patients that completed the questionnaire, we found that 50 patients had improvement of symptoms or no continuing symptoms. A significant increase of serum DAO levels was found in the patients with strict and occasional diet compliance. Therefore, we demonstrate that a HRD is not only improving symptoms in HIT, but is causing an increase in serum DAO values that correlates with the degree of diet compliance.
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http://dx.doi.org/10.1038/s41430-018-0260-5DOI Listing
January 2019

Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.

Psychoneuroendocrinology 2018 09 21;95:113-119. Epub 2018 May 21.

Institute of Pathophysiology and Immunology, Medical University of Graz, Heinrichstrasse 31A, 8010 Graz, Austria.

Background: Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.

Methods: RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).

Results: BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η = 0.005). Gene expression did not differ between euthymia, depression and mania.

Discussion: BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.
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http://dx.doi.org/10.1016/j.psyneuen.2018.05.029DOI Listing
September 2018

Beauty and the Body of the Beholder: Raters' BMI Has Only Limited Association with Ratings of Attractiveness of the Opposite Sex.

Obesity (Silver Spring) 2018 03;26(3):522-530

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Objective: Assortative mating for adiposity increases the genetic burden on offspring, but its causes remain unclear. One hypothesis is that people who have high adiposity find other people with obesity more physically attractive than lean people.

Methods: The attractiveness of sets of images of males and females who varied in adiposity were rated by opposite sex subjects (559 males and 340 females) across 12 countries.

Results: There was tremendous individual variability in attractiveness ratings. For female attractiveness, most males favored the leanest subjects, but others favored intermediate fatness, some were indifferent to body composition, and others rated the subjects with obesity as most attractive. For male images rated by females, the patterns were more complex. Most females favored subjects with low levels of adiposity (but not the lowest level), whereas others were indifferent to body fatness or rated the images depicting individuals with obesity as the most attractive. These patterns were unrelated to rater BMI. Among Caucasian males who rated the images of the thinnest females as being more attractive, the magnitude of the effect depended on rater BMI, indicating limited "mutual attraction."

Conclusions: Individual variations in ratings of physical attractiveness were broadly unrelated to rater BMI and suggest that mutual attraction is an unlikely explanation for assortative mating for obesity.
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http://dx.doi.org/10.1002/oby.22092DOI Listing
March 2018

Cultivation and Immortalization of Human B-Cells Producing a Human Monoclonal IgM Antibody Binding to MDA-LDL: Further Evidence for Formation of Atherogenic MDA-LDL Adducts in Humans .

Oxid Med Cell Longev 2017 9;2017:6047142. Epub 2017 Nov 9.

Institute of Physiological Chemistry, Center for Physiological Medicine, Medical University of Graz, Stiftingtalstrasse 6 M1/D/3 8036, Graz, Austria.

Oxidatively modified low-density lipoprotein (oLDL) is firmly believed to play an important role in the initiation and development of atherosclerosis, and malonic dialdehyde (MDA) is one of the major lipid peroxidation breakdown products involved in this process. In recent decades, antibodies against MDA-LDL have been detected in human and animal sera. In our study, human B-cells from the peripheral blood of a healthy female donor were fused with the SP2/0 mouse myeloma cell line. Antibody-producing hybridomas were detected by MDA-LDL-IgG/IgM enzyme-linked immunosorbent assays (ELISA) and Cu-oxidized LDL IgG/IgM (oLAb) ELISA. Cells with supernatants emitting positive signals for antibodies were then cloned and after sufficient multiplication frozen and stored under liquid nitrogen. Due to the loss of antibody-producing ability, we established an MDA-LDL-IgM-producing cell line by recloning. This allowed isolation and immortalization of several human B-cells. The human donor had not been immunized with MDA-modified proteins, thus obviously producing MDA-LDL antibodies . Furthermore, using these antibodies for experiments, we were able to demonstrate that MDA epitopes are among the epitopes generated during Cu-LDL oxidation as well. Finally, these antibodies compete in ELISA and cell culture experiments with MDA as a challenging toxin or ligand.
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http://dx.doi.org/10.1155/2017/6047142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700503PMC
July 2018

Non-celiac gluten sensitivity: people without celiac disease avoiding gluten-is it due to histamine intolerance?

Inflamm Res 2018 Apr 27;67(4):279-284. Epub 2017 Nov 27.

Institute of Pathophysiology, Centre for Molecular Medicine, Medical University of Graz, Heinrichstrasse 31a, 8010, Graz, Austria.

Introduction: Food intolerance/malabsorption is caused by food ingredients, carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal symptoms. Here we focus on possible etiologic factors of intolerance/malabsorption especially in people with non-celiac gluten sensitivity (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG) and histamine intolerance.

Methods: Recognizing the recently described symptoms of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance (HIT).

Results: We show that intestinal and extra-intestinal NCGS (PWCDAG) symptoms are very similar to those which can be found in histamine intolerance.

Conclusions: After a detailed diagnostic workup for all possible etiologic factors in every patient, a targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets.
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http://dx.doi.org/10.1007/s00011-017-1117-4DOI Listing
April 2018
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