An Overview of Different Vitamin D Compounds in the Setting of Adiposity.

A large body of research shows an association between higher body weight and low vitamin D status, as assessed using serum 25-hydroxyvitamin D concentrations. Vitamin D can be metabolised in adipose tissue and has been reported to influence gene expression and modulate inflammation and adipose tissue metabolism in vitro. However, the exact metabolism of vitamin D in adipose tissue is currently unknown. White adipose tissue expresses the vitamin D receptor and hydroxylase enzymes, substantially involved in vitamin D metabolism and efficacy. The distribution and concentrations of the generated vitamin D compounds in adipose tissue, however, are largely unknown. Closing this knowledge gap could help to understand whether the different vitamin D compounds have specific health effects in the setting of adiposity. This review summarises the current evidence for a role of vitamin D in adipose tissue and discusses options to accurately measure vitamin D compounds in adipose tissue using liquid chromatography tandem mass spectrometry (LC/MS-MS).

Improved quantitative LC-MS/MS analysis of vitamin D metabolites in serum after one-pot double derivatization.

In this study, we report a one-pot double derivatization scheme, which used acetylation after a Diels-Alder reaction using 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to improve separation efficiency and provide baseline separations of the five vitamin D metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), 3ß-25-hydroxyvitamin D3 (3ß-25(OH)D3), 3α-25-hydroxyvitamin D3 (3α-25(OH)D3) and vitamin D3 on a C-18 stationary phase. Vitamin D metabolites are often very challenging to measure quantitatively using mass spectrometry, due to their low serum concentration levels and low ionization efficiencies. Moreover, some of these species are isomers with virtually identical mass spectral dissociation behavior. To overcome the low ionization efficiency and unspecific fragmentation behavior, derivatization using Diels-Alder reactions with Cookson-type reagents such as PTAD are common. These derivatization reactions generally result in more complicated liquid chromatography separations, because both 6R- and 6S-isomers are formed during Diels-Alder reactions. It has been shown that separations have been particularly challenging for the 3α-25(OH)D3 and 3ß-25(OH)D3 epimers. Here, we optimized the PTAD derivatization and the esterification using acetic anhydride. By utilizing the esterification catalyst 4-dimethylaminopyridine, we avoided quenching and evaporation between the two derivatization steps, but were also able to perform the esterification at room temperature without heating. The optimized one-pot double derivatization LC-MS/MS assay was validated with respect to inter/intra-day precision, accuracy, recovery and linear dynamic range and applied to metabolic fingerprinting of vitamin D3 metabolites in serum samples. The metabolites 3α-25(OH)D3, 3ß-25(OH)D3 and 24,25(OH)2D3, were readily quantified in all investigated samples. The method was, in principle, also fit for purpose for quantification of the native vitamin D3 species; the relatively high blank concentration of the commercial vitamin D-depleted serum used for calibration, however, limited the limits of quantification for this metabolite. The method provided insufficient limits of quantification for serum levels of 1,25(OH)2D3.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Analysis of vitamin D metabolic markers by mass spectrometry: Recent progress regarding the "gold standard" method and integration into clinical practice.

Liquid chromatography/tandem mass spectrometry is firmly established today as the gold standard technique for analysis of vitamin D, both for vitamin D status assessments as well as for measuring complex and intricate vitamin D metabolic fingerprints. While the actual mass spectrometry technology has seen only incremental performance increases in recent years, there have been major, very impactful changes in the front- and back-end of MS-based vitamin D assays; for example, the extension to new types of biological sample matrices analyzed for an increasing number of different vitamin D metabolites, novel sample preparation techniques, new powerful chemical derivatization reagents, as well the continued integration of high resolution mass spectrometers into clinical laboratories, replacing established triple-quadrupole instruments. At the same time, the sustainability of mass spectrometry operation in the vitamin D field is now firmly established through proven analytical harmonization and standardization programs. The present review summarizes the most important of these recent developments.

Clostridioides difficile Infection Dysregulates Brain Dopamine Metabolism.

Gastrointestinal illnesses and dysbiosis are among the most common comorbidities reported in patients with neurodevelopmental disorders. The manuscript reports that C. difficile infection (CDI), predisposed by antibiotic-induced gut dysbiosis, causes significant alterations in dopamine metabolism in major dopaminergic brain regions in mice (P < 0.05). In addition, C. difficile infected mice exhibited significantly reduced dopamine beta-hydroxylase (DBH) activity compared to controls (P < 0.01). Moreover, a significantly increased serum concentration of p-cresol, a DBH inhibiting gut metabolite produced by C. difficile, was also observed in C. difficile infected mice (P < 0.05). Therefore, this study suggests a potential mechanistic link between CDI and alterations in the brain dopaminergic axis. Such alterations may plausibly influence the precipitation and aggravation of dopamine dysmetabolism-associated neurologic diseases in infected patients. IMPORTANCE The gut-brain axis is thought to play a significant role in the development and manifestation of neurologic diseases. This study reports significant alterations in the brain dopamine metabolism in mice infected with C. difficile, an important pathogen that overgrows in the gut after prolonged antibiotic therapy. Such alterations in specific brain regions may have an effect on the precipitation or manifestation of neurodevelopmental disorders in humans.

Association between fat-soluble vitamins and self-reported health status: a cross-sectional analysis of the MARK-AGE cohort.

Self-rated health (SRH) is associated with higher risk of death. Since low plasma levels of fat-soluble vitamins are related to mortality, we aimed to assess whether plasma concentrations of vitamins A, D and E were associated with SRH in the MARK-AGE study. We included 3158 participants (52 % female) aged between 35 and 75 years. Cross-sectional data were collected via questionnaires. An enzyme immunoassay quantified 25-hydroxyvitamin D and HPLC determined α-tocopherol and retinol plasma concentrations. The median 25-hydroxyvitamin D and retinol concentrations differed significantly (P < 0·001) between SRH categories and were lower in the combined fair/poor category v. the excellent, very good and good categories (25-hydroxvitamin D: 40·8 v. 51·9, 49·3, 46·7 nmol/l, respectively; retinol: 1·67 v. 1·75, 1·74, 1·70 µmol/l, respectively). Both vitamin D and retinol status were independently associated with fair/poor SRH in multiple regression analyses: adjusted OR (95 % CI) for the vitamin D insufficiency, deficiency and severe deficiency categories were 1·33 (1·06-1·68), 1·50 (1·17-1·93) and 1·83 (1·34-2·50), respectively; P = 0·015, P = 0·001 and P < 0·001, and for the second/third/fourth retinol quartiles: 1·44 (1·18-1·75), 1·57 (1·28-1·93) and 1·49 (1·20-1·84); all P < 0·001. No significant associations were reported for α-tocopherol quartiles. Lower vitamin A and D status emerged as independent markers for fair/poor SRH. Further insights into the long-term implications of these modifiable nutrients on health status are warranted.

Analytical considerations for accurately capturing the relevant species contributing to vitamin D status in liquid chromatography-tandem mass spectrometry assays.

This tutorial review focuses on analytical challenges encountered with the liquid chromatography-tandem mass spectrometry determination of 25-hydroxyvitamin D, which is currently still considered the metabolite that is most representative of vitamin D status. It describes how multiple binding states of circulating 25-hydroxyvitamin D (phase II metabolites, epimers, free/bioavailable/protein-bound species) can influence the accuracy of the analytical determination. It also summarizes important chemical species that can inadvertently contribute to vitamin D status and thus cause systematic errors. These interfering endogenous and exogenous compounds might be isomers of vitamin D, constitutional isomers or isobars and the article outlines techniques to eliminate or minimize these interferences, including chromatographic separations, ion mobility spectrometry, and high-resolution mass spectrometry.

Ancient genomics reveals tripartite origins of Japanese populations.

Prehistoric Japan underwent rapid transformations in the past 3000 years, first from foraging to wet rice farming and then to state formation. A long-standing hypothesis posits that mainland Japanese populations derive dual ancestry from indigenous Jomon hunter-gatherer-fishers and succeeding Yayoi farmers. However, the genomic impact of agricultural migration and subsequent sociocultural changes remains unclear. We report 12 ancient Japanese genomes from pre- and postfarming periods. Our analysis finds that the Jomon maintained a small effective population size of ~1000 over several millennia, with a deep divergence from continental populations dated to 20,000 to 15,000 years ago, a period that saw the insularization of Japan through rising sea levels. Rice cultivation was introduced by people with Northeast Asian ancestry. Unexpectedly, we identify a later influx of East Asian ancestry during the imperial Kofun period. These three ancestral components continue to characterize present-day populations, supporting a tripartite model of Japanese genomic origins.

Excess Body Weight and Gallstone Disease.

BACKGROUND: Approximately one fifth of adults are diagnosed with gallstones worldwide. Of these, around 25% develop gallstone disease (indicated by the presence of symptoms) and undergo cholecystectomy. SUMMARY: The risk of gallstones is influenced by a combination of genetic and lifestyle factors, such as excess body weight. In fact, body mass has been demonstrated to be a major risk factor for symptomatic gallstones. Rapid weight loss can also initiate a prolithogenic state and further increase the likelihood of either gallstone formation or existing gallstones becoming symptomatic; however, sensible weight loss strategies can mitigate this risk. This review discusses the role of excess body weight and the risk of gallstone disease, as well as the options available for the prevention of symptomatic gallstones. KEY MESSAGES: Healthy weight loss diets combined with regular physical activity can promote successful weight loss and weight maintenance and reduce the risk of gallstones. Should rapid weight loss be required for health reasons or be expected, e.g., after bariatric surgery, prophylactic ursodeoxycholic acid during the period of weight reduction has been demonstrated to reduce the incidence of gallstones formation or symptomatic gallstone occurrence. The recent German guidelines on gallstones recommend simultaneous cholecystectomy during bariatric surgery but only for those with preexisting symptomatic stones.

Noninvasive monitoring of liver fat during treatment with GLP-1 analogues and SGLT-2 inhibitors in a real-world setting.

INTRODUCTION: Patients with NAFLD have a two-fold increased risk of diabetes, and conversely, NAFLD affects up to 80% of patients with type 2 diabetes. Due to the co-occurrence of both diseases and the lack of approved pharmacotherapy for NAFLD, the anti-steatogenic potential of diabetes-related drugs is being explored. In this study, we aim to monitor liver fat noninvasively during treatment with SGLT-2 inhibitors or GLP-1 analogues in a real-world setting. METHODS: Overall, 39 patients (49% women, age 57.7 ± 10.9 years) with type 2 diabetes and hepatic steatosis (defined by controlled attenuation parameter [CAP] values ≥ 215 dB/m) were observed for 6 months and routinely monitored with respect to hepatic fat contents and liver stiffness (VCTE); body composition (BIA); and blood biochemistry, including liver function tests (LFTs), serum lipids and glucose metabolism markers. RESULTS: Median liver fat contents were significantly (P = .026) reduced by 9% in patients taking either SGLT-2 (n = 22) or GLP-1 (n = 17) for 6 months (absolute median CAP decrease: -32 dB/m [-58 to 32 dB/m]). In parallel, serum ALT and γ-GT activities decreased significantly (P = .002 and P = .049, respectively). These improvements were accompanied by significant (P < .0001) changes to body weight and BMI (-2.5 ± 3.3 kg and -0.9 ± 1.2 kg/m2, respectively) and glucose homeostasis, with significant reductions in HbA1c and fasting plasma glucose (FDG) (both P < .0001). Of note, significant reductions of intrahepatic lipid contents occured in patients receiving SGLT-2 inhibitors only. CONCLUSIONS: In this real-world observational evaluation of fatty liver monitored noninvasively in patients with type 2 diabetes treated with either SGLT2 or GLP-1, improvements in measures of hepatic steatosis, glucose and weight parameters were observed after 6 months, with significant reductions of intrahepatic lipid contents seen specifically in the SGLT2 subgroup.

The Role of Paternal Accommodation of Paediatric OCD Symptoms: Patterns and Implications for Treatment Outcomes.

Family accommodation (FA) refers to the participation of family members in obsessive-compulsive disorder (OCD) rituals. Most studies have focused on maternal accommodation; consequently, little is known about fathers' accommodation of OCD. The current study aims to extend the existing literature by examining maternal versus paternal accommodation of OCD symptoms.The sample consisted of 209 children with OCD (Mean [M] age = 14.1 years) and their parents (NMothers = 209, NFathers = 209) who had completed the Family Accommodation Scale- Parent Report (FAS-PR). Paired t-test and chi-square analyses were used to compare FA of OCD symptoms between mothers and fathers. Linear regression was used to examine correlates of maternal and paternal FA and its impact on treatment outcomes.Mothers reported significantly higher levels of daily FA than fathers. Correlates of maternal and paternal accommodation included OCD symptom severity, emotional and behavioral difficulties, and parent psychopathology. Both maternal and paternal FA significantly predicted worse treatment outcomes.Both mothers and fathers accommodate child OCD symptoms with high frequency, and in similar ways. Although mothers accommodate to a greater extent than fathers, both maternal and paternal involvement in rituals are a significant predictor of the child's treatment response. Results emphasise the need to consider the whole family system, including fathers, in understanding and treating OCD in children.

The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0-120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): -0.343, 95% confidence interval (CI): -0.867, 0.181, p = 0.200) and insulin (SMD: -0.141; 95% CI: -0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: -0.151; 95% CI: -0.610, 0.309; p = 0.521), HbA1c (SMD: -0.380; 95% CI: -0.870, 0.110; p = 0.129), AUC 0-120 glucose (SMD: -0.558; 95% CI: -1.380, 0.264; p = 0.183), and AUC 0-120 insulin (SMD: -0.068; 95% CI: -0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism.

Vitamin D in Preclinical Models of Fatty Liver Disease.

Simple steatosis in non-alcoholic fatty liver disease (NAFLD) progresses to non-alcoholic steatohepatitis (NASH) when excessive fat accumulation is accompanied by ballooning, inflammation, and progressive hepatocellular injury. Due to the increasing global incidence of NAFLD/NASH and the lack of effective drugs, current treatment options are currently dominated by lifestyle interventions, including dietary and physical activity modifications. In this regard, vitamin D has received widespread attention in recent years. In line with its pleiotropic physiological effects, preclinical animal models and patient cohorts have demonstrated anti-inflammatory, anti-fibrotic and anti-proliferative effects of vitamin D on NAFLD and NASH. Several animal models have confirmed the association of vitamin D deficiency and NALFD/NASH severity in humans and revealed potential benefits of dietary vitamin D supplementation. These preclinical models also provide critical guidance to define the roles and therapeutic potential of vitamin D as well as its downstream functional mechanisms in the pathogenesis of fatty liver disease. This review summarizes vitamin D research in currently available animal models of fatty liver disease.

Conceptualizing and managing risk in pediatric OCD: Case examples.

It is not uncommon for patients with obsessive-compulsive disorder (OCD) to present with symptoms that suggest possible risk. This can include apparent risk, which reflects the content of obsessional fears, and genuine risk arising as the unintended consequence of compulsive behaviors. In both situations, risk can cause confusion in relation to diagnosis and treatment. The current article adds to the small existing literature on risk in OCD by presenting case examples illustrating different types of risk in the context of pediatric OCD, along with a discussion of their implications for management. The cases highlight that it is crucial that risk in OCD is considered carefully within the context of the phenomenology of the disorder. Guidance is offered to support clinical decision making and treatment planning.

Hepatic steatosis in patients with acromegaly.

OBJECTIVE: Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly. DESIGN: A cross-sectional study including 22 patients with acromegaly. METHODS: Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays. RESULTS: In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild-type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild-type patients. CONCLUSIONS: This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted.

Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study.

BACKGROUND/AIMS: The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant. METHODS: Twenty subjects with hepatic steatosis (50% women, age 18-77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared. RESULTS: Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0-431.0] vs. 564.5 [range 509.0-682.0] µmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group. CONCLUSIONS: Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.

Serum 25-hydroxyvitamin D levels and mortality risk in patients with liver cirrhosis: a protocol for a systematic review and meta-analysis of observational studies.

BACKGROUND: Liver cirrhosis represents a substantial global burden in terms of morbidity and mortality. Observational studies have reported an increased risk of death with low circulating 25-hydroxyvitamin D concentrations in such patients. Because the occurrence of inadequate vitamin D status is very common in patients with liver cirrhosis, the aim of this study is to conduct a meta-analysis of observational studies in such patients to assess whether vitamin D deficiency increases their risk of mortality. METHODS: We will search electronic databases (MEDLINE, Embase, Web of Science, CENTRAL and Google Scholar from time of inception until now), conference proceedings and conduct manual searches to identify studies eligible for inclusion. There will be no restrictions based on publication status or language, and the meta-analysis will be reported in accordance with the MOOSE guidelines. We will employ random-effects meta-analysis to assess the relationship between vitamin D deficiency and risk of mortality. Quality of studies will be judged using the Newcastle-Ottawa scale, and between-trial heterogeneity will be evaluated by means of subgroup and sensitivity analyses. DISCUSSION: The study will assess the effects of serum 25-hydroxyvitamin D concentrations on mortality in patients with liver cirrhosis. The results will be published in a high-quality peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42016052007 .

[Sensitivity and Specificity of the Reizdarm-Fragebogen]. / Sensitivität und Spezifität des Reizdarm-Fragebogens.

BACKGROUND: The Reizdarm-Fragebogen (RDF) is the first German questionnaire to assess subjectively perceived symptom severity of irritable bowel syndrome (IBS). Thus far, this was only possible in the context of a medical examination by a practitioner. The goal of the current study was to assess differences in RDF scores among IBS patients and other clinical and non-clinical populations. Further, the study aimed to define a cut-off score for the presence of IBS and thereby, to evaluate the RDF as screening instrument in IBS diagnosis. MATERIALS AND METHODS: The study sample consisted of 372 individuals (62.6% male, mean age=41±17 years). 17.5% (of the sample) were IBS patients, 9.9% received treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants filled out the 13 item RDF. RESULTS: The IBS patients' RDF scores differed significantly from those of other clinical and non-clinical subsamples [t(98.82)=13.61, p<0.001]. Except for the subscale "bloating" this difference was consistently found for all RDF subscales ("diarrhea", "constipation", and "pain and feeling of tension"). With respect to the identification of a cut-off for IBS diagnosis, a score of 32 showed both good sensitivity (90.80%) and specificity (75.56%). DISCUSSION AND CONCLUSION: The RDF is an efficient instrument for the assessment of subjectively perceived symptom severity in IBS. Based on the current findings and its good psychometric properties it can be used as a screening instrument for IBS in both clinical practice and research.

Short-term Dietary Interventions for the Management of Nonalcoholic Fatty Liver.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects millions of individuals on a global scale and currently no gold standard treatment exists. The risk of developing NAFLD is considerably higher with increasing body mass index. Consequently, weight loss should be recommended to all overweight patients with fatty liver. However, lifestyle interventions, irrespective of weight status, may also influence the condition. The aim herein is to present examples of short-term interventions which assess direct effects of dietary-related components on hepatic steatosis. METHODS: This review includes studies with short-term dietary-related interventions of up to 16 weeks that evaluate their efficacy in reducing intrahepatic lipid contents (hepatic steatosis). This review primarily focuses on the three main macronutrients: dietary carbohydrates, fats and proteins. RESULTS: High saturated fat intake and high consumption of carbohydrates, particularly from simple sugars such as fructose are reported as risk factors for hepatic steatosis. Overall, shortterm hypocaloric diets have shown beneficial effects in reducing intrahepatic lipid contents. Macronutrient manipulations such as carbohydrate restriction as well as the consumption of unsaturated fatty acids are also reported to have efficacious effects. CONCLUSION: This review highlights the different dietary interventions that can influence hepatic steatosis in the short term, illustrating both pro and anti-steatotic effects.