The Effects of 5-Hydroxytryptophan in Combination with Different Fatty Acids on Gastrointestinal Functions: A Pilot Experiment

Background. Fat affects gastric emptying (GE). 5-Hydroxythryptophan (5-HTP) is involved in central and peripheral satiety mechanisms. Influence of 5-HTP in addition to saturated or monounsaturated fatty acids (FA) on GE and hormone release was investigated. Subjects/Methods. 24 healthy individuals (12f : 12m, 22-29 years, BMI 19-25.7 kg/m(2)) were tested on 4 days with either 5-HTP + short-chain saturated FA (butter), placebo + butter, 5-HTP + monounsaturated FA (olive oil), or placebo + olive oil in double-blinded randomized order. Two hours after FA/5-HTP or placebo intake, a C-13 octanoid acid test was conducted. Cortisol, serotonin, cholecystokinin (CCK), and ghrelin were measured, as were mood and GE. Results. GE was delayed with butter and was normal with olive (P < 0.05) but not affected by 5-HTP. 5-HTP supplementation did not affect serotonin levels. Food intake increased plasma CCK (F = 6.136; P < 0.05) irrespective of the FA. Ghrelin levels significantly decreased with oil/5-HTP (F = 9.166; P < 0.001). The diurnal cortisol profile was unaffected by FA or 5-HTP, as were ratings of mood, hunger, and stool urgency. Conclusion. Diverse FAs have different effects on GE and secretion of orexigenic and anorexigenic hormones. Supplementation of 5-HTP had no effect on plasma serotonin and central functions. Further studies are needed to explain the complex interplay

Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action

Classical cadherins control nucleus and centrosome position and cell polarity

Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell–cell interactions, we show that in the absence of other polarizing cues, cell–cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell–cell interactions induce nucleus and centrosome off-centering toward cell–cell contacts, and promote orientation of the nucleus–centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus–centrosome axis is determined by the geometry of N-cadherin–mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells

Conventional weight loss therapy in morbid obesity during COVID-19 pandemic: degree of burdens at baseline and treatment efficacy

IntroductionCOVID-19 affected global physical and psychological health. The purpose of this study was to explore the pandemics impact on health-related quality of life (HRQoL), mental health (anxiety, depression, and perceived stress) and eating behavior in people with severe obesity participating in a multimodal conservative behavioral weight loss (BWL) program conducted via videoconferencing. Additionally, the efficacy of the six-month BWL program in a virtual video-based setting during the pandemic was examined.Methods297 participants of a face-to-face multimodal behavioral weight loss program prior to the pandemic (PrePAN, May 2014–September 2019) and 146 participants of the in terms of content same intervention in a videoconference-based setting during the pandemic (PAN, July 2020–April 2022) were questioned and compared using standardized questionnaires for HRQoL, symptoms of depressive and anxiety disorders, perceived stress, and eating behavior at baseline and at the end of treatment.ResultsSymptoms for anxiety, depression and perceived stress were similar between PrePAN and PAN at baseline. In addition, PAN tended to show lower disinhibition of eating behavior and feelings of hunger than PrePAN. During the pandemic, the BWL intervention resulted in body weight loss (67%) or stabilization (16%) in most of the participants. It also contributed by improving physical HRQoL, lower worries, and improved eating behaviors compared to baseline.ConclusionDuring the COVID-19 pandemic, baseline mental health of people with morbid obesity was not worse than before the pandemic. Additionally, the BWL intervention in the virtual video-based setting stabilized and improved physical and mental health during the COVID-19 pandemic

Policies for biosimilar uptake in Europe : an overview

Background: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. Objectives: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. Methods: An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. Results: In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. Conclusions: Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

F420H2-Dependent Degradation of Aflatoxin and other Furanocoumarins Is Widespread throughout the Actinomycetales

Two classes of F420-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F420 is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F420H2 to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F420 to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Correction: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 96 Issue: 5 Pages: 852-852 DOI: 10.1016/j.ajhg.2015.04.001 Published:MAY 7 2015Peer reviewe