Abstract Study question Is there any link between intestinal microbiome and endometriosis? Summary answer The aetiopathogenesis of endometriosis might be linked to intestinal dysbiosis. ...Microorganisms could be used as potential microbiota-mediated metabolites therapy to target the estrobolome in endometriosis. What is known already Endometriosis (EMs) is a chronic estrogenic-dependent gynaecological condition with a complex and multifactorial aetiology, characterized by the presence of endometrial glands and endometrial-like tissue outside the uterus, accompanied by a severe inflammatory process. Sampson’s theory of retrograde menstruation is considered one of the most convincing hypotheses for the origin of EMs. Recently, the human microbiome has been linked to its pathogenesis, and exits some evidence that it might modulate the immune system from the gut, therefore the generation of a dysfunctional immune response caused by intestinal dysbiosis might play an important role in the initiation and progression of EMs. Study design, size, duration A case-control study was designed to analyse intestinal microbiome from EMs patients and age-matched healthy women. Herein, we aim to investigate for potential intestinal biomarkers related to the pathology. The recruitment was through health questionnaires such as EHP-5 setting the initial cohort at 243 women. This initial cohort was screened according to inclusion and exclusion criteria. Participants/materials, setting, methods Seventy-seven women met eligibility criteria and were enrolled in the study. Stool samples from the controls group (n = 43) and patients with a positive diagnosis of EMs (n = 34) were collected and subjected to 16S rRNA gene sequencing using the V3-V4 regions. Various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota. Main results and the role of chance The number of significantly different taxa between healthy controls and EMs patients were 18 (p-value<0.05). Among these 18 taxa, we found 3 families: Bacteroidaceae, Lactobacillaceae and Desulfovibrionaceae; 3 genera: Blautia, Anaerostipes and Lachnospira; and 12 species: Roseburia intestinalis, Bacteroides uniformis, Anaerobutyricum hallii, among others), with a higher diversity of families and genera in the patient group, while the control group had a higher diversity of species, according to the results of Shannon and Simpsońs indexes. This suggests that EMs is dominated by a few species belonging to a wide variety of families and genera, while in the control group there is a greater variability of intestinal species belonging to a smaller number of families and genera. These taxa were related with molecular routes implied in the management of inflammation and estrogens signalling. Additionally, the data were correlated with clinical parameters through the Endometriosis Health Profile-5 questionnaire (EHP-5). This correlation shows significant differences specifically into the «self-image» variable and the total score with the genus diversity (positive and negative correlations were reported), with a strong positive correlations between the variable “Infertility” and the genus Anaerostipes. Limitations, reasons for caution Pronacera develops molecular tests for several conditions that involve the analysis of genes, proteins, and microbes in human samples. Neither the patients nor the healthcare professionals participating in this study have been paid or influenced whatsoever. Hence, the authors report no other potential conflicts of interest. Wider implications of the findings The aetiopathogenesis of EMs might be linked to intestinal dysbiosis. In this sense, the taxa identified in this study and its estrobolome-related metabolite could play a key role in the initiation of the disease, proposing themselves as potential prognostic, diagnostic and therapeutic targets for the future. Trial registration number not applicable
Objectives
The effects of antiretroviral drugs on the response to pegylated interferon plus ribavirin remain uncertain. We evaluated whether antiretroviral drugs affected the response to pegylated ...interferon plus ribavirin in patients co-infected with HIV and hepatitis C virus (HCV).
Methods
We conducted a retrospective analysis of two cohorts of HIV/HCV-co-infected patients treated with pegylated interferon plus ribavirin between 2001 and 2007 in Spain. The outcome measure was sustained virological response (SVR). Logistic regression models were used to test possible associations between non-response and pre-treatment characteristics, including accompanying antiretroviral drugs.
Results
The study sample comprised 1701 patients: 63% were infected with HCV genotype (G) 1 or 4 and 88% were taking highly active antiretroviral therapy (HAART). Factors independently associated with increased odds of SVR were G2 or 3, HVC RNA <500 000 IU/mL and CDC clinical category A or B. When we adjusted for these prognostic factors and dose of ribavirin/kg, the adjusted odds ratio (AOR) of SVR for patients without HAART was 1.31 95% confidence interval (CI) 0.91-1.88; P = 0.144. Taking the backbone of tenofovir and lamivudine/emtricitabine as a reference, we found that, with the exception of regimens including zidovudine, the effect of other nucleoside reverse transcriptase inhibitor backbones had little effect on SVR. The AOR of SVR for zidovudine and lamivudine was 0.65 (95% CI 0.46-0.93, P = 0.017). We carried out several sensitivity analyses, the results of which were consistent with the findings of the primary analysis.
Conclusions
Our results suggest that, with the exception of regimens including zidovudine, accompanying antiretroviral drugs have little effect on the virological response to pegylated interferon plus ribavirin in HIV/HCV-co-infected patients.
A total of 125 accessions of one-flowered vetch (Vicia articulata Hornem.) mostly from the Iberian Peninsula have been analysed for total protein, L-canavanine and condensed tannins. It was observed ...a high variability in the composition: the protein content ranged from 18.20 to 30.07%, L-canavanine from 0.27 to 0.67%, and condensed tannins from 0.13 to 0.35%, which indicates a scarce domestication of the crop. The inclusion of the seeds into a diet to non-ruminants should be limited to marginal percentages because of the contents of L-canavanine and it suggests that a reduction of this compound by breeding should be encouraged. The protein and the L-canavanine contents showed a low and positive significant correlation (r = 0.55, P < 0.001), which complicates the selection of seeds having simultaneously low L-canavanine and high protein contents. On the other hand, no correlation between protein and condensed tannins or between L-canavanine and condensed tannins was observed. There was a poor relationship between the origin and the composition of the accessions and only the protein content was able to discriminate among the regions.
The influence of body mass index (BMI) on oral cancer risk was evaluated in 375 incident cases and 375 age-gender-matched hospital-based controls. Low BMIs at diagnosis and 2 years before diagnosis ...were associated with significantly elevated odds ratios (OR for BMI < or =22 vs >26 kg m(-2); 3.64; 95% confidence interval, CI: 2.27-5.82 and 3.31; 95% CI: 2.04-5.39, respectively). The association with low BMI, however, tended to be weaker and nonsignificant among never smokers and never drinkers.
OBJECTIVESTo analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. MATERIAL AND METHODSWe evaluated 32 ...consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. RESULTSIn our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. CONCLUSIONSDespite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression.
► Prospects for DM searches with CTA at various targets. ► Prospects for ALP searches with CTA. ► Prospects for LIV searches with CTA. ► Prospects for neutrinos, magnetic monopoles and gravitational ...waves searches with CTA.
The Cherenkov Telescope Array (CTA) is a project for a next-generation observatory for very high energy (GeV–TeV) ground-based gamma-ray astronomy, currently in its design phase, and foreseen to be operative a few years from now. Several tens of telescopes of 2–3 different sizes, distributed over a large area, will allow for a sensitivity about a factor 10 better than current instruments such as H.E.S.S, MAGIC and VERITAS, an energy coverage from a few tens of GeV to several tens of TeV, and a field of view of up to 10°. In the following study, we investigate the prospects for CTA to study several science questions that can profoundly influence our current knowledge of fundamental physics. Based on conservative assumptions for the performance of the different CTA telescope configurations currently under discussion, we employ a Monte Carlo based approach to evaluate the prospects for detection and characterisation of new physics with the array.
First, we discuss CTA prospects for cold dark matter searches, following different observational strategies: in dwarf satellite galaxies of the Milky Way, which are virtually void of astrophysical background and have a relatively well known dark matter density; in the region close to the Galactic Centre, where the dark matter density is expected to be large while the astrophysical background due to the Galactic Centre can be excluded; and in clusters of galaxies, where the intrinsic flux may be boosted significantly by the large number of halo substructures. The possible search for spatial signatures, facilitated by the larger field of view of CTA, is also discussed. Next we consider searches for axion-like particles which, besides being possible candidates for dark matter may also explain the unexpectedly low absorption by extragalactic background light of gamma-rays from very distant blazars. We establish the axion mass range CTA could probe through observation of long-lasting flares in distant sources. Simulated light-curves of flaring sources are also used to determine the sensitivity to violations of Lorentz invariance by detection of the possible delay between the arrival times of photons at different energies. Finally, we mention searches for other exotic physics with CTA.
Around one third of the point-like sources in the Fermi-LAT catalogs remain as unidentified sources (unIDs) today. Indeed, these unIDs lack a clear, univocal association with a known astrophysical ...source. If dark matter (DM) is composed of weakly interacting massive particles (WIMPs), there is the exciting possibility that some of these unIDs may actually be DM sources, emitting gamma rays from WIMPs annihilation. We propose a new approach to solve the standard, Machine Learning (ML) binary classification problem of disentangling prospective DM sources (simulated data) from astrophysical sources (observed data) among the unIDs of the 4FGL Fermi-LAT catalogue. We artificially build two {\it systematic} features for the DM data which are originally inherent to observed data: the detection significance and the uncertainty on the spectral curvature. We do it by sampling from the observed population of unIDs, assuming that the DM distributions would, if any, follow the latter. We consider different ML models: Logistic Regression, Neural Network (NN), Naive Bayes and Gaussian Process, out of which the best, in terms of classification accuracy, is the NN, achieving around \(93.3\% \pm 0.7\%\) performance. Other ML evaluation parameters, such as the True Negative and True Positive rates, are discussed in our work. Applying the NN to the unIDs sample, we find that the degeneracy between some astrophysical and DM sources can be partially solved within this methodology. Nonetheless, we conclude that there are no DM source candidates among the pool of 4FGL Fermi-LAT unIDs.
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