Background: Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism.
Design: This was a prospective study to evaluate the uric acid levels and ...fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment.
Results: The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17β (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01).
Conclusions: Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an ...active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of
and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.
Introduction
Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain ...cases genotype–phenotype correlations are important for predicting the clinical course of the disease and to allow tailor‐made follow‐up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next‐generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost.
Aim
The aim of this study was to design and to analyse the applicability of a 23‐gene NGS panel in the molecular diagnosis of patients with IBCDs.
Methods
A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology.
Results
In all patients, our NGS approach detected causative mutations. Twenty‐one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant.
Conclusion
Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.
Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.Design Prospective cohort study with estimates of ...relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension.Setting Spanish university department.Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.Main outcome measures Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.
The origin of the unification model for active galactic nuclei (AGN) was the detection of broad hydrogen recombination lines in the optical polarized spectrum of the Seyfert 2 galaxy (Sy2) NGC 1068. ...Since then, a search for the hidden broad-line region (HBLR) of nearby Sy2s started, but polarized broad lines have only been detected in ∼30–40 per cent of the nearby Sy2s observed to date. Here we present new VLT/FORS2 optical spectropolarimetry of a sample of 15 Sy2s, including Compton-thin and Compton-thick sources. The sample includes six galaxies without previously published spectropolarimetry, some of them normally treated as non-hidden BLR (NHBLR) objects in the literature, four classified as NHBLR, and five as HBLR based on previous data. We report ≥4σ detections of a HBLR in 11 of these galaxies (73 per cent of the sample) and a tentative detection in NGC 5793, which is Compton-thick according to the analysis of X-ray data performed here. Our results confirm that at least some NHBLRs are misclassified, bringing previous publications reporting differences between HBLR and NHBLR objects into question. We detect broad Hα and Hβ components in polarized light for 10 targets, and just broad Hα for NGC 5793 and NGC 6300, with line widths ranging between 2100 and 9600 km s−1. High bolometric luminosities and low column densities are associated with higher polarization degrees, but not necessarily with the detection of the scattered broad components.
Microorganisms drive the degradation of organic matter thanks to their enzymatic versatility. However, the structure of lignocellulose poses a great challenge for the microbiota inhabiting a compost ...pile. Our purpose was to increase the biodegradability of vegetable waste in the early stages of the composting process by applying a microbial consortium with lignocelllulolytic capacity. For this, a previous screening was performed among the culturable microbiota from different composting processes to find inoculants with ligninocellulolytic activity. Selected strains were applied as a pure culture and as a microbial consortium. The starting material was composed of tomato plant and pruning remains mixed in a ratio (50:50 v/v), whose humidity was adjusted to around 65%. To determine the ability of both treatments to activate the biodegradation of the mixtures, moisture, organic matter, ash, C/N ratio, 4-day cumulative respirometric index (AT4) and degradation rates of cellulose, hemicellulose and lignin were evaluated. Subsequently, a real composting process was developed in which the performance of the microbial consortium was compared with the composting process without inoculum (control). According to our tests, three microbial strains (Bacillus safensis, Bacillus licheniformis and Fusarium oxysporum) were selected. The results showed that the application of the bacteria strains at low doses (104 CFU g−1 on the complete residual material of the pile) resulted in higher rates of lignocelullose degradation after 10 days of treatment compared to that observed after application of the fungus in pure culture or untreated controls. The implementation of the strategy described in this work resulted in obtaining compost with better agronomic quality than the uninoculated controls. Therefore, the application of this consortium could be considered as an interesting tool for bioactivation of lignocellulosic waste prior to the composting process.
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•Resident lignocellulolytic microbiota is useful to improve the composting process.•A simple protocol for the pretreatment of plant wastes was developed.•Bacillus spp. represent an excellent biotechnological tool in composting processes.•10 days of pretreatment at low inoculum doses improves the final product quality.
The abuse of chemical fertilizers in recent decades has led the promotion of less harmful alternatives, such as compost or aqueous extracts obtained from it. Therefore, it is essential to develop ...liquid biofertilizers, which in addition of being stable and useful for fertigation and foliar application in intensive agriculture had a remarkable phytostimulant extracts. For this purpose, a collection of aqueous extracts was obtained by applying four different Compost Extraction Protocols (CEP1, CEP2, CEP3, CEP4) in terms of incubation time, temperature and agitation of compost samples from agri-food waste, olive mill waste, sewage sludge and vegetable waste. Subsequently, a physicochemical characterization of the obtained set was performed in which pH, electrical conductivity and Total Organic Carbon (TOC) were measured. In addition, a biological characterization was also carried out by calculating the Germination Index (GI) and determining the Biological Oxygen Demand (BOD5). Furthermore, functional diversity was studied using the Biolog EcoPlates technique. The results obtained confirmed the great heterogeneity of the selected raw materials. However, it was observed that the less aggressive treatments in terms of temperature and incubation time, such as CEP1 (48 h, room temperature (RT)) or CEP4 (14 days, RT), provided aqueous compost extracts with better phytostimulant characteristics than the starting composts. It was even possible to find a compost extraction protocol that maximize the beneficial effects of compost. This was the case of CEP1, which improved the GI and reduced the phytotoxicity in most of the raw materials analyzed. Therefore, the use of this type of liquid organic amendment could mitigate the phytotoxic effect of several composts being a good alternative to the use of chemical fertilizers.
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•Compost extracts improve the biofertilizing characteristics of the compost.•Temperature and incubation periods mainly determine the quality of the extracts.•The phytotoxic effect of composts is reduced by the use of compost extracts.•Moderate temperatures guarantee the preservation of microbial functionality.
Background and purpose
Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast‐enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels in vivo. Our aim ...was to determine if CEUS‐detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis.
Methods
We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow‐up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence.
Results
We included 78 patients whose mean age was 74.3 ± 10.4 years. There were 29 (37.2%) patients with a low‐grade stenosis (<50%). The remainder presented moderate (50%–69%) or high‐grade (≥70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow‐up of 14.1 (interquartile range, 9.5‐19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS‐detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66–26.01).
Conclusion
In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.
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