Abstract
The Gene Ontology resource (GO; http://geneontology.org) provides structured, computable knowledge regarding the functions of genes and gene products. Founded in 1998, GO has become widely ...adopted in the life sciences, and its contents are under continual improvement, both in quantity and in quality. Here, we report the major developments of the GO resource during the past two years. Each monthly release of the GO resource is now packaged and given a unique identifier (DOI), enabling GO-based analyses on a specific release to be reproduced in the future. The molecular function ontology has been refactored to better represent the overall activities of gene products, with a focus on transcription regulator activities. Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations. New evidence codes for high-throughput experiments now enable users to filter out annotations obtained from these sources. GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models. We also provide the ‘GO ribbon’ widget for visualizing GO annotations to a gene; the widget can be easily embedded in any web page.
There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We ...investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients.
We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point.
We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 25th–75th percentiles: 7.8–9.9 ml kg−1 predicted body weight, PEEP was 4 1–5 cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m−2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001).
Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients.
NCT01601223.
The traditional production of wine vinegar is a lengthy process with little or no microbiological control. The aim of this study was to shorten the acetification process via three different ...strategies: changes in wood type; barrel shape; and the inoculation of an
Acetobacter pasteurianus pure culture. The barrel shape was modified by constructing two prototypes with higher liquid–air interface. We compared the changes in acetic acid bacteria (AAB) population dynamics in these barrels with those of a submerged method. The wood type had no effect on the acetification length, whereas the shape of the barrel resulted in a significant shortening of the acetification length. Although the selected AAB strain did not always take over, it reduced the biodiversity of the AAB. The inoculated strain was predominant in oak barrels, whereas in the highly aerated prototypes
Gluconacetobacter species (
Ga. intermedius and/or
Ga. europaeus) displaced
A. pasteurianus, as what occurs in the submerged method.
Objectives
We assessed the prevalence of anti‐hepatitis C virus (HCV) antibodies and active HCV infection (HCV‐RNA‐positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results ...with those of four similar studies performed during 2015–2018.
Methods
The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation.
Results
The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)‐positive (78.7% were prior injection drug users); 29 were HCV‐RNA‐positive (2.2%). Of the 29 HCV‐RNA‐positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV‐RNA‐positive patients and 68 (23.4%) of those who cleared HCV after anti‐HCV therapy (p = 0.04). The prevalence of anti‐HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti‐HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001).
Conclusions
In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct‐acting antiviral agents, HCV‐related cirrhosis remains significant in this population.
Summary
We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000‐2015), and we relate them with clinical, epidemiological and virological factors. Patients from ...29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla‐Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV‐infected patients with the following characteristics: median age 51 years (IQR, 44‐58), 67.9% male, 19.1% HIV‐coinfected, 23.5% HBV‐coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono‐infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.
We analysed hepatitis C virus (HCV) reinfection among participants in a prospective registry of HIV/HCV-coinfected patients treated with all-oral direct-acting antiretroviral (DAA)-based therapy in ...the region of Madrid.
An observational cohort study.
The study period started on the date sustained viral response (SVR) was confirmed. The censoring date was 31 December 2017. SVR was defined as negative HCV-RNA 12 weeks after completion of treatment. Reinfection was defined as a positive HCV-RNA test result after achievement of SVR.
Reinfections were detected in 17 of 2359 HIV/HCV-coinfected patients (0.72%) overall, in 12 out of 177 (6.78%) MSM and in five out of 1459 (0.34%) people who inject drugs (PWID). The incidence of reinfection 95% confidence interval (95% CI) per 100 person-years was 0.48 (0.30-0.77) overall, 5.93 (3.37-10.44) for MSM and 0.21 (0.09-0.52) for PWID. Reinfections were detected a median of 15 weeks (interquartile range 13-26) after SVR. In 10 (58.82%) patients, the reinfection was caused by a different HCV genotype. All 12 MSM with reinfection acknowledged unprotected anal intercourse with several partners, seven used chemsex, six reported fisting and four practiced slamming. A concomitant STI was detected in five patients. Four IDU with reinfection reported injecting drugs following SVR.
HCV reinfection is a matter of concern in HIV-positive MSM treated with all-oral DAA therapy in the region of Madrid. Our data suggest that prevention strategies and frequent testing with HCV-RNA should be applied following SVR in MSM who engage in high-risk practices.
Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. ...However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring.
We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously.
Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP.
Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.
Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the ...largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain.
A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection.
Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia).
HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non-Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection.
HIV coinfection is infrequent (<5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.
: Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop ...life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers.
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