The economically most important honey bee species,
Apis mellifera, was formerly considered to be parasitized by one microsporidian,
Nosema apis. Recently, Higes, M., Martín, R., Meana, A., 2006.
...Nosema ceranae, a new microsporidian parasite in honeybees in Europe, J. Invertebr. Pathol. 92, 93–95 and Huang, W.-F., Jiang, J.-H., Chen, Y.-W., Wang, C.-H., 2007. A
Nosema ceranae isolate from the honeybee
Apis mellifera. Apidologie 38, 30–37 used 16S (SSU) rRNA gene sequences to demonstrate the presence of
Nosema ceranae in
A. mellifera from Spain and Taiwan, respectively. We developed a rapid method to differentiate between
N. apis and
N. ceranae based on PCR–RFLPs of partial SSU rRNA. The reliability of the method was confirmed by sequencing 29 isolates from across the world (
N =
9 isolates gave
N. apis RFLPs and sequences,
N =
20 isolates gave
N. ceranae RFLPs and sequences; 100% correct classification). We then employed the method to analyze
N =
115 isolates from across the world. Our data, combined with
N =
36 additional published sequences demonstrate that (i)
N. ceranae most likely jumped host to
A. mellifera, probably within the last decade, (ii) that host colonies and individuals may be co-infected by both microsporidia species, and that (iii)
N. ceranae is now a parasite of
A. mellifera across most of the world. The rapid, long-distance dispersal of
N. ceranae is likely due to transport of infected honey bees by commercial or hobbyist beekeepers. We discuss the implications of this emergent pathogen for worldwide beekeeping.
In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom ...unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited.
This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed.
Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval CI, 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals.
After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
Objective:
There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response ...(SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting.
Design:
A multicentric prospective cohort study.
Methods:
HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5 kPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point.
Results:
One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7–24) months, ascites 14 (6–29) months, hepatocellular carcinoma (HCC) 17 (11–42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22–38) months (
P
= 0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) median (Q1-Q3) time to emergence 12.7 (6.6–28.2) months vs. 25.4 (12.5–41.53) months, respectively (
P
= 0.026).
Conclusion:
The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.
Abstract
Background
The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with ...hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA).
Methods
Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients.
Results
In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1–Q3) follow-up time of 43 (31–49) months, 19 (1.8%) patients developed HCC (11 3.0%; HCV-monoinfected, 81.2%; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio sHR = 0.27, 95% confidence interval CI: .08–.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5–24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01–1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01–1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11–.85).
Conclusions
Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use ...Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.
BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening ...programme to detect CTEPH in PE survivors.MethodsThis was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC.ResultsOut of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed.ConclusionsThe implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier.Trial registration numberNCT03953560.
Background. It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of ...levofloxacin. Methods. An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded. Results. CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days). Conclusions. Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.
Mapas de mercedes en Calpan Hernández Alonso, María José; Ruz Barrio, Miguel Ángel
Anales de antropología,
12/2019, Letnik:
53, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Los mapas coloniales de tradición hispanoindígena fueron un recurso legal que cumplía una función administrativa, por esta razón, no tenían una exhaustividad científica. Algunos de estos ejemplares ...se encuentran resguardados en el Archivo General de la Nación y son una fuente valiosa para la reconstrucción de ciertos espacios físicos. El objetivo de este artículo es contextualizar y reconstruir el espacio geográfico del pueblo de indios de Calpan al que hacen referencia dos mapas que tienen la característica de que representan espacios colindantes, fueron elaborados en fechas cercanas, pero son estéticamente distintos. Para esta labor, empleamos otros documentos y el trabajo de campo.
In symptomatic acute pulmonary embolism (PE), the presence of deep vein thrombosis (DVT) is a risk factor for 30- and 90-day mortality. In patients with cancer and incidental PE, the prognostic ...effect of concomitant incidental DVT is unknown. In this retrospective study, we examined the effect of incidental DVT on all-cause mortality in such patients. Adjusted Cox multivariate regression analysis was used for relevant covariates. From January 2010 to March 2018, we included 200 patients (mean age, 65.3 ± 12.4 years) who were followed up for 12.5 months (interquartile range 7.4–19.4 months). Of these patients, 62% had metastases, 31% had concomitant incidental DVT, and 40.1% (n = 81) died during follow-up. All-cause mortality did not increase in patients with DVT (hazard ratio HR 1.01, 95% confidence interval CI 0.43–2.75, p = 0.855). On multivariate analysis, weight (adjusted HR 0.96, 95% CI 0.92–0.99, p = 0.032), and metastasis (adjusted HR 10.26, 95% CI 2.35–44.9, p = 0.002) were predictors of all-cause mortality. In conclusion, low weight and presence of metastases were associated with all-cause mortality, while presence of concomitant DVT was unrelated to poorer survival.
Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic ...control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/.
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