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The causative mutation responsible for limb girdle muscular dystrophy 1F (LGMD1F) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene (TNPO3). This mutation causes a carboxy-terminal extension of 15 amino acids, producing a protein of unknown function (TNPO3_mut) that is co-expressed with wild-type TNPO3 (TNPO3_wt). TNPO3 has been involved in the nuclear transport of serine/arginine-rich proteins such as splicing factors and also in HIV-1 infection through interaction with the viral integrase and capsid. We analyzed the effect of TNPO3_mut on HIV-1 infection using PBMCs from patients with LGMD1F infected ex vivo. HIV-1 infection was drastically impaired in these cells and viral integration was reduced 16-fold. No significant effects on viral reverse transcription and episomal 2-LTR circles were observed suggesting that the integration of HIV-1 genome was restricted. This is the second genetic defect described after CCR5Δ32 that shows strong resistance against HIV-1 infection. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to characterize the bacterial microbiome of hard ticks with affinity to bite humans in La Rioja (North of Spain). Methods: A total of 88 adult ticks (22 Rhipicephalus sanguineus sensu lato, 27 Haemaphysalis punctata, 30 Dermacentor marginatus and 9 Ixodes ricinus) and 120 I. ricinus nymphs (CRETAV collection, La Rioja, Spain), representing the main anthropophilic species in our environment, were subjected to a metagenomic analysis of the V3-V4 region of the 16S rRNA gene using an Illumina MiSeq platform. Data obtained with Greengenes database were refined with BLAST. Four groups of samples were defined, according to the four tick species. Results: Proteobacteria was the predominant phylum observed in all groups. Gammaproteobacteria was the most abundant class, followed by Alphaproteobacteria for R. sanguineus, H. punctata and D. marginatus but the relative abundance of reads for these classes was reversed for I. ricinus. This tick species showed more than 46% reads corresponding to ‘not assigned’ OTUs (Greengenes), and >97% of them corresponded to ‘Candidatus Midichloriaceae’ using BLAST. Within Rickettsiales, ‘Candidatus Midichloria’, Rickettsia, Ehrlichia, ‘Candidatus Neoehrlichia’ and Wolbachia were detected. I. ricinus was the most alpha-diverse species. Regarding beta-diversity, I. ricinus and H. punctata samples grouped according to their tick species but microbial communities of some R. sanguineus and D. marginatus specimens clustered together. Conclusions: The metagenomics approach seems useful to discover the spectrum of tick-related bacteria. More studies are needed to identify and differentiate bacterial species, and to improve the knowledge of tick-borne diseases in Spain. [ABSTRACT FROM AUTHOR]

Recently, the interest in studying pancreatic cancer mortality has increased due to its high lethality. In this work a detailed analysis of pancreatic cancer mortality in Spanish provinces was performed using recent data. A set of multivariate spatial gender-age-period-cohort models was considered to look for potential candidates to analyze pancreatic cancer mortality rates. The selected model combines features of APC (age-period-cohort) models with disease mapping approaches. To ensure model identifiability sum-to-zero constraints were applied. A fully Bayesian approach based on integrated nested Laplace approximations (INLA) was considered for model fitting and inference. Sensitivity analyses were also conducted. In general, estimated average rates by age, cohort, and period are higher in males than in females. The higher differences according to age between males and females correspond to the age groups [65, 70), [70, 75), and [75, 80). Regarding the cohort, the greatest difference between men and women is observed for those born between the forties and the sixties. From there on, the younger the birth cohort is, the smaller the difference becomes. Some cohort differences are also identified by regions and age-groups. The spatial pattern indicates a North-South gradient of pancreatic cancer mortality in Spain, the provinces in the North being the ones with the highest effects on mortality during the studied period. Finally, the space-time evolution shows that the space pattern has changed little over time. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to describe prior negative screening history and symptoms around the time of diagnosis of incident cervical cancer (CC) cases diagnosed between 2000 and 2010 within the Asturias public health system. Methods: Records from 374 women diagnosed with CC between 2000 and 2010 from all public hospitals in Asturias were retrieved. Clinical information, FIGO stage and all previous cytological data were extracted from clinical and histopathological records. Proportional differences were assessed using chi-square tests. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Inter-observer agreement in cytology was checked by comparing concordance values using k-statistics. Results: No prior screening history was recorded in 60.7% of CC cases and its absence increased with age and advanced stage. Advanced stage (e.g., ≥ II) at diagnosis was associated with age (>50 years) and adenocarcinoma (ADC) compared to younger women and those with a squamous cell carcinoma (SCC). False negative smears were identified in 27.1% of women with CC (ADC 52.6% vs. SCC 16.2%, p<0.05). Conclusions: Absence of prior screening history was common among CC cases. Organized actions to reduce “under screening” and the use of highly sensitive HPV-based tests could be useful strategies in reducing the burden of CC in Asturias. [ABSTRACT FROM AUTHOR]

Abstract: Toxicovigilance is the active process of identifying and evaluating the toxic risks existing in a community, and evaluating the measures taken to reduce or eliminate them. Objective: Through a validated toxicovigilance program (SAT-HULP) we examined the characteristics of acute poisoning cases (APC) attended in the Emergency Department (ED) of La Paz Hospital (Madrid, Spain) and assessed their economic impact on the health system. Material and Methods: The active poisoning surveillance system performs a daily search for cases in the hospital´s computerized case records. Found cases are entered into a database for recording of type of poisoning episode, reasons for exposure, causative agent, signs and symptoms and treatment. We carried out a cross-sectional epidemiological study with analytical projection, based on an impact study on cost per survivor. The data for the costs attributable to cases of APC observed at HULP (outpatients and inpatients) was obtained from the based on the information provided by the diagnosis-related groups (DRG) through the corresponding hospital discharge reports (available through SAT-HULP). Results: During the first 30 month of SAT-HULP operation we found a total of 3,195 APC, a cumulative incidence rate of 1.75% of patients attended in the ED. The mean (SD) patient age was 40.9 (17.8) years and 51.2% were men. Drug abuse accounted for 47.5% of the cases. Suicide attempt was the second most frequent category (38.1%) and other causes accounted for 14.5% of APC. The total cost of hospital care for our hospital rose to €1,825,263.24 (approximately €730,105.30/year) resulting in a permanent occupation of 4 beds/year. Conclusions: SAT-HULP constitutes a validated toxicovigilance tool, which continuously integrates available data in real-time and helps health services manage APC data flexibly, including the consumption of resources from the health system. [ABSTRACT FROM AUTHOR]

Background and Aim: Serum IgG4 concentrations are commonly measured in clinical practice. The aim of this study was to investigate serum IgG4 concentrations in adults and their potential relationship with demographic, lifestyle, metabolic, and allergy-related factors. Methods: Serum IgG4 concentrations were measured with a commercial assay in 413 individuals (median age 55 years, 45% males) who were randomly selected from a general adult population. Results: Median IgG4 concentration was 26.8 mg/dL. Five out of the 413 individuals (1.2%) exhibited IgG4 concentrations >135 mg/dL, and 17 out of 411 (4.1%) exhibited an IgG4/total IgG ratio >8%. Serum IgG4 concentrations were significantly higher in males than in females and decreased with age. After adjusting for age and sex, serum IgG4 concentrations were not significantly influenced by alcohol consumption, smoking or common metabolic abnormalities (obesity and the related metabolic syndrome). Serum IgG4 concentrations were not significantly correlated with serum concentrations of proinflammatory cytokines and inflammation markers. Serum IgG4 concentrations were significantly correlated with IgE concentrations. Serum IgG4 concentrations tended to be higher in atopics (individuals with IgE-mediated sensitization to aeroallergens) than in non-atopics, particularly among atopics without respiratory symptoms. Serum IgG4 concentrations were not significantly correlated with total eosinophil blood count. Cases of IgG4-related disease were neither present at baseline nor detected after a median of 11 years of follow-up. Conclusions: Studies aimed at defining reference IgG4 values should consider partitioning by age and sex. Further studies are needed to confirm the potential influence of atopy status on serum IgG4 concentrations. [ABSTRACT FROM AUTHOR]