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OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.
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Infecciones por VIH , Hepatitis C , Minorías Sexuales y de Género , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Homosexualidad Masculina , Humanos , Incidencia , Masculino , España/epidemiologíaRESUMEN
BACKGROUND: Induction of labor (IL) involves an overload of work in hospitals, as well as increased intervention. Traditionally, the Bishop score (BS) has been used to predict the outcome of a IL, but there is a growing interest in studying the predictive capacity of ultrasound variables. OBJECTIVE: Validate a pilot predictive model performed by a single observer (Alvarez-Colomo C), based on clinical parameters and ultrasound parameters, that showed a significant association with the IL result, obtaining a correct prediction of vaginal delivery in 82.8%, with 15% false positive (FP). This validation was carried out under the usual conditions of clinical practice by four observers without distinction. METHODS: A prospective, observational study was conducted between September 2010-July 2012, recruiting 231 single pregnancies (Group 2), who were to initiate the IL process, according to the methodology and inclusion criteria of the Alvarez-Colomo study (Group 1151 patients). The outcome variable was the method of delivery. RESULTS: Only fetal head-perineal distance (FHPD), cervical length (CL) and BS showed significant association with the result of IL. After applying the logistic regression equation of the pilot study, the model developed by these four observers reached a predictive capacity of 70.74% (FP = 20%). Clinical characteristics were similar in both groups. Statistically significant differences were found between the two groups for: FHPD, posterior cervical angle (PCA) and funnel existence. CONCLUSION: It has not been possible to validate the mathematical model of Alvarez's study in the daily conditions of clinical practice, probably due to differences in the ultrasound measurement of FHPD.
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Cuello del Útero/diagnóstico por imagen , Parto Obstétrico/métodos , Trabajo de Parto Inducido/métodos , Ultrasonografía Prenatal/métodos , Adulto , Femenino , Humanos , Proyectos Piloto , Embarazo , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Soil erosion affects agricultural production by reducing the area of rural properties and altering the dynamics of watersheds. Gullies are a complex and irregular type of erosion form that can reach large dimensions, and studying gullies to stabilize erosion processes is a challenge. This study aims to understand their environmental relationships as a basis for future research and to recover land degraded by soil erosion. We combined mapping techniques using geographic information system (GIS) with temporal evolution of land use and fractal dimensions of gullies using FracLac to determine the stability of gullies in a watershed in south Minas Gerais (Brazil). We used R software to apply linear regressions and tested the statistics to verify the compatibility of the model. Environmental characteristics of the watershed contribute to the formation of gullies, but human activities influence the deflagration of these features. The temporal evolution of the land use demonstrated that nearly 50% of the watershed was used as pastures throughout the years, which contributed to soil degradation. The evolution of the fractal dimension showed fluctuations over the years, indicating that the gullies are not stable. The regressions suggest that the vegetation, geology, land use, channel order, and curvature may influence the fractal dimensions of gullies. We concluded that human activity influences the evolution of gullies; the use of techniques such as vegetation measures can contribute to the stabilization of gullies. We also concluded that fractal analysis is an interesting tool for performing environmental evaluations of irregular and complex features, such as gullies.
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Conservación de los Recursos Naturales , Sistemas de Información Geográfica , Brasil , Monitoreo del Ambiente , Fractales , SueloRESUMEN
In North America, the raccoon-associated variant of rabies virus (RRV) is of special concern, given its relatively rapid spread throughout the eastern USA and its potential public health impact due to high raccoon host densities in urban areas. Northward expansion of this epizootic included an outbreak in the Canadian province of Quebec in 2006-2009 due to trans-border spread from the State of Vermont. To inform a more proactive approach to future control efforts, this study uses phylogenetic analyses to explore the role of geography and alternative carnivore hosts in the dynamics of RRV spread within Vermont. Specifically, we sought to examine whether striped skunks, a species frequently infected by RRV, could be part of the maintenance host community. Whole genome sequencing of 160 RRV samples from Vermont and neighbouring US states were used for fine-scale phylogeographic analyses. Results, together with the complete surveillance record of raccoon rabies since its entry into Vermont in 1994, document incursions by two distinct viral lineages and identify topographical features of the landscape which have significantly influenced viral spread, resulting in a complex distribution pattern of viral variants throughout the state. Results of phylogenetic cluster analysis and discrete state reconstruction contained some evidence of skunk-to-skunk and skunk-to-raccoon transmission but overall failed to support a role for skunks as alternative maintenance hosts.
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Brotes de Enfermedades , Transmisión de Enfermedad Infecciosa , Virus de la Rabia/aislamiento & purificación , Rabia/veterinaria , Mapaches , Zoonosis/epidemiología , Animales , Análisis por Conglomerados , Monitoreo Epidemiológico , Genotipo , Geografía , Mephitidae , Epidemiología Molecular , Filogenia , Rabia/epidemiología , Rabia/transmisión , Virus de la Rabia/clasificación , Virus de la Rabia/genética , Análisis de Secuencia de ADN , Vermont/epidemiología , Secuenciación Completa del Genoma , Zoonosis/transmisiónRESUMEN
OBJECTIVES: The aim of the study was to analyse the frequency and degree of potential drug-drug interactions (DDIs) between direct-acting antivirals (DAAs) and concomitant medication used by HIV/hepatitis C virus (HCV)-coinfected patients, including antiretroviral therapy (ART) and other drugs. METHODS: All patients with HIV infection and viraemic HCV genotype 1, 3 or 4 coinfection attending a tertiary care centre in Spain (November 2014 to November 2015) were included in the study. DDIs were classified as major, i.e. drugs should not be co-administered, or minor, i.e. close monitoring, dosage alteration or change in timing may be required if drugs are co-administered, following the http://www.hep-druginteractions.org database recommendations. RESULTS: A total of 244 patients were included in the study, of whom 224 (92%) were previous injecting drug users. Major DDIs were found for: paritaprevir-r/ombitasvir plus dasabuvir (3D), in 60 (44%) of 138 individuals with genotype 1; paritaprevir-r/ombitasvir (2D), in 22 (37%) of 60 individuals with genotype 4; sofosbuvir/ledipasvir (SOF/LDV), in four (2%) of 198 patients with genotype 1 or 4; simeprevir (SMV) plus SOF, in 160 (81%) of 198 patients with genotype 1 or 4; daclatasvir (DCV) plus SOF, in seven (3%) of 244 patients with genotype 1, 3 or 4 (P < 0.001). Minor DDIs were found for: 3D, in 123 (89%) individuals with genotype 1; 2D, in 52 (87%) individuals with genotype 4; SOF/LDV, in 154 (78%) patients with genotype 1 or 4; SMV plus SOF, in 129 (65%) patients with genotype 1 or 4; DCV plus SOF, in 149 (61%) patients with genotype 1, 3 or 4 (P < 0.001). CONCLUSIONS: Drug-drug interactions between DAAs and ART or other commonly prescribed medications are frequently found among HIV/HCV-coinfected patients. Potential major and minor DDIs are more frequent with 3D, 2D and SMV plus SOF regimens.
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Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Interacciones Farmacológicas , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Centros de Atención TerciariaRESUMEN
OBJECTIVES: Fatty liver disease (FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV-infected patients. METHODS: FLD was defined as a value of the controlled attenuation parameter (CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population. RESULTS: Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [P = 0.009; adjusted odds ratio 1.88; 95% confidence interval (CI) 1.17-3.01]. CONCLUSIONS: Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Hígado Graso/genética , Predisposición Genética a la Enfermedad , Infecciones por VIH/complicaciones , Obesidad/complicaciones , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Diagnóstico por Imagen de Elasticidad , Hígado Graso/patología , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Nanocapsules (NCs) are submicron-sized core shell systems which present important advantages such as improvement of drug efficacy and bioavailability, prevention of drug degradation, and provision of controlled-release delivery. The available methods for NC production require expensive recovery and purification steps which compromised the morphology of NCs. Industrial applications of NCs have been avoided due to the aforementioned issues. In this study, we developed a new method based on a modified self-microemulsifying drug delivery system (SMEDDS) for in situ NCs production within the gastrointestinal tract. This new methodology does not require purification and recovery steps and can preserve the morphology and the functionality of NCs. The in situ formed NCs of Eudragit® RL PO were compared with nanospheres (NEs) in order to obtain evidence of their core-shell structure. NCs presented a spherical morphology with a size of 126.2 ± 13.1 nm, an ibuprofen encapsulation efficiency of 31.3% and a zeta-potential of 37.4 mV. Additionally, NC density and release profile (zero order) showed physical evidence of the feasibility of NCs in situ creation.
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Sistemas de Liberación de Medicamentos , Nanocápsulas , Administración Oral , Portadores de Fármacos , Composición de Medicamentos , Industria Farmacéutica , Emulsiones , Excipientes , Estudios de Factibilidad , Tracto Gastrointestinal/metabolismo , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , PolímerosRESUMEN
OBJECTIVES: There are scant data on the progression of hepatic steatosis (HS) in HIV infection. We therefore evaluated changes in HS over time in HIV-infected patients using the controlled attenuation parameter (CAP). METHODS: A prospective cohort of 326 HIV-infected patients was included in this study. All patients underwent a CAP measurement. Changes in steatosis were evaluated by calculating the median (Q1-Q3) difference between baseline and 12-month CAP values. RESULTS: The median (Q1-Q3) CAP was 221 (196-252) dB/m at baseline and 224 (198-257) dB/m at the 12-month visit (P = 0.617). Significant steatosis, that is, CAP ≥ 238 dB/m, was observed in 76 individuals (37%) at baseline and in 80 (39%) at the 12-month visit (P = 0.683). The following variables were associated with ΔCAP: plasma HIV RNA [< 50 vs. ≥ 50 HIV-1 RNA copies/mL: median (Q1-Q3) ΔCAP, 4 (-21, 27) vs. -21 (-49, 4) dB/m, respectively; P = 0.024]; body mass index (BMI) [no increase vs. increase: -13 (-40, 4) vs. 14 (-6, 32) dB/m, respectively; P < 0.001]; triglycerides [no increase vs. increase: -1 (-30, 22) vs. 15 (-3, 40) dB/m, respectively; P = 0.001]; fasting plasma glucose [not impaired vs. impaired: -4 (-31, 16) vs. 30 (15, 49) dB/m, respectively; P < 0.001]; and raltegravir [no vs. yes: 5 (-20, 29) vs. -11 (-37.5, 15) dB/m, respectively; P = 0.018]. The only factor independently associated with ΔCAP was BMI [B (standard error): 9.03 (1.9); P < 0.001]. CONCLUSIONS: Increases in CAP values over a period of 12 months in HIV-infected patients were strongly associated with elevations in BMI. Other metabolic factors and antiretroviral drugs were not predictors of CAP changes independent of BMI.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso/diagnóstico , Hígado Graso/patología , Infecciones por VIH/complicaciones , Adulto , Índice de Masa Corporal , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
HIV-1 induces activation of complement through the classical and lectin pathways. However, the virus incorporates several membrane-bound or soluble regulators of complement activation (RCA) that inactivate complement. HIV-1 can also use the complement receptors (CRs) for complement-mediated antibody-dependent enhancement of infection (C-ADE). We hypothesize that hypofunctional polymorphisms in RCA or CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19 RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR) = 2.27, P = 1 × 10(-4)) and rs2842704 in C4BPA (OR = 2.11, P = 2 × 10(-4)). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Although not significant (P = 0.25, OR = 1.57), similar genotypic proportions were obtained for the CR2 marker rs1567190. The results of the two association analyses were combined through a random effect meta-analysis, with a significant P-value of 2.6 x 10(-5) (OR = 2.07). Furthermore, we found that the protective CR2 genotype is correlated with lower levels CR2 mRNA as well as differences in the ratio of the long and short CR2 isoforms.
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Infecciones por VIH/genética , Infecciones por VIH/inmunología , VIH-1/inmunología , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/inmunología , Estudios de Cohortes , Susceptibilidad a Enfermedades/inmunología , Anticuerpos Anti-VIH/genética , Haplotipos , Humanos , Inmunidad Innata/genética , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.
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Enfermedad de Alzheimer/genética , Translocasas Mitocondriales de ADP y ATP/genética , Anciano de 80 o más Años , Estudios de Cohortes , Simulación por Computador , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) viral persistence in patients with spontaneous viral clearance is controversial. Several studies have shown HCV-RNA in peripheral blood mononuclear cells (PBMCs) and/or liver tissue among patients who have cleared the virus spontaneously, suggesting that viral persistence is a common situation that could involve the entire population studied. Thus, our aim was to evaluate HCV-RNA persistence in PBMCs and hepatocytes in subjects infected with the human immunodeficiency virus (HIV). A total of 1508 patients were prospectively followed and tested for anti-HCV antibodies and HCV-RNA to identify the patients who achieved spontaneous viral clearance. In all of the patients, the persistence of HCV-RNA in PBMCs was evaluated longitudinally during 2 years of follow-up. Fifty-nine patients fulfilled the inclusion/exclusion criteria and were included in the study. HCV-RNA was not detected in the PBMCs at baseline [59 PBMCs samples tested; 0 %; 95 % confidence interval (CI): 0-3.3 %] or during the follow-up (147 PBMCs samples tested; 0 %; 95 % CI: 0-2.02 %). Our study shows that HCV viral persistence is not a frequent occurrence in HIV-infected patients who have spontaneously resolved an HCV infection. Thus, the lack of serum HCV-RNA should continue to be addressed as the standard of healing.
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Infecciones por VIH/complicaciones , Hepatitis C/virología , Hepatocitos/virología , Leucocitos Mononucleares/virología , ARN Viral/aislamiento & purificación , Remisión Espontánea , Suero/virología , Adulto , Femenino , Hepatitis C/diagnóstico , Anticuerpos contra la Hepatitis C/sangre , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL). A total of 442 patients infected with HCV and treatment naive were prospectively recruited. One hundred forty-four SNPs located in 40 genes from the cholesterol synthesis/transport and IL28B were genotyped and analyzed for genetic association with pre-treatment plasma HCV VL. SNPs rs1433099 and rs2569540 of LDLR showed association with plasma HCV VL (P=4 × 10(-4) and P=2 × 10(-3)) in patients infected with genotypes 1 and 4. A haplotype including the last three exons of LDLR showed association with the cutoff level of 600 000 IU ml(-1) VL for genotypes 1 and 4 (OR=0.27; P=8 × 10(-6)), as well as a quantitative VL (mean±s.d.: 6.19±0.9 vs CC+CG 5.58±1.1 logIU ml(-1), P=8 × 10(-5)). LDLR genotypes are a major genetic factor influencing HCV VL in patients infected with genotypes 1 and 4.
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Hepacivirus/genética , Hepatitis C/genética , Hepatitis C/virología , Polimorfismo de Nucleótido Simple , Receptores de LDL/genética , Carga Viral , Adulto , Colesterol/genética , Colesterol/metabolismo , Coinfección , Exones , Femenino , Infecciones por VIH/genética , Infecciones por VIH/virología , Haplotipos , Hepacivirus/patogenicidad , Humanos , Interferones , Interleucinas/genética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Once HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH. METHODS: Cross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections. RESULTS: One hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%). CONCLUSIONS: After HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.
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Coinfección , Hígado Graso , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Coinfección/epidemiología , Coinfección/complicaciones , Estudios Transversales , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hígado Graso/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiologíaRESUMEN
Hepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194-1.339); p = 0.001], age [AOR = 1.029 (1.001-1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081-2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719-1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.
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Hígado Graso/epidemiología , Infecciones por VIH/epidemiología , VIH/patogenicidad , Hepacivirus/patogenicidad , Hepatitis C Crónica/epidemiología , Hígado/patología , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Coinfección , Estudios Transversales , Diagnóstico por Imagen de Elasticidad , Hígado Graso/diagnóstico por imagen , Hígado Graso/patología , Hígado Graso/virología , Femenino , VIH/crecimiento & desarrollo , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/patología , Infecciones por VIH/virología , Hepacivirus/crecimiento & desarrollo , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Hígado/diagnóstico por imagen , Hígado/virología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Triglicéridos/sangreRESUMEN
Whole-genome epistasis analysis may add a new layer of knowledge to whole-genome association studies, permitting the identification of new candidate genes which are completely transparent during conventional single-locus analysis. We present the first whole-genome conditional two-locus analysis in Parkinson's disease (PD). We scanned the entire genome and selected markers that interacted with a set of well-known loci previously associated to PD (SNCA, Parkin, LRRK2, UCHL1, DJ-1, PINK and MAPT). Our work describes several loci potentially related to PD risk which interact with SNCA, PARK1 and LRRK2 markers. We propose conditional whole-genome two-locus association analysis as a valuable method that might be helpful in re-analysing and re-interpreting data from whole-genome association studies.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genoma , Enfermedad de Parkinson , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Bases de Datos Genéticas , Epistasis Genética , Marcadores Genéticos , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Animals process sensory information according to specific computational rules and, subsequently, form representations of their environments that form the basis for decisions and choices. The specific computational rules used by organisms will often be evolutionarily adaptive by generating higher probabilities of survival, reproduction, and resource acquisition. Experiments with enclosed colonies of bumblebees constrained to foraging on artificial flowers suggest that the bumblebee's cognitive architecture is designed to efficiently exploit floral resources from spatially structured environments given limits on memory and the neuronal processing of information. A non-linear relationship between the biomechanics of nectar extraction and rates of net energetic gain by individual bees may account for sensitivities to both the arithmetic mean and variance in reward distributions in flowers. Heuristic rules that lead to efficient resource exploitation may also lead to subjective misperception of likelihoods. Subjective probability formation may then be viewed as a problem in pattern recognition subject to specific sampling schemes and memory constraints.
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Abejas/fisiología , Evolución Biológica , Conducta de Elección , Cognición , Animales , Abejas/genética , Fenómenos Biomecánicos , Matemática , Modelos Genéticos , ProbabilidadRESUMEN
BACKGROUND: The ESR1 AGATA haplotype is composed of five markers located within introns 5 and 6 of the human oestrogen receptor 1 (ESR1) gene. This haplotype has been studied in several male urogenital tract anomalies and male infertility. In one of these studies, a deviation from Hardy-Weinberg equilibrium (DHW) was found for the ESR1 AGATA marker rs3020375 in two groups of healthy controls. In the present study, we investigated whether the observed DHW is caused by structural variants present within the ESR1 gene. PARTICIPANTS: 229 family units achieving pregnancy through assisted reproductive technologies (n = 129) or by natural means (n = 100), 2465 general Spanish population controls and 162 men with idiopathic infertility. MAIN OUTCOME MEASUREMENTS: Segregation analyses of genetic markers in family units and case-control genetic association studies. RESULTS: We identified a new interstitial deletion of 2244 base pairs within intron 6 of the human ESR1 gene as the cause for the observed DHW. This new variant presents a 10% allelic frequency in the general Spanish population and it is associated with idiopathic male infertility (OR = 1.51; p = 0.03). The percentage of infertile couples in which both members carried the ESR1 deletion (10.08%) was also a higher than expected value of 6% (p = 0.03). CONCLUSIONS: We have characterised a novel structural variation in human ESR1 gene. The available data indicate a deleterious action of the ESR1 deletion in both male and couple fertility. The potential effects of this deletion on other oestrogen-related diseases need to be determined.
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Receptor alfa de Estrógeno/genética , Mutación de Línea Germinal , Infertilidad Masculina/genética , Eliminación de Secuencia , Secuencia de Bases , Estudios de Casos y Controles , Estudios de Cohortes , ADN/química , ADN/genética , Femenino , Marcadores Genéticos , Variación Genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Datos de Secuencia Molecular , Oportunidad Relativa , Linaje , Reacción en Cadena de la Polimerasa , EspañaRESUMEN
OBJECTIVES: The genetic basis of Alzheimer's disease (AD) is being analyzed in multiple whole genome association studies (WGAS). The GAB2 gene has been proposed as a modifying factor of APOE epsilon 4 allele in a recent case-control WGAS conducted in the US. Given the potential application of these novel results in AD diagnostics, we decided to make an independent replication to examine the GAB2 gene effect in our series. DESIGN: We are conducting a multicenter population-based study of AD in Spain. PARTICIPANTS: We analyzed a total of 1116 Spanish individuals. Specifically, 521 AD patients, 475 controls from the general population and 120 neurologically-normal elderly controls (NNE controls). METHODS: We have genotyped GAB2 (rs2373115 G/T) and APOE rs429358 (SNP112)/rs7412 (SNP158) polymorphisms using real time-PCR technologies. RESULTS: As previously reported in Spain, APOE epsilon 4 allele was strongly associated with AD in our series (OR=2.88 [95% C.I. 2.16- 3.84], p=7.38E-11). Moreover, a large effect for epsilone 4/epsilone 4 genotype was also observed (OR=14.45 [95% C.I., 3.34-125.2], p=1.8E-6). No difference between the general population and the NNE controls series were observed for APOE genotypes (P > 0.61). Next, we explored GAB2 rs2373115 SNP singlelocus association using different genetic models and comparing AD versus controls or NNE controls. No evidence of association with AD was observed for this GAB2 marker (p > 0.17). To evaluate GAB2-APOE genegene interactions, we stratified our series according to APOE genotype and case-control status, in accordance with the original studies. Again, no evidence of genetic association with AD was observed in any strata of GAB2-APOE loci pair (p > 0.34). CONCLUSION: GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.
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Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Heterocigoto , Anciano , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad Relativa , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Riesgo , España/epidemiologíaRESUMEN
The dynamics of any infectious disease are heavily dependent on the rate of transmission from infectious to susceptible hosts. In many disease models, this rate is captured in a single compound parameter, the probability of transmission P. However, closer examination reveals how beta can be further decomposed into a number of biologically relevant variables, including contact rates among individuals and the probability that contact events actually result in disease transmission. We start by introducing some of the basic concepts underlying the different approaches to modeling disease transmission and by laying out why a more detailed understanding of the variables involved is usually desirable. We then describe how parameter estimates of these variables can be derived from empirical data, drawing primarily from the existing literature on human diseases. Finally, we discuss how these concepts and approaches may be applied to the study of pathogen transmission in wildlife diseases. In particular, we highlight recent technical innovations that could help to overcome some the logistical challenges commonly associated with empirical disease research in wild populations.