Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Objetives The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. Methods Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. Results Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). Conclusions NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.Funding: M.A.M. was supported in part by: Agency for Health Technology Assessment and Research Supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PS12/02131 and PI17/02150); Agència de Gestió d´Ajuts Universitaris I de Recerca, Generalitat de Catalunya, 2017 SGR 794; and Fundació Marató TV3 project code 201824

Medically unexplained pain complaints are associated with underlying unrecognized mood disorders in primary care

<p>Abstract</p> <p>Background</p> <p>Patients with chronic pain frequently display comorbid depression, but the impact of this concurrence is often underestimated and mistreated. The aim of this study was to determine the prevalence of unrecognized major depression and other mood disorders and comorbid unexplained chronic pain in primary care settings and to explore the associated factors.</p> <p>Also, to compare the use of health services by patients with unexplained chronic pain, both with and without mood disorder comorbidity.</p> <p>Methods</p> <p>A cross-sectional study was carried out in a sample of primary care centers. 3189 patients consulting for "unexplained chronic pain" were assessed by the Visual Analogue Scales (VAS) and the Primary Care Evaluation of Mental Disorders (PRIME-MD) questionnaire.</p> <p>Results</p> <p>We report: a) a high prevalence of unrecognized mood disorders in patients suffering from unexplained chronic pain complaints (80.4%: CI 95%: 79.0%; 81.8%); b) a greater susceptibility of women to mood disorders (OR adjusted = 1.48; CI 95%:1.22; 1.81); c) a direct relationship between the prevalence of mood disorders and the duration of pain (OR adjusted = 1.01; CI 95%: 1.01; 1.02) d) a higher comorbidity with depression if the pain etiology was unknown (OR adjusted = 1.74; CI 95%: 1.45; 2.10) and, e) an increased use of health care services in patients with such a comorbidity (p < 0.0001).</p> <p>Conclusions</p> <p>The prevalence of undiagnosed mood disorders in patients with unexplained chronic pain in primary care is very high, leading to dissatisfaction with treatment processes and poorer outcomes. Consequently, it seems necessary to explore this condition more regularly in general practice in order to reach accurate diagnoses and to select the appropriate treatment.</p

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Brain and spinal cord magnetic resonance imaging in spastic paraparesis associated to human T-lymphotropic virus

Background: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. Aim: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. Material and methods: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Results: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87% of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80% of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. Conclusions: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis

Bencimidazole resistance in equine cyathostomes of the central argentina

The aim of this study was to evaluate the current state of the efficacy of benzimidazoles for control of small strongyles that parasitize horses in the central area of Argentina. In this context, two experiences were conducted involving a total of 107 horses. The first of these experiences was developed in six farms with a history of use of benzimidazoles and the second in horses whose past history of anthelmintic treatment was unknown. In both experiences a test of fecal egg count reductions (FECR) was carried out after treatment with an oral formulation of mebendazole 14% and triclorfon 48% at the dose of 5gr /100 kg of weight. The FECR was performed by comparing the averages (first experience) or individual values (second experience) on the number of eggs before and after treatment. Resistance to febendazole was observed in all farms in the first experience and approximately 60% of the horses in the second experience. Larval cultures after treatment showed only ciathostome third stage larvae. The results of this study indicate that populations of small strongyles resistant to benzimidazoles are extremely common in the central area of Argentina.Fil: Cerutti, J. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Parasitología y Enfermedades Parasitarias. Córdoba, ArgentinaFil: Cooper, L. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Parasitología y Enfermedades Parasitarias. Córdoba, ArgentinaFil: Caffe, G. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Parasitología y Enfermedades Parasitarias. Córdoba, ArgentinaFil: Cervilla, N. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Parasitología y Enfermedades Parasitarias. Córdoba, ArgentinaFil: Muchiut S. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Parasitología. Santa Fe, ArgentinaFil: Anziani, O. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Parasitología y Enfermedades Parasitarias. Córdoba, ArgentinaFil: Anziani, O. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria (EEA) Rafaela. Santa Fe, ArgentinaEl objetivo del presente estudio fue evaluar el estado actual de la eficacia de bencimidazoles para el control de pequeños estrongílidos que parasitan a equinos en el área central de Argentina. Se desarrollaron dos experiencias con un total de 107 equinos. La primera, en seis establecimientos con antecedentes de uso de bencimidazoles y la segunda, en equinos cuya historia previa de tratamientos antihelmínticos era desconocida. En todos los animales se realizó un test de reducción en el conteo de huevos (TRCH) luego del tratamiento con una formulación oral de mebendazole al 14% y triclorfon al 48% a la dosis de 5 gr/100 kg de peso vivo. El TRCH se realizó comparando promedios (primer experiencia) o valores individuales (segunda experiencia) del número de huevos pre y post tratamiento. Se observó resistencia a esta droga en todos los establecimientos de la primera experienciay en aproximadamente el 60% de animales pertenecientes a la segunda. Los coprocultivos post tratamiento mostraron solo larvas de tercer estadio pertenecientes a pequeños estrongílidos. Los resultados de este estudio indican que las poblaciones de pequeños estrongílidos con resistencia a bencimidazoles son extremadamente comunes en el área central de Argentina

Socioeconomic inequalities in victims of intimate partner violence in Europe

Costa D, Soares J, Lindert J, et al. Socioeconomic inequalities in victims of intimate partner violence in Europe. European Journal of Public Health. 2013;23(suppl_1):120