Dwyergustavsen2813
The HIV-1 epidemic in southern Brazil is mostly caused by subtype C, which contrasts the dominance of subtype B in the other regions of the country. Santa Catarina (SC), although the smallest state in the southern region, presents one of the highest incidences and mortality rates in Brazil due to AIDS. This work investigated the HIV-1 molecular diversity and phylogenetic transmission networks in SC state by analyzing a database of 3070 sequences of the national genotyping service. HIV-1C proved to be the most frequent subtype, with a significant increase in prevalence over time. HIV-1B was observed to be associated with highly educated men, suggesting a compartmentalization from other subtypes. Such observation was confirmed by the high frequency of HIV-1B circulating in MSM transmission networks. Identified transmission clusters were majority composed by individuals living up to 25 km away and interstate linkages were mainly between southern neighbor states. In general, individuals between 25 and 40 years old and sequences sampled after 2014 were more likely to be in transmission chains, in agreement with the universal treatment protocol launched in 2014. The present study brings new insights about HIV-1 transmission dynamics in southern Brazil.Microsatellites are nonrandom hypervariable iterations of one to six nucleotides, existing across the coding as well as noncoding regions of virtually all known genomes, arising primarily due to polymerase slippage and unequal crossing over during replication events. Two or more perfect microsatellites located in close proximity form compound microsatellites. We studied the distribution of compound microsatellites in 118 ssDNA virus genomes belonging to three economically important virus families, namely Anelloviridae, Circoviridae, and Parvoviridae, known to predominantly infect livestock and humans. Among these virus families, 0-58.49% of perfect microsatellites were involved in the formation of compound microsatellites, the majority being located in the coding regions. No clear relationship existed between the genomic features (genome size and GC%) and compound microsatellite characteristics (relative abundance and relative density). The majority of the compound microsatellites resulted from di-SSR couples. A strong positive relationship was observed between the maximum distance value and length of compound microsatellite, percentage of microsatellites involved in the compound microsatellite formation, and relative microsatellite density. The degree of variability among microsatellite characteristics studied was largely a species-specific phenomenon. A major proportion of compound microsatellites was represented by similar motif combinations. The findings of the present study will help in better understanding of the structural, functional, and evolutionary role of compound microsatellites prevailing in the smaller genomes.Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0-12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7-14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0-14.0) mg/L and AUC0-12h was 56.0 (16.7-202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0-12h, Cmin, and CL/F. OD36 molecular weight We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.
Non-classical class I human leukocyte antigens (HLA) molecules are known to modulate the function of cytotoxic cells (NK and T CD8+) during viral infection by interacting with inhibitory/activating receptors. However, little is known about the HLA-E/-F genetic variability on arbovirus infections.
We evaluated by massive parallel sequencing the full HLA-E/-F genetic diversity among patients infected during the arbovirus (ZIKV, DENV, and CHIKV) outbreak leading to a broad range of neurological complications in the Brazilian State of Pernambuco. In parallel, healthy blood donors from the same area were also studied. Plink and R software were used for genetic association study. To limit the false-positive results and enhance the reliability of the results, we adopted P-values <0.01 as significant levels.
Compared to controls, the HLA-F alleles -1610 C (rs17875375), +1383 G (rs17178385), and +3537 A (rs17875384), all in complete linkage disequilibrium with each other (r
=1), were overrepresented in patients presenting peripheral spectrum disorders (PSD). The HLA-F*Distal-D haplotype that harbored the -1610 C allele exhibited a trend increase in PSD group. No associations were found for HLA-E.
Our findings showed that the HLA-F genetic background seems to be more important than HLA-E on the susceptibility to PSD complications.
Our findings showed that the HLA-F genetic background seems to be more important than HLA-E on the susceptibility to PSD complications.
To develop a prototype of a complex gene expression biomarker for the diagnosis of endometriosis on the basis of differences between the molecular signatures of the endometrium from women with and without endometriosis.
Prospective observational cohort study. Evidence obtained from a well-designed, controlled trial without randomization.
Department of reproductive medicine and surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry.
A total of 33 women (aged 32-38 years) were included in this study. Patients with and without endometriosis were divided into 2 separate groups. link2 The group composed of patients with endometriosis included 19 living patients with endometriosis who underwent laparoscopic excision of endometriosis. The control group included 6 living patients who underwent laparoscopic excision of incompetent uterine scar after cesarean section, with both surgically and histologically confirmed absence of endometriosis and adenomyosis. An additional control/verification group differential gene expression analysis can be used to generate robust gene signatures using real-world clinical data.
To evaluate the efficacy of surgical management for isthmoceles in patients presenting with secondary infertility.
A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2020. The search was limited to studies published in English.
After the removal of duplicates, 3380 articles were screened for inclusion independently by 2 authors. These 2 authors assessed for studies which focused on women of reproductive age with a diagnosed isthmocele and secondary infertility who underwent any surgical intervention for defect repair with at least 1 of the goals being fertility restoration.
A total of 13 studies, comprising of 1 randomized controlled trial, 6 prospective case series, and 6 retrospective case series describing 234 patients who underwent surgical management for an isthmocele and secondary infertility were included. The methodologic quality of the included studies was assessed independently by both reviewers. Next, the data extraction was performed observational nature of most available data.
The results of this systematic review suggest that the surgical treatment of an isthmocele, particularly through hysteroscopy, in patients with residual myometrial thickness of at least 2.5 mm, may be effective in treating isthmocele-associated secondary infertility with a relatively low complication rate. link3 Further high-quality studies are needed because of the small sample sizes and observational nature of most available data.Pulmonary arterial hypertension is a rare but deadly disease with a complex pathogenesis. Recent evidence demonstrates that Krüppel-like factors, a diverse family of transcription factors, are involved in several key disease processes such as the phenotypic transition of endothelial cells and smooth muscle cells. Importantly, manipulation of certain Krüppel-like factors enables protection or attenuation against pulmonary arterial hypertension in both animal models and preliminary human studies. In this review, we discuss how Krüppel-like factors, in particular Krüppel-like factors 2, 4 and 5 contribute to the pathological phenomena seen in pulmonary arterial hypertension and how associated signaling and microRNA pathways may be suitable targets for new therapies.To differentiate between conditions of health and disease, current pathway enrichment analysis methods detect the differential expression of distinct biological pathways. System-level model-driven approaches, however, are lacking. Here we present a new methodology that uses a dynamic model to suggest a unified subsystem to better differentiate between diseased and healthy conditions. Our methodology includes the following steps 1) detecting connections between relevant differentially expressed pathways; 2) construction of a unified in silico model, a stochastic Petri net model that links these distinct pathways; 3) model execution to predict subsystem activation; and 4) enrichment analysis of the predicted subsystem. We apply our approach to the TGF-beta regulation of the autophagy system implicated in autism. Our model was constructed manually, based on the literature, to predict, using model simulation, the TGF-beta-to-autophagy active subsystem and downstream gene expression changes associated with TGF-beta, which go beyond the individual findings derived from literature. We evaluated the in silico predicted subsystem and found it to be co-expressed in the normative whole blood human gene expression data. Finally, we show our subsystem's gene set to be significantly differentially expressed in two independent datasets of blood samples of ASD (autistic spectrum disorders) individuals as opposed to controls. Our study demonstrates that dynamic pathway unification can define a new refined subsystem that can significantly differentiate between disease conditions.Patients in intensive care units are heterogeneous and the daily prediction of their days to discharge (DTD) a complex task that practitioners and computers are not always able to solve satisfactorily. In order to make more precise DTD predictors, it is necessary to have tools for the analysis of the heterogeneity of the patients. Unfortunately, the number of publications in this field is almost non-existent. In order to alleviate this lack of tools, we propose four methods and their corresponding measures to quantify the heterogeneity of intensive patients in the process of determining the DTD. These new methods and measures have been tested with patients admitted over four years to a tertiary hospital in Spain. The results deepen the understanding of the intensive patient and can serve as a basis for the construction of better DTD predictors.
