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This study examined hospitalizations in a large, all-payer, nationally representative sample of inpatient hospitalizations in the US and identified differences in rates of hospitalization for conditions by race and ethnicity in autistic adults. Conditions examined included mood disorders, epilepsy, schizophrenia, and ambulatory care sensitive conditions (ACSCs). Compared to white, non-Hispanic autistic adults, Black, Hispanic, Asian or Pacific Islander (API), and autistic adults of another race had lower prevalence of admission for a principal diagnosis of a mood disorder. Conversely, Black, Hispanic, API, and autistic adults of another race had higher odds of admission for epilepsy than white autistic adults. Black and Hispanic autistic adults were more likely to have schizophrenia as a principal diagnosis compared to white autistic adults, but only Black autistic adults had increased odds for admission for an ACSCs compared to white autistic adults. Differences in diagnosis prevalence among hospitalized autistic adults may suggest differential access to comprehensive outpatient care that could prevent such hospitalizations, while also pointing to concerns of differential validity of diagnostic tools and treatment approaches. Insurance policy and programs should prioritize optimizing outpatient care to ensure access to care and emphasize the need for equitable treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: to map the existing knowledge on nursing ethical decision making in the physical restraint of hospitalised adults. (1) Background: physical restraint is a technique that conditions the free movement of the body, with risks and benefits. The prevalence of physical restraint in healthcare suffers a wide variation, considering the environment or pathology, and it raises ethical issues that hinders decision making. This article intends to analyse and discuss this problem, starting from a literature review that will provoke a grounded discussion on the ethical and legal aspects. Inclusion criteria are: studies on physical restraint (C) and ethical nursing decision making (C) in hospitalized adults (P); (2) methods: a three-step search strategy was used according to the JBI. The databases consulted were CINAHL Plus with Full Text (EBSCOhost), MEDLINE Full Text (EBSCOhost), Nursing and Allied Health Collection: Comprehensive and Cochrane Database of Systematic Reviews (by Cochrane Library, RCAAP and Google Scholar. All articles were analysed by two independent reviewers; (3) results: according to the inclusion criteria, 18 articles were included. The categories that influence ethical decision in nursing are: consequence of the decision, the context, the nature of the decision in terms of its complexity, the principles of the ethical decision in nursing, ethical issues and universal values; (4) conclusions: the findings of this review provide evidence that there is extensive knowledge regarding nursing ethical decision making in adult physical restriction, also, it is considered an ethical issue with many associated assumptions. In this article we aim to confront all these issues from a legal perspective.

Bartonellosis is a vector-borne zoonotic disease with worldwide distribution that infect a broad spectrum of mammalian species. Despite the recent studies carried out in Brazil, information regarding Bartonella in dogs are scarce. Therefore, we performed a retrospective study to investigate the exposure to Bartonella sp. in dogs by indirect immunofluorescence assay (IFA). Three hundred and thirty-five archived serum samples from dogs previously tested for vector-borne pathogens, Toxoplasma gondii, and Neospora caninum were screened for the presence of IgG antibodies to Bartonella sp. All dogs originated from the Metropolitan region of Ribeirão Preto, northeast of the State of São Paulo. Twenty-eight samples (8.3%) were positive for Bartonella sp. at the cut-off of 64. Among the 28 seropositive samples for Bartonella sp., 16 (57.1%) were also seropositive for Ehrlichia canis, 12 (42.8%) for Babesia vogeli, five (17.8%) for T. gondii and three (10.7%) for L. infantum and N. caninum. Our results demonstrated that dogs sampled were exposed to Bartonella sp. Since all the animals sampled in the present study were from private owners, our findings demonstrate that these people may also be exposed to Bartonella sp. Further studies designed to assess whether the infection by other arthropod-borne pathogens such as B. vogeli and E. canis are risk factors for Bartonella infection are needed.

Background: Addressing health care needs is complex in autistic youth for many reasons. Increased inpatient care that has been noted in this population, particularly for ambulatory care sensitive conditions (ACSCs), may be a marker of inadequate primary and outpatient care., Methods: This study used data from hospital inpatient discharges from the National Inpatient Sample 2017. The prevalence, average length of stay, and the average cost per day of the 10 most common principal diagnoses for index stay were calculated for autistic youth and youth with mental, behavioral, and other neurodevelopmental disabilities (MBND), ages 0 to 17., Results: Of every 1000 inpatient stays, 7.3 were for autistic youth and 65.2 for youth with MBND. The rate varied by US region and zip code-level household income. The most common diagnosis associated with stays in autistic youth was mood disorders, as in youth with MBND. Nearly all top 10 principal diagnoses for autistic youth were for ACSCs. The highest average cost per day for autistic youth was for physical injuries ($4320 per day), and the longest stays were for schizophrenia (14 days)., Conclusions: High occurrence of ACSCs in autistic youth suggests that primary care may not adequately address health and mental health needs. Clinical complexity and autism characteristics may be impacting care received in the hospital. Additional considerations need to explore and examine care complexity, racial and ethnic disparities, and the large portion of Medicaid-covered youth. Strategies for the provision of care to these vulnerable populations are of great concern., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-sequencing profiles from sorted blood immune CD4 + and CD8 + T cells, CD14 + monocytes and CD19 + B cells from healthy controls (HCs) and MS patients. Results: We identified differentially accessible regions between MS patients and HCs, primarily in CD4 + and CD19 + . CD4 + regions were enriched for MS-associated single nucleotide polymorphisms and differentially methylated loci. In the vicinity of differentially accessible regions of CD4 + cells, 42 differentially expressed genes were identified. The top two dysregulated genes identified in this multilayer analysis were CCDC114 and SERTAD1 . Conclusion: These findings provide new insight into the primary role of CD4 + and CD19 +  cells in MS.

Toxoplasma gondii and Neospora caninum are Apicomplexan intracellular protozoan parasites that affect numerous animal species, thus leading to severe diseases and economic losses, depending on the vertebrate species involved. The role of the avian species in maintaining and transmission of these coccidia has been studied for several years as they tend to serve as a potential source of infection for mammals and humans. The present study aimed to assess the serological exposure of Orinoco goose (Neochen jubata) to T. gondii and N. caninum. Between 2010 and 2013, 41 free-ranging Orinoco geese were captured in the Araguaia River, Brazil. The presence and titration of IgY antibodies to both coccidia were assayed via indirect immunofluorescent antibody test (IFAT). While IgY antibodies for N. caninum were present in 5 animals, with titers of 20, the antibodies for T. gondii were found in 35 animals, with titers ranging from 20 to 640. Considering that the Orinoco goose's meat is consumed by the local population in the studied area, it may represent an important source of T. gondii infection for humans. Due to its migratory behavior, this goose may play a pivotal role in the natural dispersion of both parasites. Furthermore, molecular studies are required for genotyping the isolates of T. gondii that occurs in this avian species.

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated with MS has not been assessed in the same individuals. Here we generated paired transcriptomic (RNA-seq) and DNA methylation (Illumina 450 K array) profiles of CD4+ and CD8+ T cells (CD4, CD8), using clinically accessible blood from healthy donors and MS patients in the initial relapsing-remitting and subsequent secondary-progressive stage. By integrating the output of a differential expression test with a permutation-based non-parametric combination methodology, we identified 149 differentially expressed (DE) genes in both CD4 and CD8 cells collected from MS patients. Moreover, by leveraging the methylation-dependent regulation of gene expression, we identified the gene SH3YL1, which displayed significant correlated expression and methylation changes in MS patients. Importantly, silencing of SH3YL1 in primary human CD4 cells demonstrated its influence on T cell activation. Collectively, our strategy based on paired sampling of several cell-types provides a novel approach to increase sensitivity for identifying shared mechanisms altered in CD4 and CD8 cells of relevance in MS in small sized clinical materials.

Regulatory T cells (Tregs) act as indispensable unit for maintaining peripheral immune tolerance mainly by regulating effector T cells. T cells resistant to suppression by Tregs pose therapeutic challenges in the treatment of autoimmune diseases, while augmenting susceptibility to suppression may be desirable for cancer therapy. To understand the cell intrinsic signals in T cells during suppression by Tregs, we have previously performed a global phosphoproteomic characterization. We revealed altered phosphorylation of protein phosphatase 1 regulatory subunit 11 (PPP1R11; Inhibitor-3) in conventional T cells upon suppression by Tregs. Here, we show that silencing of PPP1R11 renders T cells resistant toward Treg-mediated suppression of TCR-induced cytokine expression. Furthermore, whole-transcriptome sequencing revealed that PPP1R11 differentially regulates not only the expression of specific T cell stimulation-induced cytokines but also other molecules and pathways in T cells. We further confirmed the target of PPP1R11, PP1, to augment TCR-induced cytokine expression. In conclusion, we present PPP1R11 as a novel negative regulator of T cell activation-induced cytokine expression. Targeting PPP1R11 may have therapeutic potential to regulate the T cell activation status including modulating the susceptibility of T cells toward Treg-mediated suppression, specifically altering the stimulation-induced T cell cytokine milieu., (©2019 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.)

The msp4 gene of A. marginale is unicodon, stable and mostly homogeneous, being considered as a useful marker for phylogeographic characterization of this bacterium. The objective of this work was to analyze the phylogeography of A. marginale based on the msp4 gene in beef cattle from the Brazilian Pantanal, compared to those found in other regions worldwide. The blood samples investigated were collected from 400 animals (200 cows and 200 calves) reared in five extensive breeding farms in this region. The results indicated that of the evaluated samples, 56.75% (227/400) were positive for A. marginale based on the msp1β gene by quantitatitve PCR (qPCR), while 8.37% (19/227) were positive for the msp4 gene in the conventional PCR. In the Network distance analysis, 14 sequences from the Brazilian Pantanal were grouped into a single group with those from Thailand, India, Spain, Colombia, Parana (Brazil), Mexico, Portugal, Argentina, China, Venezuela, Australia, Italy and Minas Gerais (Brazil). Among 68 sequences from Brazil and the world, 15 genotypes were present while genotype number one (#1) was the most distributed worldwide. Both Splitstree and network analyses showed that the A. marginale msp4 sequences detected in beef cattle from the Brazilian Pantanal showed low polymorphism, with the formation of one genogroup phylogenetically related to those found in ruminants from South and Central America, Europe, and Asia.

Toxoplasmosis is an important zoonosis for pregnant women and immunosuppressed people. The pig population also becomes infected by this pathogen, and undercooked or raw meat is an important source of infection for humans. The aims of the present study were to evaluate the rate of exposure of pigs to T. gondii in the municipality of Mossoró, Rio Grande do Norte and seek to identify associations with possible risk factors. Blood samples were collected from 412 pigs and were analyzed using the immunofluorescence assay. Among these 412 serum samples, 40.7% were seropositive for T. gondii. The IgG antibody titers were 64 (56 specimens), 128 (32), 256 (37), 512 (23), 1024 (14), 2048 (5) and 4046 (1). Seropositivity for T. gondii was found to be related (p-value < 0.05) to the following factors: female gender, semi-confined rearing system, use of well water, dewormed animals, presence of cats, goats, sheep, mice and vultures on the farm and carcasses left on the ground. In contrast, seropositivity was not related (p-value < 0.05) to the age of the pigs, type of facility or feeding with human food remains. Preventive measures need to be adopted on the farms studied here, with the aim of decreasing the animals' intake of sporulated oocysts.

There are few studies on the genetic diversity of Anaplasma marginale in Brazilian cattle herds, especially about beef cattle. The objective of this study was to evaluate the genetic diversity of A. marginale, based on the msp1α gene in Bos taurus indicus sampled from the Brazilian Pantanal. Aliquots of blood with and without EDTA were taken from 400 cattle (200 cows and 200 calves) across five extensive farms. The samples were submitted to the indirect immunoenzymatic assay (iELISA), quantitative real-time PCR (qPCR) for the msp1β gene and to the semi-nested (sn) PCR for the msp1α gene. Positive samples were sequenced by the Sanger method and subjected to diversity analysis using the RepeatAnalyser software. The percentage of positive animals by iELISA, qPCR and (sn) PCR was 72.2% (289/400), 56.7% (227/400) and 23% (52/227), respectively. Cows (154/200) showed to be significantly more seropositive than calves (135/200). In qPCR, the number of calves and average quantification value (138/200; 1.3 × 10 6 ) A. marginale msp1α copies per μL proved to be higher when compared to that found for the cows (89/200; 3.9 × 10 4 ). The microsatellite analysis of the 26 sequences obtained from the msp1α gene revealed the presence of E (77%), C (15.4%) and B (7.7%) genotypes. Fourteen A. marginale strains were identified in the studied region, with eight that have never before been described in the literature (τ-10-13-13-18; τ-27-18; EV8-EV8-17; α-β-β-β-100; EV7-11-10-15; τ-11-11-27-18; τ-11-10-15; τ-27-13-18). Beef cattle are highly exposed to A. marginale in the Brazilian Pantanal. Moreover, a high genetic diversity of A. marginale, with eight new strains, was found in the studied region. While cows may act as chronic carriers, perpetuating the pathogen within the herd, male beef calves sold to other regions may disperse these strains., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis., Methods: We measured DNA methylation in CD4 + T cells (n = 31), CD8 + T cells (n = 28), CD14 + monocytes (n = 35) and CD19 + B cells (n = 27) from relapsing-remitting (RRMS), secondary progressive (SPMS) patients and healthy controls (HC) using Infinium HumanMethylation450 arrays. Monocyte (n = 25) and whole blood (n = 275) cohorts were used for validations., Findings: B cells from MS patients displayed most significant differentially methylated positions (DMPs), followed by monocytes, while only few DMPs were detected in T cells. We implemented a non-parametric combination framework (omicsNPC) to increase discovery power by combining evidence from all four cell types. Identified shared DMPs co-localized at MS risk loci and clustered into distinct groups. Functional exploration of changes discriminating RRMS and SPMS from HC implicated lymphocyte signaling, T cell activation and migration. SPMS-specific changes, on the other hand, implicated myeloid cell functions and metabolism. Interestingly, neuronal and neurodegenerative genes and pathways were also specifically enriched in the SPMS cluster., Interpretation: We utilized a statistical framework (omicsNPC) that combines multiple layers of evidence to identify DNA methylation changes that provide new insights into MS pathogenesis in general, and disease progression, in particular. FUND: This work was supported by the Swedish Research Council, Stockholm County Council, AstraZeneca, European Research Council, Karolinska Institutet and Margaretha af Ugglas Foundation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages., Competing Interests: The authors have declared that no competing interests exist.

Mycoplasma spp. and Bartonella spp. are Gram-negative bacteria transmitted by arthropod vectors that infect red blood cells of several mammal species. This study investigated the occurrence and genetic diversity of hemoplasmas and Bartonella spp. in 68 howler monkeys kept in captivity in São Paulo, a southeastern state in Brazil. In addition, possible hematological, biochemical and electrophoretic changes of serum proteins associated with the occurrence of hemoplasmas and Bartonella spp. in captive primates were also investigated. The cPCR results showed that all sampled howler monkeys were negative for Bartonella spp. based on the gltA gene. The cPCR results indicated that 18 (26.47%) non-human primates (NHP) were positive for hemoplasmas based on the 16S rRNA gene. Monocyte and lymphocyte counts were higher in hemoplasma-positive howlers (P < 0.05). Platelet counts decreased in nonhuman primates (NHP) positive for hemoplasmas (P < 0.05). The results from the blood serum proteinogram and biochemistry analyses were not significantly different between NHPs positive and negative for hemotrophic mycoplasmas. Phylogenetic analysis using Bayesian Inference (BI) based on the 16S rRNA gene positioned the obtained sequences close to 'Candidatus Mycoplasma kahanei'. The analysis of sequence diversity of the 16S rRNA gene showed that 5 different genotypes are circulating in NHP in Brazil and in the world; besides, a clear separation between the sequences of hemoplasmas that infect NHP of the Sapajus and Alouatta genus in Brazil was found, probably corresponding to two different species. The pathogenic potential of this hemoplasma species in NHP should be further investigated., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although species of Anaplasma are highly prevalent Rickettsiales agents in domestic and wild ruminants with a wide distribution worldwide, few studies have been conducted so far to detect and/or investigate the diversity of these agentsin cattle in Mozambique. In the present study, serological and molecular assays were used to investigate the occurrence of Anaplasma spp. in 219 bovines sampled in the districts of Boane, Magude, Matutuíne, Moamba and Namaacha in Maputo, Mozambique. In the iELISA test for detection ofIgG antibodies to A. marginale, 86.3% (189/219) of the samples were positive. In qPCR assays for the gene msp1β for A. marginale and msp2 for A. phagocytophilum, 97.3% (213/219) and 2.7% (6/219) of the animals were positive, respectively. Two different cPCR protocols based on the 16S rRNA gene showed that 100% of the samples were positive for Anaplasma spp. The DNA sequences obtained were phylogenetically related to A. platys, A. phagocytophilum, Candidatus Anaplasma boleense, A. centrale, A. marginale and A. ovis. Phylogenetic inference based on the msp4 and msp5 genes positioned the obtained sequences in the clade of A. marginale, with evidence of occurrence of 8 and 5 different haplotypes for each gene, respectively. Anaplasma sp. phylogenetically associated with A. platys was evidenced in phylogenetic analyzes based on 16S rRNA and groEL genes. It is concluded that a high diversity of species of Anaplasma spp. occurs in cattle in Mozambique., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors., Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC)., Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression., Results: We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes., Conclusion: Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood., Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset., Conclusion: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as multiple sclerosis (MS). As a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells from MS patients (n = 145) to identify eQTLs in regions centered on 109 MS risk single nucleotide polymorphisms and 7 associated human leukocyte antigen variants. We identified 77 statistically significant eQTL associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40 testable eQTL effects were colocalized with the disease association signal. As many eQTLs are tissue specific, we aimed to detail their significance in different cell types. Approximately 70% of the eQTLs were replicated and characterized in at least one major peripheral blood mononuclear cell-derived cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS patients compared with non-inflammatory neurological diseases patients. In addition, we found two single nucleotide polymorphisms to be significantly associated with the proportions of three different cell types. Mapping to enhancer histone marks and predicted transcription factor binding sites added additional functional evidence for eight eQTL regions. As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. This study provides many novel and validated targets for future functional characterization of MS and other diseases.

Recently, the importance of wild-living rodents for maintenance of pathogens of the family Anaplasmataceae in the environment was investigated. These mammals play a role as reservoirs for these pathogens and act as hosts for the immature stages of tick vectors. The aim of the present study was to investigate the prevalence of Ehrlichia sp. and Anaplasma sp. in 24 specimens of Azara's agouti (Dasyprocta azarae) that had been trapped in the Itapiracó Environmental Reserve, in São Luís, Maranhão, northeastern Brazil, using molecular methods. Four animals (16.7%) were positive for Ehrlichia spp. in nested PCR assays based on the 16S rRNA gene. In a phylogenetic analysis based on the 16S rRNA gene, using the maximum likelihood method and the GTRGAMMA+I evolutionary model, Ehrlichia sp. genotypes detected in Azara's agoutis were found to be closely related to E. canis and to genotypes relating to E. canis that had previously been detected in free-living animals in Brazil. The present work showed the first molecular detection of Ehrlichia sp. in Azara's agoutis in Brazil.

Analysing the HIV-1 near full-length genome (HIV-NFLG) facilitates new understanding into the diversity of virus population dynamics at individual or population level. In this study we developed a simple but high-throughput next generation sequencing (NGS) protocol for HIV-NFLG using clinical specimens and validated the method against an external quality control (EQC) panel. Clinical specimens (n=105) were obtained from three cohorts from two highly conserved HIV-1C epidemics (India and Ethiopia) and one diverse epidemic (Sweden). Additionally an EQC panel (n=10) was used to validate the protocol. HIV-NFLG was performed amplifying the HIV-genome (Gag-to-nef) in two fragments. NGS was performed using the Illumina HiSeq2500 after multiplexing 24 samples, followed by de novo assembly in Iterative Virus Assembler or VICUNA. Subtyping was carried out using several bioinformatics tools. Amplification of HIV-NFLG has 90% (95/105) success-rate in clinical specimens. NGS was successful in all clinical specimens (n=45) and EQA samples (n=10) attempted. The mean error for mutations for the EQC panel viruses were <1%. Subtyping identified two as A1C recombinant. Our results demonstrate the feasibility of a simple NGS-based HIV-NFLG that can potentially be used in the molecular surveillance for effective identification of subtypes and transmission clusters for operational public health intervention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Support and treatment options have been widely discussed in recent decades with the aim of improving morbidity, mortality and quality of life of chronic respiratory disease (COPD) patients. Although it is believed that longer pulmonary rehabilitation programs can provide better results, most of the evidence comes from short-term programs., Aim: To determine the effects of an outpatient pulmonary rehabilitation program on exercise tolerance, dyspnoea, hemodynamic variables and quality of life., Design: Case series study., Setting: Rehabilitation Centre., Population and Methods: A convenience sample of COPD patients was enrolled in this study. The intervention consisted of a 96-wk exercise training program, including aerobic training, upper-limb exercises and inspiratory muscle training. Pulmonary function tests, blood biochemistry, six-minute walking distance test and health-related quality of life were recorded at baseline and after completion of the 6th, 12th, 18th, 24th months., Results: Forty one consecutive COPD patients were recruited and thirty six completed the study. There was a significant improvement in hemodynamics, demonstrated by the gradual reduction in heart rate, blood pressure and MvO2 (double product) starting from the 12th month. Lipid profile showed a reduction of low density lipids and an increase of the high density lipids levels starting from the 6th month. Exercise tolerance, dyspnoea, respiratory muscle strength and quality of life also improved starting from the 6th month., Conclusion: A 24-month pulmonary rehabilitation program leads to a progressive improvement in quality of life, dyspnoea and exercise tolerance, and reduces cardiovascular risk factors in patients with chronic obstructive pulmonary disease., Impact: Our study suggests that long-term pulmonary rehabilitation programs can result in further improvements in the aforementioned cardiorespiratory variables.

Background: Phyto-remedies for diabetic control are popular among patients with Type II Diabetes mellitus (DM), in addition to other diabetic control measures. A number of plant species are known to possess diabetic control properties. Costus pictus D. Don is popularly known as "Insulin Plant" in Southern India whose leaves have been reported to increase insulin pools in blood plasma. Next Generation Sequencing is employed as a powerful tool for identifying molecular signatures in the transcriptome related to physiological functions of plant tissues. We sequenced the leaf transcriptome of C. pictus using Illumina reversible dye terminator sequencing technology and used combination of bioinformatics tools for identifying transcripts related to anti-diabetic properties of C. pictus., Results: A total of 55,006 transcripts were identified, of which 69.15% transcripts could be annotated. We identified transcripts related to pathways of bixin biosynthesis and geraniol and geranial biosynthesis as major transcripts from the class of isoprenoid secondary metabolites and validated the presence of putative norbixin methyltransferase, a precursor of Bixin. The transcripts encoding these terpenoids are known to be Peroxisome Proliferator-Activated Receptor (PPAR) agonists and anti-glycation agents. Sequential extraction and High Performance Liquid Chromatography (HPLC) confirmed the presence of bixin in C. pictus methanolic extracts. Another significant transcript identified in relation to anti-diabetic, anti-obesity and immuno-modulation is of Abscisic Acid biosynthetic pathway. We also report many other transcripts for the biosynthesis of antitumor, anti-oxidant and antimicrobial metabolites of C. pictus leaves., Conclusion: Solid molecular signatures (transcripts related to bixin, abscisic acid, and geranial and geraniol biosynthesis) for the anti-diabetic properties of C. pictus leaves and vital clues related to the other phytochemical functions like antitumor, anti-oxidant, immuno-modulatory, anti-microbial and anti-malarial properties through the secondary metabolite pathway annotations are reported. The data provided will be of immense help to researchers working in the treatment of DM using herbal therapies.

This study used latent class analysis to empirically derive profiles of religious involvement among a sample of 808 young adults and describe ethnic and gender differences within such religious involvement patterns. Items on the Duke Religion Index were included as part of a larger longitudinal survey of emotional, physical, and behavioral health. The scale measured the organizational, nonorganizational, and intrinsic dimensions of religiosity (Koenig et al. 2001) in a sample of young adults at two waves of the study-age 27 and age 30. At age 27, five religious profiles were distinguishable in the sample while at age 30 six profiles emerged. Ethnic differences were found for each of the religious profiles where religious involvement manifested in different ways. Religious profiles between ages 27 and 30 changed over time and were affected by gender and ethnicity.

Anti-HBs persistence following HBV vaccination among HIV-positive children has never been systematically studied in central Brazil. An historical cohort study was performed aiming to evaluate persistence of anti-HBs in HIV-positive children in comparison with an HIV-negative child group. Fifty-eight HIV-positive and 116 HIV-negative individuals were enrolled. Birth weight, breast-feeding duration, and the time elapsed since the last hepatitis B vaccine doses were similar between the groups. Fourteen (24%) out of 58 HIV-positive participants were anti-HBs positive and 101 (87%) out of 116 were HIV-negative (p<0.001). Among anti-HBs-positive individuals, the geometric mean titres were 118 and 298 mIU/mL, respectively to HIV-positive and HIV-negative groups (p=0.04). These results disclose a worrying picture regarding the failure of standard HBV vaccination among Brazilian HIV-infected children.

A 40-year-old woman with known systemic sclerosis presented with dyspnea. She had been treated for pneumonia, 2 months prior to the present admission and at this time presented with sudden dyspnea and was found to have a spontaneous pneumomediastinum and subcutaneous emphysema. Pneumomediastinum is an extremely rare complication in patients with systemic sclerosis.