What's the best test for HSV-2 after exposure?

Enzyme-linked immunosorbent assay (ELISA ) tests based on herpes simplex virus 2's (HSV -2) glycoprotein G have demonstrated high sensitivity and specificity in determining seropositivity for HSV-2 antibodies (strength of recommendation [SOR]: C, based on cross-sectional studies). ELISA tests not based on glycoprotein G are also highly sensitive, but they are less specific for HSV-2 and are prone to false-positive results because of cross-reactivity with HSV -1 antibodies (SOR: C, based on cross-sectional studies)

Effect of Carelink, an Internet-Based Insulin Pump Monitoring System, on Glycemic Control in Children with Type 1 Diabetes Mellitus

Objective : To determine whether use of the internet-based Carelink system improved glycemic control in children on insulin pump therapy. Research Design and Methods - We reviewed records of 146 children treated with insulin pump therapy between the years 2004-2007, and compared glycemic control and diabetes self-care measures associated with Carelink use. Forty percent of the patients resided one hour or more from our clinic. Results: Patients who used the Carelink software and website showed significant improvement in HbA1c levels following use (8.0 ± 0.1 (SE) vs 7.7 ± 0.1 (SE), p=0.002). They uploaded data from their pump and glucometer 2.2 ± 1.8 times per month over 0.8 ± 0.4 (SD) years. Patients who had no access to Carelink software and were followed in a conventional manner showed no change in HbA1c ( 8.0 ± 0.1 (SE) vs 8.1 ± 0.1 (SE), p=0.27) during the study period. These patients did not differ significantly from Carelink users in diabetes self care behaviors. Patients who had Carelink access but did not use it had a higher HbA1c level at the onset and did not change over the study period (HbA1c 8.9 ± 0.2 (SE) vs 8.9 ± 0.3 (SE), p=0.76). These patients differed significantly from Carelink users in self-care behaviors, but not in the frequency of blood glucose monitoring. Patients in a rural location benefited equally as compared to patients who lived within one hour of our clinic. Conclusions: The Carelink software program is a powerful tool that can be used by diabetes care providers and parents to manage insulin pump therapy in children and to improve glycemic control, especially in states with a large rural population

EpiChIP: gene-by-gene quantification of epigenetic modification levels

The combination of chromatin immunoprecipitation with next-generation sequencing technology (ChIP-seq) is a powerful and increasingly popular method for mapping protein–DNA interactions in a genome-wide fashion. The conventional way of analyzing this data is to identify sequencing peaks along the chromosomes that are significantly higher than the read background. For histone modifications and other epigenetic marks, it is often preferable to find a characteristic region of enrichment in sequencing reads relative to gene annotations. For instance, many histone modifications are typically enriched around transcription start sites. Calculating the optimal window that describes this enrichment allows one to quantify modification levels for each individual gene. Using data sets for the H3K9/14ac histone modification in Th cells and an accompanying IgG control, we present an analysis strategy that alternates between single gene and global data distribution levels and allows a clear distinction between experimental background and signal. Curve fitting permits false discovery rate-based classification of genes as modified versus unmodified. We have developed a software package called EpiChIP that carries out this type of analysis, including integration with and visualization of gene expression data

Maintaining public health insurance benefits: How primary care clinics help keep low-income patients insured

Low-income families struggle to obtain and maintain public health insurance. We identified strategies used by Community Health Centers (CHCs) to assist patients with insurance applications, and assessed patients’ receptivity to these efforts. Observational cross-case comparative study with four CHCs in Oregon. We observed insurance assistance processes, and interviewed 26 clinic staff and 18 patients/family members. Qualitative data were analyzed using a grounded theory approach. Patients’ understanding of eligibility status, reapplication schedules, and how to apply, were major barriers to insurance enrollment. Clinic staff addressed these barriers by reminding patients when applications were due, assisting with applications as needed, and tracking submitted applications to ensure approval. Families trusted clinic staff with insurance enrollment support, and appreciated it. CHCs are effective at helping patients with public health insurance. Access to insurance expiration data, tools enabling enrollment activities, and compensation are needed to support enrollment services in CHCs

More than sense of place? Exploring the emotional dimension of rural tourism experiences

It is widely suggested that participation in rural tourism is underpinned by a sense of rural place or “rurality”. However, although nature and the countryside have long been recognised as a source of spiritual or emotional fulfilment, few have explored the extent to which tourism, itself often claimed to be a sacred experience, offers an emotional/spiritual dimension in the rural context. This paper addresses that literature gap. Using in-depth interviews with rural tourists in the English Lake District, it explores the extent to which, within respondents’ individual understanding of spirituality, a relationship exists between sense of place and deeper, emotional experiences and, especially, whether participation in rural tourism may induce spiritual or emotional responses. The research revealed that all respondents felt a strong attachment to the Lake District; similarly, and irrespective of their openness to spirituality, engaging in rural tourism activities resulted in highly emotive experiences for all respondents, the description/interpretation of such experiences being determined by individual “beliefs”. However, sense of place was not a prerequisite to emotional or spiritual experiences. Being in and engaging with the landscape � effectively becoming part of it � especially through physical activity is fundamental to emotional responses

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Community-curated and standardised metadata of published ancient metagenomic samples with AncientMetagenomeDir

Ancient DNA and RNA are valuable data sources for a wide range of disciplines. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years, and tracking this data for reuse is particularly important for large-scale ecological and evolutionary studies of individual microbial taxa, microbial communities, and metagenomic assemblages. AncientMetagenomeDir (archived at https://doi.org/10.5281/zenodo.3980833) is a collection of indices of published genetic data deriving from ancient microbial samples that provides basic, standardised metadata and accession numbers to allow rapid data retrieval from online repositories. These collections are community-curated and span multiple sub-disciplines in order to ensure adequate breadth and consensus in metadata definitions, as well as longevity of the database. Internal guidelines and automated checks to facilitate compatibility with established sequence-read archives and term-ontologies ensure consistency and interoperability for future meta-analyses. This collection will also assist in standardising metadata reporting for future ancient metagenomic studies.Competing Interest StatementThe authors have declared no competing interest.Background & Summary Methods - Repository Structure - Data Acquisition - Data Validation Data Records Technical Validation Usage Note

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression

The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1, 2, 3, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome4, 5, 6. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression

Chromatin States Accurately Classify Cell Differentiation Stages

Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the “hotspot” genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly distributed across the genome but tend to be embedded in multi-gene chromatin domains, and that specialized gene clusters tend to be embedded in stably occupied domains