Pseudoangiomatous Stromal Hyperplasia: A Case Report

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferating breast condition. It was first reported in 1986 when Vuitch, Rosen, and Erlandson described nine cases of benign well-circumscribed, breast masses that simulated vascular lesions consisting of mammary stromal proliferations (Vuitch et al. (1986)). Since then there have been few reported cases of PASH in the literature (Taira et al. (2005)). We describe a large PASH, mimicking inflammatory carcinoma in a young lady that was excised with excellent cosmetic results

Epidemiology report:Trends in sex-specific cerebrovascular disease mortality in Europe based on WHO mortality data

Aims: There have been substantial declines in cerebrovascular disease mortality across much of Europe, mirroring trends in deaths from cardiovascular disease as a whole. No study has investigated trends in cerebrovascular disease, and its subtypes within all European countries. This study aimed to examine sex-specific trends in cerebrovascular disease, and three of its sub-types: ischaemic stroke, haemorrhagic stroke, and subarachnoid haemorrhage (SAH), in Europe between 1980 and 2016. Methods and results: Sex-specific mortality data for each country of the World Health Organization (WHO) Europe region were extracted from the WHO global mortality database and analysed using Joinpoint software to examine trends. The number and location of significant joinpoints for each country by sex and subtype was determined using a log-linear model. The annual percentage change within each segment was calculated along with the average annual percentage change over the duration of all available data. The last 35 years have seen large overall declines in cerebrovascular disease mortality rates in the majority of European countries. While these declines have continued steadily in more than half of countries, this analysis has revealed evidence of recent plateauing and even increases in stroke mortality in a number of countries, in both sexes, and in all four geographical sub-regions of Europe. Analysis by stroke sub-type revealed that recent plateauing was most common for haemorraghic stroke and increases were most common for ischaemic stroke. Conclusion: These findings highlight the need for continued research into the inequalities in both current stroke mortality outcomes and trends across Europe, as well as the causes behind any recent plateauing of total cerebrovascular disease or its subtypes

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Cardiomyocyte Deletion of \u3ci\u3eBmal1\u3c/i\u3e Exacerbates QT- and RR-Interval Prolongation in \u3ci\u3eScn5a\u3c/i\u3e\u3csup\u3e+/ΔKPQ\u3c/sup\u3e Mice

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation

Combining genomics and epidemiology to track mumps virus transmission in the United States.

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by ‘genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2′-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex diseas

Evaluation of acute and convalescent antibody concentration against pneumococcal capsular polysaccharides for the diagnosis of pneumococcal infection in children with community-acquired pneumonia

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections

Teleost Growth Factor Independence (Gfi) Genes Differentially Regulate Successive Waves of Hematopoiesis

Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gfi1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors.Stem Cell and Regenerative Biolog