Project description:We report a case of an overtly symptomatic patient with delayed diagnosis of massive (>25-mm thickness), circular, constrictive pericarditis. Our patient underwent a successful surgical pericardiectomy-a high-risk procedure-revealing an armored heart, with an impressive clinical improvement. Diagnosis of constrictive pericarditis is challenging and requires high clinical suspicion.
Project description:Twenty-seven inbred strains of mice were tested for spike-wave discharge (SWD) activity by video-electroencephalographic recordings over a 24-h recording period. Eight strains had reproducible, frequent SWDs, including five strains (C57BLKS/J, CBA/J, DBA/1J, NOR/LtJ, SM/J) previously undiagnosed for this distinctive phenotype. Eighteen other strains exhibited no such activity. Spike-wave discharges usually occurred while the subject was motionless, and in a significant number of annotated instances coincided with an arrest of the subject's relatively unrestrained locomotor activity, which resumed immediately after the discharge ended. In all five new strains, SWDs were suppressed by ethosuximide administration. From the genealogy of inbred strains, we suggest that two ancestors, A and DBA, transmitted genotypes required for SWD in all positive strains. Together these strains with SWDs provide new opportunities to understand the genetic core susceptibility of this distinctive electroencephalographic activity and to explore its relationship to absence epilepsy, a human disorder for which few genes are known.
Project description:Ovine parasitic gastroenteritis is a complex disease routinely treated using anthelmintics. Although many different strongyle species may contribute to parasitic gastroenteritis, not all are equally pathogenic: in temperate regions, the primary pathogen is Teladorsagia circumcincta. In this study we investigated benzimidazole and ivermectin resistance on a commercial sheep farm in southeast Scotland. We assessed the impact of species diversity on the diagnosis of resistance using the faecal egg count reduction test and in vitro bioassays, and correlated the results with the frequency of benzimidazole resistance-associated genotypes measured in the T. circumcincta population by pyrosequencing of the ?-tubulin isotype-1?gene. Faecal egg count reduction test results showed efficacies of 65% for albendazole and 77% for ivermectin, indicating moderate resistance levels on the farm. However, PCR speciation of the same populations pre- and post-treatment revealed that removal of susceptible species had masked the presence of a highly resistant population of T. circumcincta. Less than 25% of individuals in the pre-treatment populations were T. circumcincta, the remainder consisting of Cooperia curticei, Chabertia ovina, Oesophagostomum venulosum and Trichostrongylus spp. In contrast, post-treatment with albendazole or ivermectin, the majority (88% and 100% respectively) of the populations consisted of T. circumcincta. The egg hatch test for benzimidazole resistance and the larval development test for ivermectin resistance were carried out using eggs obtained from the same populations and the results were broadly consistent with the faecal egg count reduction test. Thirty individual T. circumcincta from each sampling time point were assessed for benzimidazole resistance by pyrosequencing, revealing a high frequency and diversity of resistance-associated mutations, including within the population sampled post-ivermectin treatment. These results highlight the potential diversity of parasite species present on UK farms, and their importance in the diagnosis of anthelmintic resistance. On this particular farm, we demonstrate the presence of a highly dual-resistant population of T. circumcincta, which was strongly selected by treatment with either benzimidazoles or ivermectin, while other potentially less pathogenic species were removed.
Project description:BackgroundRepresentatives of the phylum Chloroflexi, though reportedly highly abundant in the extensive deep water habitats of both marine (SAR202 up to 30% of total prokaryotes) and freshwater (CL500-11 up to 26% of total prokaryotes), remain uncultivated and uncharacterized. There are few metagenomic studies on marine Chloroflexi representatives, while the pelagic freshwater Chloroflexi community is largely unknown except for a single metagenome-assembled genome of CL500-11.ResultsHere, we provide the first extensive examination of the community composition of this cosmopolitan phylum in a range of pelagic habitats (176 datasets) and highlight the impact of salinity and depth on their phylogenomic composition. Reconstructed genomes (53 in total) provide a perspective on the phylogeny, metabolism, and distribution of three novel classes and two family-level taxa within the phylum Chloroflexi. We unraveled a remarkable genomic diversity of pelagic freshwater Chloroflexi representatives that thrive not only in the hypolimnion as previously suspected, but also in the epilimnion. Our results suggest that the lake hypolimnion provides a globally stable habitat reflected in lower species diversity among hypolimnion-specific CL500-11 and TK10 clusters in distantly related lakes compared to a higher species diversity of the epilimnion-specific SL56 cluster. Cell volume analyses show that the CL500-11 are among the largest prokaryotic cells in the water column of deep lakes and with a biomass to abundance ratio of two they significantly contribute to the deep lake carbon flow. Metabolic insights indicate participation of JG30-KF-CM66 representatives in the global cobalamin production via cobinamide to cobalamin salvage pathway.ConclusionsExtending phylogenomic comparisons to brackish and marine habitats suggests salinity as the major influencer of the community composition of the deep-dwelling Chloroflexi in marine (SAR202) and freshwater (CL500-11) habitats as both counterparts thrive in intermediate brackish salinity; however, freshwater habitats harbor the most phylogenetically diverse community of pelagic Chloroflexi representatives that reside both in epi- and hypolimnion.
Project description:BackgroundDomestic violence (DV) is prevalent across all racial and socioeconomic classes in the United States. Little is known about whether physicians differentially screen based on a patient's race or socioeconomic status (SES) or about resident physician screening attitudes and practices.ObjectiveTo assess the importance of patient race and SES and resident and clinical characteristics in resident physician DV screening practices.Design, participantsOne-hundred and sixty-seven of 309 (response rate: 54%) residents from 6 specialties at a large academic medical center responded to a randomly assigned online survey that included 1 of 4 clinical vignettes and questions on attitudes and practices regarding DV screening.MeasurementsWe measured patient, resident, and clinical practice characteristics and used bivariate and multivariate methods to assess their association with the importance residents place on DV screening and if they would definitely screen for DV in the clinical vignette.ResultsResidents screened the African-American and the Caucasian woman (51% vs 57%, P = .40) and the woman of low SES and high SES (49% vs 58%, P = .26) at similar rates. Thirty-seven percent of residents incorrectly reported rates of DV are higher among African Americans than Caucasians, and 66% incorrectly reported rates are higher among women of lower than of higher SES. In multivariate analyses, residents who knew where to refer DV victims (adjusted odds ratio [AOR] = 3.54, 95% confidence interval [CI]: 1.43 to 8.73) and whose mentors advised them to screen (AOR = 3.46, 95% CI: 1.42 to 8.42) were more likely to screen for DV.ConclusionAlthough residents have incorrect knowledge about the epidemiology of DV, they showed no racial or SES preferences in screening for DV. Improvement of mentoring and educating residents about referral resources may be promising strategies to increase resident DV screening.
Project description:Background and purposeTentorial sinus venous channels within the tentorium cerebelli connecting various cerebellar and supratentorial veins, as well as the basal vein, to adjacent venous sinuses are a well-recognized entity. Also well-known are "dural lakes" at the vertex. However, the presence of similar channels in the supratentorial dura, serving as recipients of the Labbe, superficial temporal, and lateral and medial parieto-occipital veins, among others, appears to be underappreciated. Also under-recognized is the possible role of these channels in the angioarchitecture of certain high-grade dural fistulas.Materials and methodsA retrospective review of 100 consecutive angiographic studies was performed following identification of index cases to gather data on the angiographic and cross-sectional appearance, location, length, and other features. A review of 100 consecutive dural fistulas was also performed to identify those not directly involving a venous sinus.ResultsSupratentorial dural venous channels were found in 26% of angiograms. They have the same appearance as those in the tentorium cerebelli, a flattened, ovalized morphology owing to their course between 2 layers of the dura, in contradistinction to a rounded cross-section of cortical and bridging veins. They are best appreciated on angiography and volumetric postcontrast T1-weighted images. Ten dural fistulas not directly involving a venous sinus were identified, 6 tentorium cerebelli and 4 supratentorial.ConclusionsSupratentorial dural venous channels are an under-recognized entity. They may play a role in the angioarchitecture of dural arteriovenous fistulas that appear to drain directly into a cortical vein. We propose "dural venous channel" as a unifying name for these structures.
Project description:The first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes (BP). To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences. We use a simple yet powerful metric based on Gene Ontology BP terms to define characterized and uncharacterized proteins for human, budding yeast and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalogue of proteins' biological roles.
Project description:Genomic studies of bacteria have long pointed toward widespread prevalence of small open reading frames (sORFs) encoding for short proteins, <100 amino acids in length. Despite the mounting genomic evidence of their robust expression, relatively little progress has been made in their mass spectrometry-based detection and various blanket statements have been used to explain this observed discrepancy. In this study, we provide a large-scale riboproteogenomics investigation of the challenging nature of proteomic detection of such small proteins as informed by conditional translation data. A panel of physiochemical properties alongside recently developed mass spectrometry detectability metrics was interrogated to provide a comprehensive evidence-based assessment of sORF-encoded polypeptide (SEP) detectability. Moreover, a large-scale proteomics and translatomics compendium of proteins produced by Salmonella Typhimurium (S. Typhimurium), a model human pathogen, across a panel of growth conditions is presented and used in support of our in silico SEP detectability analysis. This integrative approach is used to provide a data-driven census of small proteins expressed by S. Typhimurium across growth phases and infection-relevant conditions. Taken together, our study pinpoints current limitations in proteomics-based detection of novel small proteins currently missing from bacterial genome annotations.
Project description:Genomic studies of bacteria have long pointed towards widespread prevalence of small open reading frames (sORFs) encoding for short proteins, less than 100 amino acids in length. Despite the mounting genomic evidence of their robust expression, little progress has been made in their mass spectrometry-based validation. Various blanket statements have been used to explain this discrepancy with the potentially low expression levels and protein instability being put forward most often. In this study we provide the first systemic investigation of the challenging nature of proteomic detection of such small proteins. A panel of physiochemical properties alongside recently developed mass spectrometry detectability metrics is interrogated to provide the first evidence-based study of SEP detectability. Moreover, a large scale proteomics and genomics compendium of proteins produced by Salmonella Typhimurium (S. Typhimurium), a model human pathogen, across a panel of growth conditions is presented and used to further support our in silico analysis. This integrative riboproteogenomic approach is used to provide a data-driven census of small proteins expressed by S. Typhimurium across growth phases and infection-relevant conditions. Taken together our study delineates current limitations in proteomics based validation of novel small proteins currently missing from bacterial genome annotations.
Project description:To investigate the relationship between Bacille Calmette-Guérin (BCG) vaccination and SARS-CoV-2 by a bioinformatics approach, two datasets for the SARS-CoV-2 infection group and BCG-vaccinated group were downloaded. Differentially Expressed Genes were identified. Gene ontology and pathways were functionally enriched, and networking was constructed in NetworkAnalyst. Lastly, the correlation between post-BCG vaccination and COVID-19 transcriptome signatures was established. A total of 161 DEGs (113 upregulated DEGs and 48 downregulated genes) were identified in the SARS-CoV-2 group. In the pathway enrichment analysis, a cross-reference of upregulated Kyoto Encyclopedia of Genes and Genomes pathways in SARS-CoV-2 with downregulated counterparts in the BCG-vaccinated group, resulted in the intersection of 45 common pathways, accounting for 86.5% of SARS-CoV-2 upregulated pathways. Of these intersecting pathways, a vast majority were immune and inflammatory pathways with top significance in interleukin-17, tumor necrosis factor, NOD-like receptors, and nuclear factor-κB signaling pathways. Given the inverse relationship of the specific differentially expressed gene pathways highlighted in our results, the BCG-vaccine may play a protective role against COVID-19 by mounting a nonspecific immunological response and further investigation of this relationship is warranted.