Correlation of thrombocytopenia with degree of atypical lymphocytosis as a prognostic indicator in dengue

Background: Dengue viral infections may occur as epidemics and are of public health concern in India especially due to high mortality in advanced stages. Early diagnosis and treatment reduces the mortality significantly. To assess the utility of atypical lymphocyte counts with relation to platelet counts as a marker for severe dengue.Methods: A total of 132 serologically proven (by rapid card method) cases of dengue with atypical lymphocytosis (≥10%) and thrombocytopenia (<150×109/l) were analyzed during November 2016. The complete blood counts (obtained from automated hematology analyzer and Leishman stained peripheral smears) were analyzed.Results: Dengue infections were mostly seen in younger age (12-25 years) with slight male predominance. The relevant haematology findings noted were leukopenia in 36% and severe thrombocytopenia (<50×109/l) in 57% of cases. The differential count showed lymphocytosis in 64% with significant (≥20%) atypical lymphocytes in 52% which inversely correlated with platelet counts. Atypical lymphocytosis (≥20%) was noted in 9% of cases with mild as against 32% of severe thrombocytopenia.Conclusions: Atypical lymphocyte count can be used as predictor of severe thrombocytopenia and severe dengue. This helps in early diagnosis and proper management and drastic reduction in mortality

To evaluate and compare the efficacy of alcoholic and aqueous extract of Lagenaria siceraria in high fat diet model in wistar rats

Background: Obesity is not only affecting the affluent society but also affecting developing countries like India. The incidence of obesity is rapidly increasing throughout the world. However, the current anti-obesity drugs have numerous limitations.Methods: The obesity was induced in male wistar rats by giving high-fat diet over 12 weeks. The variables assessed were body weight, abdominal girth, blood triglyceride level, liver weight and fat mass and histopathology of liver. Aqueous and alcoholic extracts of Lagenaria siceraria (200mg/kg and 400mg/kg Doses) were compared to orlistat (treatment control) and high-fat diet group (disease control) for different variables.Results: Alcoholic and aqueous extracts high dose (400mg/kg) of Lagenaria siceraria significantly reduced total body weight (p&lt;0.05), abdominal girth (p &lt;0.05) at week 10 and 12 compared to high fat diet group. Alcoholic extract (400mg/kg) significantly reduced total blood triglyceride level (p &lt;0.05) and total liver weight (p &lt;0.05) compared to high-fat diet group. None of the study drugs reduced % liver weight. Alcoholic extract high dose (p &lt;0.05) has shown improvement in histopathological score. Both aqueous and alcoholic extracts have shown reduced fat mass compared to high-fat diet group.Conclusions: The alcoholic extract (400mg/kg) of Lagenaria siceraria alleviated high fat diet induced obesity and dyslipidemic changes in rats. The alcoholic extract of Lagenaria siceraria is having better anti-obesity potential than aqueous extract

Ipsilateral renal dysgenesis or agenesis with tubulocystic anomalies of the mesonephric duct

Tubulocystic anomalies of the mesonephric duct (MND) are a rare group of related entities with a perplexing clinical presentation. Ultrasound is a useful screening investigation, which can help identify a dysplastic kidney or point to renal agenesis and identify cystic or tubulocystic changes in the structures derived from the ureteric bud or MND. Further evaluation with MRI can help in characterisation and direct management. The presence of a dysplastic kidney or absence of a kidney should prompt further evaluation for associated ureteric abnormalities such as ectopic insertion or ureterocoele, which could lead to a diagnosis of tubulocystic anomaly of the MND. Contribution: The authors describe two cases, briefly outline the diagnostic approach and summarise the literature on management. Reporting radiologists should be aware of these entities

Comparative analysis of module-based versus direct methods for reverse-engineering transcriptional regulatory networks

We have compared a recently developed module-based algorithm LeMoNe for reverse-engineering transcriptional regulatory networks to a mutual information based direct algorithm CLR, using benchmark expression data and databases of known transcriptional regulatory interactions for Escherichia coli and Saccharomyces cerevisiae. A global comparison using recall versus precision curves hides the topologically distinct nature of the inferred networks and is not informative about the specific subtasks for which each method is most suited. Analysis of the degree distributions and a regulator specific comparison show that CLR is 'regulator-centric', making true predictions for a higher number of regulators, while LeMoNe is 'target-centric', recovering a higher number of known targets for fewer regulators, with limited overlap in the predicted interactions between both methods. Detailed biological examples in E. coli and S. cerevisiae are used to illustrate these differences and to prove that each method is able to infer parts of the network where the other fails. Biological validation of the inferred networks cautions against over-interpreting recall and precision values computed using incomplete reference networks.Comment: 13 pages, 1 table, 6 figures + 6 pages supplementary information (1 table, 5 figures

Technical advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells

The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunit

Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy

Acknowledgements The authors are grateful to Nils Lindstrom and members of the Gillingwater laboratory for advice and assistance with this study and helpful comments on the manuscript; Neil Cashman for the NSC-34 cell line; and Ji-Long Liu for the DrosophilasmnA and smnB lines. This work was supported by grants from the SMA Trust (to T.H. Gillingwater, P.J. Young, and R. Morse), BDF Newlife (to T.H. Gillingwater and S.H. Parson), the Anatomical Society (to T.H. Gillingwater and S.H. Parson), the Muscular Dystrophy Campaign (to T.H. Gillingwater), the Jennifer Trust for Spinal Muscular Atrophy (to H.R. Fuller), the Muscular Dystrophy Association (to G.E. Morris), the Vandervell Foundation (to P.J. Young), the Medical Research Council (GO82208 to I.M. Robinson), Roslin Institute Strategic Grant funding from the BBSRC (to T.M. Wishart), the BBSRC (to C.G. Becker), the Deutsche Forschungsgemeinschaft and EU FP7/2007-2013 (grant no. 2012-305121, NeurOmics, to B. Wirth), the Center for Molecular Medicine Cologne (to B. Wirth and M. Hammerschmidt), and SMA Europe (to M.M. Reissland). We would also like to acknowledge financial support to the Gillingwater lab generated through donations to the SMASHSMA campaign.Peer reviewedPublisher PD

Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators

SummaryHematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors—GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL—in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often occurred near known hematopoietic regulators. Eight genes not previously appreciated to function in hematopoiesis that were bound by all five factors were shown to be essential for thrombocyte and/or erythroid development in zebrafish. Moreover, one of these genes encoding the PDZK1IP1 protein shared transcriptional enhancer elements with the blood stem cell regulator TAL1/SCL. Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen therefore offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes

Effective cataract surgical coverage in adults aged 50 years and older: estimates from population-based surveys in 55 countries.

BACKGROUND: Cataract is the leading cause of blindness globally. Effective cataract surgical coverage (eCSC) measures the number of people in a population who have been operated on for cataract, and had a good outcome, as a proportion of all people operated on or requiring surgery. Therefore, eCSC describes service access (ie, cataract surgical coverage, [CSC]) adjusted for quality. The 74th World Health Assembly endorsed a global target for eCSC of a 30-percentage point increase by 2030. To enable monitoring of progress towards this target, we analysed Rapid Assessment of Avoidable Blindness (RAAB) survey data to establish baseline estimates of eCSC and CSC. METHODS: In this secondary analysis, we used data from 148 RAAB surveys undertaken in 55 countries (2003-21) to calculate eCSC, CSC, and the relative quality gap (% difference between eCSC and CSC). Eligible studies were any version of the RAAB survey conducted since 2000 with individual participant survey data and census population data for people aged 50 years or older in the sampling area and permission from the study's principal investigator for use of data. We compared median eCSC between WHO regions and World Bank income strata and calculated the pooled risk difference and risk ratio comparing eCSC in men and women. FINDINGS: Country eCSC estimates ranged from 3·8% (95% CI 2·1-5·5) in Guinea Bissau, 2010, to 70·3% (95% CI 65·8-74·9) in Hungary, 2015, and the relative quality gap from 10·8% (CSC: 65·7%, eCSC: 58·6%) in Argentina, 2013, to 73·4% (CSC: 14·3%, eCSC: 3·8%) in Guinea Bissau, 2010. Median eCSC was highest among high-income countries (60·5% [IQR 55·6-65·4]; n=2 surveys; 2011-15) and lowest among low-income countries (14·8%; [IQR 8·3-20·7]; n=14 surveys; 2005-21). eCSC was higher in men than women (148 studies pooled risk difference 3·2% [95% CI 2·3-4·1] and pooled risk ratio of 1·20 [95% CI 1·15-1·25]). INTERPRETATION: eCSC varies widely between countries, increases with greater income level, and is higher in men. In pursuit of 2030 targets, many countries, particularly in lower-resource settings, should emphasise quality improvement before increasing access to surgery. Equity must be embedded in efforts to improve access to surgery, with a focus on underserved groups. FUNDING: Indigo Trust, Peek Vision, and Wellcome Trust

Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs

BACKGROUND: Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. RESULTS: We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. CONCLUSION: Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-014-0412-0) contains supplementary material, which is available to authorized users