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The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNβ were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection. Author summary: Mosquitoes carry many globally important human pathogens including a family of related viruses: dengue virus, West Nile virus, Yellow Fever virus, and recently of critical significance, Zika virus. The Zika virus epidemic emerged very rapidly in the susceptible South American population and in many cases immune responses were unable to control the infection. Immune history is a key element of susceptibility or resistance to severe disease. We examined whether pre-existing infection would skew or divert immune resources and might play a role in the severity of Zika infection in the Americas. Using samples from dengue patients and healthy controls from India, we tested functional responses to Zika virus in the context of pre-existing dengue infection. We quantified frequency and functional status of 36 individual cell subsets in depth using advanced profiling techniques and a novel deep learning algorithm. We showed an intact response to new infection with Zika virus which was enriched for early innate immune pathways and robust even during existing dengue infection. Thus, our study suggests that concurrent dengue infection would not be expected to impair immune responses to new infection with Zika virus. [ABSTRACT FROM AUTHOR]

Background: The knowledge of breast cancer risk factors and screening practices in a community is largely influenced by the practising gynaecologist in that area. We assessed the understanding and knowledge of gynaecologists about breast cancer: screening, risk factors, clinical signs, management and common benign breast diseases., Methodology: This cross-sectional study was carried out in Uttar Pradesh, India, from April to September 2017. One hundred and fifty-two gynaecologists were assessed using a self-designed and validated questionnaire to assess the knowledge of risk factors, clinical signs, screening practices and management of breast cancer as well as common benign breast diseases. Further, the results were compared based on their education: undergraduates (UGs; no residency experience in obstetrics and gynaecology) versus postgraduates (PGs; residency experience in obstetrics and gynaecology)., Results: 67 and 82.2% of gynaecologists possess excellent to very good knowledge of risk factors and clinical signs of breast cancer, respectively. The knowledge of PGs seems to be better than UGs (p < 0.01). 84.9% participants were aware that breast cancer screening decreases breast cancer-related mortality, and 61.2% considered CBE as most relevant screening investigation (66.1% PGs and 41.9% UGs; p = 0.04). 30.2% regularly offer breast cancer screening at their centre. 58.5% did not consider screening mammography as cost-effective for their patients (57.9% PGs and 61.3% UGs; p = 0.72), and 41.4% considered it to be a time-consuming process (39.7% PGs and 48.4% UGs; p = 0.38). 99.3% like to follow up a patient with familial breast cancer by themselves, and 0.7% like to refer them to specialist. 51.9% gynaecologists were convinced of breast conservation surgery (BCS) as a surgical option, however 51.3% feared leaving diseased breast behind., Conclusion: Despite the knowledge regarding risk factors, clinical signs and treatment of breast cancer and benign breast diseases was found adequate amongst the gynaecologists, this did not apply to their clinical practice. Structured and continuous training of gynaecologists is needed to improve the outcome of patients with breast diseases in terms of better management and reference.

Our earlier identification of the non-structural protein 3 (NS3) of Japanese encephalitis virus (JEV) as a dominant CD4+ as well as CD8+ T cell-eliciting antigen in a healthy JEV-endemic cohort with a wide HLA distribution implied the presence of several epitopes dispersed over the length of the protein. Use of various truncated versions of NS3 in lymphocyte stimulation and interferon (IFN)-gamma secretion assays revealed that amino acids (aa) 193-324 of NS3 were comparable with, if not superior to, the full-length protein in evoking Th1 responses. The potential of this 14.4 kDa stretch to stimulate IFN-gamma production from both subtypes of T cells in a manner qualitatively and quantitatively similar to the 68 kDa parent protein suggested the presence within it of both class I and II epitopes and demonstrated that the entire immunogenicity of NS3 was focused on aa 193-324. Interestingly, this segment contained five of the eight helicase motifs of NS3. Analysis of variability of the NS3 protein sequence across 16 JEV isolates revealed complete identity of aa 219-318, which is contained within the above segment, suggesting that NS3-specific epitopes tend to cluster in relatively conserved regions that harbour functionally critical domains of the protein.