Search

Background: Hypertension has become a very common feature in the urban areas, with atleast one member in the family being affected with the diseases. Diagnosis of hypertension maybe delayed for several years due to lack of screening. Once diagnosed as hypertensive, and initiated on treatment, patient's usually fail to go for regular health seeking behaviour or have poor compliance to medical advice resulting in uncontrolled blood pressure levels. Aims: The aim of the present study is to assess the prevalence of Hypertension, Pre-Hypertension, Awareness of Hypertension, Treatment of Hypertension and Controlled Hypertension. Settings and Design: Cross-sectional Study design conducted in an urban area of Mumbai. Methods and Material:One stage cluster sampling was used to select requisite sample size. Men and women aged 25-69 years underwent Blood Pressure measurements according to standard guidelines. Statistical analysis used: Chi-square, Age standardised prevalence rates, 95% confidence intervals were calculated. Results:Amongst the 446 men and women screened, 151(33.9%) were found to have hypertension and 108 were pre-hypertensive. One-third of the individuals were not aware of their condition. Amongst the hypertensive cases taking treatment, almost two-thirds had uncontrolled BP. Conclusions:It is important not only to conduct screening programmes in the community but also develop programmes to ensure that the diagnosed patients achieve their target BP level and delay the onset of complications thereby improving quality of life. [ABSTRACT FROM AUTHOR]

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4 + T cell and memory B cell responses. Antigen-specific CD4 + T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life., Competing Interests: Declaration of interests B.P. serves on the External Immunology Board of GSK and on the Scientific Advisory Board of Sanofi, Medicago, Boehringer Ingelheim, Icosavax, and EdJen. F.W. is a consultant for Gilead. A.S. is a consultant for Gritstone Bio, Flow Pharma, Moderna, AstraZeneca, Qiagen, Fortress, Gilead, Sanofi, Merck, RiverVest, MedaCorp, Turnstone, NA Vaccine Institute, Emervax, Gerson Lehrman Group and Guggenheim. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology 1,2 . Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14 + CD16 + inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Mass cytometry, or CyTOF (Cytometry by Time-of-Flight), permits the simultaneous detection of over 40 phenotypic and functional immune markers in individual cells without the issues of spectral overlap seen in traditional flow cytometry., Methods: In this study, we applied CyTOF to comprehensively characterize the circulating immune cell populations in elderly individuals both before and after administration of an investigational adjuvanted protein vaccine against respiratory syncytial virus (RSV) in a Phase 1a trial. Antigen-specific T cell responses to RSV by IFNγ ELISPOT had been observed in most but not all recipients in the highest dose cohort in this trial. Here, CyTOF was used to characterize the cellular response profile of ELISPOT responders and non-responders in this vaccine dose cohort., Results: Both CD4 + and CD8 + T cell antigen-specific IFNγ responses were observed. Principal components analysis revealed baseline differences between responders and non-responders, including differences in activated (HLA-DR + ) CD4 + and CD8 + T cells, which were higher in non-responders versus responders. Using viSNE to analyze RSV-responsive CD4 + and CD8 + T cells, we also found increased expression of HLA-DR, CCR7, CD127 and CD69 in non-responders versus responders., Conclusions: High parameter CyTOF can help profile immune components associated with differential vaccine responsiveness.

Background: Disparities in prevalence, human papillomavirus (HPV) status, and mortality rates for head and neck cancer have been described between African American and European American patients., Methods: We studied the HPV status and gene expression profiles in 56 oropharyngeal/oral cavity tumors and 9 normal tissue samples from European American and African American patients treated in South Carolina between 2010 and 2012., Results: Overall, 59% of tumors were HPV DNA-positive, but only 48% of those expressed E7 mRNA (HPV-active). The prevalence of HPV-active tumors was 10% in African American patients and 39% in European American patients. Tumors positive for HPV DNA but negative for HPV mRNA exhibited gene expression profiles distinct from those of both HPV-active and HPV-negative cancers, suggesting that HPV DNA-positive/RNA-negative tumors may constitute a unique group., Conclusion: This study provides a direct assessment of differential expression patterns in HPV-related oropharyngeal cancer arising from African American and European American patients, for which there is a paucity of data. © 2015 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2015., (© 2015 Wiley Periodicals, Inc.)

In our in vitro model for HPV16-mediated transformation, HPV16-immortalized human keratinocytes (HKc/HPV16) give rise to differentiation resistant, premalignant cells (HKc/DR). HKc/DR, but not HKc/HPV16, are resistant to growth inhibition by transforming growth factor beta (TGF-β), due to a partial loss of TGF-β receptor type I. We show that TGF-β activates a Smad-responsive reporter construct in HKc/DR to about 50% of the maximum levels of activation observed in HKc/HPV16. To investigate the functional significance of residual TGF-β signaling in HKc/DR, we compared gene expression profiles elicited by TGF-β treatment of HKc/HPV16 and HKc/DR on Agilent 44k human whole genome microarrays. TGF-β altered the expression of cell cycle and MAP kinase pathway genes in HKc/HPV16, but not in HKc/DR. However, epithelial-mesenchymal transition (EMT) responses to TGF-β were comparable in HKc/HPV16 and HKc/DR, indicating that the signaling pathways through which TGF-β elicits growth inhibition diverge from those that induce EMT in HPV16-transformed cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10(-6)). We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.