Immunization of Children in a Rural Area of North Kashmir, India: A KAP Study.

Background: Knowledge, attitude and practices about immunization among mothers of children aged 1-2 years was assessed. Method: 300 mothers were administered a semi-structured questionnaire at PHC Hajan from 1st march to 1st may 2011 to elicit the information about the knowledge, attitude and practices of the mothers regarding immunization. Results: 100% of mothers knew that vaccination is beneficial and protects their children from diseases. 39% knew OPV protects from polio while only 1% were aware of protective role of BCG. All mothers knew about immunization in pregnancy but 86% were unaware about its preventive role. 26% mothers believed that 3 doses of T.T (tetanus toxoid) are to be given during pregnancy. Whereas 98% of children were completely immunized, 93% completed on schedule. Eighty percent of mothers reported of fever following DPT. All mothers had received tetanus toxoid during pregnancy. Conclusion: Considering mothers' poor knowledge and good attitude, health education on immunization is emphasized to improve their practices

Education under surveillance in Kashmir in the era of Covid-19

This article focuses on how the COVID-19 lockdown intersects with academic freedom in the disputed Himalayan territory of Jammu and Kashmir. The Bhartiya Janata Party, the ruling right-wing party of India, has used COVID-19 to actively isolate Kashmir curtailing educational rights and opportunities. Punitive internet blockades and the state’s surveillance technologies associated with prolonged military occupation affect educational access

Genetic Alterations of RET: Possible Implications and Clinical Correlations in Thyroid Carcinogenesis

Thyroid cancers are malignant tumors in the thyroid gland. DNA polymorphisms are playing a decisive role in unscrambling the genomic basis of tumor formation and development in cancer. Thyroid cancer is influenced in a polygenic and low-penetrance manner by RET gene polymorphisms and this part of the world (North India) has not recorded any study regarding RET alterations in this very cancer. We assessed RET G691S (rs1799939), L769L (rs1800861) and S904S (rs1800863) polymorphisms by restriction fragment length polymorphism (RFLP) in order to explain their potential role in the diagnosis and prognosis of Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). In RET G691S polymorphism, the total dissemination of variant alleles (GA + AA) was 62.9% in cases as related to 44.5% in controls (P < 0.05). RET L769L variant alleles (TG + GG) was 70% in cases versus 88% in controls (P < 0.05). In RET S904S, occurrence of variant alleles (CG + GG) was 56% in cases versus 44% in controls (P < 0.05). G691S and L769L polymorphism advocate a “Dominant mode of inheritance”. The S904S polymorphism approves an “Additive mode of inheritance”. In conclusion, there was an over-representation of RET G691S/S904S polymorphisms and under-representation of L769L polymorphism in PTC and FTC patients. Additionally, our data suggest that some haplotypes (A T G, G T G and A T C) of RET may act as low penetrance alleles for predisposition of thyroid cancer

Molecular Alterations and Expression Dynamics in the Etiopathogenesis of Thyroid Cancer

Thyroid carcinoma is the most prevalent endocrine malignancy and accounts for 2% of all human cancers. In the past decade, knowledge of genetic alterations of thyroid cancer (TC) has rapidly expanded, which has provided new insights into thyroid cancer etiology and has offered novel diagnostic tools and prognostic markers that enable improved and personalized management of thyroid cancer patients. Alterations in key signaling effectors seem to be the hallmark of distinct forms of thyroid neoplasia. Mutations or rearrangements in genes that encode Mitogen activated protein kinase (MAPK) pathway effectors seem to be required for transformation. Mutations in BRAF were the most recently identified MAPK effector in thyroid cancer. BRAF V600E is the most common alteration in sporadic papillary carcinoma. Three RAS proto-oncogenes (NRAS, HRAS & KRAS) are implicated in human thyroid tumorigenesis. High incidence of thyroid cancer worldwide indicates the importance of studying genetic alterations that lead to its carcinogenesis. BRAF and RAS alterations represent a novel indicator of the progression and aggressiveness of thyroid carcinogenesis. The GSα-adenylyl cyclase-cyclic AMP (cAMP) cascade is effected in thyroid cancer. Promoter hypermethylation of multiple genes especially TSHR has been identified to play a role in thyroid cancers, in particular showing a close association with BRAF mutational status. So, the main aim of the study was to elucidate the involvement of BRAF and RAS gene mutations along with BRAF expression and thyroid-stimulating hormone receptor (TSHR) hypermethylation in North Indian patients and investigate their association with clinicopathological characteristics

HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite

To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole–dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole–specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A 3.5-Å cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.v5.2 trimer demonstrated that while the epitope recognized overlapped the N332 glycan supersite by contacting the GDIR motif at the base of V3, primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway

Autologous neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened in rabbits

Extensive studies with subtype A BG505-derived HIV Env immunogens have revealed that the dominant autologous neutralizing epitope in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. To test whether broader neutralization to the common glycan hole can be achieved, we immunized rabbits with B41 SOSIP alone, as well as B41 and BG505 co-immunization. We isolated autologous neutralizing antibodies (nAbs) and described their structure in complex with the B41 Env. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the >97% conserved N241 glycan, which is present in B41. Single particle cryo-electron microscopy studies confirmed that B41 and BG505-specific nAbs bind to overlapping glycan hole epitopes. We then used our high-resolution data to guide mutations in the BG505 glycan hole epitope in an attempt to broaden the reactivity of a B41-specific nAb, but only recovered partial binding. Our data demonstrate that lack of cross-reactivity in glycan hole antibodies is due to amino acid differences within the epitope and our attempts to rationally design cross-reactive trimers resulted in only limited success. Thus, even for the immunodominant glycan hole shared between BG505 and B41 the prospect of designing prime-boost immunogens remains difficult

Beyond the Boxes: Guiding Questions for Thoughtfully Measuring and Interpreting Race in Population Health Research

Race and ethnicity are key constructs underpinning social stratification and health in the US, but the use of race and ethnicity in population health research can be ritualistic and lacking careful consideration. Our team collaborated on a research project evaluating how population health research conceptualizes and uses race. We drew from lessons learned during this project to develop a blog series for the Interdisciplinary Association of Population Health Science. This six part series proposes guiding questions and considerations for how researchers can more thoughtfully define, measure, code, analyze, and interpret race and ethnicity in their own work