Identification of genetic variants affecting reproduction traits in Vrindavani cattle.

Genome-wide association studies (GWAS) are one of the best ways to look into the connection between single-nucleotide polymorphisms (SNPs) and the phenotypic performance. This study aimed to identify the genetic variants that significantly affect the important reproduction traits in Vrindavani cattle using genome-wide SNP chip array data. In this study, 96 randomly chosen Vrindavani cows were genotyped using the Illumina Bovine50K BeadChip platform. A linear regression model of the genome-wide association study was fitted in the PLINK program between genome-wide SNP markers and reproduction traits, including age at first calving (AFC), inter-calving period (ICP), dry days (DD), and service period (SP) across the first three lactations. Information on different QTLs and genes, overlapping or adjacent to genomic coordinates of significant SNPs, was also mined from relevant databases in order to identify the biological pathways associated with reproductive traits in bovine. The Bonferroni correction resulted in total 39 SNP markers present on different chromosomes being identified that significantly affected the variation in AFC (6 SNPs), ICP (7 SNPs), DD (9 SNPs), and SP (17 SNPs). Novel potential candidate genes associated with reproductive traits that were identified using the GWAS methodology included UMPS, ITGB5, ADAM2, UPK1B, TEX55, bta-mir-708, TMPO, TDRD5, MAPRE2, PTER, AP3B1, DPP8, PLAT, TXN2, NDUFAF1, TGFA, DTNA, RSU1, KCNQ1, ADAM32, and CHST8. The significant SNPs and genes associated with the reproductive traits and the enriched genes may be exploited as candidate biomarkers in animal improvement programs, especially for improved reproduction performance in bovines.

A comparative assessment of the community frontline health workers for their knowledge and practices of malaria diagnosis and treatment in three contiguous districts Mandla, Balaghat, and Dindori of Madhya Pradesh, India.

BACKGROUND: Global malaria cases rose by 14 million, and deaths by 69,000, in 2020. In India, a 46% decline has been reported between 2020 and 2019. In 2017, the Malaria Elimination Demonstration Project conducted a needs-assessment of the Accredited Social Health Activists (ASHAs) of Mandla district. This survey revealed the inadequate level of knowledge in malaria diagnosis and treatment. Subsequently, a training programme was launched for enhancing malaria-related knowledge of ASHAs. The present study was conducted in 2021 to evaluate the impact of training on malaria-related knowledge and practices of ASHAs in Mandla. This assessment was also done in two adjoining districts: Balaghat and Dindori. METHODS: A cross-sectional survey using a structured questionnaire was administered to ASHAs to measure their knowledge and practices related to malaria etiology, prevention, diagnosis, and treatment. A comparison of information collected from these three districts was performed using simple descriptive statistics, comparison of means and multivariate logistic regression analysis. RESULTS: Significant improvement was noted amongst ASHAs of district Mandla between 2017 (baseline) and 2021 (endline) in knowledge related to malaria transmission, preventive measures, adherence to the national drug policy, diagnosis using rapid diagnostic tests, and identification of age group-specific, colour-coded artemisinin combination therapy blister packs (p < 0.05). The multivariate logistic regression analysis revealed that odds of Mandla baseline was 0.39, 0.48, 0.34, and 0.07 times lower for malaria-related knowledge on disease etiology, prevention, diagnosis, and treatment, respectively (p < 0.001). Further, participants in districts Balaghat and Dindori showed significantly lower odds for knowledge (p < 0.001) and treatment practices (p < 0.01) compared to Mandla endline. Education, attended training, having a malaria learner's guide, and minimum 10 years' work experience were potential predictors for good treatment practices. CONCLUSION: The findings of the study unequivocally establishes significant improvement in overall malaria-related knowledge and practices of ASHAs in Mandla as a result of periodic training and capacity building efforts. The study suggests that learnings from Mandla district could be helpful in improving level of knowledge and practices among frontline health workers.

Assessment of Plasmodium falciparum drug resistance associated molecular markers in Mandla, Madhya Pradesh, India.

BACKGROUND: Resistance against artemisinin-based combination therapy is one of the challenges to malaria control and elimination globally. Mutations in different genes (Pfdhfr, Pfdhps, Pfk-13 and Pfmdr1) confer resistance to artesunate and sulfadoxine-pyrimethamine (AS + SP) were analysed from Mandla district, Madhya Pradesh, to assess the effectiveness of the current treatment regimen against uncomplicated Plasmodium falciparum. METHODS: Dried blood spots were collected during the active fever survey and mass screening and treatment activities as part of the Malaria Elimination Demonstration Project (MEDP) from 2019 to 2020. Isolated DNA samples were used to amplify the Pfdhfr, Pfdhps, Pfk13 and Pfmdr1 genes using nested PCR and sequenced for mutation analysis using the Sanger sequencing method. RESULTS: A total of 393 samples were subjected to PCR amplification, sequencing and sequence analysis; 199, 215, 235, and 141 samples were successfully sequenced for Pfdhfr, Pfdhps, Pfk13, Pfmdr1, respectively. Analysis revealed that the 53.3% double mutation (C59R, S108N) in Pfdhfr, 89.3% single mutation (G437A) in Pfdhps, 13.5% single mutants (N86Y), and 51.1% synonymous mutations in Pfmdr1 in the study area. Five different non-synonymous and two synonymous point mutations found in Pfk13, which were not associated to artemisinin resistance. CONCLUSION: The study has found that mutations linked to SP resistance are increasing in frequency, which may reduce the effectiveness of this drug as a future partner in artemisinin-based combinations. No evidence of mutations linked to artemisinin resistance in Pfk13 was found, suggesting that parasites are sensitive to artemisinin derivatives in the study area. These findings are a baseline for routine molecular surveillance to proactively identify the emergence and spread of artemisinin-resistant parasites.

Treating methicillin-resistant Staphylococcus aureus (MRSA) bone infection with focused ultrasound combined thermally sensitive liposomes.

OBJECTIVE: Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed 'heat-targeted, on-demand' antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection. METHODS: CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat's femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40-42 °C (∼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses. RESULTS: CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at ∼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted. CONCLUSION: HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.

What determines Hong Kong South Asians' perceptions on COVID-19 vaccine? Implications on culturally appropriate vaccine messages for ethnic minority community.

Guided by the behavioral model of health service use, this study examined the effect of South Asians' perceptions of healthcare, religious belief, and socioeconomic status on their perceived benefits and risks of COVID-19 vaccines (N = 245). Cross-sectional survey was used. Logistic regressions results showed that higher levels of perceived involvement in South Asian community health and trust in the healthcare system were associated with higher odds of reporting perceived vaccine benefits. Permanent residents, students (vs. unemployed), and Pakistani (vs. Indians) also perceived the vaccine as beneficial. On the other hand, believing that the body was sacred and being Buddhist (vs. Hindu) were associated with higher odds of perceiving severe vaccination risk. Those who believed that God would cure COVID-19 and those with higher education tended to perceive the vaccine as having a limited effect. Implications on designing culturally appropriate COVID-19 vaccines messages in interethnic settings are discussed.

Review: genetic background of milk fatty acid synthesis in bovines.

Milk fat composition is an important trait for the dairy industry as it directly influences the nutritional and technological properties of milk and other dairy products. The synthesis of milk fat is a complex process regulated by a network of genes. Thus, understanding the genetic variation and molecular mechanisms regulating milk fat synthesis will help to improve the nutritional quality of dairy products. In this review, we provide an overview of milk fat synthesis in bovines along with the candidate genes involved in the pathway. We also discuss de novo synthesis of fatty acids (ACSS, ACACA, FASN), uptake of FAs (FATP, FAT, LPL), intracellular activation and channelling of FAs (ACSL, FABP), elongation (EVOLV6), desaturation (SCD, FADS), formation of triglycerides (GPAM, AGPAT, LIPIN, DGAT), and milk lipid secretion (BTN1A1, XDH, PLIN2). The genetic variability of individual fatty acids will help to develop selection strategies for obtaining a healthier milk fat profile in bovines. Thus, this review will offer a potential understanding of the molecular mechanisms that regulate milk fat synthesis in bovines.

Significance of nested PCR testing for the detection of low-density malaria infection amongst febrile patients from the Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh, India.

BACKGROUND: Low-density malaria infections (LDMI) are defined as infections that are missed by the rapid diagnostic test (RDT) and/or microscopy which can lead to continued transmission and poses a challenge in malaria elimination efforts. This study was conducted to investigate the prevalence of LDMI in febrile cases using species-specific nested Polymerase Chain Reaction (PCR) tests in the Malaria Elimination Demonstration Project, where routine diagnosis was conducted using RDT. METHODS: Every 10th fever case from a cross-sectional community based fever surveillance was tested with RDT, microscopy and nested PCR. Parasite DNA was isolated from the filter paper using Chelex based method. Molecular diagnosis by nested PCR was performed targeting 18SrRNA gene for Plasmodium species. RESULTS: The prevalence of malaria was 2.50% (436/17405) diagnosed by PCR, 1.13% (196/17405) by RDT, and 0.68% (118/ 17,405) by microscopy. Amongst 17,405 febrile samples, the prevalence of LDMI was 1.51% (263/17405) (95% CI 1.33-1.70), which were missed by conventional methods. Logistic regression analysis revealed that illness during summer season [OR = 1.90 (p < 0.05)] and cases screened within three days of febrile illness [OR = 5.27 (p < 0.001)] were the statistically significant predictors of LDMI. CONCLUSION: The prevalence of malaria among febrile cases using PCR was 2.50% (436/17405) as compared to 1.13% (196/17405) by RDT. Higher number of the LDMI cases were found in subjects with ≤ 3 days mean duration of reported fever, which was statistically significant (p < 0.001). This observation suggests that an early detection of malaria with a more sensitive diagnostic method or repeat testing of the all negative cases may be useful for curtailing malaria transmission. Therefore, malaria elimination programme would benefit from using more sensitive and specific diagnostic methods, such as PCR.

Mass screening and treatment (MSaT) for identifying and treating asymptomatic cases of malaria-malaria elimination demonstration project (MEDP), Mandla, Madhya Pradesh.

BACKGROUND: Mass screening and treatment (MSaT) aims at reducing the spread of malaria in communities by identifying and treating infected persons regardless of the symptoms. This study was conducted to identify and treat asymptomatic cases using MSaT approaches in the community. METHODS: Three rounds of MSaT using cluster combination approaches were carried out during September 2018 to December 2019 to identify and treat asymptomatic malaria cases in the community. All individuals who were present in the household were screened using RDT irrespective of malaria related symptoms. Simultaneously thick and thin blood smear and blood spot were collected for further analysis using microscopy and diagnostic PCR done in a subset of the samples. RESULTS: Logistic regression analysis revealed that asymptomatic malaria cases significantly less among the older age groups compared with < 5 years children (OR ranged between 0.52 and 0.61; p < 0.05), lowest in cluster 4 (OR = 0.01; p < 0.0001); during third round of MSaT survey (OR = 0.11; p < 0.0001) and significantly higher in moderate to high endemic areas (OR = 88.30; p < 0.0001). CONCLUSION: Over the three rounds of MSaT, the number of asymptomatic cases were significantly less in the older age groups, and during third round. Similarly, the asymptomatic cases were significantly less in the low endemic area with API < 1 (cluster four). Therefore, the malaria elimination programme may consider the MSaT strategy to identify asymptomatic cases that would be otherwise missed by routine fever based surveillance. This MSaT strategy would help accomplish the malaria elimination goal in an expedited manner.

A 1.6 Mb region on SSC2 is associated with antibody response to classical swine fever vaccination in a mixed pig population.

Classical Swine Fever (CSF) is a contagious viral disease of pigs which is endemic in several parts of the world, including India. Prophylactic vaccination using live attenuated vaccine is the preferred method of control. However, there is significant inter-individual variation in the antibody response to vaccination. In this study, we measured the E2 antibody blocking percentage after 21 days of CSF vaccination in a mixed pig population consisting of Landrace, indigenous Ghurrah pigs, and their crossbreds. A Genome Wide Association Study (GWAS) carried out using single-SNP and haplotype based methods detected a 1.6 Mb region on SSC2 (28.92-30.52 Mb) as significantly associated with antibody response to CSF vaccination. The significant region and 1 Mb flanking sequences encompass 3 genes - EIF3M, DNAJC24 and ARL14EP, which code for proteins involved in Pestivirus replication and host immune response system. Our results combined with previous studies on immune response of pigs present this region as a suitable candidate for future functional investigations.

Focused ultrasound ablation of a large canine oral tumor achieves efficient tumor remission: a case report.

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life.

What has contributed to the large sex differentials in lifespan variation and life expectancy in South Korea?

To date, research on sex differentials in lifespan variation and life expectancy has mainly been conducted in Western countries and there is a dearth of data from South Korea. This study aimed to further the understanding of mortality transition and life expectancy in South Korea, and the associated trajectories of age-at-death variation, through an analysis of life disparity by gender. Using complete life tables for South Korea for 1970-2015, sex differentials (female-male differences) in life disparity and life expectancy at birth were estimated, and sex differentials in life expectancy were decomposed by age and cause of death. The results showed that sex differentials in life expectancy at birth have not reduced significantly in the last 45 years (1970: 7.1 years; 2015: 6.2 years). Life disparity has reduced more rapidly for females than males, and the difference increased from -0.1 year in 1981 to -1.6 years in 2015. Sex differentials in life expectancy and life disparity in South Korea were higher during 1970-2015 than in several Western countries with high life expectancy. The elderly age group (60 and above) contributed 50% of the total sex difference in life expectancy at birth in 1970, and this increased to 70% in 2015. The contribution of the age group 15-59 years reduced significantly over the period. Decomposition of life expectancy at birth by cause revealed that diseases of the circulatory system (2.2 years), followed by external causes (1.3 years), were the most important causes of the sex differences in life expectancy at birth in 1983, and in 2015 neoplasms (2.2 years) and external causes (1.1 years) explained half of the total sex differences. There has been a significant shift in the age-specific pattern of the contribution towards each cause of death. Overall, sex differentials in life disparity and life expectancy at birth have remained significant in South Korea in the last 45 years.

Does the prenatal factor or the postnatal factor contribute more to changes in the child sex ratio in India? An investigation in the context of fertility and mortality transition.

There has been a drastic decline in the child sex ratio (number of females per 1000 males between ages 0 and 4) in India and many of its states. This study aimed to examine if prenatal factors, such as change in sex ratio at birth, or postnatal factors, such as change in relative mortality of females and males, contribute to this more by analysing the dynamics of the child sex ratio. Changes in the child sex ratio during 2001-2011 were decomposed into a 'fertility' component attributable to prenatal sex selection and a 'mortality' component attributable to sex differentials in postnatal survival at the country as well as the state level. Between the prenatal factor and the postnatal factor, the contribution of the latter to the declining child sex ratio has been greater than the former in India as a whole and in most of the states. By focusing on both prenatal and postnatal factors, the imbalance in the child sex ratio in the country can be reduced to a large extent.

Identification of genes affecting milk fat and fatty acid composition in Vrindavani crossbred cattle using 50 K SNP-Chip.

The aim of this study was to identify candidate genes associated with milk fat per cent and fatty acid (FA) composition in Vrindavani cattle using the Illumina 50 K single-nucleotide polymorphism (SNP) array. After quality control, a total of 41,427 informative and high-quality SNPs were used for a genome-wide association study (GWAS) for milk fat percentage and 16 different types of fatty acids. Lactation stage, parity, test day milk yield, and proportion of exotic inheritance were included as fixed effects in the GWAS model. A total of 67 genome-wide significant (P < 1.20 × 10-06) SNPs and 176 suggestive significant (P < 2.41 × 10-05) SNPs were identified. Out of these, 15 SNPs were associated with more than one trait. The strongest associations were found on BTA14 for milk fat percentage and on BTA2 and BTA16 for polyunsaturated fatty acids. Several significant SNPs were identified close to or within the genes ELOVL6, FABP4, PMP2, PLIN1, MFGE8, GHRL2, and LDLRAD3 which are known to be associated with fat percentage and FA composition in dairy cattle breeds. This study is a step forward to better characterize the molecular mechanisms of phenotypic variation in milk fatty acids in a taurine-indicine composite cattle breed reared in tropical environments.

Copper and Zinc Status in Psoriasis: Correlation with Severity.

Psoriasis is a common and an inflammatory skin disease. Trace elements play an important role in the skin metabolism such as keratinisation and melanin formation as well as immunological and inflammatory reactions. Henceforth, the present study was aimed to evaluate the essential metals with special reference to Cu and Zn. In this study, 72 psoriatic patients and 50 controls were enrolled. On the basis of PASI score psoriatic group comprising of 48 mild and 24 severe psoriatic patients were grouped. The serum trace elements analysis in the subjects revealed that serum Cu levels and Cu/Zn ratio was significantly higher in the psoriatic patients as compared to controls. Interestingly, severity of the psoriasis was well correlated with the serum Cu levels. Taking together, all these findings suggest that Cu may be a major culprit in the pathogenesis as well as in the severity of the disease.

Using nanoparticles for in situ vaccination against cancer: mechanisms and immunotherapy benefits.

Immunotherapy to treat cancer is now an established clinical approach. Immunotherapy can be applied systemically, as done with checkpoint blockade antibodies, but it can also be injected directly into identified tumors, in a strategy of in situ vaccination (ISV). ISV is designed to stimulate a strong local antitumor immune response involving both innate and adaptive immune cells, and through this generate a systemic antitumor immune response against metastatic tumors. A variety of ISVs have been utilized to generate an immunostimulatory tumor microenvironment (TME). These include attenuated microorganisms, recombinant proteins, small molecules, physical disruptors of TME (alternating magnetic and focused ultrasound heating, photothermal therapy, and radiotherapy), and more recently nanoparticles (NPs). NPs are attractive and unique since they can load multiple drugs or other reagents to influence immune and cancer cell functions in the TME, affording a unique opportunity to stimulate antitumor immunity. Here, we describe the NP-ISV therapeutic mechanisms, review chemically synthesized NPs (i.e., liposomes, polymeric, chitosan-based, inorganic NPs, etc.), biologically derived NPs (virus and bacteria-based NPs), and energy-activated NP-ISVs in the context of their use as local ISV. Data suggests that NP-ISVs can enhance outcomes of immunotherapeutic regimens including those utilizing tumor hyperthermia and checkpoint blockade therapies.

In situ vaccination with nanoparticles for cancer immunotherapy: understanding the immunology.

FDA approval of anti-CTLA4 in 2011 for melanoma immunotherapy was paradigm shifting and dramatically accelerated cancer immunotherapy research. The investment and effort have been exceptionally large, with a commensurate impressive pace of discovery. Historical and current research has validated the following key points: tumors are recognized by the immune system; tumors develop an immunosuppressive environment which suppresses the antitumor immune response; successful immunotherapy must overcome that tumor-mediated immunosuppression. While cancer immunotherapy research expanded, a parallel effort developing nanoparticles (NP) for cancer diagnosis and therapy also received major investment and expanded. Initially the two efforts appeared to have minimal synergy. Systemically administered nanoparticles are rapidly ingested by phagocytic leukocytes, and therefore nanotechnologists developed strategies to avoid NP ingestion by leukocytes in order to accomplish nanoparticle accumulation in tumors rather than liver and spleen. Recently, nanotechnology and cancer immunotherapy have increasingly merged since phagocytic leukocytes are the key to reversing the local tumor immunosuppression and the tendency of NP to be phagocytosed can be exploited to manipulate phagocytes for immunotherapy. This review focuses on in situ vaccination (ISV), an immunotherapy approach that can utilize direct injection of immunostimulatory reagents, including NPs, into tumors to disrupt the local immunosuppression, stimulate effective immune response against the treated tumor, and most importantly, generate a systemic antitumor immune response to eliminate metastatic tumors. While there are many specific options for using NP for ISV (reviewed further in this special issue), this review focuses on immunology concepts needed to understand and design successful NP ISV approaches.

Association between the total fertility rate and under-five child sex ratio in India: a panel study among districts of the major states.

This study examined the relationship between the total fertility rate and under-five child sex ratio to understand the role of fertility in the phenomenon of missing girls in India. Using data from the last four decennial censuses for the fifteen major states of India and their districts, covering more than 90% of the population of India, the study showed that there was a major decline in the female to male child sex ratio from 1981 to 2011 in most of the major Indian states and their districts. The panel regression model showed that the total fertility rate was significantly associated with the under-five child sex ratio at the district level for the 30-year period from 1981 to 2011 in India, even after controlling for other factors and any other unobserved heterogeneity. This indicates that areas of India with the highest fertility had the higher female to male child sex ratio, while low-fertility districts had a more male-biased sex ratio.

Selection and validation of differentially expressed metabolic and immune genes in weaned Ghurrah versus crossbred piglets.

In the present investigation, differentially expressed genes (DEGs) were studied using RNA sequencing (RNA-seq) technique in porcine peripheral blood mononuclear cells (PBMC) of weaned Ghurrah and crossbred piglets at 3-month age. Transcriptomic analysis was done using three different packages, namely, EBSeq, DESeq2, and edgeR, to identify the DEGs between Ghurrah and crossbred piglets. Total 7717 DEGs were commonly identified by all three packages, out of which 4151 genes found to be up-regulated, and 3566 genes were down-regulated. Functional annotation of these DEGs indicated metabolism as the most commonly enriched category followed by the immune response. Genes related to metabolism and growth were up-regulated in crossbred piglets as compared with Ghurrah piglets, whereas immunity-related genes were up-regulated in Ghurrah piglets elucidating the disease resistance nature of this indigenous breed over crossbred counterparts. Further, eight DEGs, namely, LRP-1, ADCY4, ERRFI1, LDHD, ARG1, OASL, MGARP, and S100A8, were validated by qRT-PCR in a separate set of biological samples and found to be in concordance with RNA-seq results. Finding in the present study provides insight into genes and their molecular mechanisms governing difference in growth performance between Ghurrah and crossbred pigs.

An observational study to assess the possibility of patient participation in implementing pharmacovigilance in a busy tertiary care hospital.

BACKGROUND: Adverse drug reactions are an important cause of morbidity and mortality worldwide. Monitoring adverse drug reaction is the primary function of Pharmacovigilance Programme of India (PvPI). The national program at the inception allowed only physicians, nurses, and pharmacists to report adverse drug reactions but has recently permitted even the consumers or patients to report. The knowledge, attitude, and practice of patients toward such a program have not been studied, and hence, the present study was conducted to assess the same. METHODS: A questionnaire was prepared based on the review of literature and was filled up by the interviewer based on inputs from patients attending various outpatient departments and dispensary of a tertiary care center after obtaining informed consent. Descriptive statistical analysis was carried out, and the results are expressed in terms of means and proportions for continuous and categorical data, respectively. RESULTS: Majority of the patients were male (58.3%) and were using smart phones (63.9%). Most of the participants (91.6%) felt reporting adverse drug reaction is important, but only 37.7% thought of reporting the same. A very low percentage of participants (10%) were aware about the PvPI and the helpline number. CONCLUSION: The Indian health consumer is highly unaware about the existence of the PvPI and various tools available to report adverse drug reactions. It is the need of the hour to create awareness of the same by using the positive attitude toward the program.

Genome-wide integrated analysis of miRNA and mRNA expression profiles to identify differentially expressed miR-22-5p and miR-27b-5p in response to classical swine fever vaccine virus.

The present study was conducted to identify the differentially expressed miRNAs (DE miRNAs) in the peripheral blood mononuclear cells of crossbred pigs in response to CSF vaccination on 7 and 21 days of post vaccination as compared to unvaccinated control (0 dpv). Simultaneously, set of miRNA was predicted using mRNA seq data at same time point. The proportion of CD4-CD8+ and CD4+CD8+ increased after vaccination, and the mean percentage inhibition was 86.89% at 21 dpv. It was observed that 22 miRNAs were commonly expressed on both the time points. Out of predicted DE miRNAs, it was found that 40 and 35 DE miRNAs were common, obtained from miRNA seq analysis and predicted using mRNA seq data on 7 dpv versus 0 dpv and 21 dpv versus 0 dpv respectively. Two DE miRNAs, ssc-miR-22-5p and ssc-miR-27b-5p, were selected based on their log2 fold change and functions of their target genes in immune process/pathway of viral infections. The validations of DE miRNAs using qRT-PCR were in concordance with miRNA seq analysis. Two set of target genes, CD40 and SWAP70 (target gene of ssc-miR-22-5p) and TLR4 and Lyn (target gene of ssc-miR-27b-5p), were validated and were in concordance with results of RNA seq analysis at a particular time point (except TLR4). The first report of genome-wide identification of differentially expressed miRNA in response to live attenuated vaccine virus of classical swine fever revealed miR-22-5p and miR-27b-5p were differentially expressed at 7 dpv and 21 dpv.