Omics-driven utilization of wild relatives for empowering pre-breeding in pearl millet.

MAIN CONCLUSION: Pearl millet wild relatives harbour novel alleles which could be utilized to broaden genetic base of cultivated species. Genomics-informed pre-breeding is needed to speed up introgression from wild to cultivated gene pool in pearl millet. Rising episodes of intense biotic and abiotic stresses challenge pearl millet production globally. Wild relatives provide a wide spectrum of novel alleles which could address challenges posed by climate change. Pre-breeding holds potential to introgress novel diversity in genetically narrow cultivated Pennisetum glaucum from diverse gene pool. Practical utilization of gene pool diversity remained elusive due to genetic intricacies. Harnessing promising traits from wild pennisetum is limited by lack of information on underlying candidate genes/QTLs. Next-Generation Omics provide vast scope to speed up pre-breeding in pearl millet. Genomic resources generated out of draft genome sequence and improved genome assemblies can be employed to utilize gene bank accessions effectively. The article highlights genetic richness in pearl millet and its utilization with a focus on harnessing next-generation Omics to empower pre-breeding.

Molecular detection of Orientia tsutsugamushi in ectoparasites & their small mammal hosts captured from scrub typhus endemic areas in Madurai district, India.

BACKGROUND OBJECTIVES: Scrub typhus, caused by Orientia tsutsugamushi present in small mammals harbouring the ectoparasites. A study was undertaken to detect the pathogen present in small mammals and its ectoparasites in the scrub typhus-reported areas. METHODS: The small mammals (rodents/shrews) and its ectoparasites were screened for O. tsutsugamushi using nested PCR amplification of the groEL gene. Small mammals were collected by trapping and screened for ectoparasites (mites, ticks and fleas) by combing method. RESULTS: All the chigger mites collected were tested negative for O. tsutsugamushi . Interestingly, adult non-trombiculid mites ( Oribatida sp., Dermanyssus gallinae ), fleas ( Xenopsylla astia, X. cheopis, Ctenophalides felis and Ctenophalides sp.) and ticks ( Rhipicephalus sanguineus , R. haemaphysaloides ) screened were found to be positive for O. tsutsugamushi , which the authors believe is the first report on these species globally. Bandicota bengalensis with O. tsutsugamushi infection is reported for the first time in India. The O. tsutsugamushi groEL sequences from the positive samples were similar to the reference strains, Karp and Ikeda and phylogenetically clustered in clade IV with less evolutionary divergence. The blood samples of Rattus rattus , Suncus murinus and B. bengalensis collected from this area were tested positive for O. tsutsugamushi ; interestingly, the sequence similarity was much pronounced with their ectoparasites indicating the transmission of the pathogen to host or vice versa . INTERPRETATION CONCLUSIONS: The outcome of the present investigations widened our scope on the pathogens present in ectoparasites and rodents/shrews from this area. This will help to formulate the required vector control methods to combat zoonotic diseases.

Achieving nutritional security in India through iron and zinc biofortification in pearl millet (Pennisetum glaucum (L.) R. Br.).

The health problems caused by iron (Fe) and zinc (Zn) deficiency plague developing and underdeveloped countries. A vegetarian person mainly depends on cereal based diet with low quantity of Fe and Zn. Biofortification is an economical and sustainable approach to challenge the micronutrient malnutrition problem globally. Pearl millet (Pennisetum glaucum (L.) R. Br.) is one of the nutri-cereals and mostly grown under hot, dry conditions on infertile soils of low water-holding capacity, where other crops generally fail. It contains anti-nutrient compounds like phytic acid and polyphenols which reduce the mineral bioavailability because of their chelating properties. Biofortification of pearl millet is like a double-edged sword which cuts down the economic burden and simultaneously supplies required nutrition to the poor, offering a great scope for food security as well as nutritional security. With this background, this review focus on biofortification of grain Fe and Zn content in pearl millet. Genetic research on Fe and Zn uptake and accumulation in pearl millet grain is crucial in identifying the 'bottlenecks' in biofortification. The review also reveals the need and strategies for increasing bioavailability of Fe and Zn in humans by increasing promoters and decreasing anti-nutritional factors in pearl millet.

Patterns of repeated diagnostic testing for COVID-19 in relation to patient characteristics and outcomes.

BACKGROUND: Whilst the COVID-19 diagnostic test has a high false-negative rate, not everyone initially negative is re-tested. Michigan Medicine, a primary regional centre, provided an ideal setting for studying testing patterns during the first wave of the pandemic. OBJECTIVES: To identify the characteristics of patients who underwent repeated testing for COVID-19 and determine if repeated testing was associated with downstream outcomes amongst positive cases. METHODS: Characteristics, test results, and health outcomes for patients presenting for a COVID-19 diagnostic test were collected. We examined whether patient characteristics differed with repeated testing and estimated a false-negative rate for the test. We then studied repeated testing patterns in patients with severe COVID-19-related outcomes. RESULTS: Patient age, sex, body mass index, neighbourhood poverty levels, pre-existing type 2 diabetes, circulatory, kidney, and liver diseases, and cough, fever/chills, and pain symptoms 14 days prior to a first test were associated with repeated testing. Amongst patients with a positive result, age (OR: 1.17; 95% CI: (1.05, 1.34)) and pre-existing kidney diseases (OR: 2.26; 95% CI: (1.41, 3.68)) remained significant. Hospitalization (OR: 7.88; 95% CI: (5.15, 12.26)) and ICU-level care (OR: 6.93; 95% CI: (4.44, 10.92)) were associated with repeated testing. The estimated false-negative rate was 23.8% (95% CI: (19.5%, 28.5%)). CONCLUSIONS: Whilst most patients were tested once and received a negative result, a meaningful subset underwent multiple rounds of testing. These results shed light on testing patterns and have important implications for understanding the variation of repeated testing results within and between patients.

Rational Design of Highly Efficient Perovskite Hydroxide for Electrocatalytic Water Oxidation.

The production of hydrogen from ecofriendly renewable technologies like water electrolysis and fuel cells involves oxygen evolution reaction (OER), which plays a major role, but the slow kinetics of OER is a bottleneck of commercialization of such technologies. Herein, we have reported the formation of an efficient OER catalyst from SnCo(OH)6 (SCH) by leaching of Sn atoms during electrochemical OER studies. According to density functional theory calculations, adsorption of OH* species on Sn atoms is energetically more favorable than that of Co atoms, and as a result, highly active CoOOH is generated by leaching of Sn atoms from surface layers. We observed enhanced OER performance with superior mass activity by blending SCH with activated charcoal, which displays a low overpotential of 293 mV and higher mass activity than that of pristine SCH. More importantly, it outperforms Co(OH)2 and RuO2 having the same carbon composition because of the formation of thermodynamically stable and amorphous CoOOH on the surface of single-crystalline SCH and strong tethering ability of activated charcoal.

The economic and resource burden of e-scooter-related orthopaedic injuries: A district general hospital's experience.

PURPOSE: Electric scooters (e-scooters) are an increasingly popular method of transportation worldwide. However, there are concerns regarding their safety, specifically with regards to orthopaedic injuries. We aimed to investigate the overall burden and financial impact on orthopaedic services as a result of e-scooter-related orthopaedic injuries. METHODS: We retrospectively identified all e-scooter-related injuries requiring orthopaedic admission or surgical intervention in a large District General Hospital in England over a 16-month period between September 2020 and December 2021. Injuries sustained, surgical management, inpatient stay and resources used were calculated. RESULTS: Seventy-nine patients presented with orthopaedic injuries as a result of e-scooter transportation with a mean age of 30.1 years (SD 11.6), of which 62 were males and 17 were females. A total of 86 individual orthopaedic injuries were sustained, with fractures being the most common type of injury. Of these, 23 patients required 28 individual surgical procedures. The combined theatre and recovery time of these procedures was 5500 min, while isolated operating time was 2088 min. The total cost of theatre running time for these patients was estimated at £77,000. A total of 17 patients required hospital admission under Trauma and Orthopaedics, which accounted for total combined stay of 99 days with a mean length of stay of 5.8 days. CONCLUSION: While there are potential environmental benefits to e-scooters, we demonstrate the risks of injury associated with their use and the associated increased burden to the healthcare system through additional emergency attendances, frequent outpatient clinic appointments, surgical procedures, and hospital inpatient admissions.

A new approach used in docking study for predicting the combination drug efficacy in EML4-ALK target of NSCLC.

Combination drug treatments are usually used in many diseases, including cancers and AIDS. This treatment strategy is known as one of the cornerstone in therapies, which potentially reduces drug toxicity and drug resistance and also enhances therapeutic efficacy. Before using a drug in treatment, several experimental studies are done in vivo and in vitro to ensure the drug's efficacy. In such experimental studies, the drug's efficacy is evaluated with the help of drug dose ratio. In the combination drug experimental studies, the efficacy of the drugs is quantified with the Combination Index (CI) value and then interpreted by various terminologies like synergy, additive, and antagonism. Several computational models have now been invented for the speedy identification of combination drug efficacy. Unfortunately, none of these models have predicted the atomic level interaction of the combination drug with the target protein. This type of intermolecular interaction can be identified with the help of docking software. In the proposed work, we try to identify the intermolecular interaction and efficacy of the combination drug Crzizotinib and Temozolomide in the target of EML4-ALK in NSCLC by in silico study. The result of the study was evaluated with drug properties and Complex Energy (CE) of the docked complex rather than using docking score and binding energy. From this study, we could understand that first, Crizotinib and then after the Temozolomide drug binded on the EML4-ALK protein complex, showed very least CE and also identified that the combination of Crizotinib and Temozolomide drug are more effective in NSCLC.Communicated by Ramaswamy H. Sarma.

Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons.

Transplantation is common in clinical practice where there is availability of the tissue and organ. In the case of neurodegenerative disease such as Parkinson's disease (PD), transplantation is not possible as a result of the non-availability of tissue or organ and therefore, cell therapy is an innovation in clinical practice. However, the availability of neuronal cells for transplantation is very limited. Alternatively, immortalized neuronal progenitors could be used in treating PD. The neuronal progenitor cells can be differentiated into dopaminergic phenotype. Here in this article, the current understanding of the molecular mechanisms involved in the differentiation of dopaminergic phenotype from the neuronal progenitors immortalized with SV40 LT antigen is discussed. In addition, the methods of generating dopaminergic neurons from progenitor cells and the factors that govern their differentiation are elaborated. Recent advances in cell-therapy based transplantation in PD patients and future prospects are discussed.

Neutrino mass hierarchy and octant determination with atmospheric neutrinos.

The recent discovery by the Daya-Bay and RENO experiments, that θ(13) is nonzero and relatively large, significantly impacts existing experiments and the planning of future facilities. In many scenarios, the nonzero value of θ(13) implies that θ(23) is likely to be different from π/4. Additionally, large detectors will be sensitive to matter effects on the oscillations of atmospheric neutrinos, making it possible to determine the neutrino mass hierarchy and the octant of θ(23). We show that a 50 kT magnetized liquid argon neutrino detector can ascertain the mass hierarchy with a significance larger than 4σ with moderate exposure times, and the octant at the level of 2-3σ with greater exposure.

Frequency of extended-spectrum ß-lactamase (ESBL)-producing Gram-negative bacilli in a 200-bed multi-specialty hospital in Vellore district, Tamil Nadu, India.

PURPOSE: Extended-spectrum ß-lactamase (ESBL) producers were reported only from hospital settings previously, but, nowadays, its common presence in community settings is evident from reports. Our primary aim was to assess the frequency of ESBL-producing Gram-negative bacteria (GNB) and their antibiogram pattern among the clinical isolates received during an 8-month time period. METHODS: The clinical isolates which belonged to the family Enterobacteriaceae from the clinical specimens were included in the study. These clinical isolates were tested for ESBL production using the double-disk synergy test. RESULTS: In total, 301 patients were included in this study, of which 146 (48.50 %) were found to harbor strains of ESBL producers. The acquisition of ESBL in relation to age, sex, inhabitancy, inpatients, and outpatients was also analyzed. In our study, 50.29 % of inpatients and 45.86 % of outpatients were found to harbor ESBL producers. The difference between the two groups was not statistically significant. We found five meropenem-resistant ESBL-producing strains among the 146 ESBL producers. Rural inhabitants were found to contain more ESBLs when compared to peri-urban inhabitants. CONCLUSION: The study showed a high frequency of ESBLs in both community-acquired and hospital-acquired infections. The frequency of ESBLs was higher among isolates from patients who were from rural populations than those from peri-urban populations. The data on ESBL frequency suggests the need for a rational antibiotic use which would reduce the spread of ESBL-producing members of the family Enterobacteriaceae.

Preparation and evaluation of biocomposites as wound dressing material.

Collagen was isolated from the chrome containing leather waste (CCLW) which is a major solid waste in leather industry. Composite films were made using sago starch (SG), soya protein (SY), and collagen (C) and were cross linked with glutaraldehyde (G).The films prepared were characterized for their physico chemical properties like tensile strength, infrared spectra, thermogravimetric analysis, surface morphology, and water absorption studies. Better mechanical properties and surface morphology were observed for SG-SY-G-C films compared to other films prepared using collagen. The composite films prepared were used as wound dressing material on the experimental wounds of rats and healing pattern was evaluated using planimetric, biochemical, and histopathological studies. These studies have revealed better wound healing capacity of SG-SY-G-C film and utilization of CCLW in the preparation of value added product like wound dressing material.

Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole-substituted 9-anilinoacridine derivatives.

A convenient synthesis of novel isoxazole-substituted 9-anilinoacridine derivatives 5a-j was reported. The compounds were confirmed by physical and analytical data and screened for in vitro antioxidant activity by DPPH method, reducing power assay and total antioxidant capacity method. The cytotoxic activity of the compounds was also studied in HEp-2 cell line. The docking studies of the synthesized compounds were performed towards the key nucleoside dsDNA by using AutoDock vina 4.0 programme. All the isoxazole-substituted compounds have significant activities.

Copper alumina @ poly (aniline-co-indole) nanocomposites: synthesis, characterization, electrical properties and gas sensing applications.

Poly(aniline-co-indole)/copper alumina (PANI-co-PIN/Cu-Al2O3) with excellent AC conductivity, dielectric properties, and ammonia gas detecting capabilities were synthesised via in situ chemical oxidative polymerization. The presence of Cu-O bonding vibrations and shift of some characteristic peaks in the Fourier transform infrared spectroscopy (FT-IR) revealed the successful encapsulation of Cu-Al2O3 nanoparticles in the copolymer. The XRD studies showed the crystalline peaks of Cu-Al2O3 in the PANI-co-PIN nanocomposites. The high-resolution transmission electron microscopy (HR-TEM) images confirmed the reinforcement of the inorganic moiety in the copolymer. The results from thermogravimetric analysis (TGA) showed that the inclusion of Cu-Al2O3 in the copolymer matrix greatly increases the thermal stability of PANI-co-PIN. The alternate current (AC) conductivity and dielectric properties of nanocomposites were higher than pure PANI-co-PIN. The improved electrical properties of nanocomposites were due to strong contact between the copolymer and metal oxide surfaces. The gas sensing properties of synthesized copolymer nanocomposites showed excellent sensitivity and response towards ammonia gas at room temperature. The PANI-co-PIN/5 wt% Cu-Al2O3 nanocomposite has the best gas sensing characteristics. The higher AC conductivity, dielectric properties and gas sensing characteristics of PANI-co-PIN/Cu-Al2O3 might be used to develop electrochemical sensing devices.

Prevalence of vitamin D deficiency among South Indian pregnant women.

Background: Deficiency of vitamin D is widespread across the globe. Expectant women are one of the most vulnerable groups for vitamin D deficiency (VDD). Even in South India with abundance of sunlight, pregnant women are believed to be at a high risk of this deficiency. The objectives of this study are to assess the prevalence of VDD in antenatal women, associate it with modifiable risk factors and evaluate its correlation with low birth weight. Methods: This cross-sectional study was conducted in a tertiary care hospital, in Chennai, in 100 pregnant women in their last trimester on the basis of inclusion and exclusion criteria and their vitamin D and calcium levels were assessed. A detailed history regarding physical activity, diet, and sun exposure were collected and results were analyzed. Results: The point prevalence of VDD (serum 25-hydroxyvitamin D (25(OH) D) level <20 ng/mL) among antenatal women in our study is 62%. Univariate analysis revealed that sun exposure and socioeconomic status were the significant factors associated with higher percentage of VDD. Linear regression analysis showed that only sun exposure was a significant predictor for serum 25(OH) D levels. VDD is also associated with increased risk of low-birth-weight babies. Conclusion: VDD is highly prevalent among pregnant women in South India leading to adverse health consequences in the mother and offspring. Less physical activity, decreased sun exposure, darker skin complexion, lower socioeconomic status and lack of awareness are the major risk factors associated with VDD in our study population.

The anti-inflammatory properties of the methanolic extract of Cucumis melo Linn. against prostate enlargement in Wistar rats.

In different parts of the world, Cucumis melo Linn. (C melo) is used for its medicinal properties. The present study examined the effects of a methanolic extract of C melo Linn. (F1 hybrid, MECM) on benign prostatic hyperplasia in adult male Wistar rats and evaluated its anti-inflammatory activity in vivo. MECM treatment reduced prostate weight mildly. Histopathological studies showed that the extract produced a strong protective effect against the development of BPH by testosterone. The MECM also showed protection from testosterone-induced benign prostatic hyperplasia (BPH). MECM was tested against carrageenan-induced inflammation in rats' paws to determine its anti-inflammatory activity. It was shown that MECM had a pronounced effect on the inflammatory response in the late phase, i.e., one hour after carrageenan injection. Prostaglandins and nitric oxide are primarily responsible for this phase indicating that MECM can modify the production and release of prostaglandin and nitric oxide. A novel formulation containing C melo may be able to treat the conditions mentioned above.

Resetting the epigenome: Methylation dynamics in cancer stem cells.

The molecular mechanisms that regulate stem cell pluripotency and differentiation has shown the crucial role that methylation plays in this process. DNA methylation has been shown to be important in the context of developmental pathways, and the role of histone methylation in establishment of the bivalent state of genes is equally important. Recent studies have shed light on the role of RNA methylation changes in stem cell biology. The dynamicity of these methylation changes not only regulates the effective maintenance of pluripotency or differentiation, but also provides an amenable platform for perturbation by cellular stress pathways that are inherent in immune responses such as inflammation or oncogenic programs involving cancer stem cells. We summarize the recent research on the role of methylation dynamics and how it is reset during differentiation and de-differentiation.

Stage specific comparative transcriptomic analysis to reveal gene networks regulating iron and zinc content in pearl millet [Pennisetum glaucum (L.) R. Br.].

Pearl millet is an important staple food crop of poor people and excels all other cereals due to its unique features of resilience to adverse climatic conditions. It is rich in micronutrients like iron and zinc and amenable for focused breeding for these micronutrients along with high yield. Hence, this is a key to alleviate malnutrition and ensure nutritional security. This study was conducted to identify and validate candidate genes governing grain iron and zinc content enabling the desired modifications in the genotypes. Transcriptome sequencing using ION S5 Next Generation Sequencer generated 43.5 million sequence reads resulting in 83,721 transcripts with N50 of 597 bp and 84.35% of transcripts matched with the pearl millet genome assembly. The genotypes having high iron and zinc showed differential gene expression during different stages. Of which, 155 were up-regulated and 251 were down-regulated while during flowering stage and milking stage 349 and 378 transcripts were differentially expressed, respectively. Gene annotation and GO term showed the presence of transcripts involved in metabolic activities associated with uptake and transport of iron and zinc. Information generated will help in gaining insights into iron and zinc metabolism and develop genotypes with high yield, grain iron and zinc content.

Part 1. Short-term effects of air pollution on mortality: results from a time-series analysis in Chennai, India.

This report describes the results of a time-series analysis of the effect of short-term exposure to particulate matter with an aerodynamic diameter < or = 10 pm (PM10) on mortality in metropolitan Chennai, India (formerly Madras). This was one of three sites in India chosen by HEI as part of its Public Health and Air Pollution in Asia (PAPA) initiative. The study involved integration and analysis of retrospective data for the years 2002 through 2004. The data were obtained from relevant government agencies in charge of routine data collection. Data on meteorologic confounders (including temperature, relative humidity, and dew point) were available on all days of the study period. Data on mortality were also available on all days, but information on cause-of-death (including accidental deaths) could not be reliably ascertained. Hence, only all-cause daily mortality was used as the major outcome for the time-series analyses. Data on PM10, nitrogen dioxide (NO2), and sulfur dioxide (SO2) were limited to a much smaller number of days, but spanned the full study period. Data limitations resulting from low sensitivity of gaseous pollutant measurements led to using only PM10 in the main analysis. Of the eight operational ambient air quality monitor (AQM) stations in the city, seven met the selection criteria set forth in the common protocol developed for the three PAPA studies in India. In addition, all raw data used in the analysis were subjected to additional quality assurance (QA) and quality control (QC) criteria to ensure the validity of the measurements. Two salient features of the PM10 data set in Chennai were a high percentage of missing readings and a low correlation among daily data recorded by the AQMs. The latter resulted partly because each AQM had a small footprint (approximate area over which the air pollutant measurements recorded in the AQM are considered valid), and partly because of differences in source profiles among the 10 zones within the city. The zones were defined by the Chennai Corporation based on population density. Alternative exposure series were developed to control for these data features. We first developed exposure series based on data from single AQMs and multiple AQMs. Because neither was found to satisfactorily represent population exposures, we subsequently developed an exposure series that disaggregated pollutant data to individual zones within the city boundary. The zonal series, despite some uncertainties, was found to best represent population exposures among other available choices. The core model was thus a zonal model developed using disaggregated mortality and pollutant data from individual zones. We used quasi-Poisson generalized additive models (GAMs) with smooth functions of time, temperature, and relative humidity modeled using penalized splines. The degrees of freedom (df) for these confounders were selected to maximize the precision with which the relative risk for PM10 was estimated. This is a deviation from the traditional approaches to degrees of freedom selection, which usually aim to optimize overall model fit. Our approach led to the use of 8 df/year for time, 6 df/year for temperature, and 5 df/year for relative humidity. The core model estimated a 0.44% (95% confidence interval [CI] = 0.17 to 0.71) increase in daily all-cause mortality per 10-pg/m3 increase in daily average PM10 concentrations. Extensive sensitivity analyses compared models constructed using alternative exposure series and contributions of model parameters to the core model with regard to confounder degrees of freedom, alternative lags for exposure and meteorologic confounders, inclusion of outliers, seasonality, inclusion of multiple pollutants, and stratification by sex and age. The sensitivity analyses showed that our estimates were robust to a range of specifications and were also comparable to estimates reported in previous time-series studies: PAPA, the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), Air Pollution and Health: A European Approach (APHEA), and Air Pollution and Health: A European and North American Approach (APHENA). While the approaches developed in previous studies served as the basis for our model development, the present study has new refinements that have allowed us to address specific data limitations (such as missing measurements and small footprints of air pollution monitors). The methods developed in the study may allow better use of routine data for time-series analysis in a broad range of settings where similar exposure and data-related issues prevail. We hope that the estimates derived in this study, although somewhat tentative, will facilitate local environmental management initiatives and spur future studies.

Cytokine IP-10 and GM-CSF are prognostic biomarkers for severity in secondary dengue infection.

Dengue virus (DENV) infection is mostly prevalent in tropical and sub-tropical regions of the world. Though most DENV infections are self-limiting febrile like-illness, a small proportion of secondary infection is fatal, if untreated symptomatically. Among various factors involved in severe dengue, immune enhancement by cytokine is the major one. The objective of the study is to elucidate serum cytokine expression among primary and secondary infection and determine if any signature cytokine is correlated with disease severity. Seventy-six serum samples at acute time points were collected during the 2017 DENV outbreak in Madurai, Tamil Nadu. Among the 76 serum samples, 49 belong to primary and 27 to secondary DENV infection. Interestingly, a large number of primary infection presented with DHF/DSS symptoms and, children were found prone to DHF and DSS in secondary infection. The serum samples were analysed for inflammatory cytokines, namely IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, IP-10 and GM-CSF using ELISA assay as well as mRNA analysis using qPCR. Among the 12 inflammatory cytokines analysed IP-10 and GMCSF mRNA and protein shows significant upregulation in secondary infection. Similarly, a strong correlation was observed between GM-CSF and IP-10 with thrombocytopenia, ascites, serous effusion and spontaneous bleeding. Based on the observations, GM-CSF and IP-10 could be a potential prognostic biomarkers for secondary DENV infection.

Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile.

Dengue virus (DENV) infection is prevalent in tropical and subtropical regions of the world, which is fatal if untreated symptomatically. Emergence of new genotype within serotypes led to enhanced severity. The objective of the study is to identify the molecular characteristics of the DENV circulated during 2017 outbreak in Tamil Nadu, India, and to investigate the role of inflammatory cytokines in different "serotypes" and in "dengue severity". A total of 135 suspected samples were tested for DENV infection using IgM, IgG, and qPCR assay; where 76 samples were positive for DENV and analyzed for 12 inflammatory cytokines using ELISA. Serotyping shows 14 DENV-1, 22 DENV-2, 7 DENV-3, and 33 DENV-4, where DENV-4 was predominant. Among 76, 42 isolates were successfully sequenced for C-prM region and grouped. A lineage shift was observed in DENV-4 genotype. Irrespective of serotypes, IFNγ was significantly elevated in all serotypes than control as well as in primary infection than secondary, indicating its role in immune response. GM-CSF and IP-10 were significantly elevated in secondary infection and could be used as prognostic biomarkers for secondary infection. Our observation shows differential cytokine expression profile varied with each serotype, indicating serotype/genotype-specific viral proteins might play a major role in dengue severity. DENV-4 as dominant serotype was reported in Tamil Nadu for the first time during an outbreak with a mixed Th1/Th17 cytokine expression profile that correlated with disease severity. We conclude it is essential to identify circulating viral genotype and their fitness by mutational analysis to correlate with disease severity and immune status, as this correlation will be helpful in diagnostics and therapeutics applications.