Critical insights on "Association of the C allele of rs479200 in the EGLN1 gene with COVID­19 severity in Indian population: a novel finding".

The recent article by Harit et al. in Human Genomics reported a novel association of the C allele of rs479200 in the human EGLN1 gene with severe COVID-19 in Indian patients. The gene in context is an oxygen-sensor gene whose T allele has been reported to contribute to the inability to cope with hypoxia due to increased expression of the EGLN1 gene and therefore persons with TT genotype of EGLN1 rs479200 are more susceptible to severe manifestations of hypoxia. In contrast to this dogma, Harit et al. showed that the C allele is associated with the worsening of COVID-19 hypoxia without suggesting or even discussing the scientific plausibility of the association. The article also suffers from certain epidemiological, statistical, and mathematical issues that need to be critically elaborated and discussed. In this context, the findings of Harit et al. may be re-evaluated.

75 years' journey of malaria publications in English: what and where?

Malaria has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South-East Asian and South American countries. Proportionally, malaria has attracted global research priorities and this is evident from the number of publications related to malaria from across the globe, irrespective of its endemicity. However, formal and exhaustive analyses of these 'malaria publications' are rarely reported. The systematic review and secondary data analyses were done to retrieve information on what has been published on malaria, where is it published, and which countries are major contributors to malaria research.The study presents malaria publications from 1945 to 2020 retrieved using three databases: Web of Science™, Embase® and Scopus®. Exported data were examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.The total number of published records on malaria ranged from 90,282 to 112,698 (due to three different databases). Based on the number of publications, USA, UK, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene, and PLoS One were the most preferred journals, whereas the University of London (Institutions other than LSHTM), the National Institute of Health, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organization.A disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases differed in their output format and needed standardization to make the outputs comparable across databases.

Dried blood spots: a robust tool for malaria surveillance in countries targeting elimination.

With the advancements in analytical and molecular techniques, Dried Blood Spots (DBS) are re-emerging as attractive and cost-effective alternatives for global health surveillance. The use of DBS has been well-characterized in the neonatal screening of metabolic diseases, therapeutic screening as well as in epidemiological studies for biomonitoring. Malaria is one such infectious disease where DBS use can expedite molecular surveillance for assessing drug resistance and for refining drug usage policies. In India, malaria cases have reduced significantly over the past decade but to achieve malaria elimination by 2030, country-wide DBS-based screening should be conducted to identify the presence of molecular markers of artemisinin resistance and to study parasite reservoirs in asymptomatic populations. DBS has wide applications in genomics, proteomics, and metabolomic studies concerning both host and pathogen factors. Hence, it is a comprehensive tool for malaria surveillance that can capture both host and parasite information. In this review, we elucidate the current and prospective role of DBS in malaria surveillance and its applications in studies ranging from genetic epidemiology, parasite and vector surveillance, drug development and polymorphisms to ultimately how they can pave the roadmap for countries aiming malaria elimination.

Multimorbidity among midlife women in India: well-being beyond reproductive age.

BACKGROUND: Currently, inequality in life expectancy across gender makes women outlive men. Adult women transit towards menopause around midlife accompanied by a series of natural physiological changes leading to several conditions such as osteoporosis, depression, and urinary incontinence, which puts them at a higher risk of having multimorbidity. Multimorbidity is often associated with poorer quality of life, leading to deteriorated work productivity and associated economic loss in midlife. Hence, this study aimed to determine the magnitude and correlates of early onset of multimorbidity and explore its linkages with health-related quality of life (HRQoL) among middle-aged women in India. METHODS: We have utilized data from the first round of the Longitudinal Ageing Study in India, 2017-19. We included women aged 45-65 years (n = 23,951) for analysis. Descriptive data were presented. An ordered logistic regression was conducted and proportional odds were reported to identify the correlates of multimorbidity. To explore the linkages between multimorbidity and selected indicators of HRQoL, an array of regression models were executed. RESULTS: Multimorbidity was reported amongst 29.8% of women in midlife. Chandigarh (PR-54.8 PER 100 women) and Punjab (PR-52.8 per 100 women) reported the highest prevalence of multimorbidity. Women with multimorbidity reported compromised HRQoL indicators such as self-rated health, work-limiting health conditions, mobility, and activities of daily living. CONCLUSIONS: Multimorbidity is increasingly prevalent in midlife women associated with inferior quality of life. The reproductive health programs for women should consist of midlife women focusing on multimorbidity and overall well-being.

Seropositivity of Chlamydia trachomatis & Toxoplasma gondii among male partners of infertile couples in Odisha, India: A facility-based exploratory study.

Chlamydia trachomatis (CT) is the most common curable sexually transmitted non-viral infection, which can cause urethritis, prostatitis, orchitis and epididymitis among males. Toxoplasma gondii, a protozoan causes toxoplasmosis among humans. These infections may lead to decreased fertility. Hence, this study was aimed to estimate the seropositivity of CT and T. gondii infection among the male partners of infertile couples in Odisha, India. In this facility-based cross-sectional study, first void urine, seminal fluid and blood sample were collected from 153 males attending infertility clinics including 74 healthy controls. Urine and seminal fluid were tested through polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay was used to detect immunoglobulin (Ig) G, IgA and IgM anti-Chlamydia and IgM anti-Toxoplasma antibodies through serum. The prevalence of CT was 1.26 per cent (95% CI: 0.03-6.85) as estimated from semen samples using PCR. We detected anti-Chlamydia antibodies IgM-four per cent [95% confidence interval (CI): 0.83-11.24]; IgA-28.16 per cent (95% CI: 18.13-40.09) and IgG-12.5 per cent (95% CI: 5.87-22.4) among participants. Anti-Toxoplasma antibodies IgM were observed in 27.63 per cent (95% CI: 17.98-39.08) of participants. None of the control samples were found positive. Overall seropositivity of CT and Toxoplasma infections is comparable, which suggests that greater attention is required for screening these infections at clinics, especially among infertile couples.

Serological survey for SARS-CoV-2 antibodies among tribal communities of Odisha post-second wave.

Background & objectives: Serial national level serosurveys in India have provided valuable information regarding the spread of COVID-19 pandemic in the general population, but the impact of the ongoing pandemic on the tribal population in India is not well understood. In this study, we evaluated the seroprevalence of COVID-19 antibodies in the tribal population of Odisha post-second wave (September 2021). Methods: A population-based, age-stratified, cross-sectional study design was adopted for the survey, carried out in seven tribal districts of Odisha from 30th August to 16th September 2021. A multistage random sampling method was used where serum samples were tested for antibodies against the SARS-CoV-2 nucleocapsid (N) protein in each district, and a weighted seroprevalence with 95 per cent confidence interval (CI) was estimated for each district. Results: A total of 2855 study participants were included from the seven tribal districts of Odisha in the final analysis. The overall weighted seroprevalence was 72.8 per cent (95% CI: 70.1-75.3). Serological prevalence was the highest among 18-44 yr (74.4%, 95% CI: 71.3-77.3) and from Sambalpur district [75.90% (66.90-83.10)]. Among participants, 41.93 per cent had received at least one dose of any COVID-19 vaccine. Kandhamal district had the highest number of fully immunized participants (24.78%), and in Sundergarh district, most of the study participants (58.1%) were unimmunized. Interpretation & conclusions: This study found high seroprevalence against SARS-CoV-2 in the tribal population of Odisha. The vaccination coverage is at par with the general population, and efforts to address some knowledge gaps may be needed to improve the coverage in the future.

Is multimorbidity associated with higher risk of falls among older adults in India?

BACKGROUND: Fall, a multifaceted health condition, is one of the major causes of mortality among older adults. Rapid ageing and increased multimorbidity in low-and middle-income countries (LMICs), including India, might elevate the risk of fall. Although, fall is associated with significant healthcare utilization, it still remains an under-recognized public health issue. This accentuates a need for evidence on fall to integrate it into existing healthcare programs, a gap in geriatric care. The present study aimed to assess the association of fall with multimorbidity among older adults in India. METHODS: We included 28,567 participants aged ≥ 60 years from Longitudinal Ageing Study in India (LASI), wave-1 conducted during 2017-19. Descriptive statistics were used to compute the prevalence of self-reported falls along with 95% confidence interval as a measure of uncertainty. The association between falls and multimorbidity was assessed by multivariable logistic regression and presented as an adjusted odds ratio (AOR). RESULTS: The prevalence of falls was 12.5%, being higher among women (13.6% vs. 11.4%) than men. The major determinants of fall were females, rural residents and smokeless tobacco use. We observed multimorbidity [AOR: 1.29 (1.14-1.46)] to be significantly associated with falls. CONCLUSION: Falls are commonly prevalent among older adults having multimorbidity as its important predictor. Existing health programs should incorporate falls as an important part of geriatric care. Additionally, primary health care facilities should be strengthened to provide comprehensive care for injuries sustained due to falls.

Mapping the distribution and trends of co-circulating dengue virus serotypes in Odisha, India: A retrospective facility-based analysis.

Background Dengue, caused by mosquito bite, is an emerging disease of international concern. Evidence regarding the prevalent dengue serotypes is scarce, but essential for its management during the outbreaks. Hence, we mapped the distribution and trends of currently prevalent dengue virus (DENV) serotypes in Odisha. Methods We conducted a facility-based retrospective study from referral samples sent for the diagnosis/confirmation of dengue in 2018. The samples were serologically tested for enzyme-linked immunosorbent assay (ELISA) IgM antibody and NS1. Only NS1-positive samples were chosen for sero-typing. A pool of 8-10 NS1-positive samples were analysed for district-wise serotypes. Ribonucleic acid extraction and nested polymerase chain reaction (PCR) was done from NS1-positive samples. The PCR products were then subjected to gel electrophoresis. Results A total of 2892 samples were screened for dengue virus across various districts of Odisha where 763 samples were found to be NS1-positive. Thirteen of 18 districts covering all topographies of Odisha predominantly had DENV2 serotype. Only few districts such as Balangir, Kalahandi and Rayagada had mixed serotypes. Conclusion Although DENV2 is predominantly prevalent, mixed serotypes too exist in Odisha. Evidence based on variations of dengue serotypes across topographies, seasons, gender and age groups may support public health efforts in preventing the disease.

Innovative online care: A cross-sectional survey study of potential benefits and challenges of online lactation consultation service with paediatrician consultation.

Background: Telelactation, a virtual lactation support platform, is a convenient and effective way of providing virtual breastfeeding support services and communicating proper breastfeeding techniques to new mothers to address any breastfeeding challenges and boost overall maternal breastfeeding confidence all from the comfort of their homes. This Ontario Health Insurance Plan (OHIP) covered service benefits more mothers in the remote areas where in-person LC service is not easily accessible. Objective: The objective of this cross-sectional survey study is to explore the feasibility, potential benefits, and challenges, and level of patient satisfaction in virtual lactation consultation services along with virtual paediatrician consultation available in Ontario, Canada. Method: Patient satisfaction was assessed using a structured online survey as a part of a cross-sectional observational study that asked questions relevant to several independent demographic variables as well as specific Likert type scale questions to gauge patient satisfaction with virtual lactation consultation. Results: Data were analyzed from 177 survey responses (n=177), of which study revealed that 86.44% (153/177) were satisfied with the virtual lactation services they received. Patient satisfaction was found to be higher in the first-time mothers with high school or undergraduate education between the age group of 26 to 35 years living in the Greater Toronto Area (GTA). In terms of connectivity, participants from the GTA had a better experience overall compared those living outside the GTA. Conclusion: OHIP covered telelactation with a paediatrician consultation is an innovative and feasible health care delivery platform for providing remote professional breastfeeding support to mothers of all socio-economic strata with great potential to further improve both patient experience and efficiency in patient care.

Declining trends in smokeless tobacco use among Indian women: findings from global adult tobacco survey I and II.

BACKGROUND: Smokeless Tobacco (SLT) use is culturally rooted and more acceptable among women in India. SLT is a significant risk for oral cancers and has other adverse health outcomes on women's general as well as reproductive health. This study aimed to estimate and compare the prevalence and correlates of SLT among adult females in India using Global Adult Tobacco Survey (GATS), 2009-2010 (GATS 1) and 2016-2017 (GATS 2). METHODS: Data from a nationally representative cross-sectional study GATS 1 (n = 35,529) and GATS 2 (n = 40,265) were analysed for adult female smokeless tobacco users. Correlates of SLT exposure were assessed separately using binary logistic regression. Multivariable logistic regression analysis was done for the variables which computed p < 0.1. The association was expressed as Adjusted Odds ratio with 95% confidence intervals. RESULTS: There was a reduction in prevalence of SLT use among women in India between GATS 1 (18.4%) and GATS 2 (12.8%). SLT use was highest among the North-Eastern women in both rounds [AOR: 4.567 (3.942-5.292) during GATS-1 and 9.149 (7.722-10.839) during GATS-2]. Odisha had highest prevalence of 56.53% while Himachal Pradesh had lowest 0.14% during the recent GATS 2 survey. 33.3% vs. 34.80% of the participants were willing to quit tobacco in Central region across both rounds of survey. CONCLUSIONS: Although, smokeless tobacco prevalence among females has reduced between 2009 and 2016 in India, yet tobacco control strategies need further pace. Hence, more focused gender-based tobacco control programs and policies are the need of time.

A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium.

Commitment to and completion of sexual development are essential for malaria parasites (protists of the genus Plasmodium) to be transmitted through mosquitoes. The molecular mechanism(s) responsible for commitment have been hitherto unknown. Here we show that PbAP2-G, a conserved member of the apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, is essential for the commitment of asexually replicating forms to sexual development in Plasmodium berghei, a malaria parasite of rodents. PbAP2-G was identified from mutations in its encoding gene, PBANKA_143750, which account for the loss of sexual development frequently observed in parasites transmitted artificially by blood passage. Systematic gene deletion of conserved ApiAP2 genes in Plasmodium confirmed the role of PbAP2-G and revealed a second ApiAP2 member (PBANKA_103430, here termed PbAP2-G2) that significantly modulates but does not abolish gametocytogenesis, indicating that a cascade of ApiAP2 proteins are involved in commitment to the production and maturation of gametocytes. The data suggest a mechanism of commitment to gametocytogenesis in Plasmodium consistent with a positive feedback loop involving PbAP2-G that could be exploited to prevent the transmission of this pernicious parasite.

Comparison of statistical methods for recurrent event analysis using pediatrics asthma data.

When the same type of event is experienced by a subject more than once it is called recurrent event, which possess two important characteristics, namely "within-subject correlation" and "time-varying covariate." As a result, the traditional statistical methods do not work well on recurrent event data. Over the past few decades, many alternatives methods have been proposed for the analysis of recurrent event data. In this article, the six most prominent methods for recurrent event analysis have been compared on pediatric asthma data. Three variance corrected models (viz "Anderson and Gill [AG] model," "Prentice, William, and Peterson-Counting Process [PWP-CP] model," and "Prentice, William, and Peterson-Gap Time [PWP-GT] model") and three corresponding frailty variants (AG-frailty, PWP-CP-frailty, and PWP-GT-frailty) were compared using three mathematical criterion (AIC, BIC, and log-likelihood) and one graphical criteria (Cox-Snell goodness of fit, visual test). All model comparison indices showed the PWP-GT model as the most appropriate model on asthma data over other models. By using PWP-GT model, seven predictors of asthma exacerbation (viz "abdominal pain at previous visit," "Z5 (%) at previous visit," "diagnosis of asthma at previous visit," "calendar month of exacerbation," "history of maternal asthma," "monthly per capita income," and "emotional stress") were identified. The PWP-GT model was identified as the most appropriate model over other models on pediatrics asthma data.

Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking.

BACKGROUND: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients. In present work, methylene blue, which is proposed as an alternative to primaquine is investigated for its gametocytocidal activity amongst Indian field isolates. An effort has been made to establish Indian field isolates of P. falciparum as in vitro model for gametocytocidal drugs screening. METHODS: Plasmodium falciparum isolates were adapted to in vitro culture and induced to gametocyte production by hypoxanthine and culture was enriched for gametocyte stages using N-acetyl-glucosamine. Gametocytes were incubated with methylene blue for 48 h and stage specific gametocytocidal activity was evaluated by microscopic examination. RESULTS: Plasmodium falciparum field isolates RKL-9 and JDP-8 were able to reproducibly produce gametocytes in high yield and were used to screen gametocytocidal drugs. Methylene blue was found to target gametocytes in a concentration dependent manner by either completely eliminating gametocytes or rendering them morphologically deformed with mean IC50 (early stages) as 424.1 nM and mean IC50 (late stages) as 106.4 nM. These morphologically altered gametocytes appeared highly degenerated having shrinkage, distortions and membrane deformations. CONCLUSIONS: Field isolates that produce gametocytes in high yield in vitro can be identified and used to screen gametocytocidal drugs. These isolates should be used for validation of gametocytocidal hits obtained previously by using lab adapted reference strains. Methylene blue was found to target gametocytes produced from Indian field isolates and is proposed to be used as a gametocytocidal adjunct with artemisinin-based combination therapy. Further exploration of methylene blue in clinical studies amongst Indian population, including G6PD deficient patients, is recommended.

Evidence that the Rhodopsin Kinase (GRK1) N-Terminus and the Transducin Gα C-Terminus Interact with the Same "Hydrophobic Patch" on Rhodopsin TM5.

Phosphorylation of G protein-coupled receptors (GPCRs) terminates their ability to couple with and activate G proteins by increasing their affinity for arrestins. Unfortunately, detailed information regarding how GPCRs interact with the kinases responsible for their phosphorylation is still limited. Here, we purified fully functional GPCR kinase 1 (GRK1) using a rapid method and used it to gain insights into how this important kinase interacts with the GPCR rhodopsin. Specifically, we find that GRK1 uses the same site on rhodopsin as the transducin (Gt) Gtα C-terminal tail and the arrestin "finger loop", a cleft formed in the cytoplasmic face of the receptor upon activation. Our studies also show GRK1 requires two conserved residues located in this cleft (L226 and V230) that have been shown to be required for Gt activation due to their direct interactions with hydrophobic residues on the Gα C-terminal tail. Our data and modeling studies are consistent with the idea that all three proteins (Gt, GRK1, and visual arrestin) bind, at least in part, in the same site on rhodopsin and interact with the receptor through a similar hydrophobic contact-driven mechanism.

Rhodopsin TM6 can interact with two separate and distinct sites on arrestin: evidence for structural plasticity and multiple docking modes in arrestin-rhodopsin binding.

Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called "finger" loop (residues 67-79) and the other in the 160 loop (residues 155-165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin-rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin.

Decline in unmet needs for cataract surgery among the ageing population in India: findings from LASI, wave-1.

Introduction: Cataracts are the leading cause of blindness among older people, but they can be treated with corrective surgery. India boasts the oldest blindness control programme in the world. We aimed to assess the prevalence of cataract surgery, and we compared the determinants of undergoing cataract surgery and identified the unmet needs for cataract surgery among older adults in India. Methods: We included 52,380 individuals aged ≥50 years from the Longitudinal Ageing Study in India, wave-1. The primary outcome measures of our study were the prevalence of cataract surgery and the unmet need for cataract surgery. Multivariate analysis was executed to investigate the association between socio-demographic variables and outcomes, expressing the results as adjusted odds ratios with 95% confidence intervals (CIs). Results: The overall prevalence of cataracts was 14.85%. The coverage of cataract surgery was 76.95%, with 23% having unmet needs for cataract surgery. Notably, cataract surgery coverage was higher at 78.30% (95% CI: 76.88-79.48) among participants aged 66-80 years, while the percentage of those who did not undergo cataract surgery was higher at 24.62% (95% CI: 23.09-26.20) among participants aged 50-60 years. The most deprived group had a higher odds ratio [adjusted odds ratio: 1.20 (95% CI: 1.00-1.44)] (p < 0.05) of having unmet needs for cataract surgery. Conclusions: There is a considerable burden of age-related cataracts in India. While the coverage of cataract surgery is high, the unmet need for cataract surgery cannot be overlooked. The existing blindness control programme has contributed significantly to increasing the coverage of cataract surgery, but it still needs to be strengthened, especially to reach the most deprived sections of society.

Factors influencing implementation of mass drug administration for lymphatic filariasis elimination: a mixed-method study in Odisha, India.

Background: Lymphatic filariasis (LF) persists as a public health problem in India. Despite more than ten rounds of mass drug administration (MDA), LF continues to be endemic in the Dhenkanal district of Odisha. Hence, we assessed the coverage and compliance of the MDA program and explored the factors affecting it in the Dhenkanal district. Methods: An explanatory mixed-method study was conducted, wherein for the quantitative survey, 552 participants aged 2 years and above were recruited following a multistage cluster random sampling during February 2022. In-depth interviews were conducted among purposively selected key stakeholders and program implementers. Descriptive statistics were used to report coverage and compliance, along with a 95% confidence interval. Qualitative data were analyzed using a thematic approach. Results: We observed coverage of 99.28% and compliance of 85.87% for MDA drugs. Supervised drug administration proved to be a major pillar in increasing compliance. There was difficulty in administering drugs in urban areas due to gated societies, the absence of individuals during the day, and the perspective toward healthcare providers. Participants reported a lack of confidence in drug distributors and a fear of side effects as major causes for non-compliance. Conclusion: There is a need to strengthen MDA, especially in urban areas. An urban-specific strategy, along with surveillance, behavioral change communication, and the involvement of multi-disciplinary teams, is required.

Cost analyses for malaria molecular diagnosis for research planners in India and beyond.

BACKGROUND: Malaria elimination mandates early and accurate diagnosis of infection. Although malaria diagnosis is programmatically dependent on microscopy/RDTs, molecular diagnosis has much better diagnostic accuracy. Higher cost of molecular diagnoses is a recognized challenge for use at the point of care. Because funding is always a recognized constraint, we performed financial cost-analyses of available molecular platforms for better utilization of available budget. METHODS: Two strategies were applied to deduce the cost per sample. Strategy 1 included recurring components (RC) in minimum pack size, and biologist's time whereas strategy 2 included only RC and non-recurring components and costs are calculated for sample sizes (1-1,000,000) to infer the sample size effect. RESULTS: Spin column-based manual DNA extraction (US$ 3.93 per sample) is the lowest-cost method, followed by magnetic bead-based automated, semi-automated, and PCI-based manual method. Further, DNA extraction cost per sample via spin column-based manual method and semi-automated method decreases with an increase in sample size up to 10,000. Real-time PCRs are ~ 2-fold more economical than conventional PCR, regardless of sample size. CONCLUSIONS: This study is the first for malaria to estimate systematic molecular diagnosis financial costs. Kit-based and automated methods may replace conventional DNA extraction and amplification methods for a frugal high-throughput diagnosis.

Smart meter for the estimation of power quality indices based on second-order generalized integrator.

With the increasing integration of renewable energy sources and nonlinear loads in the grid, it is necessary to compute energy and power quality parameters for monitoring as well as analyzing the power consumption indices (PCI) and power quality indices (PQI). Smart meters (SMs) can monitor the PCI and PQI at the consumer end. SM necessitates the measurement of voltage and current, which can be further processed by an algorithm for estimating different parameters through signal processing and arithmetic operations. This paper proposes the combined dual second-order generalized integrator (SOGI) and proportionate least mean square (PLMS) algorithm-based PCI and PQI estimation for smart metering. Dual SOGIs individually process voltage and current signals to extract the respective fundamental in-phase and quadrature components. To account the variations in grid frequency, the SOGI processing the voltage also incorporates a frequency locked loop. This prevents performance degradation on account of frequency variations. The PLMS algorithm then process the output of SOGI processing the current for extracting the fundamental active and reactive components of current. Moreover, the PLMS algorithm results in further attenuation of harmonics. Also, only two separate values of learning rate are required, which is easy to tune for better dynamic performance. With only two quantities to be determined, this results in largely reduced computation. These computations facilitate in PCI and PQI computations. The proposed smart meter calculates peak value, RMS value, and phase angle for the fundamental components of voltage and current for each phase. Additionally, it assesses fundamental power factor, total harmonic distortion (THD), distortion factor, true power factor, active power, reactive power, and apparent power for each phase. The performance validation of the proposed combined dual-SOGI-PLMS algorithm-based PCI and PQI estimation for smart metering is carried out in MATLAB/SIMULINK for fifteen different operating scenarios. Further, the real-time implementation of the proposed methodology is carried out on dSPACE MicroLab Box 1202. Comparative analysis is also presented, which reveals the computational simplicity and other merits of the proposed scheme over the earlier reported scheme.

Meta-analysis on Plasmodium falciparum sulfadoxine-pyrimethamine resistance-conferring mutations in India identifies hot spots for genetic surveillance.

BACKGROUND: India is on track to eliminate malaria by 2030 but emerging resistance to first-line antimalarials is a recognised threat. Two instances of rapid development, spread, and natural selection of drug-resistant mutant parasites in India (chloroquine across the country and artesunate + sulfadoxine-pyrimethamine [AS+SP] in the northeastern states) translated into drug policy changes for Plasmodium falciparum malaria in 2010 and 2013, respectively. Considering these rapid changes in the SP drug resistance-conferring mutation profile of P. falciparum, there is a need to systematically monitor the validated mutations in Pfdhfr and Pfdhps genes across India alongside AS+SP therapeutic efficacy studies. There has been no robust, systematic countrywide surveillance reported for these parameters in India, hence the current study was undertaken. METHODS: Studies that reported data on WHO-validated SP resistance markers in P. falciparum across India from 2008 to January 2023 were included. Five major databases, PubMedⓇ, Web of ScienceTM, ScopusⓇ, EmbaseⓇ, and Google Scholar, were exhaustively searched. Individual and pooled prevalence estimates of mutations were obtained through random- and fixed-effect models. Data were depicted using forest plots created with a 95% confidence interval. The study is registered with PROSPERO (CRD42021236012). RESULTS: A total of 37 publications, and 533 Pfdhfr and 134 Pfdhps National Centre of Biotechnology Information (NCBI) DNA sequences were included from >4000 samples. The study included information from 80 districts, 21 states and 3 union territories (UTs) from India. The two PfDHFR mutations, C59R (62%) and S108N (74%), were the most prevalent mutations (pooled estimates 61% and 71%, respectively) and appeared to be stabilised/fixed. Although rarest overall, the prevalence of I164L was observed to be as high as 32%. The PfDHFR double mutants were the most prevalent overall (51%; pooled 42%). The prevalence of triple and quadruple mutations was 6% and 5%, respectively, and is an immediate concern for some states. The most prevalent PfDHPS mutation was A437G (39%), followed by K540E (25%) and A581G (12%). There was a low overall prevalence of PfDHFR/PfDHPS quintuple and sextuple mutations but surveillance for these mutations is critical for some areas. CONCLUSION: The analyses span the two critical policy changes, highlight the areas of concern, and guide policymakers in strategising and refining the anti-malaria drug policy for malaria elimination. The results of the analyses also highlight the SP-resistance hot spots, critical gaps and challenges, and indicate that focal and local malaria genetic surveillance (including drug-resistance markers) is needed until malaria is successfully eliminated.