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Background: Resistance to most of the antitubercular drugs has been on rising trends due to the misuse of existing drugs. This has encouraged us to explore a novel scaffold that has the potential for quick antimicrobial action with minimum side effects. Nitrofurans have attracted us due to their extensive biological activities, such as antibacterial and antifungal activities. Objective: The antitubercular activities of 126 nitrofuran derivatives have been investigated by using indicator parameters and topological and structural fragment descriptors. Methods: The different quantitative structure activity relationship (QSAR) models have been created and validated by using two different methodologies: combinatorial protocol in multiple linear regression (CP-MLR) and partial least-squares (PLS) analysis. Results: The 16 descriptors identified in CP-MLR are from six different classes: Constitutional, Functional, Atom Centered Fragments, Topological, Galvez, and 2D autocorrelation. Indicator parameters and Dragon descriptors suggested that the presence of a furan ring substituted by nitro group is essential for antitubercular activity. Further descriptors from constitutional, and functional classes suggest that the number of double bonds, number of sulphur atoms and number of fragments like thiazole, morpholine and thiophene should be minimum, along with the positive influence of Kier-Hall electrotopological states (Ss) for improved activity. The ACF class descriptors, GALVEZ class descriptors, and 2D-AUTO descriptor GATS4p have also shown positive influence on the antitubercular activity. The TOPO class descriptor T(O…S) suggests that the minimum gap between sulphur and oxygen is favorable for activity. Conclusions: The models acknowledged in the study have explained the variance between 72 to 76% in the training set and in the prediction of the test set compounds. Also, compounds 122:, 123: and 82: were found to possess good binding affinity towards nitroreductase.

Non-wires alternatives and microgrid technologies are maturing and present great opportunities for electric utilities to increase the benefits they offer to their customers. They have the potential to decrease the cost of resolving traditional electrical system loading issues, contribute to carbon emissions reductions, and improve the electrical distribution system’s resilience to extreme weather events. The authors of this manuscript present a review of the research on microgrids and their practical applications. This is leveraged with the past work of the authors of this manuscript and other authors to develop specific objectives for microgrids, practical criteria for engineers to consider when deploying microgrids, stochastic methods to optimize microgrid designs, and black start requirements. This guidance is then used for the design of actual networked microgrids being deployed with adaptive boundaries.

Direct air capture (DAC) systems that capture carbon dioxide (CO2) directly from the atmosphere are garnering considerable attention for their potential role as negative emission technologies in achieving net-zero CO2 emission goals. Common DAC technologies are based either on liquid–solvent (L-DAC) or solid–sorbent (S-DAC) to capture CO2. A comprehensive multi-factor comparative economic analysis of the deployment of L-DAC and S-DAC facilities across various United States (U.S.) cities is presented in this paper. The analysis considers the influence of various factors on the favorability of DAC deployment, including local climatic conditions such as temperature, humidity, and CO2 concentrations; the availability of energy sources to power the DAC system; and costs for the transport and storage of the captured CO2 along with the consideration of the regional market and policy drivers. The deployment analysis in over 70 continental U.S. cities shows that L-DAC and S-DAC complement each other spatially, as their performance and operational costs vary in different climates. L-DAC is more suited to the hot, humid Southeast, while S-DAC is preferrable in the colder, drier Rocky Mountain region. Strategic deployment based on regional conditions and economics is essential for promoting the commercial adoptability of DAC, which is a critical technology to meet the CO2 reduction targets.

Aim: This article aimed to present the salient features of the in-house developed Java program for the determination of inflection point and dosimetric parameters of flattening filter-free (FFF) photon beam. Reference levels for the dosimetric parameters of the FFF photon beams were also presented. Materials and Methods: Beam profiles of 6 MV FFF and 10 MV FFF photon beams for a collimator setting of 20 cm × 20 cm measured at 10 cm depth in an isocentric setup acquired from various institutions were analyzed using an in-house developed Java program and manual method. The values of reference dose value (RDV), field size, penumbra, and degree of un-flatness (defined as the lateral separation between 90% [X90%], 75% [X75%], and 60% [X60%] dose points on the profile) were calculated and compared. The reference values of field size, penumbra, and degree of un-flatness were also determined for Varian and Elekta medical electron linear accelerators (LINACs). Results: The maximum differences for RDV determined using the Java method and manual method are 2.4% and 2.7% for 6 and 10 MV FFF photon beams, respectively. The maximum difference between the values of field size, penumbra, and degree of un-flatness determined using Java and manual methods is within 1.3 mm. The reference values of field size and penumbra for Varian LINACs are 19.94 ± 0.10 cm and 0.83 ± 0.08 cm (6 MV FFF) and 19.95 ± 0.10 cm and 0.83 ± 0.08 cm (10 MV FFF). Similarly, the reference values of field size and penumbra for Elekta LINACs are 20.02 ± 0.09 cm and 0.94 ± 0.12 cm (6 MV FFF) and 20.03 ± 0.11 cm and 0.97 ± 0.16 cm (10 MV FFF). Conclusions: A software program was developed in Java for analyzing the beam profiles of FFF photon beams. The results of Java-derived values of dosimetric parameters of FFF photon beams were found in good agreement with the values determined using the manual method. The reference values of these parameters were also derived and quoted using a large cohort of the data.

DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also highlights the existing queries and evidence gaps in DPP-4 inhibitor research. Authors have concluded that the excitement surrounding DPP-4 inhibitors is justified because in addition to controlling blood glucose level, they are good at managing risk factors associated with diabetes.

Summary: Background: The extent of food deprivation and insecurity among infants and young children—a critical phase for children's current and future health and well-being—in India is unknown. We estimate the prevalence of food deprivation among infants and young children in India and describe its evolution over time at sub-national levels. Methods: Data from five National Family Health Surveys (NFHS) conducted in 1993, 1999, 2006, 2016 and 2021 for the 36 states/Union Territories (UTs) of India were used. The study population consisted of the most recent children (6–23 months) born to mothers (aged 15–49 years), who were alive and living with the mother at the time of survey (n = 175,614 after excluding observations that had no responses to the food question). Food deprivation was defined based on the mother's reporting of the child having not eaten any food of substantial calorific content (i.e., any solid/semi-solid/soft/mushy food types, infant formula and powdered/tinned/fresh milk) in the past 24 hours (h), which we labelled as “Zero-Food”. In this study, we analyzed Zero-Food in terms of percent prevalence as well as population headcount burden. We calculated the Absolute Change (AC) to quantify the change in the percentage points of Zero-Food across time periods for all-India and by states/UTs. Findings: The prevalence of Zero-Food in India marginally declined from 20.0% (95% CI: 19.3%–20.7%) in 1993 to 17.8% (95% CI: 17.5%–18.1%) in 2021. There were considerable differences in the trajectories of change in the prevalence of Zero-Food across states. Chhattisgarh, Mizoram, and Jammu and Kashmir experienced high increase in the prevalence of Zero-Food over this time period, while Nagaland, Odisha, Rajasthan and Madhya Pradesh witnessed a significant decline. In 2021, Uttar Pradesh (27.4%), Chhattisgarh (24.6%), Jharkhand (21%), Rajasthan (19.8%) and Assam (19.4%) were states with the highest prevalence of Zero-Food. As of 2021, the estimated number of Zero-Food children in India was 5,998,138, with the states of Uttar Pradesh (28.4%), Bihar (14.2%), Maharashtra (7.1%), Rajasthan (6.5%), and Madhya Pradesh (6%) accounting for nearly two-thirds of the total Zero-Food children in India. Zero-Food in 2021 was concerningly high among children aged 6–11 months (30.6%) and substantial even among children aged 18–23 months (8.5%). Overall, socioeconomically advantaged groups had lower prevalence of Zero-Food than disadvantaged groups. Interpretation: Concerted efforts at the national and state levels are required to further strengthen existing policies, and design and develop new ones to provide affordable food to children in a timely and equitable manner to ensure food security among infants and young children. Funding: This study was supported by a grant from the Bill & Melinda Gates Foundation INV-002992.

Abstract Background There is a continuous research in the area of biomimetic coatings on the titanium (Ti) implant surfaces for improved survival and long-term successful outcomes in the field of dentistry and orthopedics. In-vitro approaches are ideal systems for studying cell-material interactions without complexity and interference observed in in-vivo models. Purpose The present study was undertaken to evaluate the osteoblast characteristics and function on Ti substrates coated with the novel composite coating of ceramic apatite-wollastonite (AW) and polymer chitosan. Materials and methods Ti substrate coated with composite AW-Chitosan was synthesized, using electrophoretic deposition. MG-63 cells were seeded onto the coated substrates and cellular morphology and growth was assessed using Scanning Electron Microscopy (SEM) and Laser Scanning Microscopy (LSM). Osteocalcin expression of the seeded cells was assessed by FITC tagging and LSM analysis. Alizarin Red S staining and Confocal LSM (CSLM) analysis was used to study the in-vitro mineralization on the titanium samples. Results The AW-Chitosan coating on Ti samples by electrophoretic deposition exerted significant positive influence on cell proliferation, growth and mineralization as compared to uncoated titanium samples. Scanning electron microscopy and laser confocal microscopy experiments revealed that the coating was non-toxic to cells, enhanced adhesion and proliferation of MG-63 cells. Increased functional activity was observed by increased production of bone-specific protein osteocalcin and mineralized calcium through day 7 and 14. Conclusions The present study underscores that optimal inorganic-organic phase nanocomposite crack-free coating created on Ti by simple, cost-effective electrophoretic deposition technique may have osteoconductive potential and may have wide application in the field of implantology. Graphical abstract

Dietary intake is a fundamental determinant of maternal and child nutrition. This paper presents evidence on whether maternal and child dietary diversity can be improved with systemic improvements focused on strengthening training, capacity building, and behavior change communication among frontline workers to encourage improved nutritional practices among mothers and children in the intervention area. The evidence is derived from Project Spotlight intervention that was jointly implemented by Department of Women and Child Development, Government of Maharashtra and Tata Trusts in tribal dominated Gadchiroli and Chandrapur districts in Maharashtra. Based on a pre-post comparison of baseline (2019) and endline (2021) household survey data it is confirmed that there is a significant association between maternal and child dietary diversity in the study area. Notably, dietary diversity in mother-child dyads is marked with a higher consumption of fruits and vegetables as well as eggs and flesh foods. Econometric analysis further reveals that the association between maternal and child dietary diversity has improved after the systems strengthening interventions. The paper concludes that local interventions such as Project Spotlight for strengthening counselling services and coverage by frontline workers and enhancing knowledge and awareness on maternal and child dietary diversity among communities are important for improving maternal and child nutrition.

Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production.

Dietary adequacy and diversity during the lactation period are necessary to ensure good health and nutrition among women and children. Behavioral interventions pertaining to health and nutrition counselling during pregnancy and lactation are critical for awareness about dietary diversity. The issue assumes salience for marginalized communities because of the Covid-19 pandemic and associated economic and societal disruptions. This paper assesses the dietary patterns among 400 lactating mothers in the tribal-dominated district of Palghar in Maharashtra, India in 2020. The study is based on primary data regarding consumption of 10 food groups among women across 10 food groups based on 24-hour recall period. The primary outcome variable was binary information regarding Minimum Dietary Diversity defined as consumption from at least 5 food groups. Econometric analysis based on multilevel models and item-response theory is applied to identify food groups that were most difficult to be received by mothers during the early and late lactation period. We find that the daily diet of lactating mothers in Palghar primarily consists of grains, white roots, tubers, and pulses. In contrast, the intake of dairy, eggs, and non-vegetarian food items is much lower. Only Half of the lactating women (56.5 percent; 95% CI: 37.4; 73.8) have a minimum diversified diet (MDD). The prevalence of lactating women with MDD was higher among households with higher income (73.1 percent; 95% CI: 45.2; 89.9) than those in lower income group (50.7 percent; 95% CI: 42.3; 58.9). Lactating Women (in early phase) who received health and nutrition counseling services are more likely (OR: 2.37; 95% CI: 0.90; 6.26) to consume a diversified diet. Food groups such as fruits, meat, poultry, fish, nuts, and seeds were among the rare food items in daily diet. The dietary pattern lacking in fruits, nuts, and heme (iron) sources indicates more significant risks of micronutrient deficiencies. The findings call for improving dietary diversity among lactating mothers, particularly from the marginalized communities, and are driven by low consumption of dairy products or various fruits and vegetables. Among the different food items, the consumption of micronutrient-rich seeds and nuts is most difficult to be accessed by lactating mothers. Also, diet-centric counseling and informing lactating mothers of its benefits are necessary to increase dietary diversity for improving maternal and child nutrition.

Abstract We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications. Several genes are studied in multiple years in all complications with high proportion in cardiovascular (75.8%) and atherosclerosis (51.3%). T2DM Patients’ skeletal muscle tissues showed high fold change in differentially expressed genes. Among the differentially expressed genes, VEGFA is associated with several complications of T2DM. A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued. Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents. This information emerging from the integrative approach used in this work could benefit further therapeutic approaches. The T2DiACoD is available at www.http://t2diacod.igib.res.in/ .

The studies on influence of temperature and carbon dioxide levels on food consumption and growth of Spodoptera litura on cauliflower were conducted in controlled environment during 2015-16 with two different temperature (25:11oC and 25:14oC) and three carbon dioxide regimes (350, 400, 450 ppm). Temperature and carbon dioxide had significant effect on food consumption parameters of S. litura.Overall the food consumption of S. litura increased from 0.18g larva-1 at temperature of 25: 11oC and CO2 of 350 ppm to 0.31g larva-1 at temperature of 25: 14oC and CO2 of 450 ppm.Similarly, relative growth rate increased from 0.15 to 0.27 mg mg-1 day-1 and larval weight gain increased from 0.14 to 0.28 gday-1. However, with increase in CO2 concentration at 450 ppm, the larval weight gain decreased from 0.28 to 0.22g day-1.

Human studies on the effects of probiotics on lowering blood cholesterol levels have not yielded conclusive results. A meta-analysis of randomized controlled trials evaluating the effect of probiotics on lipid profile was conducted. Articles were reviewed systematically from web search bases; PubMed, Cochrane Clinical Trial Registry. Those studies which were meeting the inclusion criteria-providing matching placebo, at least single blind for probiotics and placebo, providing mean and standard deviations and not involving the use of probiotics were selected. 14 studies from 12 randomized controlled trials were analyzed providing information of 606 normo/hypercholesterolemic patients using Review Manager 5.3 (The Cochrane Collaboration, Oxford, UK). The pooled mean net change for total cholesterol (TC) is −8.40 mg/dl (−13.63, −3.61), for low-density lipoprotein (LDL) is −6.63 mg/dl (−10.63, −2.63), for high-density-lipoprotein-cholesterol is 0.59 mg/dl (−0.92, 2.09), and for triglycerides is −1.32 mg/dl (−6.49, 3.85). The findings of the analysis conclude that probiotics supplementation does lower serum TC and LDL-cholesterol levels significantly and hence a reduction in the risk factor of developing coronary heart disease.

The studies on influence of temperature and carbon dioxide levels on growth and development of Spodoptera litura on cauliflower were conducted with six different temperature and carbon dioxide regimes viz. 25:11oC and 25:14oC at 350, 400, 450 ppm carbon dioxide concentrations. Observations on different biological indices were recorded to estimate the influence of elevated temperature and carbon dioxide on growth and development of S. litura. The study revealed temperature and carbon dioxide had significant effect on developmental indices of S. litura. It was observed that incubation period, larval duration, pupal duration, male adult longevity, female adult longevity decreased from 4.5, 23.4, 9.3, 6.8, 7.5, respectively at 25:11oC to 3.9, 21.2, 8.7, 6.5, 7.4 days respectively, at 25:14oC. Whereas fecundity of S litura increased from 363.6 to 420.9 with increase in temperature and carbon dioxide indicating reduced generation time which could lead to more number of generations per year.

The present study was conducted for three years (2012-13 to 2014-15) on sugar beet crop at PAU, Ludhiana to establish the relationship between weather parameters and insect pests infesting sugar beet crop. The observations on the incidence of insect pests recorded at weekly intervals were analyzed to correlate the effects of the abiotic factors on population of insect pests. Aphid, Myzus persicae Sulzer population showed negative correlation with maximum and minimum temperature and positive correlation with relative humidity. Spodoptera litura Fabricius and Helicoverpa armigera (Hubner) showed positive correlation with maximum and minimum temperature and negative with relative humidity. Regression analysis was also worked out between population of these insect pests infesting sugar beet.

Members of the Bcl-2 family are major regulators of apoptosis in mammalian cells and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. In this investigation, we uncover a novel role of host Bcl-2 in sustaining Leishmania donovani infection. A rapid two-fold increase in Bcl-2 expression occurred in response to parasite challenge. Downregulation of post infection Bcl-2 increase using siRNA or functional inhibition using Bcl-2 small molecule inhibitors interfered with intracellular parasite survival confirming the necessity of elevated Bcl-2 during infection. An increased nitric oxide (NO) response and reduced parasitic burden was observed upon Bcl-2 inhibition, where restitution of the NO response accounted for parasite mortality. Mechanistic insights revealed a major role of elevated Th2 cytokine IL-13 in parasite induced Bcl-2 expression via the transcription factor STAT-3, where blocking at the level of IL-13 receptor or downstream kinase JAK-2 dampened Bcl-2 induction. Increase in Bcl-2 was orchestrated through TLR-2-MEK-ERK signaling and changes in TLR-2 levels affected parasite uptake. In a mouse model of visceral leishmaniasis (VL), Bcl-2 inhibitors partially restored the anti-microbial NO response by at least two-fold increase that resulted in significantly reduced parasite burden. Interestingly, monocytes derived from the peripheral blood of six out of nine human VL subjects demonstrated Bcl-2 expression at significantly higher levels and sera from these patients showed only marginally quantifiable nitrites. Collectively, our study for the first time reveals a pro-parasitic role of host Bcl-2 and the capacity of host-derived IL-13 to modulate NO levels during infection via Bcl-2. Here, we propose Bcl-2 inhibition as a possible therapeutic intervention for VL.

Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment.

Purpose: To report our experience of dosimetric comparison of IPSA and manual plans, with a focus on the use ofhelp structures (HS) during optimization. Material and methods: 33 patients who underwent MR image-based HDR intracavitary-brachytherapy for cervixcancer based on GYN-ESTRO recommendations were selected for evaluation. Tandem/ovoid (T/O) and Vienna applicatorswere used. HS of diameter of 5 mm were drawn around the tandem/needles/ovoid and ring. Three plans weregenerated: manual optimized plan (MOPT), IPSA without help structures (IPSA_woHS) and IPSA with help structures(IPSA_wHS). Dose-volume parameters and the loading pattern were evaluated. Results: For T/O, the use of HS did not make significant impact in the dose-volume parameters and in the loadingof tandem and ovoids, however steep variation was found in the individual dwell time. In case of Vienna applicator,inclusion of HS in the optimization made a significant impact in loading of needles. The percentage ratio oftotal time of needles to the tandem (TN/T%) was found to be 14 ± 2.5, 53 ± 9, 22 ± 6 for MOPT, IPSA_woHS andIPSA_wHS, respectively, which implies that in IPSA_woHS the dwell time in needles were half of the dwell time inthe tandem, while in MOPT the needles were loaded only in 14%, and in IPSA_wHS it was 22% of the dwell timeof tandem. Inclusion of HS in the optimization has reduced the contribution of dwell time of needle in IPSA_wHS.The individual variation of dwell time was also reduced in IPSA_wHS, however drawing of HS is a time consumingprocedure and may not be practical for a routine practice. Conclusion: The role of HS was evaluated for IPSA for T/O and Vienna-applicator, the use of HS may be beneficialin case of combined intracavitary – interstitial approach.

Climate change has direct influence on the development and survival of herbivores in addition to indirect effects through trophic interactions. The present studies were carried out to observe the effect of increase in minimum temperature on development and food consumption of Helicoverpa armigera Hubner, Pieris brassicae Linnaeus and Spodoptera litura Fabricius. The mean food consumption increased by 12.78 and 32.64 per cent with increase in minimum temperature of 30C and 60C, respectively accompanied by decrease in larval duration by 10.37 and 27.97 per cent. Similarly, observations on P. brassicae larvae at four temperature ranges indicated that the mean food consumption increased by 4.87 with rise in minimum temperature by 30C accompanied by faster development. Likewise, effect of temperature ranges viz. 21°C: 7°C and 21°C: 10°C for 16: 8 hrs on biology of S. litura was estimated. The observations revealed faster growth when the mean minimum temperature was raised from 7 to 10°C. The rise in minimum temperature by 3°C resulted in decrease in larval and pupal duration by 5.36 and 10.43 per cent, respectively. The survival per cent was also increased by 1.44 per cent when rise in minimum temperature by 3°C.