Studies have shown that transcription factor AP2A2 (activator protein-2 alpha-2) is involved in the expression of DLEC1, a tumor suppressor gene, which, when mutated, will cause breast cancer and is thus an excellent target for breast cancer studies. Therefore, in the present research, a synergistic approach toward combating breast cancer is proposed by blocking AP2A2 factor, and allowing the cancer cells to be sensitive to anti-cancer drugs. The effect of AP2A2 on breast cancer was first understood via gene analysis from cBioPortal. AP2A2 was then modeled using RaptorX and its structure was validated from Ramachandran plots. Using all ligands from MolPort database, molecular docking was performed against AP2A2, from which the top three best docked ligands were studied for toxicity in humans using Protox-II. Once the ligands passed these tests, the best complexes were simulated at 200ns in Desmond Maestro, to comprehend their stabilities, followed by the computations of free energies of binding via Molecular mechanics- Generalized Born Solvent Accessibility method (MM-GBSA). The results showed that molecules MolPort-005-945-556 (sachharolipids), MolPort-001-741-124 (flavonoids), and MolPort-005-944-667 (lignan glycosides) with AP2A2 passed toxicity evaluation and belonged to toxicity classes 6, 5, and 5, respectively, with good docking energies. 200ns simulations revealed stable complexes with slight conformational changes. Stability of ligands was confirmed via snapshots at every 20ns of the trajectory. Radial distribution of these molecules against the protein revealed very slight deviation from binding pocket. Additionally, the free binding energies for these complexes were found to be -54.93 ± 12.982kcal/mol, -44.39 ± 14.393kcal/mol, and -66.51 ± 13.522kcal/mol, respectively. A preliminary computational validation of the inability of AP2A2 to bind to DLEC1 in the presence of ligands offers beneficial insights into the potential of these ligands. Therefore, this study sheds light on the potential natural molecules that could stably block AP2A2 with least deviation and act in synergy to aid anti-cancer drugs work on breast cancer cells.

The concept of omics-based technological approaches has promoted translational research by integrating knowledge from diverse areas. This area of research provides sound knowledge on the mechanics of plant diseases and hence is able to provide insights on crop quality enhancement and plant disease control. Consequently, this area has become the subject of extensive research in the recent decade and therefore, has been very useful in addressing concerns in plant disease control. In this review, the contributions of different omics technologies including genomics, transcriptomics, proteomics, and metabolomics in understanding and identifying their significant omics-based parameters that are involved in the plant pathogen interactions are discussed. Furthermore, opportunities and perspectives of omics linked to signaling mechanisms that are significantly connected to plant-microbe interactions with the potential to provide conceptual leads in plant disease control, have also been highlighted.

Coarse-grained simulations have emerged as a valuable tool in the study of large and complex biomolecular systems. These simulations, which use simplified models to represent complex biomolecules, reduce the computational cost of simulations and enable the study of larger systems for longer periods of time than traditional atomistic simulations. GROMACS is a widely used software package for performing coarse-grained simulations of biomolecules, and several force fields have been developed specifically for this purpose. In this protocol paper, we explore the advantages of using coarse-grained simulations in the study of biomolecular systems, focusing specifically on simulations performed using GROMACS. We discuss the force fields required for these simulations and the types of research questions that can be addressed using coarse-grained simulations. We also highlight the potential benefits of coarse-grained simulations for the development of new force fields and simulation methodologies. We then discuss the expected results from coarse-grained simulations using GROMACS and the various techniques that can be used to analyze these results. We explore the use of trajectory analysis tools, as well as thermodynamic and structural analysis techniques, to gain insight into the behavior of biomolecular systems.

The high prevalence of vaccine booster hesitancy, with the concomitant waning of humoral vaccine or hybrid immunity, and the emergence of SARS-CoV-2 variants of concern can accentuate COVID-19 morbidity and mortality. The study objective was to ascertain the COVID-19 vaccination coverage, including the administration of precaution (booster) dose vaccination, among the older population in an urban slum and resettlement colony population in Delhi, India. We conducted a cross-sectional survey in an urban resettlement colony, slum, and village cluster in the Northeast district of Delhi among residents aged ≥50 years. A total of 2217 adults (58.28%) had obtained a COVID-19 booster (precaution) dose vaccine, 1404 (36.91%) had received two doses of a COVID-19 vaccine without booster dose, 121 (3.18%) were unvaccinated, while 62 (1.63%) participants received a single dose. Based on adjusted analysis, older adults (>65 years), higher education, and higher per-capita income were statistically significant predictors of booster dose vaccination. More than four in ten adults in an urban slum and resettlement colony in Delhi lacked COVID-19 booster dose vaccination despite high rates of double-dose vaccination (~95%). Public health programming should provide an enhanced focus on reducing complacency with renewed prioritization for improving ease of access to COVID-19 vaccination services, particularly in underserved areas.

Six diverse Demographic Development and Environmental Surveillance System (DDESS) sites were established in urban slum, urban resettlement, peri-urban, rural, and tribal areas located in Northern, North-East, Eastern, and Southern regions of India from June 2020 to March 2022. Understanding the community dynamics and engaging people in the community is critically important in the process of establishing DDESS. We ascertained the barriers, challenges, and facilitators during the establishment of multiple DDESS sites across India. This was a cross-sectional descriptive mixed-methods study. Multiple barriers and challenges encountered were reported in the process of community engagement (CE), such as geographical inaccessibility, language barriers, adverse weather, non-responsiveness due to perceived lack of individual benefit or financial gain, fear of contracting COVID-19, COVID-19 vaccine hesitancy, etc. Facilitators in the CE process were pre-existing links with the community, constitution of community advisory boards, community need assessment, concomitant delivery of outreach health services, and skill-building facilities. Most community barriers in the development of DDESS sites in resource-limited settings can be overcome through a multipronged approach, including effective community engagement by focusing on demonstrating trust at the local level, enlisting community mobilization and support, utilizing pre-existing community linkages, initiating community diagnosis, and meeting perceived community health needs.

BackgroundIn urban slums, pregnant women are a high-risk group with limited access to health facilities due to reported barriers to utilization of maternal health services linked with sociodemographic variations in a few studies. ObjectiveOur objective is to assess barriers and opportunities in the current utilization of maternal healthcare services during the antenatal period in urban slum settings followed by the development of a conceptual framework utilizing this information to promote the utilization of maternal services in urban slums. MethodsA search was conducted using PubMed with articles published from January 2011 to May 2022. The search terms used were a combination of ‘maternal health services, ‘antenatal care’, ‘urban slums’, and ‘India. Results: A total of eleven studies met inclusion criteria and was critically appraised by two independent reviewers to retrieve relevant information. Most of them were cross-sectional surveys and only one study was a randomized trial that was conducted in the slums of Delhi and Mumbai. The most common age group included in all studies was 15–49 years. The different barriers found in this review include poor access to healthcare, cost, prior experience, domestic responsibility, long distance to facility, long waiting time at the hospital, non-co-operative hospital staff, multiparity, lack of information, and low literacy. ConclusionAccessibility to healthcare services in urban slums is poor and slum dwellers are still subjected to the hazards of unsafe home deliveries. It is imperative to address different barriers such as poor accessibility, cost, long waiting time, hospital staff behaviour, and efforts to improve maternal literacy. We also proposed a framework to develop an Artificial Intelligence guided tool that will help identify high-risk pregnancies so that they can be motivated to avail of maternal health services more efficiently.

The online version contains supplementary material available at 10.1007/s13197-022-05633-8.

ObjectiveTo determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care.DesignIndividually randomised factorial trial.SettingLow and middle income neighbourhoods of Delhi, India.Participants13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D).InterventionsHealth, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods.Main outcome measuresThe primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D).ResultsThe proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction −3.80%, 98.3% confidence interval −6.99% to −0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; −1.71%, −4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; −5.59%, −10.32% to −0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; −8.32%, −12.31% to −4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; −7.98%, −14.24% to −1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564).ConclusionsAn intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes.Trial registrationClinical Trial Registry—India CTRI/2017/06/008908.

Health is multi-dimensional, determined by physical, mental, environmental, social, political, cultural factors, etc., inuenced by various emerging and ongoing viral infections and diseases. COVID-19 is the name of existing novel viral pneumonia which is coined by WHO in 2020 whereas the International Committee on Taxonomy of Viruses suggested this as “Severe Acute Respiratory Coronavirus-2” based on phylogenetic and taxonomic analysis of pandemic novel coronavirus. Due to its fatal clinical symptoms, WHO has declared it a pandemic outbreak. To combat this, “AAROGYA SETU”, a contact tracing app, developed and approved by the Indian government and National Informatics Centre, warns the users if they have crossed paths with any infected person recently. The critical review of this application helps to evaluate its potency in terms of its usability, learnability, and acceptability amongst the users using a system usability scoring system (SUS). This paper shows how such applications can be tested using SUS based out of technical glitches, client's understanding and acceptability to their social expectations, in proactively reaching out to and informing the users of the app regarding risks, best practices, and relevant advisories pertaining to the containment of COVID-19.

Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.