UHPLC-MS/MS-Based Identity Confirmation of Amino Acids Involved in Response to and Side Effects from Antiseizure Medications.

Real-time breath analysis using secondary electrospray ionization coupled with high-resolution mass spectrometry is a fast and noninvasive method to access the metabolic state of a person. However, it lacks the ability to unequivocally assign mass spectral features to compounds due to the absence of chromatographic separation. This can be overcomed by using exhaled breath condensate and conventional liquid chromatography-mass spectrometry (LC-MS) systems. In this study, to the best of our knowledge, we confirm for the first time the presence of six amino acids (GABA, Oxo-Pro, Asp, Gln, Glu, and Tyr) previously reported to be involved in response to and side effects from antiseizure medications in exhaled breath condensate and by extension in exhaled human breath. Raw data are publicly available at MetaboLights with the accession number MTBLS6760.

Real-Time Volatile Metabolomics Analysis of Dendritic Cells.

Dendritic cells (DCs) actively sample and present antigen to cells of the adaptive immune system and are thus vital for successful immune control and memory formation. Immune cell metabolism and function are tightly interlinked, and a better understanding of this interaction offers potential to develop immunomodulatory strategies. However, current approaches for assessing the immune cell metabolome are often limited by end-point measurements, may involve laborious sample preparation, and may lack unbiased, temporal resolution of the metabolome. In this study, we present a novel setup coupled to a secondary electrospray ionization-high resolution mass spectrometric (SESI-HRMS) platform allowing headspace analysis of immature and activated DCs in real-time with minimal sample preparation and intervention, with high technical reproducibility and potential for automation. Distinct metabolic signatures of DCs treated with different supernatants (SNs) of bacterial cultures were detected during real-time analyses over 6 h compared to their respective controls (SN only). Furthermore, the technique allowed for the detection of 13C-incorporation into volatile metabolites, opening the possibility for real-time tracing of metabolic pathways in DCs. Moreover, differences in the metabolic profile of naïve and activated DCs were discovered, and pathway-enrichment analysis revealed three significantly altered pathways, including the TCA cycle, α-linolenic acid metabolism, and valine, leucine, and isoleucine degradation.

Health insurance support on maternal health care: evidence from survey data in India.

BACKGROUND: Maternal health care financing is key to the smooth functioning of health systems in a country. In India, maternal health care still persists as a major public health issue. Adequate health insurance could transform the utilization of maternal health care services. Therefore, we aim to examine the health insurance policies that cover maternal health and their performance in India. METHODS: The unit-level data of social consumption on health by the National Sample Survey Organizations, conducted in India (2017-18), are used. Bivariate analysis, logistic regression and propensity scoring matching are applied. RESULTS: About 14.1% women are covered by health insurance support at the national level. Uninsured women are less likely to receive full antenatal care (ANC) services and institutional delivery. Socio-economic characteristics play a significant role in utilizing maternal health care benefits through health insurance support. CONCLUSIONS: Our study concludes that the health insurance coverage is the most significant contributor to the better utilization of full ANC and institutional delivery at the national level and hindrances in accessing them. There is a need for proactive and inclusive policy development by the Government of India to incentivize public financing through health insurance, which can shrink the challenges of public health burden and reduce the health risk.

Comparison of Plasma Ionization- and Secondary Electrospray Ionization- High-resolution Mass Spectrometry for Real-time Breath Analysis.

Real-time breath analysis by high-resolution mass spectrometry (HRMS) is a promising method to noninvasively retrieve relevant biochemical information. In this work, we conducted a head-to-head comparison of two ionization techniques: Secondary electrospray ionization (SESI) and plasma ionization (PI), for the analysis of exhaled breath. Two commercially available SESI and PI sources were coupled to the same HRMS device to analyze breath of two healthy individuals in a longitudinal study. We analyzed 58 breath specimens in both platforms, leading to 2,209 and 2,296 features detected by SESI-HRMS and by PI-HRMS, respectively. 60% of all the mass spectral features were detected in both platforms. However, remarkable differences were noted in terms of the signal-to-noise ratio (S/N), whereby the median (interquartile range, IQR) S/N ratio for SESI-HRMS was 115 (IQR = 408), whereas for PI-HRMS it was 5 (IQR = 5). Differences in the mass spectral profiles for the same samples make the inter-comparability of both techniques problematic. Overall, we conclude that both techniques are excellent for real-time breath analysis because of the very rich mass spectral fingerprints. However, further work is needed to fully understand the exact metabolic insights one can gather using each of these platforms.

Combination of Exhaled Breath Analysis with Parallel Lung Function and FeNO Measurements in Infants.

Breath analysis by secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) offers the possibility to measure comprehensive metabolic profiles. The technology is currently being deployed in several clinical settings in Switzerland and China. However, patients are required to exhale directly into the device located in a dedicated room. Consequently, clinical implementation in patients incapable of performing necessary exhalation maneuvers (e.g., infants) or immobile (e.g., too weak, elderly, or in intensive care) remains a challenge. The aim of this study was to develop a method to extend such breath analysis capabilities to this subpopulation of patients by collecting breath samples remotely (offline) and promptly (within 10 min) transfer them to SESI-HRMS for chemical analysis. We initially assessed the method in adults by comparing breath mass spectra collected offline with Nalophan bags against spectra of breath samples collected in real time. In total, 13 adults provided 176 pairs of real-time and offline measurements. Lin's concordance correlation coefficient (CCC) was used to estimate the agreement between offline and real-time analyses. Here, 1249 mass spectral features (55% of total detected) exhibited Lin's CCC > 0.6. Subsequently, the method was successfully deployed to analyze breath samples from infants (n = 16), obtaining as a result SESI-HRMS breath profiles. To demonstrate the clinical feasibility of the method, we measured in parallel other clinical variables: (i) lung function, which characterizes the breathing patterns, and (ii) nitric oxide, which is a surrogate marker of airway inflammation. As a showcase, we focused our analysis on the exhaled oxidative stress marker 4-hydroxynonenal and its association with nitric oxide and minute ventilation.

Temporal evolution of activation products in a zircaloy-4 guide tube and the estimation of its external gamma dose rate for decommissioning activities.

The dismantling of structural objects during the decommissioning of nuclear facilities needs radioactive source characterisation for the planning of decommissioning strategies in compliance with the ALARA (as low as reasonably achievable) principle. The sources may arise from neutron activation of the structural components in the reactor core as well as contamination due to the radioactive release from the fuel occurred during normal operation or unplanned events in a nuclear power plant (NPP). In a pressurised heavy water reactor (PHWR), various in-core components are predominantly made of either zircaloy-2 or 4. The nuclides present as impurities in the zircaloy, playing a crucial role in the activity inventory due to neutron activation of those nuclides, which in turn determine the external gamma dose rate. The activity of the activation products depend on the neutron flux seen by the component, duration of irradiation and cooling period, half-lives of the daughter products and the amount of the impurities present in the structural components. To illustrate this, a guide tube made up of zircaloy-4 has been considered. A guide tube assembly is a part of the primary shut down system (PSS) which guides the movement of absorber elements in the upward and downward direction in the calandria. This study has identified and quantified the activity inventory in a guide tube at the end of the operation of the reactor using the ORIGEN2 code, and then estimated the associated external gamma dose rate using the FLUKA Monte Carlo code. The findings will help the management of radioactive waste, cost optimisation and collective dose budgeting during the decommissioning stage of a typical PHWR.

C-terminally encoded peptides (CEPs) are potential mediators of abiotic stress response in plants.

Intracellular signaling is a critical determinant of the normal growth and development of plants. Signaling peptides, also known as peptide hormones, along with classical phytohormones, are the significant players of plant intracellular signaling. C-terminally encoded peptide (CEP), a 15-amino acid post-translationally peptide identified in Arabidopsis, plays a pivotal role in lateral root formation, nodulation, and act as long-distance root to shoot signaling molecule in N-starvation conditions. Expression of CEP gene members in Arabidopsis is perturbed by nitrogen starvation; however, not much is known regarding their role in other abiotic stress conditions. To gain a comprehensive insight into CEP biology, we identified CEP genes across diverse plant genera (Glycine max, Sorghum bicolor, Brassica rapa, Zea mays, and Oryza sativa) using bioinformatics tools. In silico promoter analysis revealed that CEP gene promoters show an abundance of abiotic stress-responsive elements suggesting a possible role of CEPs in abiotic stress signaling. Spatial and temporal expression patterns of CEP via RNA seq and microarray revealed that various CEP genes are transcriptionally regulated in response to abiotic stresses. Validation of rice CEP genes expression by qRT-PCR showed that OsCEP1, OsCEP8, OsCEP9, and OsCEP10 were highly upregulated in response to different abiotic stress conditions. Our findings suggest these CEP genes might be important mediators of the abiotic stress response and warrant further overexpression/knockout studies to delineate their precise role in abiotic stress response.

Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry.

Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) offers a number of advantages (e.g., real-time, yet wide, metabolome coverage) that makes it ideal for untargeted and targeted studies. However, so far, SESI-HRMS has relied mostly on lab-built prototypes, making it difficult to standardize breath sampling and subsequent analysis, hence preventing further developments such as multi-center clinical studies. To address this issue, we present here a number of new developments. In particular, we have characterized a new SESI interface featuring real-time readout of critical exhalation parameters such as CO2, exhalation flow rate, and exhaled volume. Four healthy subjects provided breath specimens over a period of 1 month to characterize the stability of the SESI-HRMS system. A first assessment of the repeatability of the system using a gas standard revealed a coefficient of variation (CV) of 2.9%. Three classes of aldehydes, namely 4-hydroxy-2-alkenals, 2-alkenals and 4-hydroxy-2,6-alkedienals-hypothesized to be markers of oxidative stress-were chosen as representative metabolites of interest to evaluate the repeatability and reproducibility of this breath analysis analytical platform. Median and interquartile ranges (IQRs) of CVs for CO2, exhalation flow rate, and exhaled volume were 3.2% (1.5%), 3.1% (1.9%), and 5.0% (4.6%), respectively. Despite the high repeatability observed for these parameters, we observed a systematic decay in the signal during repeated measurements for the shorter fatty aldehydes, which eventually reached a steady state after three/four repeated exhalations. In contrast, longer fatty aldehydes showed a steady behavior, independent of the number of repeated exhalation maneuvers. We hypothesize that this highly molecule-specific and individual-independent behavior may be explained by the fact that shorter aldehydes (with higher estimated blood-to-air partition coefficients; approaching 100) mainly get exchanged in the airways of the respiratory system, whereas the longer aldehydes (with smaller estimated blood-to-air partition coefficients; approaching 10) are thought to exchange mostly in the alveoli. Exclusion of the first three exhalations from the analysis led to a median CV (IQR) of 6.7 % (5.5 %) for the said classes of aldehydes. We found that such intra-subject variability is in general much lower than inter-subject variability (median relative differences between subjects 48.2%), suggesting that the system is suitable to capture such differences. No batch effect due to sampling date was observed, overall suggesting that the intra-subject variability measured for these series of aldehydes was biological rather than technical. High correlations found among the series of aldehydes support this notion. Finally, recommendations for breath sampling and analysis for SESI-HRMS users are provided with the aim of harmonizing procedures and improving future inter-laboratory comparisons. Graphical abstract.

Real-Time Monitoring of Tricarboxylic Acid Metabolites in Exhaled Breath.

The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids. Alteration in intracellular levels of its intermediates has been linked with a wide range of illnesses ranging from cancer to cellular necrosis or liver cirrhosis. Therefore, there exists an intrinsic interest in monitoring such metabolites. Our goal in this study was to evaluate whether, at least the most volatile metabolites of the TCA cycle, could be detected in breath in vivo and in real time. We used secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS) to conduct this targeted analysis. We enrolled six healthy individuals who provided full exhalations into the SESI-HRMS system at different times during 3 days. For the first time, we observed exhaled compounds that appertain to the TCA cycle: fumaric, succinic, malic, keto-glutaric, oxaloacetic, and aconitic acids. We found high intraindividual variability and a significant overall difference between morning and afternoon levels for malic acid, oxaloacetic acid, and aconitic acid, supporting previous studies suggesting circadian fluctuations of these metabolites in humans. This study provides first evidence that TCA cycle could conveniently be monitored in breath, opening new opportunities to study in vivo this important metabolic pathway.

Evidence-based public health: Barriers and facilitators to the transfer of knowledge into practice.

This paper underscores some of the barriers and facilitators in the practice of evidence-based public health (EBPH). A large body of evidence-based interventions (EBIs) exists, which has been generated through highly robust systematic reviews. These EBIs have been widely disseminated and promoted by public health researchers and the World Health Organization (WHO) as effective public health interventions against various preventable/treatable diseases. The inability of many low- and middle-income countries to contextually adapt and effectively implement evidence-informed interventions (EBIs) has been identified as a major obstacle to progress in achieving Millennium Development Goals (MDGs). Hence, it is imperative to identify and understand the factors that are detrimental to the successful transfer of evidence into policy as well as practice. This paper discusses how factors such as political, contextual, and organizational factors; nature of evidence; and community participation influence the practice of EBPH.

Post-introduction evaluation (PIE) of rotavirus vaccine in India.

Background: India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. Methods: The evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. Results: A total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. Conclusions: Overall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.

Enhancing COVID-19 Vaccine Uptake among Tribal Communities: A Case Study on Program Implementation Experiences from Jharkhand and Chhattisgarh States, India.

Tribal populations in India have health care challenges marked by limited access due to geographical distance, historical isolation, cultural differences, and low social stratification, and that result in weaker health indicators compared to the general population. During the pandemic, Tribal districts consistently reported lower COVID-19 vaccination coverage than non-Tribal districts. We assessed the MOMENTUM Routine Immunization Transformation and Equity (the project) strategy, which aimed to increase access to and uptake of COVID-19 vaccines among Tribal populations in Chhattisgarh and Jharkhand using the reach, effectiveness, adoption, implementation, and maintenance framework. We designed a qualitative explanatory case study and conducted 90 focus group discussions and in-depth interviews with Tribal populations, community-based nongovernmental organizations that worked with district health authorities to implement the interventions, and other stakeholders such as government and community groups. The active involvement of community leaders, targeted counseling, community gatherings, and door-to-door visits appeared to increase vaccine awareness and assuage concerns about its safety and efficacy. Key adaptations such as conducting evening vaccine awareness activities, holding vaccine sessions at flexible times and sites, and modifying messaging for booster doses appeared to encourage vaccine uptake among Tribal populations. While we used project resources to mitigate financial and supply constraints where they arose, sustaining long-term uptake of project interventions appears dependent on continued funding and ongoing political support.

Digitizing tools for post introduction evaluation of rotavirus vaccine introduction in India.

Background and aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools. Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment. Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard. Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE.

Metabolic trajectories of diabetic ketoacidosis onset described by breath analysis.

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy. Methods: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). Results: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis. Conclusion: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.

Prediction of systemic free and total valproic acid by off-line analysis of exhaled breath in epileptic children and adolescents.

Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently showcased the possibility of predicting systemic concentrations of valproic acid (VPA), an anti-seizure medication by real-time breath analysis in two real clinical settings. This approach, however, comes with the limitation of the patients having to physically exhale into the mass spectrometer. This restricts the possibility of sampling from patients not capable or available to exhale into the mass spectrometer located on the hospital premises. In this work, we developed an alternative method to overcome this limitation by collecting the breath samples in customized bags and subsequently analyzing them by secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). A total ofn= 40 patients (mean ± SD, 11.5 ± 3.5 y.o.) diagnosed with epilepsy and taking VPA were included in this study. The patients underwent three measurements: (i) serum concentrations of total and free VPA, (ii) real-time breath analysis and (iii) off-line analysis of exhaled breath collected in bags. The agreement between the real-time and the off-line breath analysis methods was evaluated using Lin's concordance correlation coefficient (CCC). CCC was computed for ten mass spectral predictors of VPA concentrations. Lin's CCC was >0.6 for all VPA-associated features, except for two low-signal intensity isotopic peaks. Finally, free and total serum VPA concentrations were predicted by cross validating the off-line data set. Support vector machine algorithms provided the most accurate predictions with a root mean square error of cross validation of 29.0 ± 7.4 mg l-1and 3.9 ± 1.4 mg l-1for total and free VPA (mean ± SD), respectively. As a secondary analysis, we explored whether exhaled metabolites previously associated with side-effects and response to medication could be rendered by the off-line analysis method. We found that five features associated with side effects showed a CCC > 0.6, whereas none of the drug response-associated peaks reached this cut-off. We conclude that the clinically relevant free fraction of VPA can be predicted by this combination of off-line breath collection with rapid SESI-HRMS analysis. This opens new possibilities for breath based TDM in clinical settings.

Harnessing the Power of Collaboration to Expand the Coverage and Equity of COVID-19 Vaccinations in India: A Community Collaboration Model.

Early in 2021, India embarked on the uphill journey of the COVID-19 vaccination of the largest population group in the world in a prioritized manner and in the shortest possible time. Considering the endless variety of geography and diverse socio-economic demographic, religious, and community contexts, there was a high likelihood of certain population subgroups with known vulnerabilities facing inequities, which were anticipated to be further accentuated by a digital divide. This necessitated devising solutions for such communities in a localized manner to aid the local government in breaking the service access and uptake barriers with an inclusive approach. To bridge this vital gap, the Momentum Routine Immunization Transformation and Equity project implemented a three-tiered collaboration, viz., government, non-governmental organizations (NGOs), and a wide range of vulnerable and at-risk communities, utilizing knowledge exchange and use of data. The project implemented localization strategies through the NGOs for community engagement in conjunction with government vaccination teams to universalize COVID-19 vaccination uptake up to the last mile. The collaboration resulted in reaching close to 50 million beneficiaries through messaging and facilitated the administration of more than 14 million vaccine doses, including 6.1 million doses for vulnerable and marginalized communities in 18 States and Union territories in India, along with suggesting implications for public health practice and research.

An Equity Analysis of Zero-Dose Children in India Using the National Family Health Survey Data: Status, Challenges, and Next Steps.

Background While immunization programs across the world have made considerable progress, children and communities continue to be beyond the reach of healthcare services. Globally, they are now referred to as zero-dose (ZD) children (those who have not received a single dose of diphtheria, pertussis, and tetanus-containing vaccine). Pre-COVID-19 pandemic analyses suggest that nearly 50% of vaccine-preventable deaths occur among ZD children. Two-thirds of these children live in extremely poor households suffering from multiple deprivations including lack of access to reproductive health services, water, and sanitation. Hence, ZD children have now been prioritized as a key cohort for identification and integration with the health systems as we build back from the pandemic. Methodology Extracting data from the last two National Family Health Survey (NFHS) rounds (NFHS 4, 2015-2016 and NFHS 5, 2019-2021), this study aims to ascertain the status of ZD children aged 12-23 months in India, the challenges, and the necessary action agenda going forward. Data were analyzed for equity determinants such as gender, place of residence, religion, birth order, caste, and mother's schooling. Key determinants included the change in ZD prevalence at the national, state, and district levels; variations across equity parameters and states with maximum improvements; and disparity across these indicators. A correlation analysis was also conducted to understand the nature of the association between ZD prevalence and critical maternal and child health indicators. Results The overall ZD prevalence between the two rounds was reduced by 4.1% (10.5-6.4%). A total of 26 states in the country reported a ZD prevalence of <10% in NFHS 5 compared to 18 in NFHS 4. In total, 324 districts reported a ZD prevalence of <5%, and 145 districts reported a prevalence of >10%. The equity parameters reflected a slow-footed reduction among ZD for girl children, across urban geographies, firstborn children, mothers with 12 or more years of schooling, and children in families with the highest wealth quintiles. A negative correlation accentuated between the two NFHS rounds was established between first-trimester registration, four or more antenatal visits, institutional deliveries, and ZD prevalence. Conclusions The findings point toward sustained improvement across key equity parameters, however, challenges do exist. Moreover, the impact of the pandemic on immunization programs across the globe and in India is bound to halt and reverse the progress and potentiate further inequities. It is thus imperative that continued and augmented efforts are continued to identify, integrate, and immunize ZD children, families, and communities.

Balancing Routine and Pandemic: The Synergy of India's Universal Immunization Program and COVID-19 Vaccination Program.

The COVID-19 pandemic posed substantial challenges to healthcare systems globally and severely disrupted essential health services, including routine immunization programs. In India, these disruptions were exacerbated due to the sudden emergence of the pandemic and lockdown measures, leading to mass migrations and a shortage of healthcare workers. Caregivers' concerns about routine immunization sessions further compounded the problem, resulting in a sharp increase in zero-dose children. This review paper examines India's strategies for conducting one of the world's largest COVID-19 vaccination programs while effectively restoring and perpetuating its Universal Immunization Program (UIP). The UIP played a pivotal role in sustaining immunization services during the pandemic, ultimately improving immunization coverage compared to pre-pandemic levels. India's accomplishments in this regard are highlighted through key performance indicators, the reach of immunization services, a reduction in zero-dose children, and antigen-wise coverage. The paper also discusses the successful integration of COVID-19 vaccination within the UIP framework, underscoring the significance of existing infrastructure, technology, and capacity building. India's dedication to concurrently managing routine immunization and COVID-19 vaccination showcases the adaptability and resilience of its healthcare system. India's journey serves as a global example of efficient mass immunization during challenging times, emphasizing the importance of political will, healthcare infrastructure investment, skilled healthcare workforces, and comprehensive vaccination programs. In a world grappling with the dual challenge of COVID-19 and routine immunization, India's experience provides a roadmap for strengthening healthcare systems and promoting public health as the critical agenda in challenging times.

Preservation of exhaled breath samples for analysis by off-line SESI-HRMS: proof-of-concept study.

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of allm/zsignals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.

India's efforts to achieve 1.5 billion COVID-19 vaccinations: a narrative review.

The initial case of coronavirus disease 2019 (COVID-19) in India was reported on January 30, 2020, and subsequently, the number of COVID-19-infected patients surged during the first wave of April 2020 and the second wave in the same month of 2021. The government of India imposed a strict nationwide lockdown in April 2020 and extended it until May 2020. The second wave of COVID-19 in India overwhelmed the country's health facilities and exhausted its medical and paramedical workforce. This narrative review was conducted with the aim of summarizing the evidence drawn from policy documents of governmental and non-governmental organizations, as well as capturing India's COVID-19 vaccination efforts. The findings from this review cover the Indian government's vaccination initiatives, which ranged from steps taken to combat vaccine hesitancy to vaccination roadmaps, deployment plans, the use of digital health technology, vaccination monitoring, adverse effects, and innovative strategies such as Har Ghar Dastak and Jan Bhagidari Andolan (people's participation). These efforts collectively culminated in the successful administration of more than 1.8 billion doses of COVID-19 vaccines in India. This review also provides insights into other countries' responses to COVID-19 and guidance for future pandemics.