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.

Exploring Vaccine Hesitancy and Uptake during COVID-19: A Review of PM's Mann Ki Baat Dialogue.

Public health programmes are interlinked and intertwined with communication, advocacy and social mobilisation for their success. The unprecedented situation created by COVID-19 brought a medical emergency all over the world, the like of which was probably not seen after the Spanish Flu outbreak, a century ago. First there seemed no solution in sight when tens of thousands of people lost their lives to the coronavirus in various countries, but when the vaccine arrived, there were, in general, doubts about its efficacy and safety. Indian scenario was not any different. When the government launched the vaccine in a campaign mode in January 2021, it was also battling with misperceptions and vaccine hesitancy. Prime Minister Narendra Modi took it upon himself to address the issue through his various addresses to the nation and his signature programme Mann ki Baat (MKB) on the radio. This review paper examines the empirical research on MKB coverage of the COVID-19 pandemic, the media multiplier impact of the MKB, people's voices through their engagement with various social media platforms, and what is the impact on vaccine uptake.

Long-chain polyunsaturated lipids associated with responsiveness to anti-PD-1 therapy are colocalized with immune infiltrates in the tumor microenvironment.

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with varying treatment sensitivity at the baseline and at three time points post-anti-PD-1 therapy. These imaging experiments revealed specific alterations in the lipid profiles associated with the degree of response to treatment and allowed us to identify a significant increase of long-chain polyunsaturated lipids within responsive tumors following anti-PD-1 therapy. Immunofluorescence imaging of tumor tissues also demonstrated that the altered lipid profile associated with treatment response is localized to dense regions of tumor immune infiltrates. Overall, these results indicate that effective anti-PD-1 therapy modulates lipid metabolism in tumor immune infiltrates, and we thereby propose that further investigation of the related immune-metabolic pathways may be useful for better understanding success and failure of anti-PD-1 therapy.

Mission Indradhanush and Intensified Mission Indradhanush-Success Story of India's Universal Immunization Program and the Role of Mann Ki Baat in Bridging the Immunization Gap.

Child immunization is crucial for reducing the morbidity and mortality associated with vaccine-preventable diseases (VPDs). The program grew over the years, however, progress towards full immunization coverage (FIC) remained slow, with only 44% of children fully immunized in 1992-1993, and 62% in 2015-2016, as reported in the National Family Health Survey. To address this challenge, Government of India launched Routine Immunization intensification drive- Mission Indradhanush (MI) in 2014, with the aim of achieving 90% FIC. The success of MI led to the launch of Intensified Mission Indradhanush (IMI) in 2017, with more intensive planning, monitoring, review, and inter-sectoral partnerships.

Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes Mellitus Fasting During Ramadan: A Real-World Study from Bangladesh.

Aim: In Bangladesh, there is a large population of Muslims with type 2 diabetes mellitus (T2DM) who fast during Ramadan. Changes in the pattern of meal and fluid intake during this long-fasting hours may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. Our key point of focus was to evaluate the efficacy and safety of Empagliflozin, a sodium-glucose co transporter 2 inhibitor (SGLT2i), in patients with T2DM while fasting during Ramadan. Methods: This was a 24-weeks, multi-centre, open-label, two-arm parallel-group study. In this prospective type of observational study, we enrolled patients taking Empagliflozin and Metformin with or without a DPP-4 inhibitor in one group (n = 274) and a parallel group (n = 219) who were treated with Metformin with or without a DPP-4 inhibitor. The primary endpoint of this study was HbA1c reduction, weight loss and the number of reported or symptomatic hypoglycemic events. In secondary endpoints, we evaluated the changes from baseline in blood pressure, estimated glomerular filtration rate (eGFR), serum creatinine, and serum electrolyte, the proportion of volume depletion (≥1 event) and incidence of other adverse events (AEs) of interest potentially related to SGLT2 inhibitor. Results: During Ramadan, HbA1c reduction was significant in Empagliflozin arm (-0.49% vs -0.12%); [p < 0.001]. From before to the end of the study, significant weight reduction was seen in the Empagliflozin arm (-1.4 kg vs -0.09 kg); [p < 0.001]. We observed no significant increase in the incidence of hypoglycemia (0.7% vs 0.4%, p = 0.267) and volume depletion (2.6% vs 1.8%; p = 0.55) in both arm. All these milder forms events did not require any hospital admission. There was no report of serious adverse events or any discontinuation, or reduction of prescribed doses of empagliflozin during Ramadan. Conclusion: Empagliflozin is efficacious and safe for treating adults with T2DM during Ramadan.

Identifying Clinically Relevant Bacteria Directly from Culture and Clinical Samples with a Handheld Mass Spectrometry Probe.

BACKGROUND: Rapid identification of bacteria is critical to prevent antimicrobial resistance and ensure positive patient outcomes. We have developed the MasSpec Pen, a handheld mass spectrometry-based device that enables rapid analysis of biological samples. Here, we evaluated the MasSpec Pen for identification of bacteria from culture and clinical samples. METHODS: A total of 247 molecular profiles were obtained from 43 well-characterized strains of 8 bacteria species that are clinically relevant to osteoarticular infections, including Staphylococcus aureus, Group A and B Streptococcus, and Kingella kingae, using the MasSpec Pen coupled to a high-resolution mass spectrometer. The molecular profiles were used to generate statistical classifiers based on metabolites that were predictive of Gram stain category, genus, and species. Then, we directly analyzed samples from 4 patients, including surgical specimens and clinical isolates, and used the classifiers to predict the etiologic agent. RESULTS: High accuracies were achieved for all levels of classification with a mean accuracy of 93.3% considering training and validation sets. Several biomolecules were detected at varied abundances between classes, many of which were selected as predictive features in the classifiers including glycerophospholipids and quorum-sensing molecules. The classifiers also enabled correct identification of Gram stain type and genus of the etiologic agent from 3 surgical specimens and all classification levels for clinical specimen isolates. CONCLUSIONS: The MasSpec Pen enables identification of several bacteria at different taxonomic levels in seconds from cultured samples and has potential for culture-independent identification of bacteria directly from clinical samples based on the detection of metabolic species.

Plasma Based Protein Signatures Associated with Small Cell Lung Cancer.

Small-cell-lung cancer (SCLC) is associated with overexpression of oncogenes including Myc family genes and YAP1 and inactivation of tumor suppressor genes. We performed in-depth proteomic profiling of plasmas collected from 15 individuals with newly diagnosed early stage SCLC and from 15 individuals before the diagnosis of SCLC and compared findings with plasma proteomic profiles of 30 matched controls to determine the occurrence of signatures that reflect disease pathogenesis. A total of 272 proteins were elevated (area under the receiver operating characteristic curve (AUC) ≥ 0.60) among newly diagnosed cases compared to matched controls of which 31 proteins were also elevated (AUC ≥ 0.60) in case plasmas collected within one year prior to diagnosis. Ingenuity Pathway analyses of SCLC-associated proteins revealed enrichment of signatures of oncogenic MYC and YAP1. Intersection of proteins elevated in case plasmas with proteomic profiles of conditioned medium from 17 SCLC cell lines yielded 52 overlapping proteins characterized by YAP1-associated signatures of cytoskeletal re-arrangement and epithelial-to-mesenchymal transition. Among samples collected more than one year prior to diagnosis there was a predominance of inflammatory markers. Our integrated analyses identified novel circulating protein features in early stage SCLC associated with oncogenic drivers.

Integrating the MasSpec Pen with Sub-Atmospheric Pressure Chemical Ionization for Rapid Chemical Analysis and Forensic Applications.

Analytical methods that allow rapid, sensitive, and specific chemical measurements are central to forensic analysis and essential to accelerating compound screening and confirmation. We have previously reported the development of the MasSpec Pen technology as an easy-to-use and disposable hand-held device integrated to a mass spectrometer for direct analysis and molecular profiling of biological samples. In this Technical Note, we describe a new apparatus that integrates the MasSpec Pen device with a subatmospheric pressure chemical ionization (sub-APCI) source and an ion trap mass spectrometer for detection and semiquantitative analysis of forensic-related compounds. Coupling the MasSpec Pen device to a sub-APCI source allowed semiquantitative analysis of the drugs cocaine and oxycodone, the agrochemicals atrazine and azoxystrobin, and the explosives trinitrotoluene and dinitroglycerin in under 20 s. Using chemical ionization, improved reproducibility and sensitivity for targeted chemical detection and compound identification was achieved while maintaining the user-friendly features of the hand-held MasSpec Pen device. Limits of detection in the high picogram to low nanogram range were obtained for the compounds analyzed, which are within the range of federal screening cutoffs and those reported for other ambient ionization MS techniques. Altogether, the MasSpec Pen sub-APCI system described enabled rapid and semiquantitative chemical analysis for forensic applications and could be further adapted and applied to other areas of chemical testing.

A Systematic Review of Interpathologist Agreement in Histologic Classification of Lupus Nephritis.

INTRODUCTION: Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), resulting in increased morbidity and mortality. The gold standard for diagnosis of LN is a renal biopsy. Considering the importance of the biopsy in determining long-term prognostication and treatment decisions, it is crucial to assess renal histopathology with utmost accuracy and precision. This review represents a systematic search of published literature to estimate the degree of interpathologist reproducibility in current assessment of LN. METHODS: Using the PubMed and Google Scholar search engines, studies analyzing the agreement of 4 or more pathologists assessing LN slides using the ISN/Renal Pathology Society (RPS) classification, activity index, and chronicity index were selected for analysis in this systematic review. RESULTS: In reviewing 6 qualifying studies (those analyzing the agreement of 4 or more pathologists using the ISN/RPS classification, activity index, and chronicity index) for the assignment of ISN/RPS class was 0.325 (interquartile range [IQR] 0.2405-0.425), which is "poor." The median interpathologist concordance values for the assigned activity index and chronicity index were "moderate": 0.52 (IQR 0.51-0.69) and 0.49 (IQR 0.36-0.58), respectively. CONCLUSION: Thus, the current scoring using the ISN/RPS classification system and activity and chronicity indices for LN exhibits poor interpathologist agreement, which limits its use in clinical practice. Given that this can have severe repercussions on a patient's treatment and prognosis, efforts to update pathology assessment guidelines, objectively measurable biomarkers, and deep learning approaches are strongly warranted.

Urine protein biomarkers for the detection, surveillance, and treatment response prediction of bladder cancer.

The "gold standard" diagnostic procedure for bladder cancer is cystoscopy, a technique that can be invasive, expensive, and a possible cause of urinary tract infection. Unlike techniques such as histology, PCR, and staining, assays for protein biomarkers lend themselves well to the creation of efficient point-of-care tests, which are easy to use and yield fast results. A couple of urine-based tests have been approved by the U.S. FDA, but these tests suffer from low sensitivity. Hence, there is clearly a need for more reliable non-invasive biomarkers of bladder cancer. Urinary biomarkers are particularly attractive due to the direct contact of the urine with the urothelial tumor and the ease of sample collection. With these considerations, this review aims to provide a comprehensive listing of the most promising protein biomarkers of bladder cancer in urine. Biomarkers are organized by their potential role in detection, surveillance, or monitoring of treatment response. The purpose of this review is to assess progress towards the goal of identifying ideal urinary proteins for use in each of the above three biomarker applications in bladder cancer.