Immunoinformatics-based multi-epitope containing fused polypeptide vaccine design against visceral leishmaniasis with high immunogenicity and TLR binding.

Visceral leishmaniasis (VL) is the most lethal among all leishmaniasis diseases and remains categorized as a neglected tropical disease (NTD). This study aimed to develop a peptide-based multi-epitope vaccine construct against VL using immunoinformatics methodologies. To achieve this, four distinct proteins were screened to identify peptides consisting of 9-15 amino acids with high binding affinity to toll-like receptors (TLRs), strong antigenicity, low allergenicity, and minimal toxicity. The resulting multi-epitope vaccine construct was fused in a tandem arrangement with appropriate linker peptides and exhibited superior properties related to cytotoxic T lymphocytes (CTLs), helper T lymphocytes (HTLs), and B-cell epitopes. Subsequently, a three-dimensional (3D) model of the vaccine construct was generated, refined, and validated for structural stability and immune response capabilities. Molecular docking and simulations confirmed the vaccine construct's stability and binding affinities with TLRs, with TLR4 displaying the highest binding affinity, followed by TLR2 and TLR3. Additionally, simulations predicted robust cellular and humoral antibody-mediated immune responses elicited by the designed vaccine construct. Notably, this vaccine construct includes proteins from various pathways of Leishmania donovani (LD), which have not been previously utilized in VL vaccine design. Thus, this study opens new avenues for the development of vaccines against diverse protozoan diseases.

Assessing the Prevalence of Financial Toxicity, its Predictors and Association with Health- Related Quality of Life Among Radiation Oncology Patients in India: A Cross-Sectional Patient Reported Outcome Study.

PURPOSE: Financial toxicity has been associated with several clinical outcomes such as early mortality and poor quality of life. The aim of this study was to evaluate the magnitude of financial toxicity among radiation oncology patients and its association with health-related quality of life (HRQOL) in Indian health care settings. METHODS AND MATERIALS: This cross-sectional study was conducted among patients with cancer who had completed radiation therapy, either standalone or as part of a multimodal treatment. Financial toxicity and HRQOL were assessed using the Comprehensive Score for Financial Toxicity (COST) and Functional Assessment of Cancer Therapy: General (FACT-G) measures, respectively. Associations between financial toxicity and HRQOL were assessed using Pearson correlation. Univariate and multivariate regression analyses were conducted to identify the factors associated with financial toxicity. RESULTS: A total of 350 patients were included in this study. Of the 350 participants, 57.7% were male, 95.7% had no health insurance, and 61% were diagnosed with Head & Neck cancers. The average COST score was 15.38 ± 9.18 (range, 2-35), and the average FACT-G score was 69.63 ± 12.25 (range, 33-99). Based on the total COST score, 7.4% of participants reported grade 3 and 44.9% reported grade 2 financial toxicity. A significant positive correlation was observed between the COST and FACT-G scores, with a correlation coefficient of 0.58 (P < .001), indicating a large effect size. The COST score also significantly predicted the FACT-G score (ß = 0.77; 95% confidence interval [CI], 0.66-0.88; P < .001). The results of multivariate linear regression identified annual household income (ß = 3.9; 95% CI, 3.29-4.57; P < .001) and cancer type (ß = 3.74; 95% CI, 2.33-5.14; P < .001) as significant predictors of the COST score. CONCLUSIONS: More than 80% of the participants experienced financial toxicity in this study. The results highlight the need for interventions to alleviate the growing financial toxicity among cancer survivors in India.

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct.

Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility.

Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.

Assessing the reliability and validity of comprehensive score for financial toxicity (COST) among radiation oncology patients in India: a cross-sectional pilot study.

BACKGROUND: Besides physical toxicity, cancer care imposes significant financial distress referred to as financial toxicity (FT). FT has become a growing concern among cancer patients. Researchers have associated FT among cancer patients with clinical outcomes like mortality, poor quality of life and non-adherence. Currently, no reliable tools are available for assessing FT among cancer patients in India. The aim of this pilot study was to test the reliability and validity of the Comprehensive Score for Financial Toxicity (COST) questionnaire among patients undergoing radiotherapy in India. MATERIAL AND METHODS: This cross-sectional pilot study was conducted among head and neck cancer patients on follow-up in radiation oncology department. The reliability of COST measure was assessed using Cronbach's α. The underlying construct of COST was verified by Exploratory Factor Analysis (EFA). EFA was performed using parallel analysis technique. RESULTS: Based on inclusion and exclusion criteria, the COST questionnaire was administered to 29 patients using the interview method after written informed consent. The COST measure demonstrated excellent reliability with Cronbach's α of 0.92. A Kaiser-Meyer-Olkin of 0.87 verified the sample adequacy and a p-value of ˂0.001on Bartlett's sphericity test indicated that the strength of the correlation between 11 COST items was good to perform the EFA. Parallel analysis technique identified one factor on scree plot with eigenvalue of 6.21 explaining 56.5% of the variance by non-rotated solution. All the factor loadings in one factor model were ˃0.3 (range 0.35-0.97). The factor loadings indicated that the underlying construct can be considered as one factor domain as intended by the original COST development study. However, Chi-square goodness of fit test revealed the one factor model did not adequately depict the data. However, the results were consistent with the construct obtained in the original scale development study. CONCLUSION: This pilot study demonstrated excellent reliability of COST for measuring FT among radiation oncology patients. Further studies are warranted to study the clinical implications of FT in the Indian population for making better strategies and policies to ease the financial burden on cancer patients.

Development and Validation of Subjective Financial Distress Questionnaire (SFDQ): A Patient Reported Outcome Measure for Assessment of Financial Toxicity Among Radiation Oncology Patients.

BACKGROUND: Financial toxicity is a consequence of subjective financial distress experienced by cancer patients as a result of treatment expenditures. Financial toxicity has been associated with poor quality of life, early mortality, and non-adherence. It is evident from the literature that the currently available instruments for the assessment of financial toxicity do not measure coping and support seeking domains. The aim of this study was to develop an instrument for the assessment of financial toxicity among radiation oncology patients that captures and integrates all the relevant domains of subjective financial distress. MATERIALS AND METHODS: The study was conducted among Head & Neck cancer (HNC) patients (age ≥18 years) who have completed the radiotherapy either as stand-alone or part of a multimodal treatment. Literature review, expert opinion, and patient interviews were used for scale item generation. The validity and underlying factor structure were evaluated by Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). The reliability and internal consistency of the final scale was assessed using Cronbach's alpha coefficient. RESULTS: A total of 17 items were identified for scale development. The preliminary 17-item instrument was administered to 142 HNC patients. Among 142 participants, 85.9% were male and 98.6% were from rural areas. EFA was performed on 17 items and three items were removed (factor loadings <0.5). The remaining 14 items loaded onto three factors (eigenvalue >1) explaining 62.0% of the total variance. The Chi-square goodness of fit test in CFA and the values of other model fit indices, namely, RMSEA = 0.045, SRMR = 0.014, GFI = 0.92, CFI = 0.98, and TLI=0.97 indicate a good model fit suggesting the three-factor model adequately fits the data. The Cronbach's α for the final 14-item scale was 0.87 indicating excellent reliability and the Cronbach's α coefficient of all the individual 14 items was ≥0.85 (range 0.85-0.88). CONCLUSION: The SFDQ showed excellent validity and reliability. SFDQ captures and integrates all the relevant domains of financial toxicity. However, the provisional SFDQ instrument warrants further larger sample studies for validation and psychometric evaluation in different primary cancer subsites and treatment modalities from multiple cancer centers to improve the generalizability of this instrument.