A New Epitope Selection Method: Application to Design a Multi-Valent Epitope Vaccine Targeting HRAS Oncogene in Squamous Cell Carcinoma

We developed an epitope selection method for the design of MHC targeting peptide vaccines. The method utilizes predictions for several clinical checkpoint filters, including binding affinity, immunogenicity, antigenicity, half-life, toxicity, IFNγ release, and instability. The accuracy of the prediction tools for these filter variables was confirmed using experimental data obtained from the Immune Epitope Database (IEDB). We also developed a graphical user interface computational tool called ‘PCOptim’ to assess the success of an epitope filtration method. To validate the filtration methods, we used a large data set of experimentally determined, immunogenic SARS-CoV-2 epitopes, which were obtained from a meta-analysis. The validation process proved that placing filters on individual parameters was the most effective method to select top epitopes. For a proof-of-concept, we designed epitope-based vaccine candidates for squamous cell carcinoma, selected from the top mutated epitopes of the HRAS gene. By comparing the filtered epitopes to PCOptim’s output, we assessed the success of the epitope selection method. The top 15 mutations in squamous cell carcinoma resulted in 16 CD8 epitopes which passed the clinical checkpoints filters. Notably, the identified HRAS epitopes are the same as the clinical immunogenic HRAS epitope-based vaccine candidates identified by the previous studies. This indicates further validation of our filtration method. We expect a similar turn-around for the other designed HRAS epitopes as a vaccine candidate for squamous cell carcinoma. Furthermore, we obtained a world population coverage of 89.45% for the top MHC Class I epitopes and 98.55% population coverage in the absence of the IFNγ release clinical checkpoint filter. We also identified some of the predicted human epitopes to be strong binders to murine MHC molecules, which provides insight into studying their immunogenicity in preclinical models. Further investigation in murine models could warrant the application of these epitopes for treatment or prevention of squamous cell carcinoma.

Design of Epitope Based Peptide Vaccine against Brucella Abortus OmpW Family Protein using Immunoinformatics

Brucella abortus is a small aerobic, non-spore-forming, non-motile intracellular coccobacilli localized in the reproductive organs of host animals and causes acute or chronic disorders. It infects approximately 200 cases per 100,000 of the population and has become endemic in many countries. OmpW family protein is an outer membrane protein involved in the initial interaction between the pathogen and its host. This study predicts an effective epitope-based vaccine against OmpW family protein of Brucella abortus using immunoinformatics tools. Sequences were obtained from NCBI and prediction tests were accomplished to analyze possible epitopes for B and T cells. Seven B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Forty-three MHC I epitopes were the most promising, while 438 from MHC II. For the population coverage, the epitopes covered 99.97% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove its effectiveness.

COVID -19 VACCINATION COVERAGE IN HIMACHAL PRADESH

The Covid 19 Pandemic is the most tough situation to humanity in a century. It was widely believed that pre-pandemic life will never return until a safe and effective vaccine strategy become available. But now Covid-19 vaccination is offering a way to escape out of this tough phase of this pandemic. Vaccination drive against Covid 19 has been going on across the world. In India it began th th st nd on 16 January 2021. In India till 30 September 2021 1 doses are 64.64 crores with 46 % coverage and 2 doses are 23.7 crores with 17 % total th st nd population coverage. In Himachal Pradesh till 30 September 2021 ( in 9 months) 1 and 2 doses are 5.66 millions and 2.7 millions with 72% st and 32 % population coverage with District Solan is on the top in 1 dose coverage of Covid 19 vaccine with 98.18% followed by Lahol and Spiti (84.05%) , Kinnaur (77.98%), Una (72.75%), Bilaspur(72.11%), Hamirpur (71.67%), Shimla (69.43%), Kullu (69.04%), Kangra (67.97%), nd Sirmour (67.83%), Mandi (66.67%) and Chamba is in last (59.76%). In 2 dose coverage Kinnaur is on the top with 54% coverage followed by Lahol and spiti (47%) it might be because in both districts population is less than other districts. Chamba (23%) and Sirmour (22 %) are in the last nd position in vaccination coverage of 2 dose it might be because population is more as well as area is hilly, difcult to reach and literacy rate is also low in these districts.

Analysis of Structure, Process and Result Indicators in the Family Health Strategy in Mato Grosso: A Comparative Study

This research aimed to correlate the indicators of Primary Health Care in their structural components with those of the process and with the results in the municipalities of Mato Grosso, Brazil, from 2008 to 2015. This is an evaluative, quantitative, retrospective research with the use of secondary data from information systems. A matrix is composed of components of the structure (potential population coverage) the process (medical consultation, home visit of doctor and nurse, referral to the specialist, and request of clinical pathology exams), and the result (hospitalization rate due to sensitive causes). It was constructed when primary care, the proportion of live births of mothers with seven or more prenatal consultations, and the infant mortality coefficient) and the descriptive analysis and Spearman correlation coefficient (rho) were performed. The study found that population coverage remained high above 83% and the process indicators suggest an improvement in family health strategy, with a reduction of 63.13% in the average referral to a specialist and 49.71% in the request for clinical pathology exams. However, there was a 7.13% reduction in the average home visit during the study period. There is a correlation between the structure and process component and between structure and result. It has been found that with the evolution of the Family Health Strategy, there were changes in some indicators of primary care, but it is not possible to state that there was a change in the care model.

Engagement of non-governmental organisations in moving towards universal health coverage: a scoping review

Background Developing essential health services through non-governmental organisations (NGOs) is an important strategy for progressing towards Universal Health Coverage (UHC), especially in low- and middle-income countries. It is crucial to understand NGOs’ role in reaching UHC and the best way to engage them. Objective This study reviewed the role of NGOs and their engagement strategies in progress toward UHC. Method We systematically reviewed studies from five databases (PubMed, Web of Science (ISI), ProQuest, EMBASE and Scopus) that investigated NGOs interventions in public health-related activities. The quality of the selected studies was assessed using the mixed methods appraisal tool. PRISMA reporting guidelines were followed. Findings Seventy-eight studies met the eligibility criteria. NGOs main activities related to service and population coverage and used different strategies to progress towards UHC. To ensure services coverage, NGOs provided adequate and competent human resources, necessary health equipment and facilities, and provided public health and health care services strategies. To achieve population coverage, they provided services to vulnerable groups through community participation. Most studies were conducted in middle-income countries. Overall, the quality of the reported evidence was good. The main funding sources of NGOs were self-financing and grants from the government, international organisations, and donors. Conclusion NGOs can play a significant role in the country’s progress towards UHC along with the government and other key health players. The government should use strategies and interventions in supporting NGOs, accelerating their movement toward UHC.

Health Services Coverage Regulation: an Evaluation of Policy Options for New Zealand

<p>An important feature of New Zealand's 1993 health reforms was the promise to define an explicit list of 'core' services - i.e. the health services to which all New Zealanders would have access. This thesis examines public policy issues surrounding an explicit core of services, and by extension, policies which regulate health services coverage. Coverage regulation is defined as the rules about which population groups and services are covered by a health insurance plan. Part One of the thesis develops frameworks for defining and evaluating alternative models of coverage regulation. First, four key elements of coverage regulation are identified: population coverage; service coverage; whether coverage is implicit or explicitly defined; and insurability for services covered under principal health plan coverage. Second, a formal decision-making schema is developed which establishes benchmarks in the form of lower-level health policy objectives, which alternatives models of coverage regulation must meet in order to promote the higher-level policy goals of allocative efficiency, equal access for equal need, choice and expenditure control. In Part Two of the thesis, the decision-making schema is used to provide a framework for an in-depth discussion of how alternative models of coverage regulation contribute to lower-level health policy objectives and hence to higherlevel policy goals. The schema is then used to value how well alternative models of coverage regulation contribute to these objectives and goals. This involves two steps. First, it involves scoring each alternative model of coverage regulation for its contribution to policy objectives and goals, based on the discussion described above. Second, it involves weighting the different objectives and goals in order to value the contribution alternative models of coverage regulation make to each of the four policy goals individually and overall. For this thesis, it is the author's values that are used to weight the policy goals. Given the judgements required in scoring alternatives and in weighting objectives and goals, sensitivity analysis is used to explore, the impact that different scores and weights have on the overall Scores. The analysis identifies the limitations of current New Zealand arrangements for coverage regulation, and demonstrates the policy trade-offs which must be made in deciding which coverage regulation model New Zealand should adopt in the future. The current model performs only adequately in relation to each of the policy goals. A model with similar population coverage, comprehensive service coverage and an explicit, detailed service specification is shown to improve performance in relation to efficiency and equity goals albeit at a cost of limiting choice and potentially losing short-term expenditure control. In a managed competition system, the same conclusions apply. New Zealand should therefore investigate the types of, services where a more explicit and detailed service specification might be developed, in order to better support efficiency and equity goals in New Zealand health care.</p>

Health Services Coverage Regulation: an Evaluation of Policy Options for New Zealand

<p>An important feature of New Zealand's 1993 health reforms was the promise to define an explicit list of 'core' services - i.e. the health services to which all New Zealanders would have access. This thesis examines public policy issues surrounding an explicit core of services, and by extension, policies which regulate health services coverage. Coverage regulation is defined as the rules about which population groups and services are covered by a health insurance plan. Part One of the thesis develops frameworks for defining and evaluating alternative models of coverage regulation. First, four key elements of coverage regulation are identified: population coverage; service coverage; whether coverage is implicit or explicitly defined; and insurability for services covered under principal health plan coverage. Second, a formal decision-making schema is developed which establishes benchmarks in the form of lower-level health policy objectives, which alternatives models of coverage regulation must meet in order to promote the higher-level policy goals of allocative efficiency, equal access for equal need, choice and expenditure control. In Part Two of the thesis, the decision-making schema is used to provide a framework for an in-depth discussion of how alternative models of coverage regulation contribute to lower-level health policy objectives and hence to higherlevel policy goals. The schema is then used to value how well alternative models of coverage regulation contribute to these objectives and goals. This involves two steps. First, it involves scoring each alternative model of coverage regulation for its contribution to policy objectives and goals, based on the discussion described above. Second, it involves weighting the different objectives and goals in order to value the contribution alternative models of coverage regulation make to each of the four policy goals individually and overall. For this thesis, it is the author's values that are used to weight the policy goals. Given the judgements required in scoring alternatives and in weighting objectives and goals, sensitivity analysis is used to explore, the impact that different scores and weights have on the overall Scores. The analysis identifies the limitations of current New Zealand arrangements for coverage regulation, and demonstrates the policy trade-offs which must be made in deciding which coverage regulation model New Zealand should adopt in the future. The current model performs only adequately in relation to each of the policy goals. A model with similar population coverage, comprehensive service coverage and an explicit, detailed service specification is shown to improve performance in relation to efficiency and equity goals albeit at a cost of limiting choice and potentially losing short-term expenditure control. In a managed competition system, the same conclusions apply. New Zealand should therefore investigate the types of, services where a more explicit and detailed service specification might be developed, in order to better support efficiency and equity goals in New Zealand health care.</p>

Analysis and Outlook for the Development of Measles Epidemic Situation during the COVID-19 Pandemic

Relevance. The success of the global community in the fight against measles through vaccination at the beginning of the twentyfirst century allowed WHO to declare the goal of eliminating this infection by 2010. However, ten years later, the problem of the growing incidence of measles has become relevant again for all countries of the world. The pandemic of the new coronavirus infection (COVID-19) has affected all spheres of human life and has exacerbated the situation in the fight against other infections, including those managed with the help of specific prophylaxis. Since the measles contagiosity index and mortality rate are significantly higher than similar characteristics of COVID-19, the risk of increasing the incidence of this infection in the coming years is difficult to overestimate.Aim of the study: to assess the epidemic situation of measles in the context of the COVID-19 pandemic, as well as the prospects for its development; to propose preventive measures.Materials and methods. The article analyzes the statistical materials available on the official websites of the WHO (WHO). https://www.who.int/data/), the CDC US (https://www. cdc.gov) and the Federal Service of Rospotrebnadzor (https://www.rospotrebnadzor.ru/) on vaccination coverage and measles incidence in 13 countries in the WHO European Region and the United States. The epidemic situation on measles, as well as the level of population coverage with vaccination against its pathogen in the Russian Federation, were assessed according to the Federal State Statistical Observation forms 2010 – 2020: Form 2 «Information on infectious and parasitic diseases» and Form 6 «Information on the populations of children and adults vaccinated against infectious diseases».Results. It has been established that the increase in the measles incidence occurred in 2017–2019 worldwide, including European countries with a population coverage of two vaccine doses at the 97% level between 2010 and 2019. The prevalence of measles cases in children under the age of 10 is shown, as well as the wide range (from 56.9% to 10.9%) in the proportion of vaccinated persons among them. The results obtained indicate the existence of problems in the organization of modern vaccine prevention. The introduction of widespread restrictive and quarantine measures against the COVID-19 pandemic, on the one hand, has reduced the incidence of measles and, on the other hand, has exacerbated the difficulties in implementing measles prevention. Thus, the results indicate a possible increase in measles incidence in the population after the end of the COVID-19 pandemic.Conclusion. It is necessary to immediately develop an action plan to catch up on the coverage and increase the rate of routine vaccination, to improve the statistical record of persons subject to the introduction of the vaccine and vaccinated, as well as to overcome anti-vaccination attitude among the population.