The value of mathematical modelling approaches in epidemiology for public health decisión making

It is discussed the relevance of quantitative approaches, specifically mathematical modelling in epidemiology, in the public health decision-making process. This topic is discussed here based on the experience of various experts in mathematical epidemiology and public health. First, the definition of mathematical modelling is presented, especially in the context of epidemiology. Second, the different uses and socio-political implications, including empirical examples of recent experiences that have taken place at the international level are addressed. Finally, some general considerations regarding the challenges encountered in the use and application of mathematical modelling in epidemiology in the decision-making process at the local and national levels.

Se trata sobre la importancia de los abordajes cuantitativos, específicamente la formulación de modelos matemáticos en epidemiología, dentro del proceso de toma de decisiones en salud pública. Esta importante temática se analiza basándose en la experiencia de algunos expertos en epidemiología matemática y salud pública. En primer lugar, se presenta la definición de modelación matemática, particularmente dentro del contexto de la epidemiología. En segundo lugar, se abordan los diferentes usos y las implicaciones socio-políticas, incluyendo ejemplos de experiencias recientes que han ocurrido a nivel internacional. Finalmente, se hace referencia a ciertas consideraciones generales respecto a los retos que representa el uso y la aplicación de modelos matemáticos en epidemiología para el proceso de toma de decisiones a nivel local y nacional.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking / Aplicação da ferramenta PolyPRep em poliproteínas de protease de HIV usando docking molecular

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Binding interaction of laccases from Bacillus Subtilis after industrial dyes exposure: Molecular docking and molecular dynamics simulation studies

Dyes are becoming more widely used around the world wide, but there is no effective bioremediation approach for removing them completely from the environment. Several dyes are mentioned to be degraded through bacteria; however, it's still unknown how the particular enzymes act throughout the dye degradation. The behavior and function of these enzymes in the biodegradation of azo dyes (Textile dyes) had been investigated experimentally by the numbers of the researchers, however, the molecular mechanisms remain unclear. Therefore, the interaction mechanisms of textile dye (methyl orange) with laccase from B. subtilis were explored through molecular docking and molecular dynamics simulations, the three selected dyes (methyl orange, malachite green, and acid blue 62) that interact positively with laccase on the basis of their maximum binding energy, molecular docking results indicate that one of the three dyes is more stable as a target for degradation through Bacillus subtilis laccase. Therefore, subsequent research focused solely on one substrate: methyl orange. Molecular Dynamics simulation study was applied after the molecular docking to determine the interaction between laccases and methyl orange dyes. The trajectory was proved with root mean square deviation and root mean square fluctuation analysis. According to the molecular dynamics simulation results, laccase-methyl orange complexes remain stable during the catalytic reaction. So, this study demonstrates how laccase is involved in methyl orange bioremediation.

The potential impact of vaccination on tuberculosis burden in India: A modelling analysis

Background & objectives: Vaccination will play an important role in meeting the end tuberculosis (TB) goals. While certain vaccine candidates in advanced stages of clinical trials raise hope for the future availability of new tools, in the immediate term, there is also increasing interest in Bacille Calmette– Guérin revaccination among adults and adolescents as a potential strategy. Here, we sought to estimate the potential epidemiological impact of TB vaccination in India. Methods: We developed a deterministic, age-structured, compartmental model of TB in India. Data from the recent national prevalence survey was used to inform epidemiological burden while also incorporating a vulnerable population who may be prioritized for vaccination, the latter consistent with the burden of undernutrition. Using this framework, the potential impact on incidence and mortality of a vaccine with 50 per cent efficacy was estimated, if rolled out in 2023 to cover 50 per cent of the unvaccinated each year. Simulated impacts were compared for disease- vs. infection-preventing vaccines, as well as when prioritizing vulnerable groups (those with undernutrition) rather than the general population. A sensitivity analyses were also conducted with respect to the duration, and efficacy, of vaccine immunity. Results: When rolled out in the general population, an infection-preventing vaccine would avert 12 per cent (95% Bayesian credible intervals (Crl): 4.3-28%) of cumulative TB incidence between 2023 and 2030, while a disease-preventing vaccine would avert 29 per cent (95% Crl: 24-34%). Although the vulnerable population accounts for only around 16 per cent of India’s population, prioritizing this group for vaccination would achieve almost half the impact of rollout in the general population, in the example of an infection-preventing vaccine. Sensitivity analysis also highlights the importance of the duration and efficacy of vaccine-induced immunity. Interpretation & conclusions: These results highlight how even a vaccine with moderate effectiveness (50%) could achieve substantial reductions in TB burden in India, especially when prioritized for the most vulnerable.

The Discovery of Putative Small Molecules via Ligand-based Pharmacophore Modelling Targeting Human Tau Protein for an Effective Treatment of Parkinson’s Disease

@#Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based (LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552 kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, & 4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates upon further translational study.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication / 药物分析学报

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively character-izing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear time-invariant dynamical model.It is shown that the transition matrices of dynamical cell systems signifi-cantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Muito além do trauma: uma investigação sobre o papel das reações peritraumáticas sobre o transtorno de estresse pós-traumático / Beyond the trauma: an investigation of the role of peritraumatic reactions on posttraumatic stress disorder

O Transtorno de Estresse Pós-Traumático (TEPT) é uma condição debilitante que impacta significativamente a qualidade de vida dos seus portadores. Dentre vários fatores de risco para o TEPT, as reações peritraumáticas (RP), como a imobilidade tônica peritraumática (ITP), dissociação (DP) e reações físicas de pânico (RFP), estão entre as mais investigadas. No entanto, a maioria dos estudos avaliou essas RP separadamente, e o elo entre elas e o TEPT ainda não foi bem compreendido. Portanto, essa tese teve como objetivos: (i) estimar simultaneamente o efeito das três RP sobre o TEPT utilizando um instrumento validado; e (ii) avaliar se há efeito indireto da ITP sobre o TEPT mediado pelo sentimento de culpa/vergonha. Utilizamos modelagem de equações estruturais para analisar dados de 3211 participantes do Rio de Janeiro e de São Paulo. Tratamos as RP como variáveis latentes, selecionando desconfundidores específicos para cada reação. Nossas exposições foram as RP, sendo TEPT o desfecho. Calculamos odds ratios e intervalos de confiança de 95%. Utilizamos o Bayesian Information Criterion para comparar o ajuste de modelos não aninhados. Quando analisadas separadamente, todas as RP alcançaram significância estatística. No entanto, apenas DP (ORDP=1,8; IC95%:1,3-2,4) e RFP (ORRFP=2,5; IC95%:1,8-3,4) permaneceram estatisticamente significativas quando incluímos as três reações em um modelo com seus respectivos desconfundidores e correlações entre elas. Os resultados sugeriram um possível efeito da ITP sobre o TEPT (ORITP=1,4; IC95%:1,0-1,9). As interações entre as RP não foram estatisticamente significativas. Ao investigarmos o sentimento de culpa/vergonha como mediador entre ITP e TEPT, o efeito indireto alcançou apenas significância estatística limítrofe (ORITP(TNIE)=1,1; IC95%:1,0-1,2). Os efeitos direto (ORITP(PNDE)=1,3; IC95%: 0,8-1,8) e total (ORITP(TE)=1,4; IC95%:0,9-1,9) para ITP perderam significância quando todas as RP, seus desconfundidores e correlações entre elas fizeram parte do mesmo modelo. As demais RP, no entanto, permaneceram estatisticamente significativas (ORDP=1,7; IC95%:1,3-2,3 e ORRFP=2,5; IC95%:1,8-3,4). Nossos resultados mostraram que a DP e as RFP aumentaram o risco de TEPT mesmo quando consideradas em conjunto. A ITP pode ter efeito sobre o risco de TEPT, mas esse achado deve ser interpretado com cautela devido a significância limítrofe dessa RP em nosso modelo final. Também não identificamos uma mediação significativa entre ITP e TEPT pelos sentimentos de culpa/vergonha. Contudo, a significância limítrofe encontrada para o efeito indireto demanda investigações adicionais. Nossos achados reforçam a ideia de que as reações peritraumáticas devem ser analisadas e compreendidas como ocorrências simultâneas. Também seria oportuno que estudos envolvendo culpa/vergonha, ITP e TEPT focalizassem traumas caracterizados por aprisionamento e impossibilidade de escapar, dado que estas experiências são apontadas como mais susceptíveis para desencadear a ITP. (AU)

Posttraumatic stress disorder (PTSD) is a debilitating condition that greatly impacts quality of life. Among several PTSD risk factors, peritraumatic reactions (PR) such as peritraumatic tonic immobility (PTI), dissociation (PD) and physical panic reactions (PPR) are some of the most investigated. However, several studies have assessed these PR separately, and the pathway connecting them to PTSD is not well understood. Therefore, this thesis aimed to: (i) simultaneously estimate the effect of the three PR on PTSD using a validated instrument; and (ii) assess if there is an indirect effect of PTI on PTSD mediated by feelings of guilt/shame. We used structural equation modelling to analyse data from 3211 participants from Rio de Janeiro and São Paulo. We treated the PR as latent variables and selected specific confounders for each reaction. Our exposures were the PR, and PTSD was the outcome. We calculated odds ratios and 95% confidence intervals for each analysis. We also employed the Bayesian Information Criterion to compare the goodness of fit between non-nested models. Separately, all PR achieved statistically significant results. However, only PD (ORPD=1.8; 95%CI:1.3-2.4) and PPR (ORPPR=2.5; 95%CI:1.8-3.4) remained statistically significant when all three were included in a model with their respective confounders and correlations among all PR. Our findings suggested a possible effect of PTI on PTSD (ORPTI=1.4; 95%CI:1.0-1.9). Interactions between the PR were not statistically significant. When we investigated feelings of guilt/shame as the mediator between PTI and PTSD, the indirect effect achieved a borderline statistical significance (ORPTI(TNIE)=1.1; 95%CI:1.0-1.2). Direct (ORPTI(PNDE)=1.3; 95%CI:0.8-1.8) and total (ORPTI(TE)=1.4; 95%CI:0.9-1.9) effects lost their significance when all PR, their confounders and correlations were included in the same model. The other PR remained statistically significant (ORPD=1.7; 95%CI:1.3-2.3 and ORPPR=2.5; 95%CI:1.8-3.4). Our findings showed PD and PPR to increase the risk of PTSD even when considered in tandem. PTI could have an effect on PTSD, but this must be considered cautiously, as this PR only reached borderline significance in our final model. Feelings of guilt/shame did not significantly mediate PTI's effect on PTSD. However, a borderline statistical significance in the indirect effects warrants further investigation. Our findings reinforce the hypothesis that peritraumatic reactions should be analysed and understood as simultaneous occurrences, not as separate entities. It would also be appropriate for studies concerning guilt/shame, PTI and PTSD to focus on traumas characterized by imprisonment and feelings of inescapability, given that these experiences are allegedly more likely to trigger PTI. (AU)

Cárie na primeira infância, má oclusão, fatores psicossociais e qualidade de vida relacionada à saúde bucal de crianças e suas famílias / Early childhood caries, malocclusion, psychosocial factors and oral health-related quality of life in children and their families

Cárie na primeira infância (CPI) e má oclusão podem afetar a qualidade de vida relacionada à saúde bucal (QVRSB) de crianças e suas famílias. Fatores psicossociais relacionados às crianças, suas famílias e comunidade na qual estão inseridas devem ser estudados. Diante disso, os objetivos desta tese foram: 1) verificar a associação entre fatores psicossociais associados à CPI e à QVRSB em pré-escolares e suas famílias (Artigo 1); 2) avaliar o impacto da mordida aberta anterior (MAA) e da mordida profunda (MP) na QVRSB de préescolares, e verificar o papel da resiliência parental como um fator moderador nessa associação (Artigo 2). Foi realizado um estudo transversal representativo com pré-escolares de 4-6 anos de idade e seus pais/responsáveis em Ribeirão das Neves, MG, Brasil. Os pais/responsáveis responderam às versões brasileiras do Early Childhood Oral Health Impact Scale (ECOHIS) e Escala de Resiliência, e um questionário com dados socioeconômicos e de comportamento de saúde bucal da criança. Os pré-escolares foram examinados por duas dentistas treinadas e calibradas para o diagnóstico de CPI e consequências pulpares de lesões cariosas não tratadas (Kappa>0,95), utilizando-se a versão epidemiológica do International Caries Detection and Assessment System (ICDASepi) combinado com o índice pufa e, assim categorizados: sem cárie, estágio inicial (opacidade notável/pigmentação retida em fundo de fóssulas e fissuras), estágio moderado (cavitação em esmalte/sombreamento em dentina subjacente), estágio extenso sem consequências pulpares (cavitação com exposição dentinária) e estágio extenso com consequências pulpares (cavitação com exposição dentinária, com envolvimento pulpar e/ou presença de fístulas/abscessos). A presença de MAA e MP foi avaliada através do índice de Foster e Hamilton. Os dados foram analisados por meio da modelagem por equações estruturais, utilizando-se o software Mplus, versão 8.6 (Artigo 1) e por meio da análise de moderação, utilizando-se o PROCESS (PROCESS for SPSS, version 3.4) (Artigo 2). Os resultados do artigo 1 demonstraram que menor status socioeconômico (ß =-0,250; p<0,001) e maior frequência de consumo de açúcares livres (ß=0,122; p=0,033) foram associados diretamente com estágio extenso de cárie com consequência pulpar, enquanto menor resiliência dos pais impactou indiretamente estágios mais avançados da CPI, por meio da variável frequência de consumo de açúcares livres (ß =-0,089; p=0,048). Além disso, CPI foi associada com piores escores tanto da QVRSB da criança (b=0,587; p<0,001) quanto da família (ß =0,506; p<0,001). Os resultados do artigo 2 demonstraram que préescolares filhos de pais com baixa resiliência, e que possuíam MAA apresentaram impacto negativo na QVRSB (ß:3,95;p=0,025) em comparação àqueles que apresentaram oclusão normal. A resiliência parental não atuou como fator moderador na associação entre MP e QVRSB (p>0,05). Conclui-se que quanto maior a gravidade da CPI, maior o impacto negativo na QVRSB de pré-escolares e suas famílias. Os principais fatores associados à CPI mais grave foram menor nível socioeconômico, maior frequência de consumo de açúcar livre e menor resiliência parental (Artigo 1). MAA interferiu negativamente na QVRSB dos pré-escolares, sendo essa associação mais forte quando a resiliência parental era baixa. Portanto, a resiliência dos pais atuou como fator moderador na relação entre MAA e QVRSB (Artigo 2).

Early childhood caries (ECC) and malocclusion can affect the oral health-related quality of life (OHRQoL) of children and families. Psychosocial factors related to children, their families and the community in which they are inserted must be studied. Therefore, the objectives of this thesis were: 1) to verify the association between psychosocial factors with ECC and OHRQoL in preschoolers and their families (Manuscript #1); 2) to evaluate the impact of anterior open bite (AOB) and deep bite (DB) on the OHRQoL of preschool children and the role of parental resilience as a moderating factor in such association (Manuscript #2). A representative crosssectional study was carried out with 4-to-6-year-old preschoolers and their parents/caregivers from Ribeirão das Neves, MG, Brazil. Parents/caregivers selfadministered the Brazilian versions of the Early Childhood Oral Health Impact Scale (ECOHIS) and the Resilience Scale, as well as a questionnaire about socioeconomic and child's oral health behavior data. Preschoolers were examined by two trained and calibrated dentists for the diagnosis of ECC and pulpal consequences of untreated carious lesions (Kappa>0.95), using the epidemiological version of the International Caries Detection and Assessment System (ICDASepi) index combined with the pufa index: no caries, early stage (notable opacity/retained pigmentation in the background of pits and fissures), moderate stage (cavitation in enamel/shading in underlying dentin), extensive stage without pulpal consequences (cavitation with dentin exposure) and extensive stage with pulpal consequences (cavitation with dentin exposure, and pulp involvement and/or fistulas/abscesses). The presence of AOB and DB were evaluated using the Foster and Hamilton index. Data were analysed through Structural Equation Model (SEM), using the Mplus software, version 8.6 (Manuscript #1) and through moderation analysis, using PROCESS (PROCESS for SPSS, version 3.4) (Manuscript #2). The results of the Manuscript #1 demonstrated that lower socioeconomic status (b=-0.250; p<0.001) and higher frequency of consumption of free sugars (ß=0.122; p=0.033) were directly associated with an extensive stage of caries with pulpal consequences, while lower parental resilience indirectly impacted more advanced stages of ECC, through the variable frequency of consumption of free sugars (b=-0.089; p=0.048). In addition, ECC was associated with worse scores in both the child's (ß=0.587; p<0.001) and the family's (ß=0.506; p<0.001) OHRQoL. The results of the Manuscript #2 demonstrated that preschoolers whose parents presented low resilience, and preschoolers who presented OAB, had a negative impact on OHRQoL (ß:3.95; p=0.025) compared to those who had normal occlusion. Parental resilience did not act as a moderating factor in the association between DB and OHRQoL (p>0.005). It is concluded that the severity of ECC negatively impacted the OHRQoL of preschoolers and their families, and the main factors associated with the severity of ECC were lower socioeconomic status, higher frequency of free sugar consumption and lower parental resilience (Manuscript #1). OAB negatively interfered with the OHRQoL of preschoolers, with this association being stronger when parental resilience was low. Therefore, parental resilience acted as a moderating factor in the relationship between OAB and OHRQoL (Manuscript # 2).

Cost-effectiveness analysis of ‘test and treat’ policy for antiretroviral therapy among heterosexual HIV population in India

Background & objectives: The World Health Organisation recommended immediate initiation of antiretroviral therapy (ART) in all adult human immunodeficiency virus (HIV) patients regardless of their CD4 cell count. This study was undertaken to ascertain the cost-effectiveness of implementation of these guidelines in India. Methods: A Markov model was developed to assess the lifetime costs and health outcomes of three scenarios for initiation of ART treatment at varying CD4 cell count <350/mm3, <500/mm3 and test and treat using health system perspective using life-time horizon. A few input parameters for this model namely, transition probabilities from one stage to another stage of HIV and incidence rates of TB were calculated from the data of Centre of Excellence for HIV treatment and care, Chandigarh; whereas, other parameters were obtained from the published literature. Total HIV-related deaths averted, HIV infections averted and incremental cost-effectiveness ratio per quality adjusted life years (QALYs) gained were calculated. Result: Test and treat intervention slowed down the progression of disease and averted 18,386 HIV-related deaths, over lifetime horizon. It also averted 16,105 new HIV infections and saved 343,172 QALYs as compared to the strategy of starting ART at CD4 cell count of 500/mm3. Incremental cost per QALY gained for the immediate initiation of ART as compared to ART at CD4 cell count of 500/mm3 and 350/mm3 was ? 46,599 and 80,050, respectively at reported rates of adherence to the therapy. Interpretation & conclusions: Immediate ART (test and treat) is highly cost-effective strategy over the past criteria of delayed therapy in India. Cost-effectiveness of this policy is largely because of reduction in the transmission of HIV

In silico study to predict promiscuous T cell and B cell-epitopes derived from the vaccine candidate antigens of Plasmodium vivax binding to MHC class-II alleles

Malaria is one of the major causes of health and disability globally, even after tremendous efforts to eradicate it. Till date no highly effective vaccine is available for its control. The primary reason for the low efficacy of vaccines is extensive polymorphism in potential vaccine candidate antigen genes and HLA polymorphisms in the human population. This problem can be resolved by developing a vaccine using promiscuous peptides to combine the number of HLA alleles. This study predicted T and B cell epitopes (promiscuous peptides) by targeting PPPK-DHPS and DHFR-TS proteins of Plasmodium vivax, using different in silico tools. Selected peptides were characterized as promiscuous peptides on the basis of their immunogenicity, antigenicity and hydrophobicity. Furthermore, to confirm their immunogenicity, these peptides were utilized for molecular modelling and docking analysis. For determining the requisite affinity with distinct HLA Class-I, and HLA Class-II alleles, only five peptides for DHFR-TS and 3 peptides for PPPK-DHPS were chosen as promiscuous peptides. The D1 peptide has the maximum binding energy with HLA alleles, according to HLA-peptide complex modelling and binding interaction analyses. These findings could lead to the development of epitope-based vaccinations with improved safety and efficacy. These epitopes could be major vaccine targets in P. vivax as they possess a higher number of promiscuous peptides. Also, the B cell epitopes possess maximum affinity towards different alleles as analyzed by docking scores. However, further investigation is warranted in vitro and in vivo.

Modelamiento in silica de la liasa organomercurial (MerB) de Pseudamanas fluarescens / In silico modeling of Pseudomonas fluoresceins organomercurial lyase (MerB) / Modelagem in silica da liase organomercurial (MerB) de Pseudamanas fluarescens

Resumen El modelamiento ¡n silíco ha sido de gran contribución en los procesos proteómicos, desarrollando estructuras de las secuencias proteicas ya existentes, que por motivos de altos costos y las diferentes tecnologías necesarias para el desarrollo de estas metodologías, se encuentran deficientes en el número de modelamientos de proteínas disponibles. Entre aquellas secuencias con carencia de estructura proteica se encuentra la proteína liasa organomercurial (MerB) de Pseudomonas /luorescens, importante en la resistencia al mercurio. En el presente artículo se analizó tanto estructural como funcionalmente la proteína MerB en Pseudomonas jluorescens, utilizando la herramienta de la química estructural "modelamiento por homología" mediante plataformas bioinformáticas, con el fin de obtener un modelo que represente la estructura 3D más precisa y que capturen las mejores variantes estructurales entre todas las posibles conformaciones de las proteínas en la familia. En este trabajo, se desarrolló un método comparativo de la secuencia estudiada con las reportadas en las bases de datos para las proteínas MerB del género Pseudomonas. Se propone un modelo tridimensional para la enzima (MerB) en P. jluorescens, mediante el modelamiento por homología, se muestra la caracterización en la estructura secundaria, terciaria, la caracterización del dominio catalítico y los motivos estructurales presentes.

Abstract In silico modeling has made a great contribution to proteomic processes, developing structures of the already existing protein sequences, which for reasons of high costs and the different technologies necessary for the development of these methodologies, are deficient in the number of models of available proteins. Among those sequences lacking protein structure is the organomercurial lyase (MerB) protein from Pseudomonas fluoresceins, important in mercury resistance. In this article, the MerB protein in Pseudomonas fluorescens was analyzed both structurally and functionally, using the structural chemistry tool "homology modeling" using bioinformatic platforms, in order to obtain a model that represents the most accurate 3D structure and that captures the best structural variants among all the possible conformations of the proteins in the family. In this work, a comparative method of the sequence studied with those reported in the databases for MerB proteins of the genus Pseudomonas was developed. A three-dimensional model for the enzyme (MerB) in P. fluorescens is proposed, through homology modeling, the characterization at the secondary and tertiary structure level, the characterization of the catalytic domain and the structural motifs present is shown.

Resumo A modelagem in silico tem dado um grande contributo para os processos proteómicos, desenvolvendo estruturas de sequências de proteínas já existentes, as quais, pelos elevados custos e pelas diferentes tecnologias necessárias ao desenvolvimento destas metodologias, são deficientes no número de modelos de proteínas disponíveis. Entre as sequências sem estrutura protéica está a proteína organomercurial liase (MerB) de Pseudomonas fluorescens, importante na resistência ao mercúrio. Neste artigo, a proteína MerB em Pseudomonas fluorescens foi analisada estrutural e funcionalmente, usando a ferramenta de química estrutural "modelagem de homologia" usando plataformas de bioinformática, a fim de obter um modelo que represente a estrutura 3D mais precisa e que capture as melhores variantes estruturais. entre todas as conformações possíveis das proteínas da família. Neste trabalho, foi desenvolvido um método comparativo da sequência estudada com aqueles relatados em bancos de dados para proteínas MerB do gênero Pseudomonas. Um modelo tridimensional para a enzima (MerB) em P. fluorescens é proposto, através de modelagem por homologia, a caracterização em nível de estrutura secundária e terciária, a caracterização do domínio catalítico e os motivos estruturais presentes são mostradas.

Estimation of lactation curves of Gyr cattle and some associated production parameters in the Colombian low tropic

Background: The Gyr breed is widely used in Colombian low tropic dairy production systems. During the last 10 years, the Asociación Colombiana de Criadores de Ganado Cebú† ASOCEBU, has been leading a dairy milk control program which led to the creation of a dataset that permits to carry out the first analysis of milk yield in Gyr cattle in the country using records from several herds. Objectives: To study milk production dynamics of Gyr cattle in the Colombian low tropic through the estimation of lactation curves and four derived production parameters: total milk yield between 5 and 305 days (TMY305), peak milk yield (PMY), days at peak (DP) and persistency (P). Methods: 13,798 daily milk yield records from 1,510 cows performing in 103 herds were used; the total number of lactations was 2,480. Four models were considered: Wood, Wiltmink, Papajcsik & Bordero, and a second-degree polynomial. Mean square error, mean absolute error, mean square error of prediction, Akaike and Bayesian information criteria were used to select the model better describing each lactation using the majority rule, that is, the model selected by most criteria was the chosen one. The shape of each fitted lactation curve was checked using basic results from calculus which permitted the classification of the estimated curves into two groups: typical and atypical; only typical functions were used to compute the four aforementioned production parameters. Results: The second-order polynomial was the model most frequently selected, while the Papajcsik & Bordero model had the lowest frequency. Average TMY305, PMY, DP and P were 3,489.86 kg, 17.28 kg, 57.17 days, and 0.83, respectively, with coefficients of variation: 0.27, 0.21, 0.41, and 0.16. Conclusions: This study permitted to identify individuals with outstanding phenotypic performance. To the best of our knowledge, this is the first study of this kind involving thousands of lactations from Gyr cows performing in several regions of Colombian low tropic.

Antecedentes: La raza Gyr es ampliamente utilizada en las lecherías de trópico bajo en Colombia. Durante los últimos 10 años, la Asociación Colombiana de Criadores de Ganado Cebú ASOCEBU, ha liderado un programa de control lechero que generó una base de datos que permite llevar a cabo el primer análisis de producción de leche de la raza Gyr en el país, considerando individuos de varias fincas. Objetivos: Caracterizar la dinámica de producción de leche de ganado Gyr en el trópico bajo colombiano mediante la estimación de curvas de lactancia y cuatro parámetros de producción derivados: producción total entre 5 y 305 días (TMY305), pico de lactancia (PMY), días al pico (DP) y persistencia (P) Métodos: Se utilizaron 13.798 registros de producción diaria de leche de 1.510 vacas provenientes de 103 fincas, el total de lactancias fue 2.480. Se consideraron cuatro modelos: Wood, Wiltmink, Papajcsik & Bordero, y un polinomio de segundo grado. Los criterios usados para elegir el modelo que mejor describió cada lactancia fueron: error cuadrático medio, error absoluto medio, error cuadrático medio de predicción, criterio de información de Akaike y criterio de información Bayesiano. Se utilizó el criterio de mayoría, esto es, el modelo seleccionado fue aquel elegido por más criterios. La forma de cada una de las curvas de lactancia estimadas fue chequeada utilizando resultados básicos del cálculo, esto permitió clasificar las curvas estimadas en dos grupos: típicas y atípicas; solamente las curvas típicas fueron empleadas para calcular los cuatro parámetros antes mencionados. Resultados: El polinomio de segundo grado fue el modelo que se seleccionó con mayor frecuencia, mientras que el modelo Papajcsik & Bordero tuvo la menor frecuencia. Los promedios para TMY305, PMY, DP y P fueron 3.489,86 kg, 17,28 kg, 57,17 días, y 0,83, respectivamente, con coeficientes de variación 0,27, 0,21, 0,41 y 0,16 Conclusiones: Este estudio permitió identificar individuos con desempeño fenotípico sobresaliente. De acuerdo al estado del arte, este es el primer estudio de este tipo que considera miles de lactancias de vacas Gyr provenientes de varias regiones del trópico bajo colombiano.

Antecedentes: Gir é uma raça Bos indicus amplamente utilizada em sistemas de produção leiteira no trópico baixo Colombiano. A Asociación Colombiana de Criadores de Ganado CebúASOCEBU, lidera um programa de controle de leite nos últimos 10 anos, o que permitiu à coleta de um conjunto de dados para realizar a primeira análise de produção de leite em bovinos Gir no país com informações de vários rebanhos. Objetivo: Estudar a dinâmica da produção de leite por meio da estimativa das curvas de lactação e quatro parâmetros de produção derivados: produção total de leite entre 5 e 305 dias (TMY305), produção de leite no pico de lactação (PMY), dias em produção de leite no pico de lactação (DP) e persistência (P). Métodos: Foram utilizados 13.798 registros de produção diária de leite de 1.510 vacas de 103 fazendas , totalizando 2.480 lactações. Foram considerados quatro modelos: Wood, Wiltmink, Papajcsik & Bordero e um polinômio de segundo grau. Para selecionar o modelo que melhor descreve cada lactação foram utilizados os seguintes critérios: erro quadrado médio, erro absoluto médio, e erro quadrado médio de predição. O modelo selecionado pela maioria dos parâmetros, de acordo com os critérios de informação de Akaike e Bayesiano, foi o escolhido. A forma de cada curva de lactação ajustada foi verificada utilizando os resultados básicos do cálculo, isso permitiu classificar as curvas estimadas em dois grupos: típico e atípico, e apenas funções típicas foram utilizadas para calcular os quatro parâmetros de produção acima mencionados Resultados: O polinômio de segunda ordem foi o modelo mais frequentemente selecionado, enquanto o modelo Papajcsik & Bordero apresentou a menor frequência. A média de TMY305, PMY, DP e P foram 3.489,86 kg, 17,28 kg, 57,17 d e 0,83, respectivamente, com coeficientes de variação de 0,27, 0,21, 0,41 e 0,16. Conclusões: Este estudo permitiu identificar indivíduos com excelente desempenho fenotípico. De acordo com a literatura atual, este é o primeiro estudo envolvendo milhares de lactações de vacas Gir em várias regiões do trópico baixo colombiano.

Thin-layer drying characteristics, modeling and quality attributes of tomato slices dried with infrared radiation heating

An Infrared dryer was used to examine the drying of tomato slices. In this investigation, the influence of infrared radiation (IR) on the rate of drying, physical quality, energy combustion of tomato was estimated at three different levels of intensity at 0.15, 0.20, and 0.35 W/cm² under different air flows of 0.5, 1, and 1.5 m/s. Tomato slices were dried with an initial moisture content of 19.7 to 0.17 g water/g dry solids by infrared drying. The moisture content and drying rates are found to be dramatically affected by infrared density. An increase in the drying rate and a decrease in the drying period occurred with increasing infrared intensity. A decrease in energy consumption was detected with the increase of radiation intensity. The results clarified that the shrinkage ratio increased with increasing infrared intensity. The rehydration ratio raised with the increase in radiation intensity. The change in the colour difference of dried slices increased with an increase in radiation intensity. The models were in comparison using (R²) coefficient of determination, modelling efficiency (EF), and (χ²) reduced chi-square. Midilli model was fit for simulation of all drying conditions and could be used to estimate tomato moisture content at any time during the infrared drying process.

Development of a large-scale rainfall simulator for urban hydrology research / Desenvolvimento de um simulador de chuva de grande escala para pesquisa em hidrologia urbana

ABSTRACT This work presented the development and testing of a large-scale rainfall simulator (LSRS) to be used as a research tool on rainfall-runoff and associated transport processes in urban areas. The rainfall simulator consists of a pressurized water supply system which supplies a set of 16 full-cone nozzles. Artificial rainfall with different rainfall intensities can be produced over an area of 100 m2 in a V shape. The assembly is housed in a tailor-made acrylic structure to eliminate the influence of wind and natural rainfall. Runoff is measured and collected at the outlet of the drainage basin, from where it is pumped to a storage tank that enables the reuse of water. Runoff hydrographs and pollutographs are presented as examples of possible outcomes from this facility. The LSRS is showed to be able to reproduce the rainfall-runoff and pollutant transport processes under simulated rainfall events with intensity and spatial uniformity similar to other experiments described in the literature.

RESUMO Este trabalho apresentou o desenvolvimento e teste de um simulador de chuva em larga escala (large-scale rainfall simulator — LSRS) para utilização em pesquisa sobre o processo de chuva-vazão e processos associados em áreas urbanas. O simulador é composto por um sistema pressurizado de abastecimento de água que abastece um conjunto de 16 bicos aspersores. Chuvas artificiais com diferentes intensidades de precipitação podem ser produzida sobre uma bacia de drenagem com área de 100.0 m2 em forma de V. O simulador é protegido por uma estrutura em acrílico que elimina a influência do vento e da chuva natural. A vazão é medida e coletada no exutório da bacia de drenagem, de onde é bombeada para um reservatório de armazenamento que permite a reutilização da água. Hidrogramas de vazão e polutogramas são apresentados como exemplos de possíveis resultados de ensaios a serem realizados com este equipamento. O LSRS demonstrou ser possível reproduzir o processo de chuva-vazão e processos associados sob eventos de chuva simulada com intensidade e distribuição espacial semelhantes a outros experimentos descritos na literatura.

Calibração do modelo hidrológico SWMM para a bacia do ribeirão vai e volta — Poços de Caldas, Minas Gerais / Calibration of SWMM's hydrological model for the watershed vai e volta stream — Poços de Caldas, Minas Gerais

RESUMO A impermeabilização de áreas em centros urbanos, resultante do processo de ocupação desordenada do solo, contribui para o aumento e a aceleração do escoamento superficial e, consequentemente, para a ocorrência de enchentes e inundações em bacias urbanas. Nesse contexto, atualmente, modelos hidrológicos vêm sendo empregados no desenvolvimento de políticas públicas de gestão das águas urbanas, com vistas à drenagem urbana sustentável. O presente trabalho teve como objetivo usar um modelo hidrológico para a bacia do ribeirão Vai e Volta, localizada no município de Poços de Caldas, Minas Gerais, para simular o hidrograma de cheia em um canal urbano. Utilizou-se o software Storm Water Management Model (SWMM) calibrando o modelo a dados de chuva e vazão medidos. Realizou-se a calibração manual do modelo para dois eventos de precipitação com a obtenção do coeficiente de eficiência de Nash-Sutcliffe (NSE) médio de 0,73 e erros da vazão de pico e do volume escoado inferiores a 15%. O modelo foi validado para outros três eventos distintos e obteve-se ajuste NSE médio de 0,79 e erros da vazão de pico e do volume escoado inferiores a 5%.

ABSTRACT The waterproofing of areas in urban centers, resulting from the disorderly occupation of the soil, contributes to increase and accelerate the runoff and, consequently, to the occurrence of floods and inundation in urban watersheds. In this context, hydrological models are currently being used in the development of public policies for urban water management, related to sustainable urban drainage. The present work aimed to use a hydrological model for the watershed of the Vai e Volta stream, located in the city of Poços de Caldas, Minas Gerais, to simulate the flood hydrograph in an urban open channel. The Storm Water Management Model (SWMM) software was used, calibrating the model to measured rainfall and flow data. The model was manually calibrated for two rainfall events with an average Nash-Sutcliffe coefficient (NSE) of 0.73 and errors in peak flow and runoff volume below 15%. The model was validated for three other distinct events and an average NSE adjustment of 0.79 was obtained and errors in peak flow and runoff volume below 5%.

Video Modelling to Improve Hand Dexterity in Students with Learning Disabilities: Special Education Teachers' Perspectives (Permodelan Video Bagi Meningkatkan Kecekatan Tangan Murid Dengan Masalah Pembelajaran: Persepsi Guru Pendidikan Khas) / Jurnal Sains Kesihatan Malaysia

@#Proficient hand dexterity (HD) may help students with learning disabilities (LDs) perform various hand tasks efficiently. Video modelling (VM) is a strategy that uses a model to improve desired skills. However, the limited study focuses on VM to improve HD among students with LDs. Therefore, this study explores VM implementation in the learning and teaching process to improve the HD of students with LDs. Five Special Education (SE) teachers who taught the Hand Manipulative Component lessons in two different states were purposefully selected and invited to participate in this study. A one-toone interview was conducted with individual SE teachers. The interview sessions were audio-recorded and transcribed verbatim, and the data was analysed through thematic analysis. Rigorous approaches were performed to ensure the findings' trustworthiness, such as triangulation, member checking, and an audit trail. Four key themes emerged: conventional learning and teaching methods, challenges faced by students with LDs in improving HD, and the advantages of implementing VM in learning and teaching to improve HD and develop a video module. This study suggests SE teachers can implement VM in their learning and teaching processes to improve the HD performance of students with LDs. This current study concludes that VM can be a supportive strategy in the teaching process to improve HD performance among students with LDs.

Provincial differentials of the effect of internal migration on teenage fertility in South Africa

This study investigated the association between internal migration and teenage fertility in South Africa. Data were from the 2007 and 2016 South African community surveys, N2007= 89800 and N2016=239733, age range 12 to 19, black teenagers= 81.5% and 89.4%, respectively. Results showed that between 2007 and 2016 internal migration levels decreased by 2% nationally, but increased for Gauteng, Western Cape and KwaZulu Natal provinces. Teenage fertility levels decreased in all provinces except the Northern Cape in the study period. In both years teenage fertility was observed at higher levels among girls that were older, heads of households, and who were in secondary schooling. Random-intercept multilevel binary logistic regression revealed that the risk of teenage fertility differed between more rural and urban provinces. In provinces that were predominantly rural the risk of teenage pregnancy increased as community-levels of internal migration increased while the risk decreased as internal migration increased in provinces that were predominantly urban. Findings suggest that the effects of internal migration on teenage pregnancy are largely dependent on the local context making it necessary to create interventions that are context-specific at sub-national levels.

Using signalling theory to assess the Government of Ghana's risk communication during the COVID-19 pandemic

Background: The proliferation of information through social media and on other communication networks during the corona virus disease 2019 (COVID-19) era altered information transfer in many countries. The content of the messages from government officials, media coverage and alternative narratives, affected the level of compliance in adhering to the various health protocols amongst the public. Aim: This article aimed to determine the relationship between the message used, media coverage, alternative narratives, the public's attitude towards staying at home and their commitment to stay at home during the COVID-19 pandemic campaign period in Ghana. Setting: A total of 352 respondents was sampled from the Kumasi metropolis. Methods: A survey sample strategy and a convenience sampling technique were used while structural equation modelling with Partial least square (PLS) version 3.0 was used for the analysis. Results: The study revealed that the nature of media coverage employed and the alternative narratives had a significant positive effect on the attitude of the respondents, whilst the content of the message had insignificant effects on the attitude of the public. Finally, the attitude of the people had a significant positive influence on their respective commitment to stay home. Conclusion: Developing countries in Africa need to fight pandemics using purely subsidised health officials or directorates rather than have government-appointed health experts and officials spearheading activities during a pandemic.

Drivers of contraceptive use choice in Zambia

Modern approaches of birth control have emerged as broadly accepted family planning methods in replacement of traditional alternatives. However, the effectiveness of modern contraceptives has been challenged by serious side effects, either experienced or expected, with inhibiting consequences on the acceptability and utilisation of family planning service. This paper disentangles the drivers of none-use, traditional and modern contraceptive use in Zambia using the 2018 Zambian Demographic Health Surveys (DHS) data. The Conditional logit choice modelling technique is employed to account not only for the differences in alternative contraceptive options but also the socioeconomic and demographic characteristics of individual woman making the choice. Empirical results indicate that educated, older and poorer women are likely to adopt the traditional contraceptive methods whereas employed women are indifferent between traditional and modern birth control options. Furthermore, Christian women and those from other religions as well as women with no education prefer no birth control method. The study concludes that employment has the potential to serve as an alternative and safer birth control tool in developing countries and namely in Zambia. Therefore, government's effort to expand family planning program should mainly target non-educated women while promoting safer contraceptive methods. This can be achieved through women education and job creation. (Afr J Reprod Health 2022; 26[5]:13- 27).