Host metabolomic responses in recurrent P. vivax malaria.

Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate ß-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.

Hospitalizations for ambulatory care-sensitive conditions in children, Rondônia, Brazil, 2008-2019. / Internações por condições sensíveis à atenção primária em crianças, Rondônia, Brasil, 2008-2019.

This study aimed to define the profile of hospitalizations of children in public hospitals of 52 municipalities of the state of Rondônia, Brazil. We performed an ecological time series study using secondary data provided by the Hospital Information System. The annual trend of Hospitalizations was presented by age group and health region. Linear regression was performed using the Prais-Winsten technique of the statistical package Stata, version 11.0. Hospitalizations for gastrointestinal diseases were found to be decreasing in all age groups, just as those for vaccine-preventable diseases in children aged between 1 and 9 years. Hospitalizations for skin and subcutaneous tissue diseases were increasing in all ages, as well as those caused by epilepsies in children aged 1 to 9 and those caused by diseases related to childbirth and puerperium. Health regions showed a varied hospitalization profile. A stable trend was found in the Cone Sul, Madeira-Mamoré, Café, Vale do Guaporé, and Vale do Jamari regions, whereas a declining trend was found in the Central and Zona da Mata regions. The high rates of hospitalizations for ambulatory care-sensitive conditions in children show how inefficient strategies and investments in primary care have been in the state of Acre, Brazil.

Objetivou-se caracterizar o perfil de internações de crianças na rede pública dos 52 municípios do estado de Rondônia, Brasil, no período de 2008 a 2019. Trata-se de um estudo de série temporal do tipo ecológico, com dados secundários do Sistema de Informações Hospitalares. A tendência anual das internações foi apresentada por faixa etária e regional de saúde. Foi realizada regressão linear aplicando a técnica de Prais-Winsten no pacote estatístico Stata, versão 11.0. As internações por doenças gastrointestinais tiveram declínio em todas as faixas etárias, assim como pelas doenças previníveis por imunizantes entre 1 a 9 anos. As internações por doenças de pele e tecido subcutâneo foram crescentes em todas as idades, as epilepsias em idades de 1 a 9 anos e pelas doenças relacionadas ao parto e puerpério foi crescente. As regiões de saúde apresentaram perfil de internações variável, com tendência estável nas regiões Cone Sul, Madeira-Mamoré, Café, Vale do Guaporé, Vale do Jamari; e em declínio nas regiões Central e Zona da Mata. As elevadas taxas de internações por condições sensíveis à atenção primária em crianças refletem a pouca efetividade das estratégias e dos investimentos na esfera da atenção primária no estado.

Internações por condições sensíveis à atenção primária em crianças, Rondônia, Brasil, 2008-2019 / Hospitalizations for ambulatory care-sensitive conditions in children, Rondônia, Brazil, 2008-2019

Resumo Objetivou-se caracterizar o perfil de internações de crianças na rede pública dos 52 municípios do estado de Rondônia, Brasil, no período de 2008 a 2019. Trata-se de um estudo de série temporal do tipo ecológico, com dados secundários do Sistema de Informações Hospitalares. A tendência anual das internações foi apresentada por faixa etária e regional de saúde. Foi realizada regressão linear aplicando a técnica de Prais-Winsten no pacote estatístico Stata, versão 11.0. As internações por doenças gastrointestinais tiveram declínio em todas as faixas etárias, assim como pelas doenças previníveis por imunizantes entre 1 a 9 anos. As internações por doenças de pele e tecido subcutâneo foram crescentes em todas as idades, as epilepsias em idades de 1 a 9 anos e pelas doenças relacionadas ao parto e puerpério foi crescente. As regiões de saúde apresentaram perfil de internações variável, com tendência estável nas regiões Cone Sul, Madeira-Mamoré, Café, Vale do Guaporé, Vale do Jamari; e em declínio nas regiões Central e Zona da Mata. As elevadas taxas de internações por condições sensíveis à atenção primária em crianças refletem a pouca efetividade das estratégias e dos investimentos na esfera da atenção primária no estado.

Abstract This study aimed to define the profile of hospitalizations of children in public hospitals of 52 municipalities of the state of Rondônia, Brazil. We performed an ecological time series study using secondary data provided by the Hospital Information System. The annual trend of Hospitalizations was presented by age group and health region. Linear regression was performed using the Prais-Winsten technique of the statistical package Stata, version 11.0. Hospitalizations for gastrointestinal diseases were found to be decreasing in all age groups, just as those for vaccine-preventable diseases in children aged between 1 and 9 years. Hospitalizations for skin and subcutaneous tissue diseases were increasing in all ages, as well as those caused by epilepsies in children aged 1 to 9 and those caused by diseases related to childbirth and puerperium. Health regions showed a varied hospitalization profile. A stable trend was found in the Cone Sul, Madeira-Mamoré, Café, Vale do Guaporé, and Vale do Jamari regions, whereas a declining trend was found in the Central and Zona da Mata regions. The high rates of hospitalizations for ambulatory care-sensitive conditions in children show how inefficient strategies and investments in primary care have been in the state of Acre, Brazil.

Photochemical Upconversion.

Photochemical upconversion is a process whereby two lower-energy photons are converted into a higher-energy photon by sensitized triplet-triplet annihilation. While recent interest in this process has been motivated by improving the efficiencies of solar cells, many applications are being explored. In this review, we address the underlying physicochemical phenomena that are responsible for photochemical upconversion. We review their kinetics, and the requirements for annihilators and sensitizers to design efficient upconversion systems. We discuss the spin physics of the bi-excitonic interactions and how the spin character of the triplet pairs can fundamentally limit the upconversion efficiency and give rise to the magnetic field effect on delayed photoluminescence. Finally, we address light-matter coupling phenomena that could be employed to enhance photochemical upconversion.

Flexible cloglog links for binomial regression models as an alternative for imbalanced medical data.

The complementary log-log link was originally introduced in 1922 to R. A. Fisher, long before the logit and probit links. While the last two links are symmetric, the complementary log-log link is an asymmetrical link without a parameter associated with it. Several asymmetrical links with an extra parameter were proposed in the literature over last few years to deal with imbalanced data in binomial regression (when one of the classes is much smaller than the other); however, these do not necessarily have the cloglog link as a special case, with the exception of the link based on the generalized extreme value distribution. In this paper, we introduce flexible cloglog links for modeling binomial regression models that include an extra parameter associated with the link that explains some unbalancing for binomial outcomes. For all cases, the cloglog is a special case or the reciprocal version loglog link is obtained. A Bayesian Markov chain Monte Carlo inference approach is developed. Simulations study to evaluate the performance of the proposed algorithm is conducted and prior sensitivity analysis for the extra parameter shows that a uniform prior is the most convenient for all models. Additionally, two applications in medical data (age at menarche and pulmonary infection) illustrate the advantages of the proposed models.

Descarte de antimicrobianos vencidos e/ou em desuso: estudo de caso / Disposal of expired and/or discontinued antimicrobials - case study / Descarto de antimicrobiales muertos y/o desaparecidos: estudio de casos

A temática do descarte inadequado de medicamentos e sua relevância no desenvolvimento dos mecanismos de resistência aos antibióticos são os menos debatidos na literatura. Portanto, este trabalho tem como objetivo apresentar e discutir os dados obtidos sobre o recebimento de antimicrobianos vencidos e/ou sem uso descartados no ponto de coleta de medicamentos localizado no Departamento de Ciências Farmacêuticas, da Universidade Federal de Pernambuco, Campus Recife. Ao todo foram recolhidos 50,03 kg de medicamentos, dos quais 4,12 kg eram de antimicrobianos, sendo a terceira classe farmacológica mais frequente; destes, 93,07% (n=1.948 unidades) estavam vencidos e a forma farmacêutica mais encontrada foram os comprimidos (36,32%). Entre as classes de antibióticos predominaram, em relação ao mecanismo de ação, os que inibem a síntese proteica (29,33%), e pela estrutura química, as quinolonas (17,45%). A realização do descarte adequado desses medicamentos possibilita uma redução dos impactos que esse quantitativo recolhido causaria no meio ambiente. Portanto, deve-se investir em campanhas de conscientização sobre o uso correto dos medicamentos e seguimento da prescrição médica para evitar consumo indiscriminado destes fármacos. Com base o que estabelece o Decreto n° 10.388/2020, o descarte correto de medicamentos precisa ser divulgado, para que os estabelecimentos realizem a logística reversa dessas substâncias.

The issue of inappropriate disposal of medicines and its relevance in development of mechanisms of resistance to antibiotics is the least discussed in the literature. Therefore, this work aims to present and discuss the data obtained on the receipt of expired and/or unused antimicrobials discarded at the medication collection point located in the Department of Pharmaceutical Sciences, Federal University of Pernambuco, Campus Recife. In all, 50.03 kg of drugs were collected, of which 4.12 kg were antimicrobials, being the third most frequent pharmacological class; of these, 93.07% (n=1,948 units) were expired and the most common pharmaceutical form was pills (36.32%). Among the classes of antibiotics, in terms of mechanism of action, those that inhibit protein synthesis (29.33%) and chemical structure, quinolones (17.45%) predominated. Carrying out the proper disposal of these medicines makes it possible to reduce the impacts that this collected quantity would cause on the environment. Therefore, one should invest in awareness campaigns about the correct use of medicines and follow-up of medical prescriptions to avoid indiscriminate consumption of these drugs. Based on the provisions of Decree No. 10.388/2020, the correct disposal of medicines needs to be disclosed, so that establishments carry out the reverse logistics of these substances.

La cuestión de la eliminación inadecuada de los medicamentos y su relevancia en el desarrollo de mecanismos de resistencia a los antibióticos son los menos discutidos en la literatura. Por lo tanto, este trabajo tiene el objetivo de presentar y discutir los datos obtenidos sobre la recepción de antimicrobianos perdidos y/o no utilizados desechados en el punto de recolección de medicamentos ubicado en el Departamento de Ciencias Farmacéuticas de la Universidad Federal de Pernambuco, Campus Recife. En total, se tomaron 50,03 kg de medicamentos, de los cuales 4,12 kg fueron antimicrobianos, siendo la tercera clase farmacológica más común el 93,07% (n=1.948 unidades) retrasada y la forma farmacéutica más encontrada fueron los comprimidos (36,32%). Entre las clases de antibióticos predominaron, en relación con el mecanismo de acción, las que inhiben la síntesis de proteínas (29,33%), y por la estructura química, las quinolonas (17,45%). La eliminación adecuada de estos medicamentos permite reducir el impacto que esta cantidad recolectada podría causar en el medio ambiente. Por lo tanto, se deberían invertir en campañas de sensibilización sobre el uso correcto de medicamentos y el seguimiento de las recetas médicas para evitar el consumo indiscriminado de estos medicamentos. Sobre la base del Decreto no 10.388/2020, es necesario hacer pública la eliminación correcta de los medicamentos, para que los establecimientos realicen la logística inversa de estas sustancias.

Algorithm for screening and management of locomotive syndrome in elderly individuals and development of a short version of the 25-question Geriatric Locomotive Function Scale-Portuguese.

OBJECTIVE: To develop a short version of the 25-question Geriatric Locomotive Function Scale-Portuguese and to create an algorithm for locomotive syndrome screening and management. METHODS: The 25-question Geriatric Locomotive Function Scale-Portuguese was applied to individuals aged 60 years or older seen at the Geriatrics and Gerontology Department of Universidade Federal de São Paulo, between 2016 and 2018. Items of the 25-question Geriatric Locomotive Function Scale-Portuguese were submitted to exploratory factor analysis using the principal component method. Internal consistency was investigated using Cronbach's alpha coefficient. The ROC curve was used to determine the cut-off point of the short version developed. Finally, a simple and objective algorithm was created for locomotive syndrome screening and management using the Delphi method. RESULTS: A total of 202 elderly individuals aged 61 to 101 years (mean age, 84.67 years) were evaluated. Fifteen items were excluded from the 25-question Geriatric Locomotive Function Scale-Portuguese to compose the 10-question Geriatric Locomotive Function Scale-Portuguese, a 10-item instrument with appropriate psychometric properties. A cut-off point of ten (ROC curve) was determined for potential locomotive syndrome, with 96.5% sensitivity and 86.2% specificity. A very simple algorithm was developed for locomotive syndrome screening and management. CONCLUSION: The short version (10-question) of the Geriatric Locomotive Function Scale-Portuguese has appropriate psychometric properties and provides a practical tool for detection of locomotive problems in elderly individuals.

Performance of a pharmaceutical services regionalization strategy policy in Minas Gerais, Brazil: Pre-post analysis from ERAF project.

Background: In 2016, the Brazilian state of Minas Gerais (∼20 million people), implemented the ERAF policy ("Regionalization Strategy of Pharmaceutical Services") in an effort to improve medicine procurement and distribution within primary care. We evaluated the impact of the policy on three main goals: price reductions, volume increases, and expansion of therapeutic options. Methods: We analyzed the procurement data from the Integrated System of Management of Pharmaceutical Services database in 2012 and 2018. We estimated the volume, drug mix, and expenditure indicators for all major therapeutic classes, and, in detail, for cardiovascular and nervous system drugs. We evaluated the expenditure drivers using decomposition analyses. Results: Overall, the expenditure increased by 14.5%, drug mix almost doubled, while the volume decreased by a third. Cardiovascular and neurological system drugs followed similar patterns. Decomposition analyses showed that prices and drug mix had positive effects while the volume had negative effects, resulting in an overall increase in expenditure. Conclusion: Our findings suggest that the ERAF policy cannot be considered effective as it has not fulfilled its intended purposes so far. Strategies to address the identified problems and to build a platform for a more sustainable long-lasting policy should be put in place by the government.

Fuerza muscular en pacientes adultos con insuficiencia renal crónica del Hospital Nacional y Hospital Militar en 2021

Introducción: la fuerza muscular puede disminuir en los pacientes con insuficiencia renal crónica por diversas causas. Objetivo: determinar las variables antropométricas, clínicas y la fuerza muscular en pacientes adultos con insuficiencia renal crónica. Metodología: se aplicó un diseño observacional, descriptivo, transversal. Se incluyeron varones y mujeres, mayores de 17 años, portadores de insuficiencia renal crónica que asistían al Hospital Nacional (Itauguá) y Hospital Militar (Asunción), Paraguay, entre abril y noviembre 2021. Se determinaron variables antropométricas, clínicas y laboratoriales. La fuerza muscular se midió con un dinamómetro de mano. Se utilizó un grupo de sujetos jóvenes sanos para la comparación de la fuerza muscular. Se aplicó estadística descriptiva con el programa estadístico Epi Info 7™. La investigación fue aprobada por el Comité de Ética de la Universidad Privada del Este, Paraguay. Resultados: ingresaron al estudio 119 sujetos, siendo 62 (52 %) del sexo masculino con edad media 56±15 años y 57 (48 %) del sexo femenino, con edad media 51±16 años. La media de la depuración de creatinina fue 16,4±17,9 mL/min. La etiología más común fue la asociación de hipertensión arterial y diabetes mellitus (45 %). El grupo se sujetos sanos se constituyó con 99 mujeres con edad media 25±5 años y 51 varones con edad media 26±5 años. Al comparar la fuerza entre los pacientes y los sujetos sanos se halló 66,4 % de fuerza muscular disminuida entre los portadores de insuficiencia renal crónica. Conclusión: la fuerza muscular se halla disminuida en 66,4 % de los pacientes insuficiencia renal crónica. Se recomienda la detección oportuna y el tratamiento precoz del déficit de la fuerza muscular en este grupo de pacientes.

Introduction: muscle strength may decrease in patients with chronic kidney failure due to various causes. Objective: to determine the anthropometric and clinical variables and muscle strength in adult patients with chronic kidney failure. Methodology: an observational, descriptive, cross-sectional design was applied. Men and women, older than 17 years, with chronic kidney failure who attended the National Hospital (Itauguá) and Military Hospital (Asunción), Paraguay, between April and November 2021 were included. Anthropometric, clinical and laboratory variables were determined. Muscle strength was measured with a hand dynamometer. A group of healthy young subjects was used for the comparison of muscle strength. Descriptive statistics were applied with the statistical program Epi Info 7 ™. The research was approved by the Ethics Committee of the Universidad Privada del Este, Paraguay. Results: 119 subjects entered the study, being 62 (52%) males with a mean age 56 ± 15 years and 57 (48%) females, with a mean age 51 ± 16 years. The mean creatinine clearance was 16.4 ± 17.9 mL / min. The most common etiology was the association of arterial hypertension and diabetes mellitus (45%). The healthy group included 99 women with a mean age 25 ± 5 years and 51 men with a mean age 26 ± 5 years. When comparing strength between patients and healthy subjects, 66.4% decreased muscle strength was found among patients with chronic renal failure. Conclusion: muscle strength is decreased in 66.4% of chronic kidney failure patients. Early detection and early treatment of muscle strength deficit is recommended in this group of patients.

Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure.

Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages.

Two-colour light activated covalent bond formation.

We introduce a photochemical bond forming system, where two colours of light are required to trigger covalent bond formation. Specifically, we exploit a visible light cis/trans isomerization of chlorinated azobenzene, which can only undergo reaction with a photochemically generated ketene in its cis state. Detailed photophysical mapping of the reaction efficiencies at a wide range of monochromatic wavelengths revealed the optimum irradiation conditions. Subsequent small molecule and polymer ligation experiments illustrated that only the application of both colours of light affords the reaction product. We further extend the functionality to a photo reversible ketene moiety and translate the concept into material science. The presented reaction system holds promise to be employed as a two-colour resist.

Prevalence and Factors Associated With Out-of-Pocket Pharmaceutical Expenditure Among Primary Healthcare Patients: Evidence From the Prover Project.

OBJECTIVES: This study aimed to determine the prevalence and associated factors of out-of-pocket pharmaceutical expenditure (OOPPE) among primary healthcare patients. METHODS: The study is part of the Prover Project, an exit survey conducted in 2017 in a large city (population 234 937) in Minas Gerais State, Brazil. A representative sample of patients (n = 1219) from pharmaceutical services based on primary healthcare was selected. Three components of OOPPE were assessed: the general prevalence, the types of medicines purchased (medicines for the treatment of chronic diseases, medicines for the treatment of acute diseases, or herbal medicines), and coverage by the National Health System. The factors associated with OOPPE were examined applying a modified Andersen's behavioral model of health services use. Data were analyzed using descriptive statistics and logistic regression. RESULTS: The overall prevalence of OOPPE was 77%. Most patients who had OOPPE purchased medicines to treat chronic diseases (94%). In addition, these patients purchased medicines covered by public insurance but were out of stock (85%). OOPPE was associated with enabling factors, such as higher personal income (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.02-3.62), holding health insurance (OR 1.40; 95% CI 1.01-1.95), and higher neighborhood trust (OR 1.34; 95% CI 1.01-1.79), and with need factors, that is, poorer perception of health (OR 1.63; 95% CI 1.20-2.21), multiple comorbidities (OR 1.70; 95% CI 1.18-2.46), and higher number of prescribed medicines (OR 2.84; 95% CI 1.90-4.26). CONCLUSIONS: We found a high prevalence of OOPPE, identifying individuals more likely to incur these expenses. These findings are useful to inform policy makers from the healthcare system to plan and implement the needed interventions to protect primary care patients from this financial burden.

Algorithm for screening and management of locomotive syndrome in elderly individuals and development of a short version of the 25-question Geriatric Locomotive Function Scale-Portuguese

ABSTRACT Objective To develop a short version of the 25-question Geriatric Locomotive Function Scale-Portuguese and to create an algorithm for locomotive syndrome screening and management. Methods The 25-question Geriatric Locomotive Function Scale-Portuguese was applied to individuals aged 60 years or older seen at the Geriatrics and Gerontology Department of Universidade Federal de São Paulo, between 2016 and 2018. Items of the 25-question Geriatric Locomotive Function Scale-Portuguese were submitted to exploratory factor analysis using the principal component method. Internal consistency was investigated using Cronbach's alpha coefficient. The ROC curve was used to determine the cut-off point of the short version developed. Finally, a simple and objective algorithm was created for locomotive syndrome screening and management using the Delphi method. Results A total of 202 elderly individuals aged 61 to 101 years (mean age, 84.67 years) were evaluated. Fifteen items were excluded from the 25-question Geriatric Locomotive Function Scale-Portuguese to compose the 10-question Geriatric Locomotive Function Scale-Portuguese, a 10-item instrument with appropriate psychometric properties. A cut-off point of ten (ROC curve) was determined for potential locomotive syndrome, with 96.5% sensitivity and 86.2% specificity. A very simple algorithm was developed for locomotive syndrome screening and management. Conclusion The short version (10-question) of the Geriatric Locomotive Function Scale-Portuguese has appropriate psychometric properties and provides a practical tool for detection of locomotive problems in elderly individuals.

Multiplexed Microsphere-Based Flow Cytometric Assay to Assess Strain Transcending Antibodies to Plasmodium vivax Duffy Binding Protein II Reveals an Efficient Tool to Identify Binding-Inhibitory Antibody Responders.

Malaria remains a major public health problem worldwide, and Plasmodium vivax is the most widely distributed malaria parasite. Naturally acquired binding inhibitory antibodies (BIAbs) to region II of the Duffy binding protein (DBPII), a P. vivax ligand that is critical for reticulocyte invasion, are associated with a reduced risk of clinical malaria. Owing to methodological issues in evaluating antibodies that inhibit the DBPII-DARC interaction, a limited number of studies have investigated DBPII BIAbs in P. vivax-exposed populations. Based on the assumption that individuals with a consistent BIAb response are characterized by strain-transcending immune responses, we hypothesized that detecting broadly reactive DBPII antibodies would indicate the presence of BIAb response. By taking advantage of an engineered DBPII immunogen targeting conserved DBPII neutralizing epitopes (DEKnull-2), we standardized a multiplex flow cytometry-based serological assay to detect broadly neutralizing IgG antibodies. For this study, a standard in vitro cytoadherence assay with COS-7 cells expressing DBPII was used to test for DBPII BIAb response in long-term P. vivax-exposed Amazonian individuals. Taken together, the results demonstrate that this DBPII-based multiplex assay facilitates identifying DBPII BIAb carriers. Of relevance, the ability of the multiplex assay to identify BIAb responders was highly accurate when the positivity for all antigens was considered. In conclusion, the standardized DBPII-based flow cytometric assay confirmed that DBPII-BIAb activity was associated with the breadth rather than the magnitude of anti-DBPII antibodies. Altogether, our results suggest that multiplex detection of broadly DBPII-reactive antibodies facilitates preliminary screening of BIAb responders.

Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing? / Tendência nos gastos com medicamentos neuropsiquiátricos em Minas Gerais, Brasil: há aumento da oferta de antiparkinsonianos?

Neuropsychiatric drugs are used for a wide variety of neurological and psychiatric conditions. This article aims to analyze the trend and determinants of public expenditure of these medicines in Minas Gerais, from 2010 to 2017. Data from the Integrated Materials and Services Administration System (SIAD) database were used to estimate volumes of acquisition and expenditure. A breakdown analysis was performed, and the list of purchased drugs was reviewed, and the Drug Utilization technique (DU90%) applied concerning anti-Parkinson drugs. Annual expenditure dropped by 36%, from R$ 111.7 million in 2010 to R$ 40.9 million in 2017, and the determinant factors were the falling prices and volume, associated with changes in the drug mix, which favored the acquisition, on average, of more expensive products. Higher levels of expenditure for anti-Parkinson drugs stand out, however, with a significant change in the list purchased. This study contributed to a better understanding of public spending on neuropsychiatric drugs. A reduced volume can increase the risk of shortages. Regarding anti-Parkinson drugs, there is no evidence to suggest an increased supply to the population.

Medicamentos neuropsiquiátricos são utilizados para variadas condições neurológicas e psiquiátricas. O objetivo deste artigo é analisar evolução e determinantes dos gastos públicos com esses medicamentos em Minas Gerais de 2010 a 2017. Dados do Sistema Integrado de Administração de Materiais e Serviços (SIAD) foram usados para estimar volumes de aquisição e gastos. Realizou-se análise de decomposição e, para os medicamentos antiparkinsonianos foi avaliado o elenco adquirido, aplicando-se, ainda, a técnica de Drug Utilization (DU90%). O gasto anual diminuiu 36%, passando de R$ 111,7 milhões em 2010 para R$ 40,9 milhões em 2017, tendo como fatores determinantes a queda de preços e de volume, associada às mudanças do drugmix, optando-se pela aquisição de produtos, em média, mais caros. Destaca-se o aumento dos gastos para a classe dos antiparkinsonianos, porém, com significativa mudança no elenco adquirido. Esse estudo contribuiu para um melhor entendimento dos gastos públicos com medicamentos neuropsiquiátricos. A redução do volume pode elevar o risco de desabastecimento. Com relação aos antiparkinsonianos, não há evidências que sugiram aumento da oferta para a população.

Tendência nos gastos com medicamentos neuropsiquiátricos em Minas Gerais, Brasil: há aumento da oferta de antiparkinsonianos? / Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing?

Resumo Medicamentos neuropsiquiátricos são utilizados para variadas condições neurológicas e psiquiátricas. O objetivo deste artigo é analisar evolução e determinantes dos gastos públicos com esses medicamentos em Minas Gerais de 2010 a 2017. Dados do Sistema Integrado de Administração de Materiais e Serviços (SIAD) foram usados para estimar volumes de aquisição e gastos. Realizou-se análise de decomposição e, para os medicamentos antiparkinsonianos foi avaliado o elenco adquirido, aplicando-se, ainda, a técnica de Drug Utilization (DU90%). O gasto anual diminuiu 36%, passando de R$ 111,7 milhões em 2010 para R$ 40,9 milhões em 2017, tendo como fatores determinantes a queda de preços e de volume, associada às mudanças do drugmix, optando-se pela aquisição de produtos, em média, mais caros. Destaca-se o aumento dos gastos para a classe dos antiparkinsonianos, porém, com significativa mudança no elenco adquirido. Esse estudo contribuiu para um melhor entendimento dos gastos públicos com medicamentos neuropsiquiátricos. A redução do volume pode elevar o risco de desabastecimento. Com relação aos antiparkinsonianos, não há evidências que sugiram aumento da oferta para a população.

Abstract Neuropsychiatric drugs are used for a wide variety of neurological and psychiatric conditions. This article aims to analyze the trend and determinants of public expenditure of these medicines in Minas Gerais, from 2010 to 2017. Data from the Integrated Materials and Services Administration System (SIAD) database were used to estimate volumes of acquisition and expenditure. A breakdown analysis was performed, and the list of purchased drugs was reviewed, and the Drug Utilization technique (DU90%) applied concerning anti-Parkinson drugs. Annual expenditure dropped by 36%, from R$ 111.7 million in 2010 to R$ 40.9 million in 2017, and the determinant factors were the falling prices and volume, associated with changes in the drug mix, which favored the acquisition, on average, of more expensive products. Higher levels of expenditure for anti-Parkinson drugs stand out, however, with a significant change in the list purchased. This study contributed to a better understanding of public spending on neuropsychiatric drugs. A reduced volume can increase the risk of shortages. Regarding anti-Parkinson drugs, there is no evidence to suggest an increased supply to the population.

Child mortality for avoidable causes in Rondônia: temporal series study, 2008-2018.

OBJECTIVE: To investigate the trend of infant mortality from preventable causes in children under one year of age in Rondônia from 2008 to 2018. METHOD: Epidemiological study of time series with data from the Mortality and Live Birth Information Systems, driven by STATA® version 11.0, trend measured by Prais-Winsten linear regression and autocorrelation with Durbin and Watson test. RESULTS: The infant mortality rate was 14.57 deaths / 1,000 live births, 9.14 / 1,000 due to preventable causes. Deaths decreased by 2.88% annually (95% CI: - 4.67; -1.06). However, causes that can be reduced by running immunization actions, to women during pregnancy and fetal and non-childbirth growth, have stable rates. Deaths from preventable causes in the late neonatal period were declining (-11.69%; 95% CI -19.56; -3.05). CONCLUSION: Managers need to qualify maternal and child care, considering the performance of the team of professionals in assisting the pregnant-puerperal cycle as well as improving the quality of infant mortality records in the region.

Wavelength-Gated Photochemical Synthesis of Phenalene Diimides.

Herein, we pioneer a wavelength-gated synthesis route to phenalene diimides. Consecutive Diels-Alder reactions of methylisophthalaldehydes and maleimides afford hexahydro-phenalene-1,6-diol diimides via 5-formyl-hexahydro-benzo[f]isoindoles as the intermediate. Both photoreactions are efficient (82-99 % yield) and exhibit excellent diastereoselectivity (62-98 % d.r.). The wavelength-gated nature of the stepwise reaction enables the modular construction of phenalene diimide scaffolds by choice of substrate and wavelength. Importantly, this synthetic methodology opens a facile avenue to a new class of persistent phenalenyl diimide neutral radicals, constituting a versatile route to spin-active molecules.

Child mortality for avoidable causes in Rondônia: temporal series study, 2008-2018 / Mortalidad infantil por causas evitables en Rondônia: estudio serie temporal, 2008-2018 / Mortalidade infantil por causas evitáveis em Rondônia: estudo de série temporal, 2008-2018

ABSTRACT Objective To investigate the trend of infant mortality from preventable causes in children under one year of age in Rondônia from 2008 to 2018. Method Epidemiological study of time series with data from the Mortality and Live Birth Information Systems, driven by STATA® version 11.0, trend measured by Prais-Winsten linear regression and autocorrelation with Durbin and Watson test. Results The infant mortality rate was 14.57 deaths / 1,000 live births, 9.14 / 1,000 due to preventable causes. Deaths decreased by 2.88% annually (95% CI: - 4.67; -1.06). However, causes that can be reduced by running immunization actions, to women during pregnancy and fetal and non-childbirth growth, have stable rates. Deaths from preventable causes in the late neonatal period were declining (-11.69%; 95% CI -19.56; -3.05). Conclusion Managers need to qualify maternal and child care, considering the performance of the team of professionals in assisting the pregnant-puerperal cycle as well as improving the quality of infant mortality records in the region.

RESUMEN Objetivo Investigar la tendencia de la mortalidad infantil por causas prevenibles en menores de un año en Rondônia de 2008 a 2018. Método Estudio epidemiológico de series de tiempo con datos de los Sistemas de Información de Mortalidad y Nacidos Vivos, impulsado por STATA® versión 11.0, tendencia medida por regresión lineal de Prais-Winsten y autocorrelación con la prueba de Durbin y Watson. Resultados La tasa de mortalidad infantil fue de 14,57 defunciones / 1.000 nacidos vivos, 9,14 / 1.000 por causas prevenibles. Las muertes disminuyeron en un 2,88% anual (IC del 95%: -4,67; -1,06). Sin embargo, las causas que pueden reducirse ejecutando acciones de inmunización, a las mujeres durante el embarazo y el crecimiento fetal y no durante el parto, tienen tasas estables. Las muertes por causas prevenibles en el período neonatal tardío estaban disminuyendo (-11,69%; IC del 95% -19,56; -3,05). Conclusión Es necesario que los gestores califiquen la atención materno-infantil, considerando el desempeño del equipo de profesionales en la atención al ciclo gestante-puerperal y mejorando la calidad de los registros de mortalidad infantil en la región.

RESUMO Objetivo Investigar a tendência da mortalidade infantil por causas evitáveis em crianças menores de um ano em Rondônia de 2008 a 2018. Método Estudo epidemiológico de série temporal com dados dos sistemas de Informação sobre Mortalidade e sobre Nascidos Vivos, analisados pelo STATA® versão 11.0, tendência aferida por regressão linear de Prais-Winsten e autocorrelação com teste de Durbin e Watson. Resultados A taxa de mortalidade infantil foi de 14,57 óbitos/1.000 nascidos vivos, 9,14/1.000 por causas evitáveis. Óbitos tiveram decréscimo anual de 2,88% (IC95%:-4,67; -1,06). Entretanto, causas reduzíveis por ações adequadas de imunização, à mulher na gestação e crescimento fetal e no parto, tiveram taxas estáveis. Óbitos por causas evitáveis no período neonatal tardio estiveram em declínio (-11,69%; IC95%-19, 56;-3,05). Conclusão Gestores precisam qualificar o cuidado materno-infantil, considerando a atuação da equipe de profissionais na assistência ao ciclo gravídico-puerperal bem como melhorar a qualidade dos registros de mortalidade infantil na região.

Avaliação da integralidade na atenção primária à saúde da criança na perspectiva dos cuidadores / Assessment of comprehensiveness in children's primary health care as seen by caregivers / Evaluación de la integralidad en la atención primaria de salud infantil según la perspectiva de los cuidadores

Objetivo: avaliar, sob a ótica do cuidador, o atributo da integralidade na atenção primária à saúde da criança no município de Porto Velho, Brasil. Método: estudo avaliativo, transversal realizado com 420 cuidadores de crianças atendidas em um hospital infantil em 2017. Utilizou-se o Primary Care Assessment Tool Brasil - versão criança e os dados foram analisados pelo software Statistic 13.0. A pesquisa foi aprovada pelo Comitê de Ética e Pesquisa. Resultados: na avaliação das dimensões do atributo integralidade, o escore médio dos serviços disponíveis (4,67) e dos serviços prestados (5,26) à criança mostrou baixa orientação para a atenção primária à saúde, principalmente no que tange às orientações recebidas pelos profissionais, sobre crescimento, segurança, benefícios sociais, problemas visuais e de comportamento da criança. Conclusão: o atributo integralidade na saúde da criança está presente, porém de forma fragmentada, necessitando que os serviços revejam as prioridades nos cuidados à criança junto ao familiar/cuidador.

Objective: to assess, from the caregiver's perspective, the comprehensiveness of children's primary health care in Porto Velho, Brazil. Method: in this evaluative, cross-sectional study of 420 caregivers at a children's hospital in 2017, the Primary Care Assessment Tool Brazil ­ children's version was used and data were analyzed using Statistic 13.0 software. The research was approved by a research ethics committee. Results: in evaluation of dimensions of comprehensiveness, children's services available scored an average of 4.67 and services provided, 5.26, showing poor orientation towards primary health care, particularly as regards the guidance received by health personnel on children's growth, safety, social benefits, eyesight and behavioral problems. Conclusion: comprehensive child health care is present, although fragmented, requiring that services review child care priorities with family members/caregivers.

Objetivo: evaluar, desde la perspectiva del cuidador, la integralidad de la atención primaria de salud infantil en Porto Velho, Brasil. Método: en este estudio evaluativo, transversal de 420 cuidadores en un hospital infantil en 2017, se utilizó la Herramienta de Evaluación de Atención Primaria Brasil - versión infantil y los datos se analizaron mediante el software Estadística 13.0. La investigación fue aprobada por un comité de ética en investigación. Resultados: en la evaluación de las dimensiones de integralidad, los servicios disponibles para la infancia obtuvieron un promedio de 4,67 y los servicios prestados, 5,26, mostrando una mala orientación hacia la atención primaria de salud, particularmente en lo que respecta a la orientación que recibe el personal de salud sobre el crecimiento, la seguridad, los beneficios sociales, la vista del niño y problemas de comportamiento. Conclusión: la atención integral de la salud infantil está presente, aunque fragmentada, lo que requiere que los servicios revisen las prioridades del cuidado infantil con los miembros de la familia / cuidadores.