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BACKGROUND: Decentralization of a health system is a complex and multidimensional phenomenon that demands thorough investigation of its process logistics, predisposing factors and implementation mechanisms, within the broader socio-political environment of each nation. Despite its wide adoption across both high-income countries (HICs) and low-and-middle-income countries (LMICs), empirical evidence of whether decentralization actually translates into improved health system performance remains inconclusive and controversial. This paper aims to provide a comprehensive description of the decentralization processes in three countries at different stages of their decentralization strategies - Pakistan, Brazil and Portugal. MAIN BODY: This study employed a systematic analysis of peer-reviewed academic journals, official government reports, policy documents and publications from international organizations related to health system decentralization. A comprehensive search was conducted using reputable databases such as PubMed, Google Scholar, the WHO repository and other relevant databases, covering the period up to the knowledge cutoff date in June 2023. Information was systematically extracted and organized into the determinants, process mechanics and challenges encountered during the planning, implementation and post-decentralization phases. Although decentralization reforms have achieved some success, challenges persist in their implementation. Comparing all three countries, it was evident that all three have prioritized health in their decentralization reforms and aimed to enhance local decision-making power. Brazil has made significant progress in implementing decentralization reforms, while Portugal and Pakistan are still in the process. Pakistan has faced significant implementation challenges, including capacity-building, resource allocation, resistance to change and inequity in access to care. Brazil and Portugal have also faced challenges, but to a lesser extent. The extent, progress and challenges in the decentralization processes vary among the three countries, each requiring ongoing evaluation and improvement to achieve the desired outcomes. CONCLUSION: Notable differences exist in the extent of decentralization, the challenges faced during implementation and inequality in access to care between the three countries. It is important for Portugal, Brazil and Pakistan to address these through reinforcing implementation strategies, tackling inequalities in access to care and enhancing monitoring and evaluation mechanism. Additionally, fostering knowledge sharing among these different countries will be instrumental in facilitating mutual learning.

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OBJECTIVE: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. METHODS: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). RESULTS: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. CONCLUSION: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.

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A novel trypsin inhibitor from Cajanus cajan (TIC) fresh leaves was partially purified by affinity chromatography. SDS-PAGE revealed one band with about 15 kDa with expressive trypsin inhibitor activity by zymography. TIC showed high affinity for trypsin (Ki = 1.617 µM) and was a competitive inhibitor for this serine protease. TIC activity was maintained after 24 h of treatment at 70 °C, after 1 h treatments with different pH values, and ß-mercaptoethanol increasing concentrations, and demonstrated expressive structural stability. However, the activity of TIC was affected in the presence of oxidizing agents. In order to study the effect of TIC on secreted serine proteases, as well as on the cell culture growth curve, SK-MEL-28 metastatic human melanoma cell line and CaCo-2 colon adenocarcinoma was grown in supplemented DMEM, and the extracellular fractions were submitted salting out and affinity chromatography to obtain new secreted serine proteases. TIC inhibited almost completely, 96 to 89%, the activity of these serine proteases and reduced the melanoma and colon adenocarcinoma cells growth of 48 and 77% respectively. Besides, it is the first time that a trypsin inhibitor was isolated and characterized from C. cajan leaves and cancer serine proteases were isolated and partial characterized from SK-MEL-28 and CaCo-2 cancer cell lines. Furthermore, TIC shown to be potent inhibitor of tumor protease affecting cell growth, and can be one potential drug candidate to be employed in chemotherapy of melanoma and colon adenocarcinoma.

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Frequent droughts have led to an expansion of irrigated common bean (Phaseolus vulgaris L.) cultivation areas. An effective strategy to enhance water use efficiency and optimize crop growth is the application of silicon (Si) and potassium (K). However, the interaction between Si dosage, water regimes, and plant potassium status, as well as the underlying physiological mechanisms, remains unknown. This study aimed to assess the effects of Si doses applied via fertigation under various water regimes, in the presence and absence of potassium fertilization, on gas exchange, water use efficiency, and growth of Common beans in field conditions. Two experiments were conducted, one with and one without K supply, considering that the potassium content in the soil was 6.4 mmolc dm-3 in both experiments and a replacement dose of 50 kg ha was applied in the with K treatment, with the same treatments evaluated in both potassium conditions. The treatments comprised a 3 × 4 factorial design, encompassing three water regimes: 80% (no deficit), 60% (moderate water deficit), and 40% (severe water deficit) of soil water retention capacity, and four doses of Si supplied via fertigation: 0, 4, 8, and 12 kg ha-1. Where it was evaluated, content of photosynthetic pigments, fluorescence of photosynthesis, relative water content, leaf water potential and electrolyte extravasation, dry mass of leaves, stems and total. The optimal doses of Si for fertigation application, leading to increased Si absorption in plants, varied with decreasing soil water content. The respective values were 6.6, 7.0, and 7.1 kg ha-1 for the water regimes without deficit, with moderate water deficit, and with severe water deficit. Fertigation application of Si improved plant performance, particularly under severe water deficit, regardless of potassium status. This improvement was evident in relative water content, leaf water potential, and membrane resistance, directly impacting pigment content and gas exchange rates. The physiological effects resulted in enhanced photosynthesis in water-deficient plants, mitigating dry mass production losses. This research demonstrates, for the first time in common bean, the potential of Si to enhance irrigation efficiency in areas limited by low precipitation and water scarcity.

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ABSTRACT Objective: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. Methods: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). Results: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. Conclusion: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.

RESUMO Objetivo: Examinar a função física e a força muscular respiratória de pacientes que se recuperaram da COVID-19 grave após a alta da unidade de terapia intensiva para a enfermaria nos Dias 1 e 7 e investigar as variáveis associadas ao comprometimento funcional. Métodos: Trata-se de estudo de coorte prospectivo de pacientes adultos com COVID-19 que necessitaram de ventilação mecânica invasiva, ventilação mecânica não invasiva ou cânula nasal de alto fluxo e tiveram alta da unidade de terapia intensiva para a enfermaria. Os participantes foram submetidos aos testes Medical Research Council sum-score, força de preensão manual, pressão inspiratória máxima, pressão expiratória máxima e short physical performance battery. Os participantes foram agrupados em dois grupos conforme a necessidade de ventilação mecânica invasiva: o Grupo Ventilação Mecânica Invasiva (Grupo VMI) e o Grupo Não Ventilação Mecânica Invasiva (Grupo Não VMI). Resultados: Os pacientes do Grupo VMI (n = 31) eram mais jovens e tinham pontuações do Sequential Organ Failure Assessment mais altas do que os do Grupo VMI (n = 33). As pontuações do short physical performance battery (intervalo de zero a 12) nos Dias 1 e 7 foram 6,1 ± 4,3 e 7,3 ± 3,8, respectivamente para o Grupo Não VMI, e 1,3 ± 2,5 e 2,6 ± 3,7, respectivamente para o Grupo VMI. A prevalência de fraqueza adquirida na unidade de terapia intensiva no Dia 7 foi de 13% para o Grupo Não VMI e de 72% para o Grupo VMI. A pressão inspiratória máxima, a pressão expiratória máxima e a força de preensão manual aumentaram no Dia 7 em ambos os grupos, porém a pressão expiratória máxima e a força de preensão manual ainda eram fracas. Apenas a pressão inspiratória máxima foi recuperada (ou seja, > 80% do valor previsto) no Grupo Não VMI. As variáveis sexo feminino, e necessidade e duração da ventilação mecânica invasiva foram associadas de forma independente e negativa à pontuação do short physical performance battery e à força de preensão manual. Conclusão: Os pacientes que se recuperaram da COVID-19 grave e receberam ventilação mecânica invasiva apresentaram maior incapacidade do que aqueles que não foram ventilados invasivamente. No entanto, os dois grupos de pacientes apresentaram melhora funcional marginal durante a fase inicial de recuperação, independentemente da necessidade de ventilação mecânica invasiva. Esse resultado pode evidenciar a gravidade da incapacidade causada pelo SARS-CoV-2.

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Objetivo: compreender as concepções e práticas dos profissionais da Atenção Primária à Saúde acerca dos cuidados paliativos. Método: estudo descritivo-exploratório, de abordagem qualitativa realizado com profissionais atuantes em três Unidades Básicas em município no sul do Brasil. Os dados foram coletados em junho de 2021, mediante entrevistas presenciais, audiogravadas junto a 36 profissionais de saúde selecionados por conveniência e submetidos à análise de conteúdo, modalidade temática. Resultados: muitos profissionais da Atenção Primária, sobretudo os agentes comunitários, técnicos e auxiliares de enfermagem, possuem pouco conhecimento ou uma visão distorcida a respeito de cuidados paliativos, mas em seu cotidiano assistem pacientes e familiares. Considerações finais: embora não suficientemente preparados, os profissionais de saúde precisam estar junto, orientar e assistir usuários e familiares que necessitam de cuidados paliativos, necessitam portanto serem sensibilizados quanto a importância e benefícios dos cuidados paliativos e serem devidamente intrumentalizados para prestar essa assistência que valorize seus princípios.

Objective: to understand the conceptions and practices of Primary Health Care professionals regarding palliative care. Method: descriptive-exploratory study, with a qualitative approach carried out with professionals working in three Basic Units in a city in southern Brazil. Data were collected in June 2021, through face-to-face, audio-recorded interviews with 36 health professionals selected for convenience and subjected to content analysis, thematic modality. Results: many Primary Care professionals, especially community workers, technicians and nursing assistants, have little knowledge or a distorted view of palliative care, but in their daily lives they assist patients and families. Final considerations: although not sufficiently prepared, health professionals need to be together, guide and assist users and families who need palliative care, they therefore need to be made aware of the importance and benefits of palliative care and be properly equipped to provide this assistance that values its principles.

Objetivos: comprender las concepciones y prácticas de los profesionales de la Atención Primaria de Salud sobre los cuidados paliativos. Método: estudio descriptivo-exploratorio, con enfoque cualitativo, realizado con profesionales de tres Unidades Básicas de una ciudad de Brasil. Los datos fueron recolectados en junio de 2021, mediante entrevistas presenciales, audio grabadas, a 36 profesionales seleccionados por conveniencia y sometidos a análisis de contenido, modalidad temática. Resultados: muchos profesionales, especialmente trabajadores comunitarios, técnicos y auxiliares de enfermería, tienen pocos conocimientos o una visión distorsionada de los cuidados paliativos, pero en su vida diaria asisten a pacientes y familiares. Consideraciones finales: aunque no están suficientemente preparados, los profesionales de la salud necesitan estar juntos, orientar y asistir a los usuarios y familias que necesitan cuidados paliativos, por lo que deben ser conscientes de la importancia y los beneficios de estes Cuidados y estar adecuadamente equipados para brindar esta asistencia que valora sus principios.

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Intensive fertilization of vegetables can promote phosphorus (P) toxicity. However, it can be reversed using silicon (Si), although there is a lack of research clarifying its mechanisms of action. This research aims to study the damage caused by P toxicity to scarlet eggplant plants and whether Si can mitigate this toxicity. We evaluated the nutritional and physiological aspects of plants. Treatments were arranged in a 2 × 2 factorial design of two nutritional levels of adequate P (2 mmol L-1 of P) and toxic/excess P (8 to 13 mmol L-1 of P) combined with the absence or presence of nanosilica (2 mmol L-1 Si) in a nutrient solution. There were six replications. The excess P in the nutrient solution caused damage to scarlet eggplant growth due to nutritional losses and oxidative stress. We found that P toxicity can be mitigated by supplying Si, which decreases P uptake by 13%, improves C:N homeostasis, and increases iron (Fe), copper (Cu), and zinc (Zn) use efficiency by 21%, 10%, and 12%, respectively. At the same time, it decreases oxidative stress and electrolyte leakage by 18% and increases antioxidant compounds (phenols and ascorbic acid by 13% and 50%, respectively), and decreases photosynthetic efficiency and plant growth by 12% (by increasing 23% and 25% of shoot and root dry mass, respectively). These findings allow us to explain the different Si mechanisms used to reverse the damage caused by P toxicity to plants.

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OBJECTIVES: to analyze the association between recurrence of emergency service visits due to lack of blood pressure and/or glycemic control with sociodemographic variables and disease registration in Primary Care. METHODS: quantitative study, which consulted medical records of people who attended these services two or more times for 26 months. Descriptive statistics and multiple logistic regression models were used in analysis. RESULTS: most people did not have hypertension and/or diabetes record in their Primary Care records. The absence of this record was more frequent in males, aged between 18 and 59 years, with low education and lack of blood pressure. There was association between greater number of people seeking these services in the same year and not monitoring the chronic condition in specialized care. CONCLUSIONS: people who do not follow up hypertension and/or diabetes in Primary Care are more likely to need assistance due to blood pressure and/or glycemic management.

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Pharmaceutical chemistry has many industrial processes that must be studied and adapted to a new reality where the environment must be the focus of all production chains. Thus, new technologies that are cleaner and use renewable sources of raw materials still need to be developed and applied to materials that go to the market, and they need to reach a level that is less harmful to the environment. This applies especially in areas related to the pharmaceutical industries since chemical products are used in the production of medicines and used in many other areas of everyday life and are included in the Sustainable Development Goals proposed by the United Nations. This article intends to provide insight into some relevant topics that can stimulate researchers toward medicinal chemistry that can contribute to a sustainable future of the biosphere. This article is structured around four interconnected themes that influence how green chemistry can be important for a future where science, technology and innovation are key to mitigating climate change and increasing global sustainability.

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Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis. Norfloxacin apparent aqueous solubility using the cocrystals is also presented, with higher values being obtained for all the investigated systems when compared to the pure drug. Norfloxacin has 3 polymorphs and several solvents/hydrates, which represents a challenge for obtaining pure cocrystal forms from solvent crystallization. This challenge was successfully overcome in this work, as experimental conditions to obtain the pure cocrystals (the new ones and also norfloxacin-nicotinic acid and norfloxacin-saccharin) were established using Crystal16 equipment. This is a crucial step to envisage future scale-up procedures and therefore a valuable information for the pharmaceutical industry.

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