Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Leishmania braziliensis Infection in BALB/c Mice: A Preclinical Study.

BACKGROUND: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. OBJECTIVE: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. MATERIALS AND METHODS: We assessed 17-DMAG's cytotoxic effect on bone marrow-derived macrophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. RESULTS: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-γ, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. CONCLUSIONS: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

Legume-rhizobia symbiosis: Translatome analysis.

Leguminous plants can establish endosymbiotic relationships with nitrogen-fixing soil rhizobacteria. Bacterial infection and nodule organogenesis are two independent but highly coordinated genetic programs that are active during this interaction. These genetic programs can be regulated along all the stages of gene expression. Most of the studies, for both eukaryotes and prokaryotes, focused on the transcriptional regulation level determining the abundance of mRNAs. However, it has been demonstrated that mRNA levels only sometimes correlate with the abundance or activity of the coded proteins. For this reason, in the past two decades, interest in the role of translational control of gene expression has increased, since the subset of mRNA being actively translated outperforms the information gained only by the transcriptome. In the case of legume-rhizobia interactions, the study of the translatome still needs to be explored further. Therefore, this review aims to discuss the methodologies for analyzing polysome-associated mRNAs at the genome-scale and their contribution to studying translational control to understand the complexity of this symbiotic interaction. Moreover, the Dual RNA-seq approach is discussed for its relevance in the context of a symbiotic nodule, where intricate multi-species gene expression networks occur.

Water deficit response in nodulated soybean roots: a comprehensive transcriptome and translatome network analysis.

BACKGROUND: Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status-whether it is nodulated or not-can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit. RESULTS: Here, we analyzed soybean roots' differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination. CONCLUSIONS: Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

Characterization of optical fibers doped with nanoparticles for distributed displacement sensing.

High-scattering optical fibers have emerged as a key component in distributed sensing systems, primarily due to their capacity to enhance signal-to-noise ratio. This paper presents an experimental characterization of optical fibers doped with oxide nanoparticles for displacement sensing. They were manufactured using the phase-separation technique and different doping compounds, including calcium, strontium, lanthanum and magnesium. The Rayleigh backscattering (RBS) signatures in time and frequency domains were acquired using an Optical Backscatter Reflectometer (OBR). The maximum representative length, backscattering gain and strain sensitivity were evaluated. The results indicate that the fiber co-doped with magnesium and erbium chlorides offered the best compromise between strain sensitivity (0.96 pm/µ ϵ) and maximum length (17 m). For conditions of single and multiple perturbations, strain saturation was reached at ≥7000 µm and <1500 µm, respectively. In addition, the results reveal that, under a condition of variable temperature (30-60 °C), the sensor response becomes significantly nonlinear over length, requiring a technique for temperature cross-sensitivity mitigation that accounts for nonlinearities in sensitivity and hysteresis.

Epidemiological Assessment of a Pediatric Palliative Care Clinic at a Brazilian Quaternary Hospital: 20 Years of Experience.

Background: The pediatric palliative care (PPC) sets up an interdisciplinary approach of chronic complex diseases throughout birth to adolescence. It encompasses countless contrasts in development and diagnosis scopes, which make this area a challenge to nonpediatric practitioners. Objective: We sought to assess the most prevalent diseases in follow-up of the PPC team. Methods: We analyzed the medical records of PPC clinic during the years 2001 and 2021 and the diagnosis of outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC. Results: The most prevalent diseases were epidermolysis bullosa (36.9%), followed by neurological Inherited Errors of Metabolism (IEM) diseases (19.0%), IEM diseases (14.3%), dysmorphological and chromosomal disorders (8.5%), skeletal disorders mainly osteogenesis imperfecta (6.9%), and liver transplantation conditions (5.5%) (p < 0.001). The less frequent conditions were external causes, such as neonatal insults or traffic accidents (2.8%), cancer (1.7%), congenital cardiopathies (1.4%), congenital infectious diseases (1.1%), gastrointestinal and hepatic conditions (0.8%), and rheumatological conditions (0.3%). The patients were older at diagnosis (6.9 years) and at PPC referral (13.2 years) than patients with epidermolysis bullosa and skeletal disorders and dysmorphological and chromosomal disorders were younger on referral. Conclusion: There are a lot of complex chronic conditions which could benefit from palliative care in pediatric setting. However, epidemiological and symptomatological assessment of the health service is necessary to provide an appropriate care to the country's reality.

Assessing the contributions of an urban population health initiative to shift political priority towards cardiovascular health: three case studies from Brazil, Mongolia and Senegal.

BACKGROUND: The urban population health initiative was designed as a multidisciplinary, multisector programme to address cardiovascular (CV) disease, specifically hypertension and its underlying causes in the cities of Ulaanbaatar, Mongolia; Dakar, Senegal; and São Paulo, Brazil. This article aims to provide an overview of the history and dynamics of CV disease policy making in the three countries, to present the policy reform contributions of the initiative and its role in the policy agenda-setting framework/process in each country and to identify the enablers and challenges to the initiative for doing so. METHODS: A qualitative case study was conducted for each setting from November 2020 to January 2021, comprised of a document review, semi-structured in-depth interviews and unstructured interviews with stakeholders involved in the initiative. The literature review included documents from the initiative and the peer-reviewed and grey literature with a total of 188 documents screened. Interviews were conducted with 21 stakeholders. Data collection and thematic analysis was guided by (i) the Kingdon multiple streams conceptual framework with the main themes being CV disease problems, policy, politics and the role of policy entrepreneurs; and (ii) the study question inquiring on the role of the urban population health initiative at the CV disease policy level and enabling and challenging factors to advancing CV disease policy. Data were thematically analysed using the Framework Method. RESULTS: Each setting was characterized by a high hypertension and CV disease burden combined with an aware and proactive political environment. Policy outcomes attributed to the initiative were updating the guidelines and/or algorithms of care for hypertension and including revised physical and nutritional education in school curricula, in each city. Overall, the urban health initiative's effects in the policy arena, were most prominent in Mongolia and Senegal, where the team effectively acted as policy entrepreneur, promoting the solutions/policies in alignment with the most pressing local problems and in strong involvement with the political actors. The initiative was also involved in improving access to CV disease drugs at primary health levels. Its success was influenced by the local governance structures, the proximity of the initiative to the policy makers and the local needs. In Brazil, needs were expressed predominantly in the clinical practice. CONCLUSIONS: This multi-country experience shows that, although the policy and political environment plays its role in shaping initiatives, often the local priority needs are the driving force behind wider change.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

An Intersectoral Approach to Hypertension Care: Solutions for Improving Blood Pressure Control in São Paulo, Brazil.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases (CVDs) and a major public health issue worldwide. In Brazil, it affects approximately 52.5% of the adult population. We describe the solutions package and the impact of a population health initiative in São Paulo city, following the CARDIO4Cities approach for the management of cardiovascular risk. METHODS: Using a design thinking approach, interventions were developed with a coalition of local and international stakeholders to address needs of patients, healthcare professionals, and the health system. The resulting solution package was checked to comply with guidelines for non-communicable disease and hypertension management. Clinical impact was measured by extracting the hypertension cascade of care-monitored, diagnosis, treatment, and control-from medical records. RESULTS: Under the leadership of the municipal health authorities, nine solutions were piloted and scaled across the city. Solutions conform with local and international best-practices. Between October 2017 and December 2021, 11,406 patient records were analyzed. Results showed a 40% increase in monitored patients (patients with at least one blood pressure, BP, measurement); reduced proportions of patients diagnosed among those with available BP measurements (72%-53%) and treated among diagnosed (93%-85%); and an improvement in controlled patients among those receiving treatment (16%-27%). CONCLUSIONS: The solution package described in this study was correlated with increased BP control. The implementation methodology and results add to the body of real-world evidence supporting population health implementation science in Brazil and beyond.

Encapsulation of pomegranate polyphenols by ionic gelation: Strategies for improved retention and controlled release.

This study aimed at producing pectin hydrogel beads by ionic gelation proce to carry pomegranate extract (PE) evaluating approaches to increase its retention and protect the polyphenols from environmental conditions that interfere in the stability and color of these compounds, such as the pH of the medium. Several strategies were tested to reduce the mass transfer and consequently increase its retention. The insertion of a filler (gelatinized starch), the employment of different concentrations from the external environment, the adsorption using blank pectin-starch beads, and the electrostatic coating using chitosan were performed. The release of entrapped compounds over time was employed to evaluate the release pattern of PE in water media. Diffusion coefficients calculated from these experiments were then used to estimate the PE release behavior. The encapsulation efficiency (EE) was significantly improved (42 % to 101 %) when equalizing the concentration of the external medium with that from the beads formulation. Furthermore, the increase in the PE concentration was proportional to the rise in the mechanical strength (MS) of the beads which indicates a modification of internal structure due to the presence of polyphenols. The adsorption was efficient in entrapping the active compound, and despite the high PE content observed for all beads (average value of 2960.26 mg of gallic acid equivalent/100 g sample), they had the lowest diffusion coefficient from the release in water media. Finally, the coating was able to reduce the release rate in most of the tests (DAB uncoated = 0.5 DAB coated), however, during the electrostatic deposition a loss of about 32 % of the phenolic compounds in the chitosan solution was observed which led to a reduced EE. Despite the obtention of retarded release, coating studies need to be improved. Some adjustments in the execution of this technique are necessary so that the losses are reduced and the process becomes viable for the use of beads in food.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. OBJECTIVE: To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. METHODS: An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. RESULTS: Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. CONCLUSION: Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

ANTECEDENTES: A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. OBJETIVO: Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. MéTODOS: Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. RESULTADOS: Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. CONCLUSãO: O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants / Consenso de especialistas brasileiros sobre o tratamento da síndrome dos espasmos infantis em lactentes

Abstract Background Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. Objective To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. Methods An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. Results Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. Conclusion Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

Resumo Antecedentes A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. Objetivo Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. Métodos Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. Resultados Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. Conclusão O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Correction: Sainz et al. Analysis of Thioredoxins and Glutaredoxins in Soybean: Evidence of Translational Regulation under Water Restriction. Antioxidants 2022, 11, 1622.

In the original publication [...].

Faceta Direta de Resina Composta utilizando Pigmentos Opacificadores para Reabilitação Estética Anterior de Dente Escurecido: Relato de Caso / Direct Composite Resin Veneer using Opacifying Pigments for Anterior Aesthetic Rehabilitation of Discolored Teeth: Case Report

O tratamento estético de dentes com alteração de cor é um grande desafio na Odontologia Restauradora. Nesse sentido, a utilização de técnicas de estratificação com resina composta associada ao uso de pigmentos opacificadores permite que seja possível restaurar por meio de uma técnica direta, que resulta em um menor desgaste da estrutura dental durante o preparo. Dessa forma, o presente trabalho apresenta um caso clínico de faceta direta de resina composta utilizando associação de três pigmentos opacificadores. Paciente do sexo masculino, 54 anos, procurou atendimento apresentando alteração de cor severa do dente 21, relato de trauma dental, tratamento endodôntico e contraindicação de novo protocolo de clareamento interno, sendo sugerido, como plano de tratamento, a restauração direta com resina composta. Para a confecção da faceta direta de resina, foi utilizada uma mistura de três opacificadores na consistência fluida. Para verificar o valor da camada aplicada da mistura, foram feitas fotografias em preto e branco. A estratificação prosseguiu com camadas de resina translúcida para a base palatina, resina opaca de dentina e resina acromática translúcida para o esmalte. Como resultado, constatou-se a função e eficácia do uso da associação de pigmentos opacificadores na resolução do caso, em seguida, foi realizada uma reavaliação após 30 dias e 7 meses do procedimento restaurador, quando verificou-se a estabilidade de cor da restauração. Concluiu-se, portanto, que a utilização da técnica de estratificação de resinas compostas associada a utilização de pigmentos opacificadores traz resultados estéticos satisfatórios e favoráveis por meio de uma técnica direta, realizada em sessão clínica única e com alta previsibilidade.

The esthetic treatment of teeth with discoloration is a major challenge in restorative dentistry. In this sense, the use of composite resin veneering techniques associated with the use of opacifying stains allows restorations to be made using a direct technique, which results in less wear to the tooth structure during preparation. Thus, the present study presents a clinical case of a direct composite resin veneer using an association of three opacifying pigments. A 54-year-old male patient presented with severe color change on the central upper left incisor, a report of dental trauma, endodontic treatment, and contraindication for a new internal bleaching protocol. In order to make the direct resin veneer, a mixture of three opacifiers in a fluid consistency was used. To check the value of the applied layer of the mixture, black and white photographs were taken. Layering proceeded with translucent resin layers for the palatal base, opaque dentin resin and translucent achromatic resin for the enamel. As a result, the function and efficacy of the use of the association of opacifying pigments was verified in the resolution of the case. A reevaluation was performed 30 days and 7 months after the restorative procedure, when the color stability of the restoration was verified. This case allows to conclude that using composite resin layering technique associated with the use of opacifying pigments brings satisfactory and favorable aesthetic results through a direct technique, performed in a single clinical session and with high predictability.

Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

MorphoMacro for in vivo and ex vivo quantitative morphometric analysis of microglia.

Microglia cells dynamically survey the central nervous system microenvironment and, in response to tissue damage inflicted by radiation therapy, disease or infection, undergo morphological and functional changes that culminate in microglia activation. Cell shape transformation can be assessed descriptively or, alternatively, it can be quantified as a continuous variable for parameters including total cell size as well as protrusion length, ramification and complexity. The purpose of the MorphoMacro method is to quantitatively profile multiple and single microglia cells using the available ImageJ platform. This method outlines the required steps and ImageJ plugins to convert fluorescence and bright-field photomicrographs into representative binary and skeletonized images and to analyze them using the MorphoMacro software plugin for multiparametric and multilevel description of microglia cell morphology in vivo and ex vivo. Overall, the protocol provides a quantitative and comprehensive tool that can be used to identify, stratify, and monitor diverse microglia morphologies in homeostatic, different disease conditions and subsequent therapeutic monitoring.

Incidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease?

OBJECTIVE: to determine the prevalence of incidental gallbladder cancer (IGBC) in cholecystectomies performed in a tertiary public hospital and to describe technical and epidemiological aspects of performing cholecystectomies for presumably benign disease. METHOD: descriptive, retrospective observational study, based on analysis of medical records of patients undergoing cholecystectomy with preoperative hypothesis of benign disease between January 2018 and January 2022. RESULTS: prevalence of gallbladder adenocarcinoma in our sample was 0.16%, similar to data in the literature. Technical aspects during cholecystectomy were also described with a frequency similar to that found in the literature. CONCLUSION: despite a rare disease, IGBC is relevant in the routine of the General Surgeon. Its diagnosis, staging and treatment directly affect the prognosis. Technical aspects during cholecystectomy are not always remembered by surgeons and can interfere with the prognosis and subsequent treatment of the patient.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Use of digital screens by adolescents and association on sleep quality: a systematic review.

This study aimed to analyze the influence of digital screen use on adolescents' quality of sleep. This systematic review was recorded on PROSPERO (CRD42020203403) and conducted according to PRISMA guidelines. Studies covering adolescents from 10 to 19 years were included without language or publication restrictions which answered the following guiding question: "Does the use of digital screen influence adolescents' quality sleep?". Article search included the following databases: (MEDLINE/PubMed), LILACS, SciELO, Scopus, EMBASE, Web of Science, IBECS, Cochrane Library, ClinicalTrials.gov, and Open Gray. The following descriptors were used: "Sleep Quality", "Screen Time", and "Adolescent". The Newcastle-Ottawa Scale (NOS) assessed the methodological quality of the cohort studies, and a modified NOS was used to assess the cross-sectional ones. In total, 2,268 articles were retrieved, of which 2,059 were selected for title and abstract reading, after duplicates were deleted. After this stage, 47 articles were selected for full reading, resulting in the 23 articles which compose this review. Excessive use of digital screens was associated with worse and shorter sleep, showing, as its main consequences, night awakenings, long sleep latency, and daytime sleepiness. The use of mobile phones before bedtime was associated with poor quality of sleep among adolescents. Our evaluation of the methodological quality of the chosen studies found seven to be poor and 16, moderate.

Analysis of Thioredoxins and Glutaredoxins in Soybean: Evidence of Translational Regulation under Water Restriction.

Soybean (Glycine max (L.) Merr.) establishes symbiosis with rhizobacteria, developing the symbiotic nodule, where the biological nitrogen fixation (BNF) occurs. The redox control is key for guaranteeing the establishment and correct function of the BNF process. Plants have many antioxidative systems involved in ROS homeostasis and signaling, among them a network of thio- and glutaredoxins. Our group is particularly interested in studying the differential response of nodulated soybean plants to water-deficit stress. To shed light on this phenomenon, we set up an RNA-seq experiment (for total and polysome-associated mRNAs) with soybean roots comprising combined treatments including the hydric and the nodulation condition. Moreover, we performed the initial identification and description of the complete repertoire of thioredoxins (Trx) and glutaredoxins (Grx) in soybean. We found that water deficit altered the expression of a greater number of differentially expressed genes (DEGs) than the condition of plant nodulation. Among them, we identified 12 thioredoxin (Trx) and 12 glutaredoxin (Grx) DEGs, which represented a significant fraction of the detected GmTrx and GmGrx in our RNA-seq data. Moreover, we identified an enriched network in which a GmTrx and a GmGrx interacted with each other and associated through several types of interactions with nitrogen metabolism enzymes.