Blend of Baru (Dipteryx alata Vog.) By-Products as Nutritive and Healthy Food Ingredients: Chemical Composition, Functional Properties and Application in Plant-Based Burger.

The chemical composition, antioxidant capacity and functional properties of mixtures of baru by-products, named baru food ingredients (BFI), were investigated and applied in a plant-based burger formulation. BFI were prepared from wasted baru by-products - partially defatted baru nut cake and baru pulp plus peel. A plant-based burger was developed and its chemical composition, antioxidant capacity, cooking and texture parameters were determined. BFI1 (50% partially defatted baru nut cake + 50% baru pulp plus peel) had the highest content of carbohydrate (31.9%), and dietary fibre (28.3%). BFI2 (75% partially defatted baru nut cake + 25% baru pulp plus peel) and BFI3 (90% partially defatted baru nut cake + 10% baru pulp plus peel) showed high concentration of protein and dietary fibre, and BFI3 had the highest protein content (29.5%). All BFI showed high concentration of total phenolics (402-443 mg GAE/100 g). Replacing textured pea protein of control burger (PPB) with 35% of BFI3 in the formulation of baru protein burger (BPB) resulted in a low-fat product (2.9%), with protein content (19.2%) comparable to the PPB (15.9%) and the commercial burger (mixed plant proteins - 16.3%). The BPB also showed a higher concentration of dietary fibre (4.9%) and phenolic compounds (128 mg GAE/100 g) than the control burger. BPB's cooking yield was the highest among the tested burgers. BPB had a softer texture when compared to other burgers. Baru food ingredients can be used as nutritive ingredients of health-promoting foods, especially in plant-based products, such as burger and meat analogues, or in hybrid meat products. BPB showed a healthy and nutritious profile.

Glucocorticoid receptor-dependent therapeutic efficacy of tauroursodeoxycholic acid in preclinical models of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models. Here, we pinpointed tauroursodeoxycholic acid (TUDCA) as an efficient therapeutic, improving the motor and neuropathological phenotype of SCA3 nematode and mouse models. Surprisingly, transcriptomic and functional in vivo data showed that TUDCA acts in neuronal tissue through the glucocorticoid receptor (GR), but independently of its canonical receptor, the farnesoid X receptor (FXR). TUDCA was predicted to bind to the GR, in a similar fashion to corticosteroid molecules. GR levels were decreased in disease-affected brain regions, likely due to increased protein degradation as a consequence of ATXN3 dysfunction being restored by TUDCA treatment. Analysis of a SCA3 clinical cohort showed intriguing correlations between the peripheral expression of GR and the predicted age at disease onset in presymptomatic subjects and FKBP5 expression with disease progression, suggesting this pathway as a potential source of biomarkers for future study. We have established a novel in vivo mechanism for the neuroprotective effects of TUDCA in SCA3 and propose this readily available drug for clinical trials in SCA3 patients.

Patentes, acesso e produção local de medicamentos: reflexões a partir de experiências no SUS / Patents, access, and local production of medicines: reflections from experiences in the SUS

Resumo Este artigo procurou contribuir para a literatura e para o debate nacional e global sobre a superação de uma polarização relacionada ao aspecto jurídico e administrativo do processo de inovação, procurando se concentrar nas patentes como um fator condicionante das trajetórias tecnológicas que viabilizam o aprendizado em âmbito produtivo. Baseou-se em um arcabouço teórico e político relacionado à inovação e ao acesso a medicamentos, especialmente quanto aos direitos de Propriedade Intelectual, e na análise crítico-reflexiva de instrumentos de Propriedade Intelectual utilizados em Parcerias para o Desenvolvimento Produtivo (PDP), desenvolvidas por um instituto de tecnologia em fármacos sintéticos, público e nacional. Os resultados demonstram a relevância da compatibilização dos direitos de patentes com a construção de uma capacidade tecnológica e de inovação no país, vinculada ao acesso universal, especialmente quando envolverem produtos que se destinam ao tratamento de doenças graves, de alta complexidade tecnológica e de alto custo. Conclui-se que, para superação da dependência tecnológica e ampliação do acesso a medicamentos no Brasil, o Estado deve buscar o equilíbrio entre os interesses públicos e privados na área da saúde, a articulação entre os instrumentos jurídicos legais existentes e o alinhamento entre suas políticas de saúde, industriais, de CT&I e Propriedade intelectual.

Abstract This article aims to contribute to the literature and to the national and global debate on overcoming the polarization related to the legal and administrative aspect of the innovation process, seeking to focus on patents as a conditioning factor of the technological trajectories that enable learning in the productive scope. It was based on a theoretical and political framework related to innovation and access to medicines, especially regarding Intellectual Property rights, and on a critical-reflexive analysis of Intellectual Property instruments used in Productive Development Partnerships (PDP), developed by a public national institute for synthetic drug technology. The results demonstrate the importance of making patent rights compatible with the construction of technological and innovation capacities in the country, which are linked to universal access, especially when they involve products that are intended to treat serious, technologically complex and high-cost diseases. In conclusion, to overcome technological dependence and expand access to medicines in Brazil, the State must seek a balance between public and private interests in the healthcare area, articulate the existing legal instruments and align its health, industry, ST&I and intellectual property policies.

Electrochemical immunosensor for point-of-care detection of soybean Gly m TI allergen in foods.

Soybean is a legume with high technological functionality, commonly used by the food industry as an ingredient in different products. However, soybean is an allergenic food whose undeclared presence in processed foods may represent a public health risk. In this work, it was developed an efficient electrochemical immunosensor, targeting the soybean trypsin inhibitor (Gly m TI) allergen using commercial anti-Gly m TI IgG, aiming at detecting/quantifying minute amounts of soybean in different food formulations. For this purpose, model mixtures of different foods (sausages, cooked-hams, biscuits) were prepared to contain known amounts of soybean protein isolate (100,000-0.1 mg kg-1) and submitted to specific thermal treatments (autoclaving, oven-cooking, baking). The electrochemical immunosensor allowed quantifying down to 0.1 mg kg-1 of soybean in the three food matrices, raw and processed (0.0012 mg of Gly m TI/kg of matrix). Accordingly, the immunosensor is suitable for detecting traces of soybean in raw, processed, and complex foods, thus protecting 99 % of soybean-allergic patients.

Análise dos fatores da infeção do local cirúrgico em doentes submetidos a cirurgia ortopédica major / Analysis of risk factors for surgical site infection in patients undergoing major orthopedic surgery / Análisis de los factores de infección del sitio quirúrgico en pacientes sometidos a cirugía ortopédica mayor

Resumo Enquadramento: A infeção do local cirúrgico afeta um terço dos doentes cirúrgicos e a incidência varia consoante múltiplos fatores. Objetivo: Analisar os fatores associados à infeção do local cirúrgico na cirurgia ortopédica major. Metodologia: Estudo transversal analítico, realizado em 589 doentes submetidos a cirurgia ortopédica major entre 2020 e 2021. Recolheu-se informação constante do Sclínico, através de grelha de registo, sobre o doente, cirurgia e cumprimento de bundles. Aprovação da Comissão de Ética (N.º 46/2022). Resultados: A frequência de infeção foi (3,9%), maioritariamente do sexo masculino (56,5%), entre os 57 e 78 anos (60,9%,) índice de massa corporal elevado (91,3%), hipertensão arterial (73,9%), tabagismo (14,09%), insuficiência cardíaca (9,3%) e tremor (33,3%). Verifica-se associação, estatisticamente significativa, entre infeção do local cirúrgico e tabagismo, insuficiência cardíaca, tremor, duração da cirurgia, tempo pós-operatório e tipo de cirurgia. Conclusão: A frequência de infeção foi significativa para os fumadores com insuficiência cardíaca, tremor, maiores tempos cirúrgicos e de internamento. Sugere-se a redução tabágica, controlo da insuficiência cardíaca e diminuição dos tempos cirúrgicos e de internamento.

Abstract Background: Surgical site infection affects one-third of surgical patients. Its incidence varies according to multiple factors. Objective: To analyze risk factors for surgical site infection in patients undergoing major orthopedic surgery. Methodology: Analytical cross-sectional study with 589 patients who underwent major orthopedic surgery between 2020 and 2021. Information on the patient, the surgery, and the compliance with bundles was collected from the Sclínico platform using a registration grid. Favorable opinion of the Ethics Committee (No. 46/2022). Results: Twenty-three participants (3.9%) developed surgical site infections. They were mostly men (56.5%), aged 57 to 78 years (60.9%,) with a high body mass index (91.3%), hypertension (73.9%), smoking habits (14.09%), heart failure (9.3%), and tremor (33.3%). A statistically significant association was found between surgical site infection and smoking, heart failure, tremor, duration of surgery, postoperative time, and type of surgery. Conclusion: The frequency of infection was significant in patients with smoking habits, heart failure, tremor, and longer surgical and hospitalization times. We recommend reducing smoking, controlling heart failure, and decreasing surgical and hospitalization times.

Resumen Marco contextual: La infección del sitio quirúrgico afecta a un tercio de los pacientes quirúrgicos y su incidencia varía en función de múltiples factores. Objetivo: Analizar los factores asociados a la infección del sitio quirúrgico en una cirugía ortopédica mayor. Metodología: Estudio transversal analítico realizado en 589 pacientes sometidos a cirugía ortopédica mayor entre 2020 y 2021. La información sobre el paciente, la cirugía y el cumplimiento de los paquetes de medidas se recogió del Sclínico mediante una plantilla de registro. Aprobado por el Comité de Ética (N.º 46/2022). Resultados: La frecuencia de infección fue del 3,9%, mayoritariamente masculina (56,5%), entre 57 y 78 años (60,9%,) con índice de masa corporal elevado (91,3%), hipertensión (73,9%), tabaquismo (14,09%), insuficiencia cardiaca (9,3%) y temblor (33,3%). Hubo una asociación estadísticamente significativa entre la infección del sitio quirúrgico y el tabaquismo, la insuficiencia cardíaca, el temblor, la duración de la intervención, el tiempo posoperatorio y el tipo de cirugía. Conclusión: La frecuencia de infección fue significativa en los fumadores con insuficiencia cardiaca, temblor y tiempos quirúrgicos y de hospitalización más largos. Se propone la reducción del tabaquismo, el control de la insuficiencia cardiaca y la reducción de los tiempos quirúrgicos y de hospitalización.

Estratégias de inovação em medicamentos e vacinas no âmbito do Ceis - modelos, mecanismos e expectativas / Innovation strategies in medicines and vaccines within the scope of CEIS - models, mechanisms, and expectations

RESUMO O artigo objetivou apresentar informações relevantes e originais sobre as estratégias de inovação utilizadas por Laboratórios Farmacêuticos Oficiais (LFO) para redução das vulnerabilidades do Sistema Único de Saúde (SUS) e capacitação produtiva e tecnológica do Complexo Econômico-Industrial da Saúde. Como métodos, foram utilizadas a revisão da literatura e a análise de dados primários oriundos de entrevistas realizadas em dois dos maiores LFO do País. Foram identificados e analisados os seus esforços e resultados em Pesquisa e Desenvolvimento (P&D) assim como a incorporação de tecnologias de medicamentos e vacinas, com destaque para as Parcerias para Desenvolvimento Produtivo (PDP). Conclui-se que, apesar de as atividades de P&D ainda precisarem avançar, benefícios foram trazidos pelos acordos de transferência de tecnologia, especialmente pelas PDP. No entanto, a capacidade industrial e tecnológica dos Institutos ainda é limitada e carente de investimentos, dificultando a acumulação e a difusão tecnológica. Dessa forma, melhorias são necessárias para que as estratégias de inovação para o SUS apresentem resultados mais efetivos e possam ser revertidos para o bem-estar da sociedade.

ABSTRACT The article aimed to present relevant and original information about the innovation strategies used by Official Pharmaceutical Laboratories (LFO) to reduce the vulnerabilities of the Brazilian Unified Health System (SUS) and the productive and technological capacity of the Health Economic-Industrial Complex. The methods used included a literature review and the analysis of primary data from interviews conducted in two of the largest LFOs in the country. Their efforts and results in Research and Development (R&D) and incorporation of medicines and vaccine technologies were identified and analyzed, with emphasis on Productive Development Partnerships (PDP). Although R&D activities still need to advance, benefits were brought about by technology transfer agreements, especially by PDPs. However, the industrial and technological capacity of the Institutes is still limited and lacks investments, which hinders technological accumulation and diffusion. Thus, improvements are necessary so that the innovation strategies for the SUS present more effective results and can be reversed to the welfare of society.

Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.

Development of a new non invasive prognostic stroke scale (NIPSS) including triage elements for sleep apnea and peripheral artery disease.

BACKGROUND: Although sleep apnea and peripheral artery disease are prognostic factors for stroke, their added benefit in the acute stage to further prognosticate strokes has not been evaluated. OBJECTIVES: We tested the accuracy in the acute stroke stage of a novel score called the Non-Invasive Prognostic Stroke Scale (NIPSS). PATIENTS AND METHODS: Prospective cohort with imaging-confirmed ischemic stroke. Clinical data, sleep apnea risk score (STOPBANG) and blood pressure measures were collected at baseline. Primary outcome was the 90-day modified Rankin Scale (mRS), with poor outcome defined as mRS 3-6. Area under the ROC curve (AUC) was calculated for NIPSS and compared to six other stroke prognostic scores in our cohort: SPAN-100 index, S-SMART, SOAR, ASTRAL, THRIVE, and Dutch Stroke scores. RESULTS: We enrolled 386 participants. After 90 days, there were 56% with poor outcome, more frequently older, female predominant and with higher admission National Institute of Health Stroke Scale (NIHSS). Four variables remained significantly associated with primary endpoint in the multivariable model: age (OR 1.87), NIHSS (OR 7.08), STOPBANG category (OR 1.61), and ankle-braquial index (OR 2.11). NIPSS AUC was 0.86 (0.82-0.89); 0.83 (0.79-0.87) with bootstrapping. When compared to the other scores, NIPSS, ASTRAL, S-SMART and DUTCH scores had good abilities in predicting poor outcome, with AUC of 0.86, 0.86, 0.83 and 0.82, respectively. THRIVE, SOAR and SPAN-100 scores were fairly predictive. DISCUSSION AND CONCLUSIONS: Non-invasive and easily acquired emergency room data can predict clinical outcome after stroke. NIPSS performed equal to or better than other prognostic stroke scales.

Exploring factors associated with complete mental health of pregnant women during the COVID-19 pandemic.

OBJECTIVE: To explore a wide range of factors associated with complete mental health (i.e., positive mental health - the presence of flourishing, and the absence of mental illness - depressive and anxious symptoms) among Portuguese pregnant women, during the COVID-19 pandemic. DESIGN: Quantitative cross-sectional study. SETTING: Data were collected through an online survey placed on social media websites targeting pregnant Portuguese adult women between October 2020 and April 2021. PARTICIPANTS: The sample comprised 207 pregnant women. RESULTS: A multivariate logistic regression model showed that higher levels of self-compassion and higher engagement in mindful self-care practices increased the likelihood of reporting complete mental health during pregnancy. CONCLUSIONS: Promoting self-compassion and mindful self-care may be particularly important in pregnant women, as these psychological factors appear to contribute to complete mental health during COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: The COVID-19 pandemic represented a demanding period for pregnant women. Our findings highlight that targeting the promotion of self-compassion and mindful self-care practices during stressful periods could significantly contribute to their overall mental health.

Adenocarcinoma de vesícula biliar: una entidad poco frecuente y mortal. A propósito de un caso / Gallbladder adenocarcinoma: a rare and fatal entity. A case report

Introducción: El adenocarcinoma de vesícula biliar es de las neoplasias digestivas con peor pronóstico; es poco común, y está asociado a una alta mortalidad. La mayoría de los diagnósticos son incidentales cuando se realiza exploración quirúrgica por sospecha de colelitiasis; encontrando malignidad en el 1 a 2% de estos casos. Produce síntomas inespecíficos, llevando a diagnósticos tardíos, empeorando así el pronóstico. Las características de esta neoplasia y el diagnóstico tardío hacen que muchas veces la resección curativa no sea posible. Caso Clínico : Paciente femenino de 45 años, quien refiere inicio de enfermedad actual (IEA) en diciembre de 2021 cuando posterior a ingesta de comida presenta dolor de aparición súbita, opresivo, de fuerte intensidad en epigastrio, intermitente. Ultrasonido abdominal (USA) reporta LOE vesicular. Se decide resolución mediante colecistectomía abierta extendida, donde se encuentra vesícula biliar (VB), con tumor en su interior que ocupa 30% de la luz, se realiza biopsia intraoperatoria, diagnosticándose ADC de vesícula. La paciente evolucionó satisfactoriamente y es egresada. En controles periódicos no hay evidencia de recidiva de la enfermedad. Conclusión : El cáncer de vesícula biliar (CVB) es una patología poco común, de difícil diagnóstico y asociado a una alta tasa de mortalidad, que produce síntomas inespecíficos por lo que es necesario un alto índice de sospecha para su diagnóstico. El manejo y conducta terapéutica depende de la extensión y el estadiaje del tumor. Es necesaria la realización de más estudios para determinar y estandarizar el manejo de esta infrecuente neoplasia(AU)

Introduction: Gallbladder adenocarcinoma is one of the digestive neoplasms with the worst prognosis; it is uncommon and is associated with high mortality. Most diagnoses are incidental when surgical exploration is performed due to suspected cholelithiasis, with malignancy found in 1 to 2% of these cases. It produces nonspecific symptoms, leading to late diagnoses, thereby worsening the prognosis. The characteristics of this neoplasm and the late diagnosis often make curative resection impossible.Clinical Case : A 45-year-old female patient who reported the onset of the current illness in December 2021. After a meal, she experienced sudden, intense, and intermittent epigastric pain. Abdominal ultrasound (US) reported gallbladder wall thickening. It was decided to perform an extended open cholecystectomy, and a tumor was found inside the gallbladder, occupying 30% of its lumen. An intraoperative biopsy was performed, diagnosing gallbladder adenocarcinoma. The patient recovered satisfactorily and was discharged. Subsequent follow-up visits have shown no evidence of disease recurrence.Conclusion : Gallbladder cancer (GBC) is a rare condition with a challenging diagnosis and a high mortality rate. It produces nonspecific symptoms, so a high index of suspicion is necessary for its diagnosis. The management and therapeutic approach depend on the tumor's extent and staging. Further studies are needed to determine and standardize the management of this uncommon neoplasm(AU)

Análise da infeção do local cirúrgico em doentes submetidos a cirurgia ortopédica major / Analysis of surgical site infection in patients undergoing major orthopaedic surgery

A Infeção do Local Cirúrgico (ILC) afeta aproximadamente um terço dos doentes submetidos a um procedimento cirúrgico e a sua incidência varia entre 2-15%, dependendo de múltiplos fatores. Objetivos: Analisar os fatores associados à Infeção do Local Cirúrgico em doentes intervencionados a Cirurgia Ortopédica Major em um Serviço de Ortopedia de uma Unidade Hospitalar do Norte entre 2020 e 2021. Metodologia: Estudo transversal analítico, realizado em 589 doentes internados, num serviço de ortopedia, para serem submetidos a cirurgia ortopédica major no período compreendido entre 2020 e 2021. Como instrumento de recolha de dados foi criada uma grelha que reúne informação do doente, da cirurgia e do cumprimento de Bundles, recorrendo à informação do sistema informático SClínico, fornecida anonimizada pelo diretor de serviço. Estes, foram inseridos e analisados no programa SPSS®, versão 26.0, pelo número de codificação atribuído, respeitando o anonimato e sigilo da informação. O estudo obteve parecer favorável da Comissão de Ética no 46/2022. Resultados: A maioria dos participantes é do sexo masculino (56,5%), com idades entre os 57 e 78 anos (60,9%), com Índice de Massa Corporal elevado (91,3%) e com Hipertensão Arterial (73,9%). Foram admitidos na véspera (83,5%) com classificação III segundo a American Association of Anesthesiology (ASA) (65,2), tempo cirúrgico até uma hora (61,5%), tendo alta até ao 7o dia (68,3%). A cirurgia mais comum foi a Prótese Total do Joelho (68,3%). A prevalência de infeção foi de 3,9%, sendo a Prótese Total da Anca responsável por 60,9% das infeções. Verifica-se diferenças estatisticamente significativas, entre Infeção do Local Cirúrgico e tabagismo, insuficiência cardíaca, tremor, duração da cirurgia, tempo pós-operatório e tipo de cirurgia (p<0,05%). Conclusão: Observamos uma frequência de Infeção do Local Cirúrgico significativa em particular na Prótese Total da Anca em doente fumadores, com insuficiência cardíaca, com tremor e maiores tempos cirúrgicos e de internamento. Sugerimos, referenciar os doentes fumadores a consultas de cessação tabágica, controlo da insuficiência cardíaca e o tremor e otimizar os tempos cirúrgicos e de internamento e a realização de outros estudos que fortaleçam estes resultados.

Surgical Site Infection affects approximately one third of patients who undergo a surgical procedure and its incidence varies between 2-15%, depending on multiple factors. Objectives: To analyze the factors associated with Surgical Site Infection in patients undergoing major orthopedic surgery in an Orthopedic Service of a Northern Hospital Unit between 2020 and 2021. Methodology: Cross-sectional analytical study, conducted on 589 patients admitted to an orthopaedic service to undergo major orthopaedic surgery between 2020 and 2021. As a data collection tool, a grid was created, gathering information about the patient, the surgery and compliance with Surgical Site Infection Prevention Bundles, using information from the SClínico computer system, provided anonymized by the service director. These were entered and analyzed in the SPSS® program, version 26.0, by the assigned coding number, respecting the anonymity and confidentiality of the information. The study obtained a favorable opinion from the Ethics Committee no. 46/2022. Results: Most participants are male (56.5%), aged between 57 and 78 years (60.9%), with high Body Mass Index (91.3%) and with Hypertension (73.9%). They were admitted the day before (83.5%) with American Association of Anesthesiology classification of III (65.2), surgical time up to one hour (61.5%), being discharged within the first 7 days (68.3%) and the most common surgery was Total Knee Replacement (68.3%). The prevalence of Surgical Site Infection was 3.9%, and total hip replacement was responsible for 60.9%. A statistically significant association was found between Surgical Site Infection and smoking, heart failure, tremor, duration of surgery, postoperative time and type of surgery (p<0.05%). Conclusion: We observed a significant frequency of Surgical Site Infection particularly in total hip prosthesis in smokers, patients with heart failure, patients with tremor and longer surgical and hospitalization times. We suggest referring smoker patients to smoking cessation consultations, control of heart failure and tremor, and optimize surgical and hospitalization times, as well as further studies to strengthen these results.

A Web-Based, Mindful, and Compassionate Parenting Training for Mothers Experiencing Parenting Stress: Results from a Pilot Randomized Controlled Trial of the Mindful Moment Program.

Objectives: Mindful Moment is a self-guided, web-based, mindful, and compassionate parenting training for postpartum mothers who experience parenting stress. We aimed to assess Mindful Moment's feasibility, acceptability, and usability, and to gather preliminary evidence of its effectiveness in reducing parenting stress and outcomes such as mindful parenting, self-compassion, depressive symptoms, anxious symptoms, dispositional mindfulness, mother's perception of infant temperament, and mother-infant bonding. Methods: This pilot randomized controlled trial (RCT) was a two-arm trial and followed the CONSORT 2010, CONSORT-EHEALTH, and CONSORT-SPI 2018 extension guidelines. A total of 292 Portuguese mothers were randomly assigned to the intervention group (n = 146) or to the waiting list control group (n = 146) and completed baseline (T1) and postintervention (T2) self-reported assessments. Results: A total of 31 mothers (21.23%) completed the Mindful Moment intervention. Most mothers evaluated the program as good or excellent (90%), considered that Mindful Moment provided them the kind of help they expected or wanted (61%), were satisfied with the help provided by the program (74.6%), would recommend it to a friend in a similar situation (86.4%), and would use it again if needed (81.4%). Regarding the program's preliminary effectiveness, mothers in the intervention group presented a greater decrease in parenting stress, a greater increase in dispositional mindfulness, and a greater decrease in their perception of the difficult temperament of their infants from T1 to T2. Conclusions: This study provides preliminary evidence of the Mindful Moment's effectiveness and suggests that it is a feasible and acceptable program for postpartum mothers experiencing parenting stress. Further research is needed to confirm these results in a larger RCT. Trial Registration: ClinicalTrials.gov (NCT04892082).

Microglial Depletion Has No Impact on Disease Progression in a Mouse Model of Machado-Joseph Disease.

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder (ND). While most research in NDs has been following a neuron-centric point of view, microglia are now recognized as crucial in the brain. Previous work revealed alterations that point to an increased activation state of microglia in the brain of CMVMJD135 mice, a MJD mouse model that replicates the motor symptoms and neuropathology of the human condition. Here, we investigated the extent to which microglia are actively contributing to MJD pathogenesis and symptom progression. For this, we used PLX3397 to reduce the number of microglia in the brain of CMVMJD135 mice. In addition, a set of statistical and machine learning models were further implemented to analyze the impact of PLX3397 on the morphology of the surviving microglia. Then, a battery of behavioral tests was used to evaluate the impact of microglial depletion on the motor phenotype of CMVMJD135 mice. Although PLX3397 treatment substantially reduced microglia density in the affected brain regions, it did not affect the motor deficits seen in CMVMJD135 mice. In addition to reducing the number of microglia, the treatment with PLX3397 induced morphological changes suggestive of activation in the surviving microglia, the microglia of wild-type animals becoming similar to those of CMVMJD135 animals. These results suggest that microglial cells are not key contributors for MJD progression. Furthermore, the impact of PLX3397 on microglial activation should be taken into account in the interpretation of findings of ND modification seen upon treatment with this CSF1R inhibitor.

Target selectivity of cholesterol-phosphatidylcholine liposome loaded with phthalocyanine for breast cancer diagnosis and treatment by photodynamic therapy.

This study investigated the ability of cholesterol-phosphatidylcholine liposomes loaded with chloride aluminum phthalocyanine (CL-AlClPc) to discriminate between healthy (MCF-10A) and neoplastic (MCF-7 and MDA-MB-231) breast cells for breast cancer diagnosis and treatment by photodynamic therapy (PDT) using a new drug delivery system consisting of CL-AlClPc. When PDT treatment was applied at an energy fluence of 700 mJ/cm², CL-AlClPc was more cytotoxic to neoplastic cells than to healthy breast cells because CL-AlClPc was better internalized by the tumor cells. An even higher fluorescence signal is expected for neoplastic cells during clinical treatment than for healthy cells, which will be useful for precise and targeted tumor cell detection. CL-AlClPc also facilitated better drug distribution and targeting of essential organelles inside the cells. This selectivity is critical for future in vivo diagnosis and treatment; it prevents side effects because it prioritizes tumor cells and tissues instead of healthy ones. The CL-AlClPc system designed herein had a small size (150 nm), low zeta potential (-6 mV), low polydispersity (0.16), high encapsulation rate efficiency (82.83%), and high shelf stability (12 months).

Ensino de Enfermagem Pré-operatório: Impacto na ansiedade da pessoa submetida a cirurgia / Preoperative Nursing Teaching: Impact on the anxiety of the person undergoing surgery

A realização de uma intervenção cirúrgica constitui uma realidade que provoca alterações significativas na vida da pessoa, podendo derivar em manifestações de ansiedade e medo. O enfermeiro, mediante a aplicação de um plano de ensino pré-operatório, poderá desempenhar um papel preponderante na melhoria das respostas de saúde. Face à problemática identificada, formulou-se a questão: ?Qual o impacto do ensino de enfermagem pré-operatório, na ansiedade da pessoa submetida a cirurgia??. Com o propósito de dar resposta, enunciaram-se os objetivos: compreender o impacto do ensino de enfermagem pré-operatório, na pessoa submetida a cirurgia; avaliar o nível de ansiedade da pessoa submetida a cirurgia, nos períodos pré e pós-operatório; e identificar a influência das variáveis: idade, sexo, estado civil, tipo de cirurgia e experiências cirúrgicas anteriores, nos níveis de ansiedade no pós-operatório. Realizou-se um estudo correlacional, quase experimental, com dois grupos de doentes adultos, a aguardar intervenção cirúrgica, numa unidade de um hospital de oncologia. O grupo experimental foi submetido a um plano de ensino de enfermagem pré-operatório e o de controlo seguiu os tramites em vigor na instituição. Aplicou-se no pré-operatório aos dois grupos um questionário de caracterização da amostra e avaliação da ansiedade estado pelo Inventário de Spielberger e no pós-operatório foi novamente aplicado o mesmo Inventário de Ansiedade e aplicou-se uma escala de avaliação de informação pré-operatória. Os principais resultados revelaram não haver diminuição da ansiedade após implementação do programa de ensino pré-operatório, todavia os doentes sentiram-se melhor informados, enfatizando a importância do ensino na satisfação das suas necessidades informativas. Conclui-se que a ansiedade do doente cirúrgico pode ser influenciada por fatores clínicos, sociais e familiares, tratando-se de uma resposta emocional variável em função de circunstâncias individuais. A informação pré-operatória responde às necessidades informativas do doente e indicia produzir ganhos em saúde.

Cerebellar neuronal dysfunction accompanies early motor symptoms in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an adult-onset, progressive ataxia. SCA3 presents with ataxia before any gross neuropathology. A feature of many cerebellar ataxias is aberrant cerebellar output that contributes to motor dysfunction. We examined whether abnormal cerebellar output was present in the CMVMJD135 SCA3 mouse model and, if so, whether it correlated with the disease onset and progression. In vivo recordings showed that the activity of deep cerebellar nuclei neurons, the main output of the cerebellum, was altered. The aberrant activity correlated with the onset of ataxia. However, although the severity of ataxia increased with age, the severity of the aberrant cerebellar output was not progressive. The abnormal cerebellar output, however, was accompanied by non-progressive abnormal activity of their upstream synaptic inputs, the Purkinje cells. In vitro recordings indicated that alterations in intrinsic Purkinje cell pacemaking and in their synaptic inputs contributed to abnormal Purkinje cell activity. These findings implicate abnormal cerebellar physiology as an early, consistent contributor to pathophysiology in SCA3, and suggest that the aberrant cerebellar output could be an appropriate therapeutic target in SCA3.

Self-compassion and mindful parenting among postpartum mothers during the COVID-19 pandemic: The role of depressive and anxious symptoms.

Self-compassion is an important psychological skill that may facilitate the adoption of a mindful way of parenting, especially during the COVID-19 pandemic. However, the association between these constructs may be explained by several variables, such as maternal psychopathological symptoms, with a well-established interference in parenting. This study aimed to compare mothers who experienced and mothers who did not experience a negative emotional impact of the COVID-19 pandemic on self-compassion, mindful parenting, postpartum depressive symptoms (PPDS) and postpartum anxious symptoms (PPAS). We also explored whether mothers' self-compassion was associated with mindful parenting and whether this relationship may be mediated by PPDS and PPAS. A sample of 977 Portuguese mothers of infants aged between zero and six months completed an online survey between December 2020 and January 2021, a period of major pandemic-related restrictions. The survey included several self-report questionnaires that assessed sociodemographic, clinical, and COVID-19 information, self-compassion, mindful parenting, PPDS and PPAS. Mothers who reported having felt that the pandemic had a negative emotional impact during their postpartum period (79.5%) presented lower levels of self-compassion and mindful parenting, and higher levels of PPDS and PPAS. Regarding the mediation model, higher levels of self-compassion were related to higher levels of mindful parenting, and this association was mediated by lower levels of PPAS. These results highlight the relevance of mothers' self-compassion for helping them feel less anxious and to adopt a mindful way of parenting in the postpartum period, particularly during the pandemic. Compassion-based interventions may be particularly important in reducing PPAS and promoting mindful parenting and should be available to postpartum mothers, especially during, but also beyond the pandemic.

O papel dos produtores públicos de medicamentos e ações estratégicas na pandemia da Covid-19 / The role of public producers of medicines and strategic actions in the Covid-19 pandemic

RESUMO Na pandemia da Covid-19, os laboratórios farmacêuticos públicos adquiriram maior visibilidade em consequência de suas iniciativas para enfrentamento da doença e manutenção dos diversos programas da assistência farmacêutica. O artigo objetivou analisar as atividades cotidianas desses laboratórios durante a pandemia, a fim de compreender seu caráter estratégico para o Sistema Único de Saúde (SUS), destacando os Institutos Butantan, Bio-Manguinhos e Farmanguinhos, haja vista o protagonismo em relação a vacinas e medicamentos. Mediante estudo de caso múltiplo, com abordagem qualitativa-descritiva, apresentou dados que indicam a mudança de perfil que vêm demonstrando nas últimas décadas. Identificaram-se as ações de maior relevância no enfrentamento da pandemia, tendo, como data de corte, julho de 2021. Como resultados, trouxe informações atuais sobre suas atividades e produtos, estágio das Parcerias para Desenvolvimento Produtivo, quadro funcional, fragilidades (internas e externas) e desafios atuais. Conclui-se pela importância dessas instituições do Estado para a garantia do acesso universal do SUS e desenvolvimento e produção de medicamentos e produtos de saúde essenciais, envolvendo desde os mais básicos até os de maior complexidade e valor agregado. Destarte, identifica-se a necessidade de uma agenda de mudanças, visando sustentabilidade em longo prazo e ampliação da contribuição para fortalecimento do Complexo Econômico-Industrial da Saúde.

ABSTRACT In the Covid-19 pandemic, public pharmaceutical laboratories gained greater visibility because of their initiatives to fight the disease and maintain the various pharmaceutical assistance programs. The article aimed to analyze their daily activities during the pandemic, to understand their strategic character for the Unified Health System (SUS), highlighting the Butantan, Bio-Manguinhos, and Farmanguinhos Institutes, given their leading role in relation to vaccines and medicines, respectively. Through a multiple case study, with a qualitative-descriptive approach, it presented data that indicate the change in profile that has been demonstrated in recent decades. The most relevant actions in combating the pandemic were identified, with the cut-off date of July 2021. As a result, it brought current information about its activities and products, stage of the Partnerships for Productive Development, staff, weaknesses (internal and external), and current challenges. It is concluded that these State Institutions are important to guarantee universal access to the SUS and the development and production of essential medicines and health products, ranging from the most basic to those with greater complexity and added value. Thus, the need for an agenda of changes is identified, aiming at long-term sustainability and expanding the contribution to strengthen the Economic-Industrial Health Complex.

Profiling Microglia in a Mouse Model of Machado-Joseph Disease.

Microglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado-Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultures and microglial cells obtained from disease-relevant brain regions of neonatal and adult CMVMJD135 mice, respectively. Machine learning models were implemented to identify potential clusters of microglia based on their morphological features, and an RNA-sequencing analysis was performed to identify molecular perturbations and potential therapeutic targets. Our findings reveal morphological alterations that point to an increased activation state of microglia in CMVMJD135 mice and a disease-specific transcriptional profile of MJD microglia, encompassing a total of 101 differentially expressed genes, with enrichment in molecular pathways related to oxidative stress, immune response, cell proliferation, cell death, and lipid metabolism. Overall, these results allowed us to define the cellular and molecular profile of MJD-associated microglia and to identify genes and pathways that might represent potential therapeutic targets for this disorder.