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Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.

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Introduction: The present review aimed to systematically summarize the impacts of environmental enrichment (EE) on cerebral oxidative balance in rodents exposed to normal and unfavorable environmental conditions. Methods: In this systematic review, four databases were used: PubMed (830 articles), Scopus (126 articles), Embase (127 articles), and Science Direct (794 articles). Eligibility criteria were applied based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) strategy to reduce the risk of bias. The searches were carried out by two independent researchers; in case of disagreement, a third participant was requested. After the selection and inclusion of articles, data related to sample characteristics and the EE protocol (time of exposure to EE, number of animals, and size of the environment) were extracted, as well as data related to brain tissues and biomarkers of oxidative balance, including carbonyls, malondialdehyde, nitrotyrosine, oxygen-reactive species, and glutathione (reduced/oxidized). Results: A total of 1,877 articles were found in the four databases, of which 16 studies were included in this systematic review. The results showed that different EE protocols were able to produce a global increase in antioxidant capacity, both enzymatic and non-enzymatic, which are the main factors for the neuroprotective effects in the central nervous system (CNS) subjected to unfavorable conditions. Furthermore, it was possible to notice a slowdown in neural dysfunction associated with oxidative damage, especially in the prefrontal structure in mice. Discussion: In conclusion, EE protocols were determined to be valid tools for improving oxidative balance in the CNS. The global decrease in oxidative stress biomarkers indicates refinement in reactive oxygen species detoxification, triggering an improvement in the antioxidant network.

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The Brazilian Unified Health System provides universal health care access without regard to sexual orientation and gender identity. We conducted a nationwide study with a cross-sectional design and intentional sampling methods to investigate factors associated with Basic Health Unit (BHU) use by the LGBTQIA+ community. Data were collected via a questionnaire available through social networks. Statistical analysis included Poisson regression with robust variance. A total of 603 LGBTQIA+ community members participated in the study, of whom 417 (69.2%) had visited a BHU in the last year. The factors "transgender woman" and "self-rated health status as very good/good/fair" increased the probability of BHU use in the last year by 10% (PR: 1.10; 95% CI: 1.00-1.20) and 9% (PR = 1.09; 95% CI: 1.01-1.18), respectively. "Not suffering sexual orientation-related discrimination at a BHU" and "Not suffering discrimination by a receptionist or waiting room worker" increased the probability of use by 28% (PR = 1.28; 95% CI: 1.22-1.34) and 22% (PR = 1.22; 95% CI: 1.14-1.30), respectively. Our study supports evidence that access to primary health care services in Brazil can be influenced by the social determinants gender identity and sexual discrimination.

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BACKGROUND: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments. AIM: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD. DESIGN: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks. METHOD: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators. RESULTS: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations. CONCLUSION: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD.

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An advantageous and original synthesis of fentanyl is described. This new approach includes two efficient continuous flow reductive aminations achieved via photoredox catalysis and a final batch acylation. A telescoped protocol for the two photocatalyzed steps is also presented, and overall, this protocol provides improved sustainability, significant efficiency, reduced temperatures and reaction times, and is functional for scaling up this relevant active pharmaceutical ingredient (API).

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OBJECTIVE: To evaluate the association between the incidence of delirium in the intensive care unit and quality of life 1 month after hospital discharge. METHODS: This was a prospective cohort study conducted in the intensive care units of two medium-complexity hospitals from December 2015 to December 2016. Delirium was identified using the Confusion Assessment Method for the Intensive Care Unit scale. At the time of hospital discharge, functional capacity and cognition were assessed with the Barthel index and the Mini Mental State Examination, respectively. Thirty days after patient discharge, the World Health Organization Quality of Life-BREF questionnaire was administered by telephone. RESULTS: A total of 216 patients were included. Delirium was identified in 127 (58.8%) of them. Patients with delirium exhibited greater functional dependence (median Barthel index 50.0 [21.2 - 70.0] versus 80.0 [60.0 - 95.0]; p < 0.001) and lower cognition (Mini Mental State Examination score 12.9 ± 7.5 versus 20.7 ± 9.8; p < 0.001) at hospital discharge. There was no difference in any of the quality-of-life domains evaluated 1 month after hospital discharge between patients with and without delirium. CONCLUSION: Our findings suggest that patients with delirium in the intensive care unit do not have worse quality of life 1 month after hospital discharge, despite presenting greater cognitive impairment and functional disability at the time of hospital discharge.

OBJETIVO: Avaliar a associação entre a incidência de delirium na unidade de terapia intensiva e qualidade de vida 1 mês após a alta hospitalar. MÉTODOS: Trata-se de estudo de coorte prospectivo desenvolvido em unidades de terapia intensiva de dois hospitais de média complexidade durante o período de dezembro de 2015 a dezembro de 2016. Delirium foi identificado por meio da escala Confusion Assessment Method for the Intensive Care Unit. No momento da alta hospitalar, foram avaliadas capacidade funcional e cognição por meio do índice de Barthel e da escala de Mini Exame do Estado Mental, respectivamente. Após 30 dias da alta hospitalar do paciente, por meio de contato telefônico, aplicou-se o questionário World Health Organization Quality of Life-Bref. RESULTADOS: Foram incluídos 216 pacientes. Delirium foi identificado em 127 (58,8%) deles. Os pacientes com delirium apresentaram maior dependência funcional (mediana do índice de Barthel 50,0 [21,2 - 70,0] versus 80,0 [60,0 - 95,0]; p < 0,001) e menor cognição (escore do Mini Exame do Estado Mental 12,9 ± 7,5 versus 20,7 ± 9,8; p < 0,001) na alta hospitalar. Com relação à qualidade de vida, avaliada 1 mês após alta hospitalar, não houve diferença, em nenhum dos domínios, entre os pacientes com e sem delirium. CONCLUSÃO: Nossos achados sugerem que os pacientes com delirium na unidade de terapia intensiva não apresentam piora da qualidade de vida 1 mês após a alta hospitalar, apesar de apresentarem maior prejuízo cognitivo e incapacidade funcional no momento da alta hospitalar.

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RESUMO Objetivo: Avaliar a associação entre a incidência de delirium na unidade de terapia intensiva e qualidade de vida 1 mês após a alta hospitalar Métodos: Trata-se de estudo de coorte prospectivo desenvolvido em unidades de terapia intensiva de dois hospitais de média complexidade durante o período de dezembro de 2015 a dezembro de 2016. Delirium foi identificado por meio da escala Confusion Assessment Method for the Intensive Care Unit. No momento da alta hospitalar, foram avaliadas capacidade funcional e cognição por meio do índice de Barthel e da escala de Mini Exame do Estado Mental, respectivamente. Após 30 dias da alta hospitalar do paciente, por meio de contato telefônico, aplicou-se o questionário World Health Organization Quality of Life-Bref. Resultados: Foram incluídos 216 pacientes. Delirium foi identificado em 127 (58,8%) deles. Os pacientes com delirium apresentaram maior dependência funcional (mediana do índice de Barthel 50,0 [21,2 - 70,0] versus 80,0 [60,0 - 95,0]; p < 0,001) e menor cognição (escore do Mini Exame do Estado Mental 12,9 ± 7,5 versus 20,7 ± 9,8; p < 0,001) na alta hospitalar. Com relação à qualidade de vida, avaliada 1 mês após alta hospitalar, não houve diferença, em nenhum dos domínios, entre os pacientes com e sem delirium. Conclusão: Nossos achados sugerem que os pacientes com delirium na unidade de terapia intensiva não apresentam piora da qualidade de vida 1 mês após a alta hospitalar, apesar de apresentarem maior prejuízo cognitivo e incapacidade funcional no momento da alta hospitalar.

Abstract Objective: To evaluate the association between the incidence of delirium in the intensive care unit and quality of life 1 month after hospital discharge. Methods: This was a prospective cohort study conducted in the intensive care units of two medium-complexity hospitals from December 2015 to December 2016. Delirium was identified using the Confusion Assessment Method for the Intensive Care Unit scale. At the time of hospital discharge, functional capacity and cognition were assessed with the Barthel index and the Mini Mental State Examination, respectively. Thirty days after patient discharge, the World Health Organization Quality of Life-BREF questionnaire was administered by telephone. Results: A total of 216 patients were included. Delirium was identified in 127 (58.8%) of them. Patients with delirium exhibited greater functional dependence (median Barthel index 50.0 [21.2 - 70.0] versus 80.0 [60.0 - 95.0]; p < 0.001) and lower cognition (Mini Mental State Examination score 12.9 ± 7.5 versus 20.7 ± 9.8; p < 0.001) at hospital discharge. There was no difference in any of the quality-of-life domains evaluated 1 month after hospital discharge between patients with and without delirium. Conclusion: Our findings suggest that patients with delirium in the intensive care unit do not have worse quality of life 1 month after hospital discharge, despite presenting greater cognitive impairment and functional disability at the time of hospital discharge.

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Objective: Anxiety and depression are prevalent among medical students. Brazilian medical students have higher levels of depression and lower quality of life than their U.S. counterparts, and no preventive intervention exists for this risk group in Brazil. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP), a cognitive-behavioral treatment protocol for neuroticism, was recently adapted into a single-session, preventive intervention. This study tested the impact of this protocol on psychiatric symptoms and quality of life in Brazilian medical students. Methods: In this open trial, the intervention protocol was translated and adapted to Brazilian Portuguese. Medical students over 18 years of age without psychotic symptoms, severe depressive episodes, or acute psychiatric risk were included, undergoing a psychiatric clinical interview (Mini-International Neuropsychiatric Interview [MINI]) and evaluation at baseline and at 7 and 30 days after a single-session UP that included experimental avoidance, quality of life, self-esteem, empathy, and anxiety symptom scales. A new evaluation was performed 90 days after the intervention. Results: Sixty-two students participated. Ninety days after the intervention, there were significant reductions in the number of students who met the criteria for social anxiety disorder (p = 0.013) or panic disorder (p = 0.001). There were also significant improvements in depressive symptoms (Beck Depression Inventory, p < 0.001) and quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire, p < 0.001). Conclusion: UP improved anxiety and depressive symptoms in medical students. The single-session group format could reduce costs and facilitate application. Future placebo-controlled studies are necessary to confirm these findings.

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In this work we used Density Functional Theory to simulate the molecular electronics behavior of the nitrogenous bases of human DNA under electric field effects. The results can describe some internal effects in the use of DNA-based as photoconductor or semiconductor nanodevices. For this investigation, calculations were performed to predict structural deformations, HOMO and LUMO orbitals, and thermodynamic properties of each one of the following nitrogenous bases: adenine, thymine, guanine and cytosine. All the quantities were calculated as functions of the electric field. This analysis allows us to verify the influence of the electric field in the molecular geometry of nitrogenous bases, enabling us to determine that adenine, thymine and guanine are those bases most susceptible to presenting substantial deformations when DNA is submitted to the action of an external electric field, while the molecular structure of cytosine is highly resistant to this effect.

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OBJECTIVE: Anxiety and depression are prevalent among medical students. Brazilian medical students have higher levels of depression and lower quality of life than their U.S. counterparts, and no preventive intervention exists for this risk group in Brazil. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP), a cognitive-behavioral treatment protocol for neuroticism, was recently adapted into a single-session, preventive intervention. This study tested the impact of this protocol on psychiatric symptoms and quality of life in Brazilian medical students. METHODS: In this open trial, the intervention protocol was translated and adapted to Brazilian Portuguese. Medical students over 18 years of age without psychotic symptoms, severe depressive episodes, or acute psychiatric risk were included, undergoing a psychiatric clinical interview (Mini-International Neuropsychiatric Interview [MINI]) and evaluation at baseline and at 7 and 30 days after a single-session UP that included experimental avoidance, quality of life, self-esteem, empathy, and anxiety symptom scales. A new evaluation was performed 90 days after the intervention. RESULTS: Sixty-two students participated. Ninety days after the intervention, there were significant reductions in the number of students who met the criteria for social anxiety disorder (p = 0.013) or panic disorder (p = 0.001). There were also significant improvements in depressive symptoms (Beck Depression Inventory, p < 0.001) and quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire, p < 0.001). CONCLUSION: UP improved anxiety and depressive symptoms in medical students. The single-session group format could reduce costs and facilitate application. Future placebo-controlled studies are necessary to confirm these findings.

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Maintenance of thymus homeostasis is a delicate interplay involving hormones, neurotransmitters and local microenvironmental proteins, as well as saccharides, acting on both thymocytes and stromal cells. Disturbances in these interactions may lead to alterations on thymocyte development. We previously showed that galectin-3, a ß-galactoside-binding protein, is constitutively expressed in the thymus, interacting with extracellular matrix glycoproteins and acting as a de-adhesion molecule, thus modulating thymocyte-stromal cell interactions. In this work, we aimed to investigate the participation of galectin-3 in the maintenance of thymus homeostasis, including hormonal-mediated circuits. For that, we used genetically engineered galectin-3-deficient mice. We observed that the thymus of galectin-3-deficient mice was reduced in mass and cellularity compared to wild-type controls; however, the proportions of different thymocyte subpopulations defined by CD4/CD8 expression were not changed. Considering the CD4-CD8- double-negative (DN) subpopulation, an accumulation of the most immature (DN1) stage was observed. Additionally, the proliferative capacity of thymocytes was decreased in all thymocyte subsets, whereas the percentage of apoptosis was increased, especially in the CD4+CD8+ double-positive thymocytes. As glucocorticoid hormones are known to be involved in thymus homeostasis, we evaluated serum and intrathymic corticosterone levels by radioimmunoassay, and the expression of steroidogenic machinery using real-time PCR. We detected a significant increase in corticosterone levels in both serum and thymus samples of galectin-3-deficient mice, as compared to age-matched controls. This was paralleled by an increase of gene transcription of the steroidogenic enzymes, steroidogenic acute regulatory protein (Star) and Cyp11b1 in thymus, 11ß-Hydroxysteroid Dehydrogenase (Hsd11b1) in the adrenal, and Cyp11a1 in both glands. In conclusion, our findings show that the absence of galectin-3 subverts mouse thymus homeostasis by a mechanism likely associated to intrathymic and systemic stress-related endocrine circuitries, affecting thymocyte number, proliferation and apoptosis.

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The medial patellofemoral ligament (MPFL) and the MPFL/vastus medialis obliquus complex are essential for patellar stability. Insufficiency of the MPFL can lead to altered biomechanics and patellofemoral joint contact pressure, high recurrence rate, osteochondral lesions, compromised knee function, and patellofemoral osteoarthritis. Most frequently surgical reconstruction of the MPFL is performed to address patellar instability; however, open physis and donor site morbidity can be a concern. This Technical Note presents a surgical technique to identify the insufficient MPFL and describes in detail an anatomical retensioning repair of the MPFL to restore patellar stability.

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Belief in the healing power of prayer is found in various religious traditions. Spiritually grounded clinical interventions, such as intercessory prayer (IP), need to be understood in a broader sense. This essay features the IP trials, observing the controversial relationship between inconsistent results and allegedly inadequate methods and theoretical hypothesis. A survey of the literature was conducted including publications indexed until September 2013, focusing on the trials developed in the field and on the critics about the methodological design. Recent meta-analyses and multicenter studies found inconclusive results in the investigation of IP. Clinical trials on IP present some methodological difficulties: The intervention is not fully controlled; the primary outcome is not properly defined; and the theoretical models seem inconsistent. The "non-local consciousness" model may be appropriate for studies of IP. Directions for future research: greater emphasis on the evaluation of the effectiveness of this intervention in animal models; selection of subjects and healers who have previous connection; considering the hypothesis of non-local consciousness in the study design.

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