One touch is all it takes: the supramolecular interaction between ubiquitin and lanthanide complexes revisited by paramagnetic NMR and molecular dynamics.

The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.

Navigating Amaryllidaceae Alkaloids: Bridging Gaps and Charting Biosynthetic Territories - A Comprehensive Review.

Amaryllidaceae alkaloid (AAs) biosynthesis has garnered significant attention in recent years, particularly with the commercialisation of galanthamine as a treatment for the symptoms of Alzheimer's disease. A significant amount of research work over the last 8 decades has focused on the understanding of AA biosynthesis, starting from early radiolabelling studies to recent multi-omics analysis with modern biotechnological advancements. Those studies enabled the identification of hundreds of metabolites, the characterisation of biochemical pathway, an understanding of the environmental stimuli, and of the molecular regulation of these pharmaceutically and agriculturally important metabolites. Despite the numerous works there remain significant gaps in understanding their biosynthesis in Amaryllidaceae plants. As such, further research is needed to fully elucidate the metabolic pathway and facilitate their production. This review aims to provide a comprehensive overall summary of the current state of knowledge on AAs biosynthesis, from elicitation of transcription factors expression in the cell nucleus to alkaloid transport in the apoplast, and to highlight the challenges that need to be overcome for further advancement.

Experiences of social stigma of people living with Hansen's disease in Brazil: silencing, secrets and exclusion.

BACKGROUND: Hansen's disease is a chronic, infectious and transmissible disease that is considered a public health problem in Brazil. Hansen's disease is marked by stigma and prejudice, because it carries with it a strong negative social image, reinforced by policies of social isolation in the community. METHODS: A qualitative study was conducted in Ribeirão Preto, an inland city of the state of São Paulo, Brazil. Eleven patients under treatment for the disease were interviewed. The interviews were audio recorded and transcribed in full, then were analyzed through the stages of transcription, transposition and reconstitution, as informed by concepts proposed by Goffman. RESULTS: The results showed that the marks of stigma are still present in the twenty-first century and were presented in two axes: 'Stigma and work for the person affected by Hansen's disease' and 'The experience of stigma in the family'. The participants refer to fears of losing their jobs and of being ridiculed, which stops them talking about the disease. Regarding their families, the participants reported episodes of discrimination, the creation of family secrets and fear of relatives' reactions. CONCLUSIONS: All these aspects interfere in the follow-up and treatment of patients and need to be considered and welcomed by health professionals. It is recommended that these aspects are addressed in the initial training and continuing education of health professionals. CONTEXTE: La maladie de Hansen est une maladie chronique, infectieuse et transmissible, considérée comme un problème de santé publique au Brésil. La maladie de Hansen est marquée par la stigmatisation et les préjugés, car elle véhicule une image sociale fortement négative, renforcée par des politiques d'isolement social au sein de la communauté. MÉTHODES: Étude qualitative menée à Ribeirão Preto, une ville intérieure de l'État de São Paulo, au Brésil. Onze patients traités pour la maladie ont été interrogés. Les entretiens ont été enregistrés et transcrits intégralement, et ont été analysés en suivant les étapes de transcription, de transposition et de reconstitution, selon les concepts proposés par Goffman. RÉSULTATS: Les résultats montrent que les marques de la stigmatisation sont toujours présentes au 21ème siècle et ont été présentées selon deux axes : 'La stigmatisation et le travail pour la personne affectée par la maladie de Hansen' et 'L'expérience de la stigmatisation dans la famille'. Les participants évoquent la peur de perdre leur emploi, la peur d'être ridiculisés, ce qui les pousse à ne pas parler de la maladie. En ce qui concerne les familles, les participants ont rapporté des épisodes de discrimination, la création de secrets de famille et la peur des réactions des proches. CONCLUSIONS: Tous ces aspects interfèrent dans le suivi et le traitement des patients et doivent être pris en compte et accueillis par les professionnels de la santé. Il est recommandé que ces aspects soient abordés dans la formation initiale et la formation continue des professionnels de la santé. ANTECEDENTES: La enfermedad de Hansen es una enfermedad crónica, infecciosa y transmisible, considerada un problema de salud pública en Brasil. La enfermedad de Hansen está marcada por el estigma y el prejuicio, ya que conlleva una fuerte imagen social negativa, reforzada por políticas de aislamiento social en la comunidad. MÉTODOS: Estudio cualitativo realizado en Ribeirão Preto, una ciudad del interior del estado de São Paulo, Brasil. Se entrevistaron a once pacientes en tratamiento para la enfermedad. Las entrevistas fueron grabadas en audio, transcritas en su totalidad y analizadas a través de etapas de transcripción, transposición y reconstitución, según los conceptos propuestos por Goffman. RESULTADOS: Los resultados muestran que las marcas del estigma siguen presentes en el siglo XXI y se presentaron en dos ejes: 'Estigma y trabajo para la persona afectada por la enfermedad de Hansen' y 'La experiencia del estigma en la familia'. Los participantes mencionan el miedo a perder sus trabajos, el temor a ser ridiculizados, lo que les impide comentar sobre la enfermedad. En cuanto a las familias, los participantes reportaron episodios de discriminación, la creación de secretos familiares y el miedo a las reacciones de los familiares. CONCLUSIONES: Todos estos aspectos interfieren en el seguimiento y tratamiento de los pacientes y deben ser considerados y acogidos por los profesionales sanitarios. Se recomienda abordar estos aspectos en la formación inicial y la educación continua de los profesionales sanitarios.

La influencia de las instituciones en los consejos locales de salud / The influence of the institutions on local health councils

Objetivo: Analizar la influencia de las instituciones en el funcionamiento de los consejos locales de salud. Diseño: Estudio cualitativo, descriptivo y exploratorio. Emplazamiento: Dos servicios de atención primaria de salud de un municipio del interior del estado de São Paulo, Brasil.Participantes: Veinticuatro miembros de los consejos locales de salud y 4 informantes clave. Método: Basado en el marco teórico y metodológico del análisis institucional. Los datos fueron producidos a través de 28 entrevistas individuales con preguntas semiestructuradas, observación, participación en las actividades de los consejos y registro en el diario de investigación. Los datos fueron organizados por el proceso de transcripción, transposición y reconstitución. Resultados: Las instituciones actúan en los territorios representados por actores sociales que ocupan cargos y funciones dentro de los servicios de atención primaria de salud, evidenciando la perpetuación de la jerarquización con valorización de los discursos de los profesionales y gestores en detrimento de los pacientes y predominio de reuniones burocratizadas. Los actores sociales reproducen los ideales del colectivo al que pertenecen en estos espacios. Conclusión: No siempre los equipos de gestión de salud reconocen las diferentes fuerzas que actúan en el territorio de salud, sin embargo, estas fuerzas interfieren en las actividades desarrolladas y en la atención de la salud. Los grupos actúan tanto en espacios formales a través de representantes oficiales que se reúnen y discuten temas en colegiados como en espacios informales y constituyen fuerzas en disputa en el territorio de salud.(AU)

Objective: To analyze the influences of the institutions in the operation of the Local Health councils. Design: qualitative, descriptive and exploratory study. Study setting: 02 Primary Health Care services of a municipality in the inland of the state of São Paulo, Brazil. Participants: twenty-four members of the Local Health Councils and 4 key informants. Methods: Supported by the theoretical methodological framework of Institutional Analysis. Data were produced through 28 semi-structured interviews, observation and participation in the activities of the councils and recording in the research diary. Data were organized and analyzed by the process of transcription, transposition and reconstitution. Results: The institutions act in the territories represented by social actors who occupy positions and functions within the Primary Health Care services, evidencing the perpetuation of hierarchization with valorization of the speeches of professionals and managers to the detriment of patients and predominance of bureaucratized meetings. The social actors reproduce the ideals of the collective to which they belong in these spaces. Conclusions: The health management teams do not recognize the different forces that act in the health territory, however, these forces interfere in the activities performed and in health care. The groups act both in formal spaces through official representatives who meet and discuss issues in collegiate meetings and in informal spaces, and constitute forces in dispute in the health territory.(AU)

[The influence of the institutions on local health councils]. / La influencia de las instituciones en los consejos locales de salud.

OBJECTIVE: To analyze the influences of the institutions in the operation of the Local Health councils. DESIGN: qualitative, descriptive and exploratory study. STUDY SETTING: 02 Primary Health Care services of a municipality in the inland of the state of São Paulo, Brazil. PARTICIPANTS: twenty-four members of the Local Health Councils and 4 key informants. METHODS: Supported by the theoretical methodological framework of Institutional Analysis. Data were produced through 28 semi-structured interviews, observation and participation in the activities of the councils and recording in the research diary. Data were organized and analyzed by the process of transcription, transposition and reconstitution. RESULTS: The institutions act in the territories represented by social actors who occupy positions and functions within the Primary Health Care services, evidencing the perpetuation of hierarchization with valorization of the speeches of professionals and managers to the detriment of patients and predominance of bureaucratized meetings. The social actors reproduce the ideals of the collective to which they belong in these spaces. CONCLUSIONS: The health management teams do not recognize the different forces that act in the health territory, however, these forces interfere in the activities performed and in health care. The groups act both in formal spaces through official representatives who meet and discuss issues in collegiate meetings and in informal spaces, and constitute forces in dispute in the health territory.

Aportes conceptuales al diagnóstico para el ordenamiento territorial periurbano desde un abordaje sistémico y transdisciplinar

Los procesos de desarrollo territorial han generado un crecimiento no planificado del periurbano que genera impactos negativos en su estructura y funcionamiento; por lo tanto, el trabajo está orientado a resaltar, desde la fase diagnóstica del ordenamiento territorial, la importancia del periurbano y sus diferentes componentes. El estudio se enmarca en una aproximación conceptual sistémica del territorio y de procesos que se llevan a cabo en Europa y Latinoamérica relacionados con el suelo periurbano, la cual corresponde a una revisión documental de carácter transdisciplinar, cuya estructura hermenéutica permitió hacer énfasis en la fase diagnóstica para reconocer la importancia del periurbano como espacio de transición y control de la expansión urbana. Los resultados pueden servir de base para la formulación de una regulación normativa que permita superar las contradicciones existentes en la interfaz urbano-rural desde una visión sostenible de largo plazo.

The processes of territorial development have generated an unplanned peri-urban growth that generates negative impacts on its structure and functioning; therefore, the work is aimed at highlighting, from the diagnostic phase of territorial planning, the importance of the peri-urban and its different components. The study is framed in a systemic conceptual approach to territory and processes that are carried out in Europe and Latin America related to peri-urban land, which corresponds to a documentary review of a transdisciplinary nature, whose hermeneutic structure allowed to emphasize the diagnostic phase to recognize the importance of the peri-urban as a space of transition and control of urban expansión. The results can serve as a basis for the formulation of a normative regulation that allows to overcome the existing contradictions in the urban-rural interface from a long-term sustainable vision.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

Auxin and light-mediated regulation of growth, morphogenesis, and alkaloid biosynthesis in Crinum x powellii 'Album' callus.

Crinum x powellii 'Album' belongs to the Amaryllidaceae medicinal plant family that produces a range of structurally diverse alkaloids with potential therapeutic properties. The optimal conditions for in vitro tissue growth, morphogenesis, and alkaloid biosynthesis remain unclear. Auxin and light play critical roles in regulating plant growth, development, and alkaloid biosynthesis in several Amaryllidaceae plants. Here, we have succeeded in showing, for the first time, that the combination of auxin and light significantly influence C. x powellii "Album" in vitro tissue growth, survival, and morphogenesis compared to individual treatments. Furthermore, this combination also upregulates the expression of alkaloid biosynthetic genes and led to an increase in the content of certain alkaloids, suggesting a positive impact on the defense and therapeutic potential of the calli. Our findings provide insights into the regulation of genes involved in alkaloid biosynthesis in C. x powellii "Album" callus and underline the potential of auxin and light as tools for enhancing their production in plants. This study provides a foundation for further exploration of C. x powellii "Album" calli as a sustainable source of bioactive alkaloids for pharmaceutical and agricultural applications. Furthermore, this study paves the way to the discovery of the biosynthetic pathway of specialized metabolites from C. x powellii "Album", such as cherylline and lycorine.

Violence in the Nursing Workplace in the Context of Primary Health Care: A Qualitative Study.

Violence demands considerable attention due to its complexity and social consequences. The objective of this study was to analyze violence in the nursing professional workplace in the context of primary health care in Brazil. It is a qualitative study with theoretical and methodological reference to institutional analysis. It was carried out in basic health units in Brazil. Nursing professionals (N = 11) participated in semi-structured interviews and discussion groups, in addition to a research diary and participant observation. Data collection took place from October to December 2021. The results are presented in five categories: types of violence and aggressors from the perspective of nursing professionals; the causes of violence reported by professionals; strategies for the management of violence; professionals' proposals for preventing violence in health contexts; the consequences of violence in the workplace. Nursing professionals make up a large part of the workforce and have reported verbal, physical, moral, and psychological violence. The main causes are associated with user access to services. For the prevention of violence, professionals do not see themselves as protagonists of change. The consequences are the loss of quality of work and the health of professionals who requested sick leave and transfers. The study's findings can help in the development of public policies and educational and management actions.

The Work of Nurses in Primary Health Care: Crossings of the New Public Management.

The literature in the field of health management mentions a concept called new public management (NPM), introduced in Brazil and France at the end of the 20th century. The objective of the study was to analyze the repercussions of the work of nurses in primary health care in Brazil and France under the influence of NPM. This is an excerpt of a double-titled thesis, which is a research intervention with nurses from two Brazilian states and five French departments. Data were produced between February 2019 and July 2021. The public policy Health on the Hour acted as an institutional transducer, provoking a reduction in access and producing effects on professional practices. In both countries, NPM amplified the predominance of technical and quantifiable acts, the focus on individual care, and the loss of autonomy. Nurses reported insurmountable situations, using the metaphor "Sophie's choice". The results showed that making dilemmatic decisions has been the daily routine of nurses, which has not resulted in debureaucratization and higher quality of care.

The effect of flour-based foods intake in the reduction of cardiometabolic risk: A systematic review.

Cardiometabolic risk triggers a state of chronic and subclinical inflammation, conferring a higher risk of morbidity and mortality. Thus, minimal processing of foods with high nutritional value, in the form of flour, becomes an effective dietary strategy in preventing and treating cardiometabolic risk factors. This systematic review aims to evaluate the evidence on the effect of flour-based food intake on reducing the most common cardiometabolic risk factors. We included all randomized controlled trials published up to April 2023 in the main databases PubMed, Scopus and Web of Science. Eleven clinical trials were included. The amount of flour used in the studies ranged from 1.5 g to 36 g/day, and the supplementation period ranged from six weeks to 120 days. Green jackfruit flour, green banana flour, soy flour, flour from rind of the yellow passion fruit, and fenugreek powder demonstrated significant results in improve parameters of glucose homeostasis. Chia flour, green banana flour, soy flour, and fenugreek powder showed improvements in blood pressure measurements. Brazil nut flour and chia flour reduced total cholesterol. Chia flour also increased HDL cholesterol levels. The evidence presented in the current systematic review indicates that flour-derived foods intake is related to improve cardiometabolic risk factors parameters.

A single dose of microencapsulated cocoa supplementation attenuated eccentric exercise-induced endothelial dysfunction.

In the present study, it was evaluated whether microencapsulated cocoa supplementation could attenuate endothelial dysfunction caused by eccentric exercise in healthy subjects. Thirteen volunteers were enrolled in this double-blind, placebo-controlled, crossover study. Flow-mediated dilatation (FMD), blood flow and muscle O2 saturation (StO2) were evaluated by ultrasound and near-infrared spectroscopy (NIRS), respectively, before and after microencapsulated cocoa supplementation. The eccentric exercise was performed after microencapsulated cocoa supplementation to generate vascular dysfunction. Eccentric exercise significantly reduced FMD in the PLA condition, but cocoa attenuated this exercise effect. No significant effect was observed on muscle StO2 and blood flow after eccentric exercise and nutritional supplementation. In conclusion, the present study showed that a single dose of microencapsulated cocoa ingestion attenuated FMD-induced eccentric exercise. These findings suggest that a single dose of microencapsulated cocoa may be an alternative nutritional strategy to attenuate vascular dysfunction induced by eccentric exercise in healthy individuals.

Does sorting by color using visible and high-energy violet light improve classification of taxa in honey bee pollen pellets?

Premise: Pollen collected by honey bees from different plant species often differs in color, and this has been used as a basis for plant identification. The objective of this study was to develop a new, low-cost protocol to sort pollen pellets by color using high-energy violet light and visible light to determine whether pollen pellet color is associated with variations in plant species identity. Methods and Results: We identified 35 distinct colors and found that 52% of pollen subsamples (n = 200) were dominated by a single taxon. Among these near-pure pellets, only one color consistently represented a single pollen taxon (Asteraceae: Cichorioideae). Across the spectrum of colors spanning yellows, oranges, and browns, similarly colored pollen pellets contained pollen from multiple plant families ranging from two to 13 families per color. Conclusions: Sorting pollen pellets illuminated under high-energy violet light lit from four directions within a custom-made light box aided in distinguishing pellet composition, especially in pellets within the same color.

A Toolbox for Glutamine Use in Dissolution Dynamic Nuclear Polarization: from Enzymatic Reaction Monitoring to the Study of Cellular Metabolic Pathways and Imaging.

Glutamine is under scrutiny regarding its metabolic deregulation linked to energetic reprogramming in cancer cells. Many analytical techniques have been used to better understand the impact of the metabolism of amino acids on biological processes, however only a few are suited to work with complex samples. Here, we report the use of a general dissolution dynamic nuclear polarization (D-DNP) formulation using an unexpensive radical as a multipurpose tool to study glutamine, with insights from enzymatic modelling to complex metabolic networks and fast imaging. First, hyperpolarized [5-13 C] glutamine is used as molecular probe to study the kinetic action of two enzymes: L-asparaginase that has been used as an anti-metabolic treatment for cancer, and glutaminase. These results are also compared with those acquired with another hyperpolarized amino acid, [1,4-13 C] asparagine. Second, we explored the use of hyperpolarized (HP) substrates to probe metabolic pathways by monitoring metabolic profiles arising from hyperpolarized glutamine in E. coli extracts. Finally, a highly concentrated sample formulation is proposed for the purpose of fast imaging applications. We think that this approach can be extended to formulate other amino acids as well as other metabolites and provide complementary insights into the analysis of metabolic networks.

Hydroalcoholic Extract of Rabbiteye Blueberry (Vaccinium ashei) Leaves Mitigates Unpredictable Chronic Mild Stress Model Inducing Depressive-Like Behavior in Rats.

Several studies reported that rabbiteye blueberry (Vaccinium ashei Reade) leaves present promising biological properties. To the best of our knowledge, no study investigated the possible application of their hydroalcoholic extract for treating mood disorders. Herein, we evaluated if the hydroalcoholic extract of rabbiteye blueberry (Vaccinium ashei Reade) leaves (HEV) promotes an antidepressant-like effect in rodents using chronic experimental approaches. The effect of repeated administration of HEV (50 mg/kg, p.o.) on the immobility time was assessed in the forced swimming test (FST) in an unpredictable chronic mild stress (UCMS) model. Repeated treatment with HEV reversed the depressive-like behavior induced by UCMS by reducing the immobility time. Besides, the exposure to HEV caused no changes in relative organ weights in rats submitted to UCMS. The results indicated that HEV administration presented antidepressant-like action devoid of toxic effects. Thus, it is possible to suggest its potential as a safe and accessible therapeutic tool in the management of depression and other related mood disorders.

Incorporation and influence of natural gums in an alginate matrix for Serratia plymuthica immobilization and isomaltulose production.

Isomaltulose (IM) is a non-cariogenic sugar and substitute for sucrose that has been widely used in candies and soft drinks. This sugar is obtained from sucrose through enzymatic conversion, catalyzed by microbial glucosyltransferases. In this study, alternative gums, namely: gum Arabic (GA), algaroba gum (AG), and cashew gum (CG) were combined with alginate (ALG) for the immobilization of Serratia plymuthica, with the aim of improving its capability for conversion of sucrose into IM. Prior to the immobilization, the gums were characterized using FTIR spectroscopy, TGA, and XRD analysis. Then, they were combined with ALG and used to immobilize a cell mass of S. plymuthica by ionic gelation. The morphology of the produced beads was visualized using SEM, and the sucrose into IM conversion using the beads was performed in batch and continuous processes. CG showed the highest thermal stability and crystallinity. The use of CG (2.0 %, w/v) combined with ALG (2.0 %, w/v) showed the highest value for isomaltulose (236.46 g/L) produced in the first batch, and high stability in the continuous conversion process; resulting in an IM production of 199.24 g/L at 72 h of reaction. In addition, this combination produced less porous beads, able to maintain the entrapped cells longer. In conclusion, the production of IM by Serratia plymuthica cells immobilized in a matrix composed of ALG and CG is recommended, due to its high conversion capacity and high stability.

Photodynamic potential of hexadecafluoro zinc phthalocyanine in nanostructured lipid carriers: physicochemical characterization, drug delivery and antimicrobial effect against Candida albicans.

This study aims to develop and characterize NCL loaded with ZnF16Pc (Pc) for application in antimicrobial photodynamic therapy. For the development of the NLC, the fusion-emulsification technique followed by sonication was applied. NLC and Pc-NLC were characterized in terms of mean diameter (Dm.n), polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (%EE), transmission electron microscopy (TEM), differential scanning (DSC), photobleaching and singlet oxygen generation in cellular systems (SOSG), and in vitro release assays performed by the beaker method, using dialysis membranes. Cell viability was performed by colony forming units (CFU/mL). The mean size of NLC and Pc-NLC was 158 nm ± 1.49 to 161.80 nm and showed PdI < 0.3 and ZP between -17.8 and -19.9, and stable during storage time (90 days). The TEM presented spherical particles, the Pc-NLC promoted the encapsulation of 75.57% ± 0.58. DSC analysis confirmed that there was no incompatibility between Pc and NLC. The analysis of the photodegradation profile proved to be photostable after encapsulation and this corroborates the data obtained by SOSG. In vitro release showed controlled and prolonged release. PDT Pc-NLC exhibited greater antifungal effect against C. albicans (3 log10 reduction) than Pc-NLC without light (1 log10 reduction). NLC can be an alternative to the application of Pc and improve the effect during PDT treatment.

Determination of clozapine and norclozapine in dried plasma spot and dried blood spot by liquid chromatography-tandem mass spectrometry.

The use of alternative blood sampling strategies in clozapine (CLZ) therapeutic drug monitoring (TDM) aims to facilitate collection and improve drug therapy and adherence. This study aimed to develop and validate two methods for the determination CLZ and norclozapine (NOR) in dried blood spots (DBS) and dried plasma spots (DPS) by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The analytes were extracted from one 10 microliter volumetric DBS disc punch and from one 6 mm DPS disc punch with methyl tert-butyl ether: methanol (1:9, v/v) and injected into the HPLC-MS/MS with Atmospheric pressure chemical ionization (APCI) source. Separation was performed in a phenyl column, with mobile phase ammonium formate 1 mM pH 4.0 with methanol in gradient mode. The method was linear from 50 to 1500 ng/ml (r > 0.99), with accuracy between 98% and 105% in DBS and 91-101% in DPS, and intra- and inter-assay CV% from 5.23% to 9.35% in DBS and 2.22-11.36% in DPS for both analytes. The matrix effect was compensated by the internal standard, between - 5.1-6.89% in DBS and - 2.45-5.74% in DPS. The average extraction efficiency was 63-67% for CLZ and 58-69% for NOR with no significant impact of hematocrit (HCT). The analytes were stable in the dried matrices stored up to 42 °C for 26 days. The method was applied in the evaluation of clozapine therapy in 13 schizophrenic patients with mean serum levels of 401 ng/ml (43-914 ng/ml). Only 38% were within the therapeutic range, 46% below and 23% above. CLZ and NOR concentrations in dried samples were highly correlated to serum levels, with greater accuracy for DPS compared to DBS (97 versus 89%, and 99 versus 131%, for CLZ and NOR, respectively). Our data support the use of DBS and DPS as alternative sampling strategies in CLZ therapeutic drug monitoring, with satisfactory performance and logistics advantages.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

O Impacto da Pandemia da Covid-19 no Volume de Mamografias no Brasil: uma Análise de Previsão Baseada nos Números Históricos / The Impact of the COVID-19 Pandemic on the Volume of Mammograms in Brazil: a Forecast Analysis Based on Historical Numbers / El Impacto de la Pandemia de Covid-19 en el Volumen de Mamografías en Brasil: un Análisis de Pronóstico Basado en Cifras Históricas

Introdução: A neoplasia mamária constitui a primeira causa de óbito por câncer em mulheres brasileiras. Dados sobre o real impacto da pandemia na política de rastreamento e diagnóstico do câncer de mama no Brasil ainda são desconhecidos. Objetivo: Avaliar o efeito da pandemia da covid-19 no número de mamografias realizadas no Sistema Único de Saúde (SUS). Método: Estudo epidemiológico, quantitativo e de delineamento transversal. Foram selecionadas mamografias mensais realizadas no SUS após consulta ao Departamento de Informática do SUS (DATASUS). Foi avaliado o volume histórico, de janeiro de 2017 a março de 2020, mês seguinte ao primeiro caso de covid-19 diagnosticado no Brasil, para se construir um modelo de previsão das mamografias esperadas de março de 2020 até dezembro de 2021. Resultado: No ano de 2020, 1.705.475 mamografias deixaram de ser realizadas no Brasil em relação ao ano anterior, segundo o DATASUS. O modelo de previsão, com base nos valores históricos, mostrou um déficit de 1.635.42 mamografias. Em maio de 2020, ocorreu a maior queda na realização dos exames, representando apenas 20,69% das mamografias realizadas no mesmo mês do ano anterior. Conclusão: A detecção precoce do câncer de mama foi uma das áreas médicas impactadas pela política de restrição e isolamento impostos no ano de 2020. Nesse sentido, esforços governamentais futuros serão necessários para oferecer tratamento a eventuais pacientes com diagnóstico tardio de câncer de mama, além das mamografias que não puderam ser realizadas

Introduction: Breast cancer is the leading cause of death by cancer in Brazilian women. Data on the real impact of the pandemic on breast cancer screening and diagnosis policy in Brazil are still unknown. Objective: Evaluate the effect of the COVID-19 pandemic on the number of mammograms performed in the Brazilian Unified Health System (SUS). Method: Epidemiological, quantitative, cross-sectional study. Monthly mammograms performed at SUS through the Department of Informatics of the SUS (DATASUS) were selected. The historical volume from January 2017 to March 2020, the month following the first case of COVID-19 diagnosed in Brazil, was evaluated to build a forecast model of expected mammograms from March 2020 to December 2021. Result: In 2020, 1,705,475 mammograms were not performed compared to the previous year, according to DATASUS. The prediction model, based on historical values, showed a deficit of 1,635,420 mammograms. In May 2020, there was the biggest drop of the exams, representing only 20.69% of mammograms performed in the same month of the previous year. Conclusion: Early detection of breast cancer was one of the medical areas impacted by the restrictions and social distance policy imposed in 2020. In this sense, future government efforts will be needed to offer treatment to potential patients with late diagnosis of breast cancer, in addition to the mammograms that were not done

Introducción: El cáncer de mama es la principal causa de muerte por cáncer en las mujeres brasileñas. Aún se desconocen los datos sobre el impacto real de la pandemia en la política de tamizaje y diagnóstico de cáncer de mama en Brasil. Objetivo: Evaluar el efecto de la pandemia de covid-19 en el número de mamografías realizadas en el Sistema Único de Salud (SUS). Método: Estudio epidemiológico, cuantitativo y transversal. Se seleccionaron mamografías mensuales realizadas en el SUS a través del Departamento de Informática del SUS (DATASUS). Se evaluó el volumen histórico, de enero de 2017 a marzo de 2020, el mes siguiente al primer caso de covid-19 diagnosticado en Brasil, para construir un modelo de predicción de mamografías esperadas, de marzo de 2020 a diciembre de 2021. Resultado: En 2020, se dejaron de realizar 1.705.475 mamografías en Brasil en comparación con el año anterior, según DATASUS. El modelo de predicción, basado en valores históricos, mostró un déficit de 1.635.420 mamografías. En mayo de 2020, hubo la mayor caída en los exámenes, totalizando solo el 20,69% de las mamografías realizadas en el mismo mes del año anterior. Conclusión: La detección temprana del cáncer de mama fue una de las áreas médicas impactadas por la política de restricción y aislamiento impuesta en 2020. En este sentido, serán necesarios futuros esfuerzos gubernamentales para brindar el tratamiento de eventuales pacientes con diagnóstico tardío de cáncer de mama, además las mamografías mamografías que no se pudieron realizar