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Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed.
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Neoplasias da Mama , Nanopartículas Magnéticas de Óxido de Ferro , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Nanopartículas Magnéticas de Óxido de Ferro/química , Sistemas de Liberação de Medicamentos/métodos , Propriedades de Superfície , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Animais , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Microambiente Tumoral/efeitos dos fármacosRESUMO
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.
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BACKGROUND: The future European Health Research and Innovation Cloud (HRIC), as fundamental part of the European Health Data Space (EHDS), will promote the secondary use of data and the capabilities to push the boundaries of health research within an ethical and legally compliant framework that reinforces the trust of patients and citizens. OBJECTIVE: This study aimed to analyse health data management mechanisms in Europe to determine their alignment with FAIR principles and data discovery generating best. practices for new data hubs joining the HRIC ecosystem. In this line, the compliance of health data hubs with FAIR principles and data discovery were assessed, and a set of best practices for health data hubs was concluded. METHODS: A survey was conducted in January 2022, involving 99 representative health data hubs from multiple countries, and 42 responses were obtained in June 2022. Stratification methods were employed to cover different levels of granularity. The survey data was analysed to assess compliance with FAIR and data discovery principles. The study started with a general analysis of survey responses, followed by the creation of specific profiles based on three categories: organization type, function, and level of data aggregation. RESULTS: The study produced specific best practices for data hubs regarding the adoption of FAIR principles and data discoverability. It also provided an overview of the survey study and specific profiles derived from category analysis, considering different types of data hubs. CONCLUSIONS: The study concluded that a significant number of health data hubs in Europe did not fully comply with FAIR and data discovery principles. However, the study identified specific best practices that can guide new data hubs in adhering to these principles. The study highlighted the importance of aligning health data management mechanisms with FAIR principles to enhance interoperability and reusability in the future HRIC.
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Objectives: This study aimed to evaluate gender-based disparities in preventable adverse events due to low-value practices (LVPs) in primary care. Methods: A retrospective cohort study in Alicante, Spain. Results: A total of 1,516 patient records were examined, finding that older individuals and women experienced more LVP-related events. Female patients faced a higher volume of such events than males with the same health issue. Interaction analysis revealed patients treated by male physicians had more severe events, while those attended by females experienced milder ones. Adverse events were more frequent in LVPs associated with gender-based reasons. Conclusion: These results highlight the need for tailored healthcare professional awareness programs on overuse's impact on safety. Addressing outcome differences between male and female patients should inform awareness campaigns.
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Medicina de Família e Comunidade , Humanos , Espanha , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto , Idoso , Atenção Primária à Saúde , Disparidades em Assistência à SaúdeRESUMO
BACKGROUND: Data on overuse of diagnostic and therapeutic resources underline their contribution to the decline in healthcare quality. The application of "Do Not Do" recommendations, in interaction with gender biases in primary care, remains to be fully understood. Therefore, this study aims to identify which low-value practices (LVPs) causing adverse events are susceptible to be applied in primary care setting with different frequency between men and women. METHODS: A consensus study was conducted between November 1, 2021, and July 4, 2022, in the primary care setting of the Valencian Community, Spain. Thirty-three of the 61 (54.1%) health professionals from clinical and research settings invited, completed the questionnaire. Participants were recruited by snowball sampling through two scientific societies, meeting specific inclusion criteria: over 10 years of professional experience and a minimum of 7 years focused on health studies from a gender perspective. An initial round using a questionnaire comprising 40 LVPs to assess consensus on their frequency in primary care, potential to cause serious adverse events, and different frequency between men and women possibly due to gender bias. A second round-questionnaire was administered to confirm the final selection of LVPs. RESULTS: This study identified nineteen LVPs potentially linked to serious adverse events with varying frequencies between men and women in primary care. Among the most gender-biased and harmful LVPs were the use of benzodiazepines for insomnia, delirium, and agitation in the elderly, and the use of hypnotics without a previous etiological diagnosis. CONCLUSIONS: Identifying specific practices with potential gender biases, mainly in mental health for the elderly, contributes to healthcare promotion and bridges the gap in gender inequalities. TRIAL REGISTRATION: NCT05233852, registered on 10 February 2022.
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Atenção Primária à Saúde , Sexismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uso Excessivo dos Serviços de Saúde/prevenção & controle , Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study aimed to evaluate the efficacy, safety, and participant compliance of orthokeratology treatment for the correction of myopic refractive errors over a six-month prospective study and to define the potential reasons for early treatment discontinuation. METHODS: A total of 32 participants with low-to-moderate myopia were fitted with the spherical model of corneal refractive therapy (CRT) orthokeratology lenses (Paragon Vision Sciences) and followed over six months, with specific attention to alterations in refractive error, corneal topography, and epithelial thickness. Concurrently, participant feedback and reasons for any treatment discontinuation were documented. RESULTS: Significant changes in refractive error and in corneal topography were observed, with approximately 50% of the refractive error being corrected on the first night of use and 100% by the first two weeks ( P <0.001). Central epithelial thickness experienced substantial thinning, reducing to 15.65±4.49 µm (67.38%) ( P <0.001) after 6 months of lens use. Six participants withdrew from this study for varied reasons, including unmet visual expectations and difficulty adhering to the lens-wearing regimen. Notably, the dropout group exhibited higher baseline low-order aberrations and less prolate corneas than those who persisted with the treatment ( P <0.05). CONCLUSIONS: Orthokeratology with CRT is efficacious and safe for the correction of low-to-moderate myopia in adults, but a portion of patients discontinue the treatment in the first 6 months of contact lens wear. Special care should be taken when recommending orthokeratology in patients with higher levels of myopia and corneas with less prolate shape, providing more realistic expectations and even changing to dual axis or more sophisticated designs.
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Topografia da Córnea , Miopia , Procedimentos Ortoceratológicos , Cooperação do Paciente , Refração Ocular , Acuidade Visual , Humanos , Procedimentos Ortoceratológicos/métodos , Miopia/terapia , Miopia/fisiopatologia , Masculino , Estudos Prospectivos , Feminino , Refração Ocular/fisiologia , Adulto Jovem , Acuidade Visual/fisiologia , Adulto , Lentes de Contato , Adolescente , Resultado do Tratamento , Córnea/patologia , SeguimentosRESUMO
In monoecious species, female flowering constitutes the developmental process that determines the onset and production of fruit and is therefore closely related to crop yield. This article presents the identification and phenotypic and molecular characterization of myb62, an ethylmethane sulfonate loss-of-function mutation that completely blocks the female floral transition, converting all female flowers into male flowers. BSA-seq analysis coupled with WGS showed that myb62 corresponds to a C>T transition in the coding region of the gene CpMYB62, generating a premature stop codon and a truncated transcription factor without its N-terminal effector domain. The myb62 phenotype was partially rescued by exogenous ethylene application, indicating that the function of CpMYB62 is mediated by ethylene. Different evidence supports this conclusion: first, the reduced ethylene production of the mutant, and second, the male flower productive phenotype of the double mutant between myb62 and the ethylene-insensitive mutant etr2b, which demonstrated that myb62 is epistatic over etr2b. Furthermore, transcriptomic analysis of WT and myb62 apical shoots confirmed that CpMYB62 regulates master sex-determining genes, upregulating those encoding the ethylene biosynthesis enzymes CpACO2B and CpACS27A and those encoding for transcription factors that promote the development of carpels(CpCRC), but downregulating those involved in the arrest of carpels (CpWIP1), In the gene network controlling sex determination in cucurbits, CpMYB62 occupies the most upstream position, activating ethylene and other sex determining genes involved in female flower determination in Cucurbita pepo.
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INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.
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BACKGROUND: Sexual and gender minority youth are at greater risk of compromised mental health than their heterosexual and cisgender peers. This is considered to be due to an increased burden of stigma, discrimination, or bullying resulting in a heightened experience of daily stress. Given the increasing digital accessibility and a strong preference for web-based support among sexual and gender minority youth, digital interventions are a key means to provide support to maintain their well-being. OBJECTIVE: This paper aims to explicate the co-design processes and underpinning logic of Oneself, a bespoke web-based intervention for sexual and gender minority youth. METHODS: This study followed a 6-stage process set out by Hagen et al (identify, define, position, concept, create, and use), incorporating a systematic scoping review of existing evidence, focus groups with 4 stakeholder groups (ie, sexual and gender minority youth, professionals who directly support them, parents, and UK public health service commissioners), a series of co-design workshops and web-based consultations with sexual and gender minority youth, the appointment of a digital development company, and young adult sexual and gender minority contributors to create content grounded in authentic experiences. RESULTS: Oneself features a welcome and home page, including a free accessible to all animation explaining the importance of using appropriate pronouns and the opportunity to create a user account and log-in to access further free content. Creating an account provides an opportunity (for the user and the research team) to record engagement, assess users' well-being, and track progress through the available content. There are three sections of content in Oneself focused on the priority topics identified through co-design: (1) coming out and doing so safely; (2) managing school, including homophobic, biphobic, or transphobic bullying or similar; and (3) dealing with parents and families, especially unsupportive family members, including parents or caregivers. Oneself's content focuses on identifying these as topic areas and providing potential resources to assist sexual and gender minority youth in coping with these areas. For instance, Oneself drew on therapeutic concepts such as cognitive reframing, stress reduction, and problem-solving techniques. There is also a section containing relaxation exercises, a section with links to other recommended support and resources, and a downloads section with more detailed techniques and strategies for improving well-being. CONCLUSIONS: This study contributes to research by opening up the black box of intervention development. It shows how Oneself is underpinned by a logic that can support future development and evaluation and includes diverse co-designers. More interactive techniques to support well-being would be beneficial for further development. Additional content specific to a wider range of intersecting identities (such as care-experienced Asian sexual and gender minority youth from a minority faith background) would also be beneficial in future Oneself developments. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31036.
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OBJECTIVE: To determine whether adenomyosis is present in the cornual portion of hysterectomies of symptomatic sterilization device users and in patients hysterectomized for different benign causes and who presented with pelvic pain and/or menstrual alterations. METHODS: An observational, analytical, cross-sectional, single-center, retrospective cohort study was conducted in a secondary level hospital. Cohort 1 consisted of women who had Essure® hysteroscopic sterilization devices inserted between 2009 and 2017, who developed gynecologic symptoms (pelvic pain, heavy menstrual bleeding, and/or abnormal uterine bleeding) and who underwent a hysterectomy for explantation of the devices. Cohort 2 consisted of women with the same gynecologic symptoms, who underwent a hysterectomy for other benign causes. All surgeries were performed by the gynecology team between 2018 and 2022. A descriptive and comparative analysis of sociodemographic, clinical characteristics, and pathologic findings between cohorts was made. RESULTS: In total, 96 patients were studied (cohort 1 included 34 women, cohort 2 included 62 women). Pelvic pain was found to be more frequent in the cohort of Essure users (76.47% vs. 50%, P = 0.012), with a ratio of three times higher in this group (odds ratio 3.25, 95% confidence interval 1.27-8.28). Adenomyosis was more frequently found in the Essure group, both at corporal and cornual portions, the latter being five times higher in this cohort (relative risk = 5.47; 95% confidence interval 1.17-25.64). CONCLUSIONS: The present study may be the first to describe cornual adenomyosis related to Essure devices. These devices may play a role in the development of adenomyosis and, consequently, pelvic pain. However, causality is difficult to establish.
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Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Sarcoidose , Sarcoma de Kaposi , Humanos , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/diagnóstico , Sarcoidose/complicações , Sarcoidose/diagnóstico , Terapia Antirretroviral de Alta AtividadeRESUMO
Objective: This paper introduces a privacy-preserving federated machine learning (ML) architecture built upon Findable, Accessible, Interoperable, and Reusable (FAIR) health data. It aims to devise an architecture for executing classification algorithms in a federated manner, enabling collaborative model-building among health data owners without sharing their datasets. Materials and methods: Utilizing an agent-based architecture, a privacy-preserving federated ML algorithm was developed to create a global predictive model from various local models. This involved formally defining the algorithm in two steps: data preparation and federated model training on FAIR health data and constructing the architecture with multiple components facilitating algorithm execution. The solution was validated by five healthcare organizations using their specific health datasets. Results: Five organizations transformed their datasets into Health Level 7 Fast Healthcare Interoperability Resources via a common FAIRification workflow and software set, thereby generating FAIR datasets. Each organization deployed a Federated ML Agent within its secure network, connected to a cloud-based Federated ML Manager. System testing was conducted on a use case aiming to predict 30-day readmission risk for chronic obstructive pulmonary disease patients and the federated model achieved an accuracy rate of 87%. Discussion: The paper demonstrated a practical application of privacy-preserving federated ML among five distinct healthcare entities, highlighting the value of FAIR health data in machine learning when utilized in a federated manner that ensures privacy protection without sharing data. Conclusion: This solution effectively leverages FAIR datasets from multiple healthcare organizations for federated ML while safeguarding sensitive health datasets, meeting legislative privacy and security requirements.
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Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.
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Body biomechanics and dental occlusion are related, but this interaction is not fully elucidated. The aim of this study was to investigate the association between body posture and occlusion in patients with and without dental pathology. A cross-sectional study was carried out with 29 patients divided into a control group and a group with pathology (malocclusions). Body posture was evaluated by dynamic baropodometry, analyzing parameters such as the line of gait and the anteroposterior and lateral position of the center of pressure (CoP). Occlusion was classified radiographically according to the sagittal skeletal relationship. Results showed significant differences in mean position phase line between groups (p = 0.01-0.02), with means of 115.85 ± 16.98 mm vs. 95.74 ± 24.47 mm (left side) and 109.03 ± 18.03 mm vs. 91.23 ± 20.80 mm (right side) for controls and pathologies, respectively. The effect size was large (Cohen's d 0.97 and 0.92). There were no differences in the anteroposterior (p = 0.38) or lateral (p = 0.78) position of the CoP. In gait analysis, significant differences were observed in left (548.89 ± 127.50 N vs. 360.15 ± 125.78 N, p < 0.001) and right (535.71 ± 131.57 N vs. 342.70 ± 108.40 N, p < 0.001) maximum heel strength between groups. The results suggest an association between body posture and occlusion, although further studies are needed to confirm this relationship. An integrated postural and occlusal approach could optimize the diagnosis and treatment of dental patients.
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Oclusão Dentária , Má Oclusão , Humanos , Estudos Transversais , Postura , MarchaRESUMO
Thiabendazole (TBZ) is a broad-spectrum anthelmintic and fungicide used in humans, animals, and agricultural commodities. TBZ residues are present in crops and animal products, including milk, posing a risk to food safety and public health. ABCG2 is a membrane transporter which affects bioavailability and milk secretion of xenobiotics. Therefore, the aim of this work was to characterize the role of ABCG2 in the in vitro transport and secretion into milk of 5-hydroxythiabendazole (5OH-TBZ), the main TBZ metabolite. Using MDCK-II polarized cells transduced with several species variants of ABCG2, we first demonstrated that 5OH-TBZ is efficiently in vitro transported by ABCG2. Subsequently, using Abcg2 knockout mice, we demonstrated that 5OH-TBZ secretion into milk was affected by Abcg2, with a more than 2-fold higher milk concentration and milk to plasma ratio in wild-type mice compared to their Abcg2-/- counterpart.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Leite , Tiabendazol , Animais , Feminino , Camundongos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Lactação , Leite/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Tiabendazol/química , Tiabendazol/metabolismo , Xenobióticos , CãesRESUMO
Objetivo: Identificar fortalezas, obstáculos, cambios en el entorno y capacidades de los equipos y unidades de apoyo en atención primaria, con el objetivo de proporcionar atención de alta calidad en un área de salud integrada. Diseño: Estudio de métodos mixtos basado en la matriz DAFO y el análisis CAME. Emplazamiento: Atención primaria, Comunidad Valenciana. Participantes: En total han participado 271 profesionales de los diferentes colectivos y representantes de asociaciones de pacientes, 99 en la fase de captura de ideas, 154 en la fase de elaboración de la matriz DAFO y 18 en la fase de elaboración del análisis CAME. Intervenciones: Se condujo un análisis DAFO-CAME a partir del cual se establecieron líneas de acción. La captura de información se realizó mediante grupos nominales, la fase de consenso integrando al conjunto de profesionales mediante Delphi y conferencia de consenso. Mediciones principales: Priorización de propuestas para mantener las fortalezas, afrontar las amenazas, explotar las oportunidades, corregir las debilidades en el marco de un plan de acción de un área de salud integrada. Resultados: Se propusieron un total de 82 ideas diferentes (20 fortalezas, 40 debilidades, 4 amenazas, 12 oportunidades y 6 amenazas-oportunidades). Este análisis condujo a un plan estratégico con 7 líneas y 33 acciones/intervenciones priorizadas. Conclusiones: Atención integrada buscando fórmulas colaborativas entre niveles asistenciales, redefinición de roles, soluciones digitales, capacitación del personal y mejoras en equipamientos y procesos de soporte, junto a medidas para afrontar el envejecimiento de la población y las necesidades de centros sociosanitarios constituyen los retos sobre los que actuar.(AU)
Objective: To identify strengths, obstacles, changes in the environment, and capabilities of primary care teams and support units, with the aim of providing high-quality care in an integrated healthcare area. Design: Mixed methods study based on the SWOT matrix and CAME analysis. Location: Primary care, Valencian community. Participants: A total of 271 professionals from different collectives and patient association representatives participated. 99 in the idea generation phase, 154 in the SWOT matrix development phase, and 18 in the CAME analysis development phase. Interventions: A SWOT-CAME analysis was conducted, from which action lines were established. Information capture was carried out through nominal groups, and the consensus phase involved integrating all professionals through Delphi and consensus conference techniques. Main measurements: Prioritization of proposals to maintain strengths, address threats, exploit opportunities, and correct weaknesses within the framework of an integrated healthcare area action plan. Results: A total of 82 different ideas were proposed (20 strengths; 40 weaknesses; 4 threats; 12 opportunities; 6 threats-opportunities), which, once prioritized, were translated into 7 lines and 33 prioritized actions/interventions (CAME analysis). Conclusions: Integrated care, seeking collaborative approaches between care levels, redefining roles, digital solutions, staff training, and improvements in equipment and support processes, along with measures to address the aging population and the needs of socio-sanitary centers, constitute the challenges to be addressed.(AU)
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Humanos , Masculino , Feminino , Atenção Primária à Saúde/organização & administração , Atenção Primária à Saúde/tendências , Qualidade da Assistência à Saúde , Assistência ao Paciente , Visita Domiciliar , Espanha , Gestão em Saúde , Sistemas de SaúdeRESUMO
Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+/Mn2+-transport ATPase isoform 1 (SPCA1). We found upregulation of SPCA1 upon lipopolysaccharide stimulation of microglia BV2 cells and primary microglia, where alterations of the Golgi ribbon were also observed. Silencing and overexpression experiments revealed that SPCA1 affects cell morphology, Golgi apparatus integrity, and phagocytic functions. Since SPCA1 is also an efficient Mn2+ transporter and considering that Mn2+ excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn2+ toxicity. Our results revealed a clear effect of Mn2+ excess on the viability and morphology of microglia. Subcellular analysis showed Golgi fragmentation and subsequent alteration of SPCA1 distribution from early stages of toxicity. Removal of Mn2+ by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn2+-induced Golgi fragmentation, and preserved SPCA Ca2+-dependent activity, suggesting curcumin as a potential protective agent against Mn2+-induced Golgi alterations in microglia.
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Adenosina Trifosfatases , Curcumina , Adenosina Trifosfatases/metabolismo , Lipopolissacarídeos/toxicidade , Microglia/metabolismo , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Via Secretória , Curcumina/metabolismo , Regulação para Cima , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Proteínas de Membrana Transportadoras/metabolismo , Isoformas de Proteínas/metabolismo , Cálcio/metabolismoRESUMO
Potassium exchanged Sn-ß and Sn-USY zeolites have been tested for the transformation of various aldoses (hexoses and pentoses), exhibiting outstanding catalytic activity and selectivity toward methyl lactate. Insights into the transformation pathways using reaction intermediates-dihydroxyacetone and glycolaldehyde-as substrates revealed a very high catalytic proficiency of both zeolites in aldol and retro-aldol reactions, showcasing their ability to convert small sugars into large sugars, and vice versa. This feature makes the studied Sn-zeolites outstanding catalysts for the transformation of a wide variety of sugars into a limited range of commercially valuable alkyl lactates and derivatives. [K]Sn-ß proved to be superior to [K]Sn-USY in terms of shape selectivity, exerting tight control on the distribution of produced α-hydroxy methyl esters. This shape selectivity was evident in the transformation of several complex sugar mixtures emulating different hemicelluloses-sugar cane bagasse, Scots pine, and white birch-that, despite showing very different sugar compositions, were almost exclusively converted into methyl lactate and methyl vinyl glycolate in very similar proportions. Moreover, the conversion of a real hemicellulose hydrolysate obtained from Scots pine through a simple GVL-based organosolv process confirmed the high activity and selectivity of [K]Sn-ß in the studied transformation, opening new pathways for the chemical valorization of this plentiful, but underutilized, sugar feedstock.
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INTRODUCTION: There are no reports in the literature studying the possible relationship between Epstein-Barr virus (EBV) and optic nerve involvement in multiple sclerosis (MS). The aim of our study was to analyze the association between EBV antibodies titres and optical coherence tomography (OCT) and OCT angiography (OCTA) quantitative parameters. METHODS: We conducted a retrospective study. The study included 98 eyes of 49 patients with MS. Years of MS duration, relapse count, history of optic neuritis (ON), and immunoglobulin (Ig) G antibodies to the EBV viral capsid antigen (VCA) were recorded from each patient. Also, OCT analysis (including retinal nerve fibre layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness) and OCTA analysis (including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus) were performed in each participant. RESULTS: No significant associations were observed between anti-EBV antibody levels and OCT or OCTA parameters (p > 0,05). Correlation analysis between OCT and OCTA measurements showed a significant positive correlation between RNFL thickness and GCIPL thickness with peripapillary PD and FI (p < 0,035). Subgroup analysis revealed a significant diminution of RNFL thickness, GCIPL thickness and peripapillary PD and FI (p < 0,05) in the ON group. CONCLUSION: We were unable to demonstrate a significant association between anti-EBV VCA IgG antibody titres and OCT or OCTA parameters. Nonetheless, further longitudinal studies are needed to explore the possible association of EBV with optic nerve involvement in MS.
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INTRODUCTION: Evidence on peripapillary microvasculature in intracranial hypertension (IH) after the regression of papilledema is still scarce. The aim of this preliminary study was to determine the association between structural changes in the optic nerve and the retina and peripapillary microvasculature in patients with IIH. METHODS: We conducted a retrospective study. The study included 39 eyes of 21 patients with IIH. Treatment for IIH and history of obesity were registered from each patient. Moreover, OCT analysis including retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness, and OCTA analysis including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus were performed. RESULTS: Correlation analysis revealed a high correlation between GCIPL thickness and peripapillary PD and FI (p < 0,05, r > 0,7), whereas the degree of correlation between RNFL thickness and peripapillary microvascular parameters was low (p < 0,05, r < 0,7). Patients with regressed papilledema had significantly lower GCIPL thickness and peripapillary PD than control subjects (p < 0,05). CONCLUSION: Peripapillary microvascular measurements are highly correlated with GCIPL thickness in patients with IIH. Moreover, GCIPL thickness and peripapillary PD are significantly inferior in patients with regressed papilledema compared to control group. Thus, we suggested that peripapillary microvascular parameters may be an early indicator of optic nerve atrophy in patients with IIH.