Silver Nanoparticles (AgNPs) Uptake by Caveolae-Dependent Endocytosis is Responsible for Their Selective Effect Towards Castration Resistant Prostate Cancer.

Purpose: Castration Resistant Prostate Cancer (CRPC) is characterized by poor prognosis and limited therapeutic options. AgNPs functionalized with glucose (G-AgNPs) were observed cytotoxic to CRPC cell lines (PC-3 and Du-145) and not LNCaP. This study aims to evaluate AgNPs and G-AgNPs' uptake mechanisms in these cells and understand their role in the selective effect against CRPC cells. Methods: Uptake of AgNPs and G-AgNPs was assessed through transmission electron microscopy (TEM). A microRNA (miRNAs) analysis approach was used to uncover the main molecular differences responsible for the endocytic mechanisms' regulation. Caveolin (Cav) 1 and 2 mRNA and protein levels were assessed in the three cell lines. Caveolae-dependent endocytosis was inhibited with genistein or siCav1- and siCav2- in PC-3 and Du-145 and resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration. Caveolae-dependent endocytosis was induced with Cav1+ and Cav2+ plasmids in LNCaP, resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration and TEM to assess their location. Results: AgNPs and G-AgNPs were not uptaked by LNCaP. miRNA analysis revealed 37 upregulated and 90 downregulated miRNAs. Functional enrichment analysis of miRNAs' targets resulted in enrichment of terms related to endocytosis and caveolae. We observed that Cav1 and Cav2 are not expressed in LNCaP. Inhibiting caveolae-dependent endocytosis in Du-145 and PC-3 led to a significative reduction of cytotoxic capacity of AgNPs and G-AgNPs and induction of caveolae-dependent endocytosis in LNCaP lead to a significative increase as well as their uptake by cells. Conclusion: This study shows the potential of these AgNPs as a new therapeutic approach directed to CRPC patients, uncovers caveolae-dependent endocytosis as the uptake mechanism of these AgNPs and highlights deregulation of Cav1 and Cav2 expression as a key difference in hormone sensitive and resistant PCa cells which may be responsible for drug resistance.

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine.

BACKGROUND: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. METHODS: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. RESULTS: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. CONCLUSIONS: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

Do Juveniles Who Have Committed Sexual Offenses Have Higher Callous-Unemotional Traits Compared to Juveniles Who Have Committed General Offenses? A Systematic Review.

The importance of assessing psychopathic traits in juveniles who have committed sexual offenses has been established in individuals who demonstrate a particularly severe and violent pattern of behavior. Additionally, the assessment of these traits in other juveniles might be relevant considering that higher levels of these traits represent an increased probability of the juvenile committing offenses. This study is a systematic review of the literature about the presence of callous-unemotional (CU) traits in juveniles who have committed sexual and non-sexual offenses, in order to ascertain eventual differences between these groups regarding the presence of CU traits. Studies were obtained from multiple databases, with predefined exclusion and inclusion criteria, according to PRISMA-P guidelines. A total of 18 studies were reviewed and included in the final analysis. The 18 studies used measures of CU traits and reported descriptive categories of CU traits in juveniles who have committed general offenses or juveniles who have committed sexual offenses. Meta-analytic procedures such as pooled means, pooled variances, and pooled standard deviations are presented in this study. The main conclusion obtained is that juveniles who have committed general offenses present higher levels of CU traits compared to juveniles who have committed sexual offenses. Although the review highlights limitations in the literature, the identification of these characteristics in different types of juveniles who have committed offenses is important to shed light on the phenomenon and develop interventions better suited to their characteristics. Recommendations for future research are also presented.

Callous-Unemotional Traits and Conduct Problems in Children: The Role of Strength and Positive Characteristics.

In recent decades, many researchers have focused on the development of Conduct Problems from childhood to adolescence. Understanding behavior problems also requires an understanding of well-regulated characteristics. Focusing our assessment on strengths makes it possible, on the one hand, to help children or adolescents with deficits in important areas (e.g., socio-emotional deficits) to develop emotional regulation skills and adapt their responses to different contexts. This study aims to understand the role of self-competence, self-regulation, empathy, and responsibility (strength variables) in the relationship between Callous Unemotional characteristics and Conduct Problems, with a sample of 236 children aged between 3 and 10 years (M = 7.51, SD = 1.63), through mediation analysis. In general, our findings suggest that self-regulation significantly explains the relationship between the callous dimension of the Inventory of Callous-Unemotional Traits and Conduct Problems, pointing out that this strength variable seems to act as a protective factor against the development of behavior problems. No other mediation effects were found, and these results are considered in light of some limitations.

Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI) and the ASL MRI challenge.

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

Effects of motor imagery-based neurofeedback training after bilateral repetitive transcranial magnetic stimulation on post-stroke upper limb motor function: an exploratory crossover clinical trial.

OBJECTIVE: To examine the clinical effects of combining motor imagery-based neurofeedback training with bilateral repetitive transcranial magnetic stimulation for upper limb motor function in subacute and chronic stroke. DESIGN: Clinical trial following an AB/BA crossover design with counterbalanced assignment. SUBJECTS: Twenty individuals with subacute (n = 4) or chronic stroke (n = 16). METHODS: Ten consecutive sessions of bilateral repetitive transcranial magnetic stimulation alone (therapy A) were compared vs a combination of10 consecutive sessions of bilateral repetitive transcranial magnetic stimulation with 12 non-consecutive sessions of motor imagery-based neurofeedback training (therapy B). Patients received both therapies (1-month washout period), in sequence AB or BA. Participants were assessed before and after each therapy and at 15-days follow-up, using the Fugl-Meyer Assessment-upper limb, hand-grip strength, and the Nottingham Sensory Assessment as primary outcome measures. RESULTS: Both therapies resulted in improved functionality and sensory function. Therapy B consistently exhibited superior effects compared with therapy A, according to Fugl-Meyer Assessment and tactile and kinaesthetic sensory function across multiple time-points, irrespective of treatment sequence. No statistically significant differences between therapies were found for hand-grip strength. CONCLUSION: Following subacute and chronic stroke, integrating bilateral repetitive transcranial magnetic stimulation and motor imagery-based neurofeedback training has the potential to enhance functional performance compared with using bilateral repetitive transcranial magnetic stimulation alone in upper limb recovery.

Impact of truncating diffusion MRI scans on diffusional kurtosis imaging.

OBJECTIVE: Diffusional kurtosis imaging (DKI) extends diffusion tensor imaging (DTI), characterizing non-Gaussian diffusion effects but requires longer acquisition times. To ensure the robustness of DKI parameters, data acquisition ordering should be optimized allowing for scan interruptions or shortening. Three methodologies were used to examine how reduced diffusion MRI scans impact DKI histogram-metrics: 1) the electrostatic repulsion model (OptEEM); 2) spherical codes (OptSC); 3) random (RandomTRUNC). MATERIALS AND METHODS: Pre-acquired diffusion multi-shell data from 14 female healthy volunteers (29±5 years) were used to generate reordered data. For each strategy, subsets containing different amounts of the full dataset were generated. The subsampling effects were assessed on histogram-based DKI metrics from tract-based spatial statistics (TBSS) skeletonized maps. To evaluate each subsampling method on simulated data at different SNRs and the influence of subsampling on in vivo data, we used a 3-way and 2-way repeated measures ANOVA, respectively. RESULTS: Simulations showed that subsampling had different effects depending on DKI parameter, with fractional anisotropy the most stable (up to 5% error) and radial kurtosis the least stable (up to 26% error). RandomTRUNC performed the worst while the others showed comparable results. Furthermore, the impact of subsampling varied across distinct histogram characteristics, the peak value the least affected (OptEEM: up to 5% error; OptSC: up to 7% error) and peak height (OptEEM: up to 8% error; OptSC: up to 11% error) the most affected. CONCLUSION: The impact of truncation depends on specific histogram-based DKI metrics. The use of a strategy for optimizing the acquisition order is advisable to improve DKI robustness to exam interruptions.

Aportaciones de la alfabetización en salud a la seguridad del paciente en atención primaria: una revisión de alcance / Contributions of Health Literacy for Patient Safety in Primary Care: A Scoping Review / Contribuições do letramento em saúde para a segurança do paciente na atenção primária: scoping review

Introducción: el estudio aporta evidencias científicas sin precedentes para la expansión de la alfabetización en salud como herramienta capaz de aumentar la seguridad del paciente a través de una comunicación eficaz entre los profesionales de la salud y sus pacientes, especialmente en atención primaria. Objetivo: mapear la evidencia sobre el impacto de la alfabetización en salud en la seguridad de la atención a pacientes adultos en atención primaria. Material y método: revisión exploratoria según el método del Instituto Joanna Briggs, en la que se contemplaron cuidados, técnicas, protocolos o métodos de alfabetización en salud utilizados para mejorar la atención primaria de salud. Se utilizaron las bases de datos Medline (PubMed), Web of Science, Scientific Electronic Library Online (SciELO), Virtual Health Library, Scopus, Cinahl y Google Scholar para la literatura gris. Se incluyeron los estudios originales disponibles en su totalidad, publicados hasta enero de 2023, en todos los idiomas que cubrían el tema. Dos pares seleccionaron por título y resumen, y tres pares leyeron los textos completos y extrajeron los datos de los artículos seleccionados, que se presentaron en flujogramas, tablas y narrativas descriptivas. Resultados: se encontraron 3749 estudios, de los que se seleccionaron 23. De ellos surgieron las siguientes categorías: "impacto de la alfabetización en salud sobre el compromiso y los resultados en salud de los usuarios de atención primaria"; "intervenciones que contribuyen a la alfabetización en salud en atención primaria" y "evaluación de las perspectivas de los usuarios y los profesionales sobre la alfabetización en salud". Conclusiones: las intervenciones de alfabetización en salud centradas en la atención primaria deben fomentarse en los servicios de salud para promover la atención, prevenir enfermedades e inspirar el proceso de transformación de la población, lo que repercute directamente en la seguridad de los pacientes.

Introdução: este estudo traz evidências científicas inéditas para a ampliação do letramento em saúde, como uma ferramenta capaz de aumentar a segurança do paciente através da comunicação eficaz entre os profissionais de saúde e seus pacientes, em especial nos cuidados primários em saúde. Objetivo: mapear evidências sobre o impacto do letramento em saúde na segurança do cuidado de pacientes adultos da atenção primária à saúde. Materiais e método: revisão de escopo de acordo com o método do Instituto Joanna Briggs, em que foram contemplados cuidados, técnicas, protocolos ou métodos de letramento em saúde utilizados para melhorar a assistência primária à saúde. Utilizaram-se as bases Medline (PubMed), Web of Science, Scientific Electronic Library Online (SciELO), Biblioteca Virtual em Saúde, Scopus, Cinahl e Google Acadêmico na literatura cinzenta. Foram incluídos estudos originais disponíveis na íntegra, publicados até janeiro de 2023, em todos os idiomas que englobassem a temática. Dois revisores realizaram a triagem por título e resumo, e três revisores leram os textos completos e extraíram dados dos artigos selecionados, sendo apresentados através de fluxo, tabela e narrativa descritiva. Resultados: foram encontrados 3749 estudos, dos quais 23 foram selecionados. Destes, surgiram as seguintes categorias: "impacto do letramento em saúde no engajamento e desfechos de saúde de usuários da atenção primária à saúde"; "intervenções que contribuem para o letramento em saúde na atenção primária à saúde" e "avaliação das perspectivas de usuários e profissionais quanto ao letramento em saúde". Conclusões: intervenções para o letramento em saúde com foco nos cuidados primários devem ser estimuladas dentro dos serviços de saúde a fim de promover o cuidado, prevenir agravos e inspirar o processo de transformação da população, impactando diretamente na segurança do paciente.

Introduction: This study provides unprecedented scientific evidence for the expansion of health literacy as a tool capable of increasing patient safety through effective communication between health care professionals and their patients, especially in primary health care. Objective: To map the evidence available regarding the impact of health literacy on care safety for adult patients in primary health care. Materials and methods: This is a scoping review in line with the Joanna Briggs Institute method, which covers care, techniques, protocols, or health literacy methods used to improve primary health care. The Medline (PubMed), Web of Science, Scientific Electronic Library Online (SciELO), Virtual Health Library, Scopus, Cinahl, and Google Scholar databases were used for the gray literature search. Original studies available in full and published until January 2023, in all languages covering the topic, were included. Two reviewers screened them by title and abstract, and three reviewers read the full texts and extracted data from the selected articles presented in flowcharts, tables, and descriptive narratives. Results: A total of 3749 studies were found, of which 23 were selected. From these, the following categories emerged: 'The impact of health literacy on the engagement and health outcomes of primary health care users;' 'Interventions that contribute to health literacy in primary health care;' and 'Evaluation of users' and professionals' perspectives on health literacy.' Conclusions: Health literacy interventions focused on primary care should be encouraged within health care services to promote care, prevent illnesses, and inspire the population's transformation process, with a direct impact on patient safety.