Nuclear GAPDH in cortical microglia mediates cellular stress-induced cognitive inflexibility.

We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. At the mechanistic levels, the microglial secretion of High-Mobility Group Box (HMGB), which is known to bind with and regulate the NMDA-type glutamate receptors, was elevated. Consequently, the hyperactivation of the prelimbic layer 5 excitatory neurons, a neural substrate for cognitive inflexibility, was also observed. The upregulation of the microglial HMGB signaling and neuronal hyperactivation were normalized by the pharmacological and microglia-specific genetic interventions. Taken together, we show a pivotal role of cortical microglia and microglia-neuron interaction in stress-induced cognitive inflexibility. We underscore the N-GAPDH cascade in microglia, which causally mediates stress-induced cognitive alteration.

Efficiency of psychological interventions in the prevention of suicidal behavior and self-injury in penitentiary population: A systematic review.

INTRODUCTION: Suicidal behavior is an important public health problem, with a high prevalence in penitentiary context. Nowadays, there is a wide variety of specific treatment programs, aimed to prevent suicidal and self-injurious behavior in incarcerated people. These programs show relative efficiency depending on the model of the psychological intervention applied. This systematic review evaluates the efficiency of suicidal and self-injurious behavior prevention programs in prisons. METHOD: Empirical studies, evaluating prevention programs for suicidal and self-injurious behavior in penitentiary context were considered for inclusion. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) directives were followed. Studies from 1990 to 2022 were reviewed, based on the review developed by Winicov (2019) that covered the time lapse between 1990 and 2015. Articles from 2015 to 2022 were located by database research (EBSCOHost, ScienceDirect, PubMed & ProQuest). RESULTS: 44,050 potential studies were identified. Eighteen were included in this systematic review (9 studies by Winicov, 2019). 14 studies showed efficacy of intervention programs on self-injury behavior. The use of Cognitive Behavioral Therapy (CBT) reduced suicidal ideation. In addition, positive results were observed in 3 studies using third-generation therapies as an intervention. CONCLUSIONS: Suicidal and self-injurious behavior in prison shows lower levels of incidence when specific treatment programs are applied. It's crucial to increase the evaluation in relation to the implementation of new treatment models (i.e., Dialectical Behavior Therapy - DBT, Acceptance and Commitment Therapy - ACT, Mindfulness, Functional Analytic Psychotherapy - FAP) as to better orientate prevention strategies. Further research is needed in gender sensitive interventions.

Coping strategies for COVID-19 primary care: a mixed method study. / Estratégias de enfrentamento da COVID-19 na atenção primária: estudo de método misto.

This article aims to analyse the COVID-19 coping strategies adopted by municipal health managers in two regions. A mixed method study of the sequential explanatory type was carried out with municipal health managers and primary care coordinators. The quantitative stage was developed with the application of an instrument to 42 managers to identify coping actions and associations with demographic and epidemiological data of COVID-19 in the municipalities. The results aimed at the definition of 15 participants and the collection of data in the qualitative stage, enabling approximation of the meta inferences of the study. Of the actions implemented, there were immediate actions to monitor cases, organize new care flows and encourage the population to adopt nonpharmacological measures. Regional articulation was the device that allowed for expansion and municipal autonomy for testing, reducing contamination and deaths among citizens. Municipal coping strategies that focused on the surveillance of cases and expansion of testing showed positive outcomes in terms of the number of infections and deaths from COVID-19.

O objetivo deste artigo é analisar as estratégias de enfrentamento da COVID-19 adotadas por gestores municipais de saúde em duas regiões. Estudo de método misto do tipo explanatório sequencial, realizado com gestores municipais de saúde e coordenadores da atenção primária. A etapa quantitativa foi desenvolvida com a aplicação de instrumento a 42 gestores, para identificação de ações de enfrentamento e associação com dados demográficos e epidemiológicos da COVID-19 nos municípios. Os resultados direcionaram à definição de 15 participantes e à coleta de dados na etapa qualitativa, possibilitando aproximação das metainferências do estudo. Das ações implantadas, foram unânimes as ações de monitoramento dos casos, organização de novos fluxos de atendimento e estímulo à adoção de medidas não farmacológicas pela população. A articulação regional foi o dispositivo que permitiu ampliação e autonomia municipal para a testagem, com redução de contaminação e óbitos nos munícipes. As estratégias municipais de enfrentamento que tiveram foco na vigilância dos casos e na ampliação da testagem apresentaram desfechos positivos no que se refere a número de óbitos por COVID-19.

Estratégias de enfrentamento da COVID-19 na atenção primária: estudo de método misto / Coping strategies for COVID-19 primary care: a mixed method study

Resumo O objetivo deste artigo é analisar as estratégias de enfrentamento da COVID-19 adotadas por gestores municipais de saúde em duas regiões. Estudo de método misto do tipo explanatório sequencial, realizado com gestores municipais de saúde e coordenadores da atenção primária. A etapa quantitativa foi desenvolvida com a aplicação de instrumento a 42 gestores, para identificação de ações de enfrentamento e associação com dados demográficos e epidemiológicos da COVID-19 nos municípios. Os resultados direcionaram à definição de 15 participantes e à coleta de dados na etapa qualitativa, possibilitando aproximação das metainferências do estudo. Das ações implantadas, foram unânimes as ações de monitoramento dos casos, organização de novos fluxos de atendimento e estímulo à adoção de medidas não farmacológicas pela população. A articulação regional foi o dispositivo que permitiu ampliação e autonomia municipal para a testagem, com redução de contaminação e óbitos nos munícipes. As estratégias municipais de enfrentamento que tiveram foco na vigilância dos casos e na ampliação da testagem apresentaram desfechos positivos no que se refere a número de óbitos por COVID-19.

Abstract This article aims to analyse the COVID-19 coping strategies adopted by municipal health managers in two regions. A mixed method study of the sequential explanatory type was carried out with municipal health managers and primary care coordinators. The quantitative stage was developed with the application of an instrument to 42 managers to identify coping actions and associations with demographic and epidemiological data of COVID-19 in the municipalities. The results aimed at the definition of 15 participants and the collection of data in the qualitative stage, enabling approximation of the meta inferences of the study. Of the actions implemented, there were immediate actions to monitor cases, organize new care flows and encourage the population to adopt nonpharmacological measures. Regional articulation was the device that allowed for expansion and municipal autonomy for testing, reducing contamination and deaths among citizens. Municipal coping strategies that focused on the surveillance of cases and expansion of testing showed positive outcomes in terms of the number of infections and deaths from COVID-19.

Altered emotional response pattern related to complex trauma in patients with borderline personality disorder.

INTRODUCTION: This work aims to demonstrate, through the International Affective Picture System (IAPS) responses, an altered emotional pattern in borderline personality disorder (BPD) patients and to find a specific emotional response pattern by understanding their relationship with traumatic experiences and attachment bonds towards their primary caregivers. METHOD: A total of 50 BPD patients and 39 control patients were evaluated using the IAPS, and its assessment was carried out through the Self-Assessment Manikin (SAM). Paternal and maternal attachment bonds as well as traumatic experiences in BPD patients were evaluated. Statistical associations were analysed in the different variables. RESULTS: Significant differences between BPD and control patients were found in all emotional response components for pleasant, unpleasant and neutral images (p < .01), with one exception, the arousal in pleasant images. Patients' experience of traumatic experiences was positively related to scores on the happiness component of pleasant imagery (p = .057) and on the arousal component of unpleasant imagery (p = .058). Poorer maternal bonding in BPD patients was significantly related to lower scores on happiness (p < .01) and dominance (p < .05) components of pleasant imagery and all emotional response components for unpleasant imagery (p < .01). CONCLUSIONS: The results of the study confirm an impaired emotional response pattern in patients with borderline personality disorder (BPD), showing an emotional response to pleasant images similar to that of depression, while the pattern found to unpleasant images could be related to the complex trauma observed in these patients, which includes PTSD experiences such as sexual abuse and attachment trauma experiences.

Immunometabolic alterations in older adults with heightened depressive symptom trajectories: a network approach.

Objective: To analyse the patterns of relationships between depressive symptoms and immunometabolic markers across longitudinal depression status in older people. Methods: A sample of 3349 older adults (55.21% women; initial age: m = 58.44, sd = 5.21) from the English Longitudinal Study of Ageing was used. Participants were classified according to their longitudinal depression status: minimal depressive symptoms (n = 2736), depressive episode onset (n = 481), or chronic depression (n = 132). Network analysis was used to study the relationships between depression symptoms (CES-D 8 items), inflammatory (white blood cell, C-reactive protein, fibrinogen) and metabolic biomarkers (metabolic syndrome markers). Results: Network structure remained invariant across groups. The minimal symptom group had higher overall strength than both clinical groups (p < .01). Moreover, significant relationships between symptoms and markers were observed across group-specific networks. C-reactive protein and effort symptom were positively connected in the minimal symptom group but not in the other groups. Loneliness and diastolic blood pressure were positively associated only in the chronic depression group. Finally, metabolic markers were identified as central nodes in the clinical status networks. Conclusion: The network analysis constitutes a useful approach to disentangle pathophysiological relationships that may maintain mental disorders in old age.

Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Epidemiological and clinical characterization of a population-based cohort of cutaneous malignant melanoma patients in the South Region of Portugal.

An historical population-based cohort study was conducted aiming to estimate the incidence of cutaneous malignant melanoma in the South Region of Portugal between Jan 2016 and June 2017; to clinically characterize the diagnosed individuals; to describe instituted treatment; and to estimate survival outcomes. Data were extracted from a cancer registry (ROR-Sul) covering 4,800,000 inhabitants (46% of the Portuguese population) and included a total of 789 individuals meeting eligibility criteria. The crude incidence rate (18 months) of melanoma was 13.36/100,000 inhabitants and the Age-Standardized Incidence Rate per 100,000 World population was 9.65/100,000 inhabitants. The most common histological subtypes identified were superficial extension, followed by malignant melanoma and nodular melanoma. Most cases were diagnosed in stage I (50.39%), equally distributed by sex and with a median age of 65 years. During the study period, 174 recurrence events were recorded (23.45%) and recurrence-free survival rate was significantly lower in more advanced stages. Patients had a two-fold risk of recurrence/death when in presence of ulcerated tumors [adjusted hazard ratio (adj HR) = 2.28; 95% confidence interval (CI) 1.40-3.70]. Overall survival rate at 3-years was 80.54% (95% CI 77.58-83.15), higher than previous national reports, and considerably higher for individuals diagnosed at earlier stages (p < 0.001). We have also identified differential survival outcomes in stages II-III explained by the uptake of sentinel lymph node biopsy. The epidemiologic and clinical characteristics of malignant melanoma patients studied are consistent with international literature. The incidence and rates observed suggests additional public health campaigns are needed to modify behaviours of the Portuguese population and thus reduce their risk.

The Impact of the COVID-19 Pandemic on Medical Education: a Systematic Review of Distance Learning, Student's Perceptions, and Mental Health

Introduction: the COVID-19 pandemic has impacted on mortality and several adverse health outcomes. It has also affected education as schools and universities had to adapt to remote learning due to social isolation strategies.Objective: to analyze the pandemic's impact on medical education including undergraduate and graduate students and lecturers, as follow: i) teaching methods adopted by education institutes during shutdown, ii) students and lecturers' perceptions and iii) impacts on students' mental health.Methods: this systematic review includes the following study designs: cross-sectional, surveys, case-control, cohort, and clinical trials. The literature search was performed in four databases: PubMed, Scopus, Embase, and SciELO . The risk of bias and the quality of the evidence were evaluated.Results: a total of 1,576 articles were identified through searching databases, and 40 articles were included. We found the use of several teaching methods such as virtual platforms and social media, pre-recorded videos, discussion forums and others. Student's challenges related to interference during online study such as family distractions, lack of a study room, challenges with internet connectivity, difficulties in communication between students and lecturers, gaps encountered during clinical skills learning. Lecturers' challenges were difficulty in grasping students' progress and learning outcomes and the lack of experience in online teaching. Only five studies explored mental health issues of medical students and found the occurrence of depression, anxiety, and stress. However, their prevalence was not comparable due to the use of different diagnostic instruments.Conclusion: there has been a wide range of teaching methods implemented for distance learning of medical students globally. The perceptions of medical students about these methods and their impact were also varied. Infrastructure, family, and curriculum problems represented the greatest difficulties in adherence and satisfaction with distance learning. However, the flexibility of digital learning was one of the factors that helped reduce these problems. Regarding mental health, the occurrence of anxiety, depression, and stress was reported.

Introdução: a pandemia de COVID-19 teve impacto na mortalidade e em vários resultados adversos para a saúde. Também afetou a educação, pois escolas e universidades tiveram que se adaptar ao ensino remoto devido às estratégias de isolamento social.Objetivo: analisar o impacto da pandemia na educação médica, incluindo alunos de graduação e pós-graduação e professores, a saber: i) métodos de ensino adotados pelas instituições de ensino durante a paralisação, ii) percepções de alunos e professores e iii) impactos na saúde mental dos alunos.Método: esta revisão sistemática inclui os seguintes desenhos de estudo: transversal, surveys, caso-controle, coorte e ensaios clínicos. A pesquisa bibliográfica foi realizada em quatro bases de dados: PubMed, Scopus, Embase e SciELO. O risco de viés e a qualidade da evidência foram avaliados.Resultados: um total de 1.576 artigos foram identificados por meio de busca em bancos de dados, e 40 artigos foram incluídos. Constatamos a utilização de diversos métodos de ensino como plataformas virtuais e redes sociais, vídeos pré-gravados, fóruns de discussão e outros. Desafios dos alunos relacionados à interferência durante o estudo online, como distrações familiares, falta de uma sala de estudo, desafios com conectividade à Internet, dificuldades de comunicação entre alunos e professores, lacunas encontradas durante o aprendizado de habilidades clínicas. Os desafios dos professores foram a dificuldade em compreender o progresso dos alunos e os resultados de aprendizagem e a falta de experiência no ensino online. Apenas cinco estudos exploraram questões de saúde mental de estudantes de medicina e encontraram a ocorrência de depressão, ansiedade e estresse. No entanto, sua prevalência não foi comparável devido ao uso de diferentes instrumentos de diagnóstico.Conclusão: existe uma ampla gama de métodos de ensino implementados para o ensino a distância de estudantes de medicina em todo o mundo. As percepções dos estudantes de medicina sobre esses métodos e seu impacto também foram variadas. Problemas de infraestrutura, família e currículo representaram as maiores dificuldades de adesão e satisfação com o ensino a distância. No entanto, a flexibilidade do aprendizado digital foi um dos fatores que ajudou a reduzir esses problemas. Em relação à saúde mental, foi relatada a ocorrência de ansiedade, depressão e estresse.

Vulnerabilidades entre mulheres em situação de rua vivenciando a gestação, parto e puerpério / Vulnerabilidades entre mujeres sin hogar viviendo el embarazo, parto y puerperio / Vulnerabilities among homeless women experiencing pregnancy, childbirth and puerperium

Resumo Objetivo compreender os aspectos que conferem vulnerabilidades às mulheres que vivenciam a gestação, o parto e o puerpério nas ruas. Método pesquisa qualitativa desenvolvida com doze mulheres em um município do sul do Brasil, mediante análise temática de entrevistas em profundidade, sob a luz dos referenciais da Vulnerabilidade e dos Direitos Humanos. Resultados três categorias temáticas descrevem situações de discriminações e violências que repercutem em vulnerabilidades tanto durante a gestação e o pré-natal, quando as mulheres (invisíveis) se tornam mães (visíveis), quanto no momento do parto, em que se evidencia o (des)cuidado e a (des)assistência, e também no puerpério, marcado pelo rompimento dos vínculos com os bebês. Conclusões e implicações para a prática sucessivas intervenções de controle, descaso, desinformação e negligência, bem como a falta de acolhimento e suporte, deixaram explícitas a carência de ações e políticas públicas que valorizem as singularidades dessas mulheres. A partir dos achados, entende-se a urgência da sensibilização dos profissionais de saúde para atuar respeitando a autonomia dessas mulheres para o exercício pleno de seus direitos sexuais e reprodutivos, bem como da efetivação de estratégias para a construção de um cuidado em saúde comprometido com a justiça e proteção social, mitigando vulnerabilidades e promovendo direitos.

Resumen Objetivo comprender las vulnerabilidades de mujeres sin hogar que viven el embarazo, parto y puerperio. Método investigación cualitativa realizada con doce mujeres de un municipio del sur de Brasil, a través del análisis temático de entrevistas en profundidad, a la luz de los marcos Vulnerabilidad y Derechos Humanos. Resultados tres categorías temáticas describen situaciones de discriminación y violencia que inciden en vulnerabilidades durante el embarazo y prenatal, cuando las mujeres (invisibles) se convierten en madres (visibles), así como en el parto, cuando se evidencia la falta de cuidados y asistencia, como también en el puerperio, marcado por la ruptura de vínculos con los bebés. Conclusiones e implicaciones para la práctica sucesivas intervenciones de control, descuido, desinformación y negligencia, así como la falta de acogida y apoyo explicitaron la falta de acciones y políticas públicas que valoren las singularidades de estas mujeres. A partir de los hallazgos, se comprende la urgencia de sensibilizar profesionales de salud para actuaren respetando la autonomía de estas mujeres para el ejercicio pleno de sus derechos sexuales y reproductivos, así como la implementación de estrategias para la construcción de un cuidado en salud comprometido con la justicia y la protección social, mitigando vulnerabilidades y promoviendo derechos.

Abstract Objective to understand the aspects that confer vulnerabilities to the women who experience pregnancy, childbirth, and puerperium on the streets. Method qualitative research developed with twelve women in a southern city of Brazil, through a thematic analysis with in-depth interviews, in light of the Vulnerability and Human Rights framework. Results three thematic categories describe situations of discrimination and violence that have repercussions on vulnerabilities during pregnancy and prenatal care, when (invisible) women become (visible) mothers, and at the time of childbirth, in which (the lack of) care and assistance is evident, and also in the puerperium, marked by the breaking of bonds with the babies. Conclusions and implications for practice successive interventions of control, carelessness, misinformation and negligence, as well as the lack of acceptance and support made explicit the lack of actions and public policies that value the singularities of these women. From the findings, it is understood the urgency of raising the awareness of health professionals to act respecting the autonomy of these women for the full exercise of their sexual and reproductive rights, as well as the implementation of strategies for the construction of a health care committed to justice and social protection, mitigating vulnerabilities and promoting rights.

Uso de la toxina botulinica tipo a versus trihexifenidilo en la hiperextensión axial en niños con parálisis cerebral. Distónica en el centro de rehabilitación e inclusión infantil Estado de México / Use of botulinum toxin type a versus trihexyphenidyl in axial hiperextensión in children with distonic cerebral palsy

La distonía es, tras la espasticidad y los tics, el trastorno del movimiento más frecuente en la infancia. Los niños sufren más frecuentemente que los adultos distonías generalizadas. Las distonías secundarias más habituales son las debidas a parálisis cerebral, a menudo asociada a espasticidad y a otros movimientos anormales. Este estudio compara la efectividad de la aplicación de toxina botulínica tipo A versus trihexifenidilo en el tratamiento de la hiperextensión axial en niños con PC distónica. Hubo dos grupos de estudio, grupo A: toxina botulínica grupo B: trihexifenidilo en ambos grupos se realizó una historia clínica, se aplicó la escala de valoración de distonía (AIMS) para tronco, capacidad motora gruesa (GFCS) y escala de alineamiento y posición. El análisis estadístico se realizó mediante el paquete de SPSS-18 y prueba de U-Mann Whitney. Se incluyeron 14 niños, 7 para el grupo de toxina botulínica (50%) y 7 para el grupo de Trihexifenidilo (50%). El estudio mostró que el uso de toxina botulínica y trihexifenidilo son ´tiles para el tratamiento de hiperextensión axial en niños parálisis cerebral distónica, si embargo hubo superioridad en los resultados con el empleo de toxina botulínica en el alineamiento y posición.

Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry.

Recent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function1,2. Microglia infiltrate the neuroepithelium early in embryonic development and are maintained in the brain throughout adulthood3,4. Several maternal environmental factors-such as an aberrant microbiome, immune activation and poor nutrition-can influence prenatal brain development5,6. Nevertheless, it is unknown how changes in the prenatal environment instruct the developmental trajectory of infiltrating microglia, which in turn affect brain development and function. Here we show that, after maternal immune activation (MIA) in mice, microglia from the offspring have a long-lived decrease in immune reactivity (blunting) across the developmental trajectory. The blunted immune response was accompanied by changes in chromatin accessibility and reduced transcription factor occupancy of the open chromatin. Single-cell RNA-sequencing analysis revealed that MIA does not induce a distinct subpopulation but, rather, decreases the contribution to inflammatory microglia states. Prenatal replacement of microglia from MIA offspring with physiological infiltration of naive microglia ameliorated the immune blunting and restored a decrease in presynaptic vesicle release probability onto dopamine receptor type-two medium spiny neurons, indicating that aberrantly formed microglia due to an adverse prenatal environment affect the long-term microglia reactivity and proper striatal circuit development.

Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease.

Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas. Considering the pressing need for a better understanding of the relevance of alcohol abuse in dementia progression, here we summarize the molecular mechanisms of neuroinflammation observed in alcohol abuse and Alzheimer's disease, the most common cause of dementia. In addition, we highlight mechanisms that are already established in the field of Alzheimer's disease that may be relevant to explore in alcoholism to better understand alcohol mediated neurodegeneration and dementia, including the relevance of the liver-brain axis.

Tools for Assessing Knowledge of Back Health in Adolescents: A Systematic Review Protocol.

Back pain is common in adolescents as a result of their typical daily activities. There is a critical need for developing instruments that can assess the adolescents' knowledge of proper posture, because adequate postural habits are essential for preventing back pain and facilitating physical well-being. Unfortunately, there is insufficient understanding about appropriate back health in the general public, even though this knowledge is decisive in the development of physical skills and attainment of health literacy. Furthermore, relevant substantive literature is scarce. Therefore, the proposed systematic review aims to identify instruments that are used for assessing knowledge of back health in adolescents. Relevant search terms and descriptors will be combined, and searches will be carried out in a uniform sequence within the PubMed, Embase, CINAHL, and Cochrane Library databases. Eligible articles must present data on the assessment of the adolescents' knowledge of back health and describe the applied instrumentation. Articles will be selected by two reviewers independently; all disagreements will be resolved by a third reviewer. Mendeley and the Rayyan software will be used for the systematic review, and the checklist proposed by Brink and Louw will be used to verify the methodological quality of the included studies. Our findings may confirm the relevance of constructing and validating back health instruments for use in Brazil and other countries.

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study.

BACKGROUND: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). MATERIALS AND METHODS: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). RESULTS: A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08). CONCLUSION: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.