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Abstract Background Experimental studies have shown that repetitive trans-spinal magnetic stimulation (TsMS) decreases demyelination and enables recovery after spinal cord injury (SCI). However, the usefulness of TsMS in humans with SCI remains unclear. Therefore, the main objective of this study is to evaluate the effects of TsMS combined with kinesiotherapy on SCI symptoms. We describe a protocol treatment with TsMS and kinesiotherapy in a patient with SCI due to neuromyelitis optica (NMO)-associated transverse myelitis. Case presentation A 23-year-old white male with NMO spectrum disorders started symptoms in 2014 and included lumbar pain evolving into a mild loss of strength and sensitivity in both lower limbs. Five months later, the symptoms improved spontaneously, and there were no sensorimotor deficits. Two years later, in 2016, the symptoms recurred with a total loss of strength and sensitivity in both lower limbs. Initially, physiotherapy was provided in 15 sessions with goals of motor-sensory recovery and improving balance and functional mobility. Subsequently, TsMS (10 Hz, 600 pulses, 20-seconds inter-trains interval, at 90% of resting motor threshold of the paravertebral muscle) was applied at the 10th thoracic vertebral spinous process before physiotherapy in 12 sessions. Outcomes were assessed at three time points: prior to physiotherapy alone (T-1), before the first session of TsMS combined with kinesiotherapy (T0), and after 12 sessions of TsMS combined with kinesiotherapy (T1). The patient showed a 25% improvement in walking independence, a 125% improvement in balance, and an 18.8% improvement in functional mobility. The Patient Global Impression of Change Scale assessed the patient’s global impression of change as ‘much improved’. Conclusion TsMS combined with kinesiotherapy may safely and effectively improve balance, walking independence, and functional mobility of patients with SCI due to NMO-associated transverse myelitis.

Abstract Proteins in the open ocean represent a significant source of organic matter, and their profiles reflect the metabolic activities of marine microorganisms. Here, by analyzing metaproteomic samples collected from the Pacific, Atlantic and Southern Ocean, we reveal size-fractionated patterns of the structure and function of the marine microbiota protein pool in the water column, particularly in the dark ocean (>200 m). Zooplankton proteins contributed three times more than algal proteins to the deep-sea community metaproteome. Gammaproteobacteria exhibited high metabolic activity in the deep-sea, contributing up to 30% of bacterial proteins. Close virus-host interactions of this taxon might explain the dominance of gammaproteobacterial proteins in the dissolved fraction. A high urease expression in nitrifiers suggested links between their dark carbon fixation and zooplankton urea production. In summary, our results uncover the taxonomic contribution of the microbiota to the oceanic protein pool, revealing protein fluxes from particles to the dissolved organic matter pool.

Abstract The cell-adhesion molecule NEPH1 is required for maintaining the structural integrity and function of the glomerulus in the kidneys. In the nervous system of Drosophila and C. elegans, it is involved in synaptogenesis and axon branching, which are essential for establishing functional circuits. In the mammalian nervous system, the expression regulation and function of Neph1 has barely been explored. In this study, we provide a spatiotemporal characterization of Neph1 expression in mouse dorsal root ganglia (DRGs) and spinal cord. After the neurogenic phase, Neph1 is broadly expressed in the DRGs and in their putative targets at the dorsal horn of the spinal cord, comprising both GABAergic and glutamatergic neurons. Interestingly, we found that PRRXL1, a homeodomain transcription factor that is required for proper establishment of the DRG-spinal cord circuit, prevents a premature expression of Neph1 in the superficial laminae of the dorsal spinal cord at E14.5, but has no regulatory effect on the DRGs or on either structure at E16.5. By chromatin immunoprecipitation analysis of the dorsal spinal cord, we identified four PRRXL1-bound regions within the Neph1 introns, suggesting that PRRXL1 directly regulates Neph1 transcription. We also showed that Neph1 is required for branching, especially at distal neurites. Together, our work showed that Prrxl1 prevents the early expression of Neph1 in the superficial dorsal horn, suggesting that Neph1 might function as a downstream effector gene for proper assembly of the DRG-spinal nociceptive circuit.

The extracellular release of dissolved organic carbon (DOC) from marine macroalgae supports coastal ecosystem function by supplying photosynthetically fixed carbon to higher trophic levels via the microbial loop. Despite its widely acknowledged biogeochemical importance, DOC is not typically included in primary production estimates of coastal systems. Additionally, little is known about how changes in species composition and coverage will affect the supply of DOC to coastal systems. Within the context of the Baltic Sea, anthropogenic forces are driving a decline in habitat forming kelp species (Fucus vesiculosus) which is superseded by filamentous/turfing algal species, a pattern of change observed globally in numerous other aquatic systems. To evaluate how the drivers of this change may impact the flow of carbon within the Baltic Sea coastal system, the production of DOC by the filamentous algae (Ectocarpus siliculosus) was examined and its rate of release determined (0.095 mg C · g DW−1 · h−1 in light and 0.070 mg C · g DW−1 · h−1 in dark). In addition, bioassays were used to assess the short-term DOC use by bacteria as a proxy of the lability of the released products, with the majority (28.7% released in light and 18.6% released in dark) of the products remaining after 120 hours. This data was linked with long term macroalgae biomass and coverage surveys in order to assess changes in macroalgae community structure through time and to produce standing stock estimates of F. vesiculosus. DOC production as a metric of algal coverage was used to make a preliminary estimation of how changes in community structure may impact the flow of carbon within the system. Our results suggest that decreased levels of DOC released by filamentous algae relative to F. vesiculosus will act to reduce microbial activity. Our model estimates the presence of approximately 150,000 tonnes of F. vesiculosus (dry weight) within the Estonian coastal system translating to an annual release of 7,391 tonnes of DOC. Our study indicates that filamentous-dominated systems have likely altered carbon flow, impacting the broader ecology of the Baltic Sea. Consequently, the loss of kelp species and the expansion of filamentous algae may alter carbon dynamics, with important ecological consequences for other coastal systems globally.

Introducción: la intoxicación por monóxido de carbono (CO) es un problema grave de salud. La aparición de secuelas neurológicas tardías incluye trastornos cognitivos, mentales, síntomas piramidales o extrapiramidales. Caso clínico: paciente de 12 años, sexo femenino, luego de 15 días de una intoxicación aguda grave por CO, presenta movimientos coreoatetoideos de miembros superiores, distonías de cuello, discinesias de cara, bradipsiquia y dificultades en la memoria. Resonancia magnética: lesiones isquémicas en globo pálido bilateral, sustancia blanca de hipocampo y cerebelo. Discusión: es fundamental el seguimiento posterior al alta para reconocer las secuelas neurológicas tardías, incluyendo la realización de pruebas neuropsicológicas estandarizadas.

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.

ABSTRACTMetagenomics, metatranscriptomics, and metaproteomics are used to explore the microbial capability of enzyme secretion, but the links between protein-encoding genes and corresponding transcripts/proteins across ecosystems are underexplored. By conducting a multi-omics comparison focusing on key enzymes (carbohydrate-active enzymes [CAZymes] and peptidases) cleaving the main biomolecules across distinct microbiomes living in the ocean, soil, and human gut, we show that the community structure, functional diversity, and secretion mechanisms of microbial secretory CAZymes and peptidases vary drastically between microbiomes at metagenomic, metatranscriptomic, and metaproteomic levels. Such variations lead to decoupled relationships between CAZymes and peptidases from genetic potentials to protein expressions due to the different responses of key players toward organic matter sources and concentrations. Our results highlight the need for systematic analysis of the factors shaping patterns of microbial cleavage on organic matter to better link omics data to ecosystem processes.IMPORTANCEOmics tools are used to explore adaptive mechanism of microbes in diverse systems, but the advantages and limitations of different omics tools remain skeptical. Here, we reported distinct profiles in microbial secretory enzyme composition revealed by different omics methods. In general, the predicted function from metagenomic analysis decoupled from the expression of corresponding transcripts/proteins. Linking omics results to taxonomic origin, functional capability, substrate specificity, secretion preference, and enzymatic activity measurement suggested the substrate's source, concentration and stoichiometry impose strong filtering on the expression of extracellular enzymes, which may overwrite the genetic potentials. Our results present an integrated perspective on the need for multi-dimensional characterization of microbial adaptation in a changing environment.

BackgroundNeuronal Ceroid Lipofuscinosis (NCL) disorders, recognized as the primary cause of childhood dementia globally, constitute a spectrum of genetic abnormalities. CLN8, a subtype within NCL, is characterized by cognitive decline, motor impairment, and visual deterioration. This study focuses on an atypical case with congenital onset and a remarkably slow disease progression.MethodsWhole-genome sequencing at 30× coverage was employed as part of a national genomics program to investigate the genetic underpinnings of rare diseases. This genomic approach aimed to challenge established classifications (vLINCL and EPMR) and explore the presence of a continuous phenotypic spectrum associated with CLN8.ResultsThe whole-genome sequencing revealed two novel likely pathogenic mutations in the CLN8 gene on chromosome 8p23.3. These mutations were not previously associated with CLN8-related NCL. Contrary to established classifications (vLINCL and EPMR), our findings suggest a continuous phenotypic spectrum associated with CLN8. Pathological subcellular markers further validated the genomic insights.DiscussionThe identification of two previously undescribed likely pathogenic CLN8 gene mutations challenges traditional classifications and highlights a more nuanced phenotypic spectrum associated with CLN8. Our findings underscore the significance of genetic modifiers and interactions with unrelated genes in shaping variable phenotypic outcomes. The inclusion of pathological subcellular markers further strengthens the validity of our genomic insights. This research enhances our understanding of CLN8 disorders, emphasizing the need for comprehensive genomic analyses to elucidate the complexity of phenotypic presentations and guide tailored therapeutic strategies. The identification of new likely pathogenic mutations underscores the dynamic nature of CLN8-related NCL and the importance of individualized approaches to patient management.

6G will connect heterogeneous intelligent agents to make them natively operate complex cooperative tasks. When connecting intelligence, two main research questions arise to identify how artificial intelligence and machine learning models behave depending on (i) their input data quality, affected by errors induced by interference and additive noise during wireless communication; (ii) their contextual effectiveness and resilience to interpret and exploit the meaning behind the data. Both questions are within the realm of semantic and goal-oriented communications. With this paper, we investigate how to effectively share communication spectrum resources between a legacy communication system (i.e., data-oriented) and a new goal-oriented edge intelligence one. Specifically, we address the scenario of an enhanced Mobile Broadband (eMBB) service, i.e., a user uploading a video stream to a radio access point, interfering with an edge inference system, in which a user uploads images to a Mobile Edge Host that runs a classification task. Our objective is to achieve, through cooperation, the highest eMBB service data rate, subject to a targeted goal effectiveness of the edge inference service, namely the probability of confident inference on time. We first formalize a general definition of a goal in the context of wireless communications. This includes the goal effectiveness, (i.e., the goal achievability rate, or the probability of achieving the goal), as well as goal cost (i.e., the network resource consumption needed to achieve the goal with target effectiveness). We argue and show, through numerical evaluations, that communication reliability and goal effectiveness are not straightforwardly linked. Then, after a performance evaluation aiming to clarify the difference between communication performance and goal effectiveness, a long-term optimization problem is formulated and solved via Lyapunov stochastic network optimization tools to guarantee the desired target performance. Finally, our numerical results assess the advantages of the proposed optimization and the superiority of the goal-oriented strategy against baseline 5G-compliant legacy approaches, under both stationary and non-stationary communication (and computation) environments.

Abstract Viruses play an important role in the marine ecosystem. However, our comprehension of viruses inhabiting the dark ocean, and in particular, under the Antarctic Ice Shelves, remains limited. Here, we mine single-cell genomic, transcriptomic, and metagenomic data to uncover the viral diversity, biogeography, activity, and their role as metabolic facilitators of microbes beneath the Ross Ice Shelf. This is the largest Antarctic ice shelf with a major impact on global carbon cycle. The viral community found in the cavity under the ice shelf mainly comprises endemic viruses adapted to polar and mesopelagic environments. The low abundance of genes related to lysogenic lifestyle (

Introdução: a partir de uma respiração profunda guiada e consciente, o biofeedback cardiovascular, ferramenta tecnológica inovadora, possibilita melhorar a coerência cardíaca e a ativação do sistema nervoso parassimpático, fundamentais para a recuperação e manutenção da homeostase e da saúde psicoemocional. Objetivo: verificar o efeito do biofeedback cardiovascular sobre os parâmetros da variabilidade da frequência cardíaca dos profissionais da enfermagem. Materiais e método: ensaio clínico randomizado, com dois grupos — biofeedback e placebo —, realizado com 115 profissionais de enfermagem atuantes em unidades de internação clínica e cirúrgica de um hospital universitário, que apresentaram nível geral de estresse maior que 1, conforme a Escala de Sintomas de Estresse. Os grupos participaram de nove encontros por três semanas. O desfecho foi avaliado pelos parâmetros rMSSD e pela coerência cardíaca, ao final de cada encontro, aferidos através do EmWave Pro Plus®, que utiliza fotopletismografia para a quantificação de dados fisiológicos relacionados ao batimento cardíaco. A análise foi feita por equações de estimação generalizadas, considerando α = 5 %. Resultados: evidenciou-se interação tempo-grupo significativa nos parâmetros da coerência cardíaca; o grupo intervenção teve aumento nas médias dos parâmetros da coerência cardíaca em todos os momentos de aferição quando comparado ao grupo controle (p 0,98). Não houve interação tempo-grupo significativa nos parâmetros da rMSSD em nenhum dos momentos de aferição (p = 0,432). Como terapia mente-corpo, o biofeedback cardiovascular mostrou-se útil e promissor, ao promover ativação parassimpática e relaxamento possibilita a prevenção de efeitos deletérios associados aos estressores ocupacionais. Conclusão: intervenção com biofeedback cardiovascular demonstrou efeito superior a placebo na melhora da coerência cardíaca, refletindo em recuperação da homeostase do organismo.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

BackgroundAcceptance and commitment therapy (ACT), as an empirically based third-wave cognitive behavioral therapy, has shown promise in enhancing well-being and functioning across diverse populations. However, in the context of caregiving, the effect size of available ACT interventions remains at best moderate, sometimes accompanied by high dropout rates, highlighting the need for more effective and feasible intervention designs. ObjectiveThe objective of our study was to evaluate the feasibility and acceptability of a fully online ACT program designed for family caregivers of people with dementia. This study aimed to boost psychological flexibility and support caregivers, enabling them to realize and prioritize their own life values alongside their caregiving responsibilities. MethodsA mixed methods feasibility study using an uncontrolled pretest-posttest design was conducted. This intervention included a 9-week web-based self-help program based on ACT incorporating collaborative goal setting and weekly web-based motivational coaching for family caregivers of people with dementia. This study involved 30 informal caregivers recruited through memory clinics and social media platforms in the Netherlands and received approval from the Medical Ethics Committee of the Maastricht University Medical Center+ (NL77389.068.21/metc21-029). ResultsA total of 24 caregivers completed the postintervention assessment, indicating a high adherence rate (24/29, 83%). Caregivers reported positive feedback regarding collaborative goal setting, but some found challenges in implementing new skills due to their own habitual responses or the unpredictable context of dementia caregiving. Personalizing the intervention based on individual value preferences was highlighted as beneficial. ConclusionsCompared to other web-based self-help ACT interventions for family caregivers, this intervention showed a high adherence and sufficient level of feasibility, which underscores the use of personalization in delivering web-based interventions. Moreover, the potential of this ACT-based intervention for family caregivers of people with dementia was demonstrated, suggesting that further research and a larger-scale controlled trial are warranted to validate its effectiveness. International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2022-070499

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.

The habit of eating specific meals has been addressed in several studies, but the evaluation of meal patterns has received less attention. This study aimed to describe the meal patterns of the Brazilian population. A complex sampling design was used to select the 46,164 ≥ 10-year-old individuals examined in the Brazilian National Dietary Survey. Food consumption was assessed by two non-consecutive 24-hour recalls applied throughout a one-week period. The exploratory data analysis approach was used to determine the meal patterns, i.e., how individuals combined the main meals (breakfast, lunch, dinner) and snacks (morning, afternoon, evening/night) throughout the day. The most common meal patterns were three main meals + one snack, reported by 25.1% of the individuals, and three main meals + two snacks (24.6%). Other meal patterns identified were: three main meals + three snacks (18.5%); three main meals and no snacks (10.9%); one or two main meals + two snacks (7.4%); one or two main meals + one snack (6.9%); one or two main meals + three snacks (4.2%); and one or two main meals and no snacks (2.3%). Meal patterns varied according to gender and age group, and on typical versus atypical food consumption days. We found that eight patterns characterized the daily meal consumption in Brazil. Furthermore, around 80% of the population had three main meals every day and about 13% did not report having any snacks. The characterization of meal habits is important for tailoring and targeting health promotion actions.

ObjectiveCaring for a relative with dementia is considered a chronically stressful role associated with negative consequences for psychological health such as higher levels of depression. However, the subjective experience of depressive symptomatology is complex as it relates to two unique domains: positive affect (PA) and negative affect (NA). The objective of this study was to analyze, through a longitudinal design, the associations of caregivers' cognitive (avoidance coping, personal mastery, and coping self-efficacy) and behavioral (frequency of pleasant events) coping strategies with depressive symptoms, PA, and NA.MethodsA total of 111 caregivers of a spouse with dementia participated in this study. They were assessed yearly across 5 years. Mixed model regression analyses were conducted separately for depressive symptoms, PA, and NA, analyzing within and between-person associations of caregivers' age, gender, role overload, sleep quality, and coping variables previously mentioned.ResultsThe results showed that different coping strategies were associated with different components of depressive symptomatology. While avoidant coping was associated with NA and depressive symptoms but not PA at both within- and between-person levels, frequency of pleasant events was associated only with NA and depressive symptoms at the within-person level, showing no effect at the between-person level. Personal mastery and coping self-efficacy were found to be more transversal variables, being associated with most of the mood outcomes in both within and between-person effects.ConclusionFindings support the concept of depressive mood as a complex construct and highlights the importance of analyzing different coping strategies when trying to comprehend the caregiving stress process.

Despite the ending of social distancing and post-pandemic return to normal activities, the impacts of COVID-19 on urban mobility persist, particularly with regard to public transport. Consequently, this study looks into the post-pandemic changes in travel patterns, seeking to comprehend the effects on the municipalities and suggest helpful measures geared to achieving more sustainable patterns following the lockdown isolation. The chosen case study is the Metropolitan Area of Rio de Janeiro, Brazil. The study was divided into four distinct phases, namely understanding the problems, choosing the study area, field research and making recommendations based not only on the literature but on consultation with operators and experts. The methodological process involves the analysis of data from the field research, to assess any changes in patterns that may have been identified. The results show the changes in the means of travel, with emphasis on a preference for app-based transport services, to the detriment of sustainable transport. The study also shows the challenges facing public transport and the relationship between the choice of travel means and the socioeconomic profile of the passenger.

This study examined the association between media and Instagram interaction patterns with weight bias among undergraduate nutrition students in the Brazilian Nutritionists’ Health Study. We also explored the potential mediating role of students’ own body image perception in these relationships. A total of 406 students (78% women) participated in this cross-sectional analysis. Sociodemographic data, media influence, Instagram interaction patterns, body image perception, and weight bias were assessed using semi-structured questionnaires. Findings indicated that exposure to fitness content on Instagram (β = 0.17, p < 0.001) and the pursuit of an ideal athletic body (β = 0.12, p = 0.034) were associated with increased weight bias. In contrast, engagement with body diversity content (β = −0.23, p < 0.001) and perceived pressure from media to conform to appearance ideals (β = −0.24, p < 0.001) had a mitigating effect on weight bias. Notably, body image perception did not mediate these relationships (p > 0.05). In conclusion, this study revealed a link between media exposure and weight bias among undergraduate nutrition students, independent of their body image perception. Developing social media literacy programs that encourage students to critically evaluate media content is imperative to reduce weight bias. Additionally, a deeper examination of the media content that contributes to weight bias and the potential need for targeted regulatory measures is warranted.

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: “What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?”. The research used the descriptors: “extensively drug-resistant tuberculosis” OR “multidrug-resistant tuberculosis” AND “pediatrics”. The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific’s Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Ao longo da história o homem lutou por direito à vida, à liberdade e à igualdade. Após as guerras e as revoluções, normas foram geradas em proteção aos direitos humanos. Algumas normas foram e são fundamentais, sendo; a defesa ao direito natural por Antífona, 1100 a.C; a Carta Magna de João Sem Terra em 1215, a Petition of Rights de 1627, o Habbeas Corpus de 1679; a Bill of Rights de 1789, a Declaração dos direitos dos povos da Virgínia de 1776; a Declaração dos direitos do homem e do cidadão de 1789; e a declaração Universal dos direitos humanos de 1948, após a morte de seis milhões de Judeus, ciganos e homossexuais na segunda guerra mundial; e as Constituições do Brasil de 1988 e a de Portugual de 1976 e revisões. As constituições recepcionaram os direitos humanos estabelecidos na Declaração Universal dos direitos humanos, transformando-os em direitos fundamentais. Entre tais direitos estão os Princípios constitucionais de proteção à vida, à liberdade, à igualdade e à dignidade humana. E, os direitos da personalidade, entre eles o direito à vida, ao nome, à honra e à liberdade. Diante do avanço da ciência e da tecnologia, o direito não tem acompanhado pari passu tal evolução, coreendo-se o risco de danos irreverssíveis à pessoa humana em seus direitos personalíssimos e dignidade. Diante da desigualdade social gritante no Brasil, é preciso que os Princípios Constitucionais em proteção da igualdade e da dignidade humana sejam aplicados, tenham eficácia em defesa da pessoa humana. Quando a desigualdade social provoca a morte física e moral; quando o grito de dor não chega aos ouvidos do Estado, e a desigualdade social gritante torna-se invisível diante do poder estatal, o direito precisa estar atento e ter voz em defesa da dignidade humana. O método a ser utilizado será o dedutivo, com pesquisa em documentos históricos, a travessia do direito na história, análise da doutrina, e legislação.

El derrumbe del Estado afgano en agosto de 2021 corroboró que el state-building impulsado por la intervención internacional fracasó en el propósito de generar la legitimidad y apropiación local necesaria para su consolidación y sostenibilidad porque, al quedar la estrategia de state-building subordinada a los intereses de la lucha antiterrorista, las consideraciones de seguridad prevalecieron sobre los objetivos de reconstrucción nacional, crecimiento económico y buena gobernanza. Así, de hecho, la intervención militar y la ayuda financiera internacional contribuyeron a promover un tipo de Estado rentista y patrimonialista, que consagró los intereses de las viejas élites surgidas de la guerra civil y marginó del poder, de los beneficios de la paz y de los bienes públicos a la mayoría de la población y las regiones del país que el nuevo Estado debía proveer.

ABSTRACT Objective: to assess the burden of spouse and non-spouse caregivers of older adults with stroke-induced-dependency after discharge from a university hospital’s Specialized Care Stroke Unit in southern Brazil. Methods: a longitudinal survey. The sample consisted of 48 consenting caregivers, among which 20 were spouse caregivers. Data were collected between May 2016 and July 2018. One week after discharge, caregivers completed a sociodemographic profile, the Functional Independence Measure, and the Caregiver Burden Scale. Burden was also measured two months after discharge. Data were analyzed using Multivariate Analyses of Variance. Results: regarding time 1, non-spouse caregivers experienced greater burden with respect to social isolation (p = .01). Along with a persistently greater sense of isolation (p=.04), non-spouse caregivers felt far greater general strain (p =.01). Conclusion: statistically significant differences in burden over time highlight the importance of assessing caregiver burden after discharge and the need for a formal support program.