Myosteatosis in a systemic inflammation-dependent manner predicts favorable survival outcomes in locally advanced esophageal cancer

Increased adiposity and its attendant metabolic features as well as systemic inflammation have been associated with prognosis in locally advanced esophageal cancer (LAEC). However, whether myosteatosis and its combination with systemic inflammatory markers are associated with prognosis of esophageal cancer is unknown. Our study aimed to investigate the influence of myosteatosis and its association with systemic inflammation on progression-free survival (PFS) and overall survival (OS) in LAEC patients treated with definitive chemoradiotherapy (dCRT). We retrospectively gathered information on 123 patients with LAEC submitted to dCRT at the University of Campinas Hospital. Computed tomography (CT) images at the level of L3 were analyzed to assess muscularity and adiposity. Systemic inflammation was mainly measured by calculating the neutrophil-to-lymphocyte ratio (NLR). Median PFS for patients with myosteatosis (n = 72) was 11.0 months vs 4.0 months for patients without myosteatosis (n = 51) (hazard ratio [HR]: 0.53; 95% confidence interval [CI], 0.34-0.83; P = .005). Myosteatosis was also independently associated with a favorable OS. Systemic inflammation (NLR > 2.8) was associated with a worse prognosis. The combination of myosteatosis with systemic inflammation revealed that the subgroup of patients with myosteatosis and without inflammation presented less than half the risk of disease progression (HR: 0.47; 95% CI: 0.26-0.85; P = .013) and death (HR: 0.39; 95% CI, 0.21-0.72; P = .003) compared with patients with inflammation. This study demonstrated that myosteatosis without systemic inflammation was independently associated with favorable PFS and OS in LAEC patients treated with dCRT81669676976FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2018/23428-

Association between non-O blood type and early unexplained recurrent spontaneous abortion in women with and without inherited thrombophilia

We retrospectively evaluated the prevalence of non-O blood type – the most frequently inherited prothrombotic factor – and inherited thrombophilia (IT) in a group of women with recurrent spontaneous abortion (RSA). All consecutive women with a history of early unexplained RSA who underwent a screening for IT between December 2008 and December 2021 were considered for enrolment. A group of healthy, age-matched women with ≥1 normal pregnancy and no adverse pregnancy outcomes acted as controls. Two hundred and seventeen women were enrolled. The adjusted odds ratio (aOR) of RSA in non-O vs. O blood type was 1.37 (95% CI, 1.04-2.78), and in women with vs. without IT was 1.26 (95% CI, 1.08-3.61); aOR of RSA in women with non-O blood type and IT was 2.52 (95% CI, 1.12-5.47). We observed a significant association between non-O blood group or IT and RSA. The concomitant presence of non-O blood group and IT further increases RSA risk

Estudo Exploratório da Conceitualização de Criatividade em Estudantes Universitários

A pesquisa visa a investigar a conceitualização que estudantes universitários têm sobre o que é a criatividade, por meio de análise multidimensional baseada na Teoria das Facetas. Inicialmente solicitou-se que os alunos expressem o que pensam com a evocação da palavra-estímulo criatividade, e a partir deste levantamento, selecionaram-se as 15 palavras mais freqüentemente evocadas. A seguir investigou-se a estrutura conceitual da palavra criatividade através da técnica não-verbal de classificação livre. Os resultados das inter-relações entre todas as variáveis foram analisados por meio da Análise da Estrutura de Similaridade produzindo uma estrutura tipo radex com o item criatividade na região central e cinco regiões distribuídas ao redor da mesma. Estas regiões identificaram cinco dimensões: Estética, Emoção, Gênese, Cognição e Volição. Os significados destas dimensões, em relação às principais questões abordadas pela literatura na área, são discutidos visando a melhor compreender a estrutura representacional do conceito de criatividade.<br>This study aimed to investigate how university students conceive the concept of creativity. We used a multidimensional analysis based on Facet Theory. Initially, we requested that students express what they think following the evocation of the stimulus word creativity; on the basis of this free association, 15 of the more frequently evoked words were selected. Next, we investigated the structure of the creativity concept of the 15 words through a free sort non-verbal task. The results of the interrelations among all the variables were analyzed by means of a Similarity Structure Analysis that produced a radex structure with item creativity in the central area and with five areas distributed around it. These areas identified five dimensions: Aesthetics, Emotion, Genesis, Cognition, and Volition. The meanings of these dimensions in relation to the major conceptual issues in the literature are discussed to seek better to understand the representational structure of the creativity concept

Evaluation and Forecasting Analysis of the Association of Conditional Cash Transfer With Child Mortality in Latin America, 2000-2030

IMPORTANCE: Latin America has implemented the world's largest and most consolidated conditional cash transfer (CCT) programs during the last 2 decades. As a consequence of the COVID-19 pandemic, poverty rates have markedly increased, and a large number of newly low-income individuals, especially children, have been left unprotected. OBJECTIVE: To evaluate the association of CCT programs with child health in Latin American countries during the last 2 decades and forecast child mortality trends up to 2030 according to CCT alternative implementation options. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a multicountry, longitudinal, ecological design with multivariable negative binomial regression models, which were adjusted for all relevant demographic, socioeconomic, and health care variables, integrating the retrospective impact evaluations from January 1, 2000, to December 31, 2019, with dynamic microsimulation models to forecast potential child mortality scenarios up to 2030. The study cohort included 4882 municipalities from Brazil, Ecuador, and Mexico with adequate quality of civil registration and vital statistics according to a validated multidimensional criterion. Data analysis was performed from September 2022 to February 2023. EXPOSURE: Conditional cash transfer coverage of the target (lowest-income) population categorized into 4 levels: low (0%-29.9%), intermediate (30.0%-69.9%), high (70.0%-99.9%), and consolidated (≥100%). MAIN OUTCOMES AND MEASURES: The main outcomes were mortality rates for those younger than 5 years and hospitalization rates (per 1000 live births), overall and by poverty-related causes (diarrheal, malnutrition, tuberculosis, malaria, lower respiratory tract infections, and HIV/AIDS), and the mortality rates for those younger than 5 years by age groups, namely, neonatal (0-28 days), postneonatal (28 days to 1 year), infant (<1 year), and toddler (1-4 years). RESULTS: The retrospective analysis included 4882 municipalities. During the study period of January 1, 2000, to December 31, 2019, mortality in Brazil, Ecuador, and Mexico decreased by 7.8% in children and 6.5% in infants, and an increase in coverage of CCT programs of 76.8% was observed in these Latin American countries. Conditional cash transfer programs were associated with significant reductions of mortality rates in those younger than 5 years (rate ratio [RR], 0.76; 95% CI, 0.75-0.76), having prevented 738 919 (95% CI, 695 641-782 104) child deaths during this period. The association of highest coverage of CCT programs was stronger with poverty-related diseases, such as malnutrition (RR, 0.33; 95% CI, 0.31-0.35), diarrhea (RR, 0.41; 95% CI, 0.40-0.43), lower respiratory tract infections (RR, 0.66, 95% CI, 0.65-0.68), malaria (RR, 0.76; 95% CI, 0.63-0.93), tuberculosis (RR, 0.62; 95% CI, 0.48-0.79), and HIV/AIDS (RR, 0.32; 95% CI, 0.28-0.37). Several sensitivity and triangulation analyses confirmed the robustness of the results. Considering a scenario of moderate economic crisis, a mitigation strategy that will increase the coverage of CCTs to protect those newly in poverty could reduce the mortality rate for those younger than 5 years by up to 17% (RR, 0.83; 95% CI, 0.80-0.85) and prevent 153 601 (95% CI, 127 441-180 600) child deaths by 2030 in Brazil, Ecuador, and Mexico. CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that the expansion of CCT programs could strongly reduce childhood hospitalization and mortality in Latin America and should be considered an effective strategy to mitigate the health impact of the current global economic crisis in low- and middle-income countries

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway(1,2). Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis

PCH: a preservação do patrimônio cultural e natural como política regional e urbana

TThis paper analyzes the roots of the Historical Cities Program (PCH), its creation in 1973, and deactivation in early 1980s. The program was rooted in the insertion of IPHAN in international cooperation network, the ideas of its articulator, Arch. Renato Soeiro, and military government objectives, which included the Northeast development through cultural tourism. The presence of northeastern and northerners people in ministries and higher ranks of the military government has contributed to its creation. After 36 years, Recife replace the leadership of Rio de Janeiro on heritage policy, strengthening local groups and setting off a struggle for control within IPHAN. Without support from the Secretariat of Planning and General Coordination of the Presidency of the Republic, the PCH started to be dismounted by the government of General João Figueiredo in 1979, after a new cultural policy to create a popular base for the "gradual and controlled opening policy." Alongside this ideological shift, the regionalist dispute between groups of Recife and Rio de Janeiro was intensified and the PCH progressively dismounted.Este texto analisa as raízes do Programa das Cidades Históricas, sua criação em 1973 e sua desativação no início da década de 1980. Suas raízes estariam na inserção do Iphan na rede de cooperação internacional, no ideário de seu principal articulador, o arquiteto Renato Soeiro, e no objetivo do governo militar de promover o desenvolvimento da região Nordeste. Para sua criação, teria contribuído a presença de nordestinos e nortistas em ministérios e altos postos do governo militar. Após 36 anos da criação do Sphan, o protagonismo das ações sobre o patrimônio seria transferido do Rio de Janeiro para o Recife, fortalecendo grupos locais e dando início a uma disputa pelo controle do Iphan. Sem contar mais com o apoio da Secretaria de Planejamento e Coordenação Geral da Presidência da República, o PCH começa a ser desativado em 1979, no governo do Gal. João Figueiredo, com uma nova política cultural destinada a criar uma base popular para a "abertura política gradual e controlada". Paralelamente a essa mudança ideológica, se acirra a disputa entre os grupos do Recife e do Rio de Janeiro e se dá a progressiva desativação do PCH