Gender inequalities as contributors to dementia in Latin America and the Caribbean: what factors are missing from research?

The current knowledge of modifiable risk factors for dementia comes mainly from high-income countries. In Latin America and Caribbean countries, where the burden of gender and socioeconomic inequalities is greater than in high-income countries, the prevalence of dementia is also higher and disease onset is earlier, especially among women, even after adjustments for life expectancy. In this Personal View, we discuss socioeconomic modifiable risk factors for dementia established by previous studies and postulate further harmful and often hidden factors faced by women that might influence the gender-specific timing of onset and general prevalence of dementia. We emphasise some of the effects of gender roles, their direct and indirect effects on dementia, and how they disproportionately impact women. Finally, we highlight the importance of bringing hidden risk factors to open discussion to promote research with high-quality data and to encourage public policies to promote and preserve women's health.

Systematic review on post-stroke computerized cognitive training: Unveiling the impact of confounding factors.

Background: Stroke is a highly incapacitating disease that can lead to disabilities due to cognitive impairment, physical, emotional, and social sequelae, and a decrease in the quality of life of those affected. Moreover, it has been suggested that cognitive reserve (patients' higher levels of education or having a skilled occupation), for instance, can promote faster cognitive recovery after a stroke. For this reason, this review aims to identify the cognitive, functional, and behavioral effects of computerized rehabilitation in patients aged 50 years or older who had a stroke, considering cognitive reserve proxies. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-PRISMA, and performed the search for peer-reviewed randomized controlled trials without a date restriction on CINAHL, LILACS, PubMed, Scopus, and Web of Science databases were chosen. Results: We screened 780 papers and found 19 intervention studies, but only 4 met the inclusion criteria and shared data. These studies included computerized tools for motor and cognitive rehabilitation in the experimental groups. In all studies, computerized training was combined with other interventions, such as standard therapy, occupational therapy, and aerobic exercises. There were 104 participants affected by ischemic or hemorrhagic stroke, predominantly male (57.69%), and all with cognitive impairment. Conclusion: Despite a limited number of studies, varied methods and insufficient information available, schooling as a CR proxy combined with high-intensity computerized cognitive training was key to mediating cognitive improvement. The systematic review also identified that the associated ischemic stroke and shorter time of onset for rehabilitation contribute to the cognitive evolution of patients. Findings do not support a greater benefit of computerized cognitive training compared to conventional cognitive therapies. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=296193], identifier [CRD42022296193].

Discerning Developmental Dyscalculia and Neurodevelopmental Models of Numerical Cognition in a Disadvantaged Educational Context.

Developmental Dyscalculia (DD) signifies a failure in representing quantities, which impairs the performance of basic math operations and schooling achievement during childhood. The lack of specificity in assessment measures and respective cut-offs are the most challenging factors to identify children with DD, particularly in disadvantaged educational contexts. This research is focused on a numerical cognition battery for children, designed to diagnose DD through 12 subtests. The aims of the present study were twofold: to examine the prevalence of DD in a country with generally low educational attainment, by comparing z-scores and percentiles, and to test three neurodevelopmental models of numerical cognition based on performance in this battery. Participants were 304 Brazilian school children aged 7-12 years of both sexes (143 girls), assessed by the Zareki-R. Performances on subtests and the total score increase with age without gender differences. The prevalence of DD was 4.6% using the fifth percentile and increased to 7.4% via z-score (in total 22 out of 304 children were diagnosed with DD). We suggest that a minus 1.5 standard deviation in the total score of the Zareki-R is a useful criterion in the clinical or educational context. Nevertheless, a percentile ≤ 5 seems more suitable for research purposes, especially in developing countries because the socioeconomic environment or/and educational background are strong confounder factors to diagnosis. The four-factor structure, based on von Aster and Shalev's model of numerical cognition (Number Sense, Number Comprehension, Number Production and Calculation), was the best model, with significant correlations ranging from 0.89 to 0.97 at the 0.001 level.

Evidence for increased expression of tissue factor and protease-activated receptor-1 in human esophageal cancer.

It has been suggested that the blood clotting initiator protein, tissue factor (TF), participates in tumor growth, metastasis and angiogenesis. In addition, a family of G protein-coupled-receptors known as protease-activated receptors (PARs) has also been implicated in tumor biology. These receptors might be activated by blood coagulation proteases thus eliciting a number of pro-tumoral responses, including the expression of interleukin-8 (IL-8). Therefore, in this study we analyzed the expression of TF, PAR-1, PAR-2 and IL-8 genes in patients with esophageal cancer, one of the most aggressive neoplastic diseases. Total RNA was extracted from tissue samples (tumor and the corresponding normal mucosa) obtained from patients submitted to esophagectomy or endoscopy and further analyzed by semi-quantitative reverse transcriptase-polymerase (RT-PCR) and/or real-time quantitative PCR (qPCR). Expression of full-length transmembrane TF was significantly higher in tumor samples whereas no differences were observed in alternatively spliced TF transcripts. Tumor tissue showed increased mRNA levels for PAR-1 but not PAR-2. Remarkably, IL-8 expression was not detected in most normal tissues but showed very high expression in tumor samples. As expected, qPCR revealed greater differences in the expression pattern of all transcripts analyzed but the general profile was very similar to that observed by RT-PCR. Altogether our data suggest a possible role for blood clotting proteins in the biology of human esophageal cancer.

TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: association with risk factors and tumor characteristics.

Somatic mutations in the TP53 gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern of TP53 mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence of TP53 mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence of TP53 mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous studies, which report the presence of TP53 mutations in tumors with poor prognosis. This correlation between tumor aggressiveness and TP53 mutations could be a crucial variable for the treatment and prognosis of breast cancer.