Zika virus congenital microcephaly severity classification and the association of severity with neuropsychomotor development.

BACKGROUND: Zika virus infection during pregnancy is linked to birth defects, most notably microcephaly, which is associated with neurodevelopmental delays. OBJECTIVE: The goals of the study were to propose a method for severity classification of congenital microcephaly based on neuroradiologic findings of MRI scans, and to investigate the association of severity with neuropsychomotor developmental scores. We also propose a semi-automated method for MRI-based severity classification of microcephaly. MATERIALS AND METHODS: We conducted a cross-sectional investigation of 42 infants born with congenital Zika infection. Bayley Scales of Infant and Toddler Development III (Bayley-III) developmental evaluations and MRI scans were carried out at ages 13-39 months (mean: 24.8 months; standard deviation [SD]: 5.8 months). The severity score was generated based on neuroradiologist evaluations of brain malformations. Next, we established a distribution of Zika virus-microcephaly severity score including mild, moderate and severe and investigated the association of severity with neuropsychomotor developmental scores. Finally, we propose a simplified semi-automated procedure for estimating the severity score based only on volumetric measures. RESULTS: The results showed a correlation of r=0.89 (P<0.001) between the Zika virus-microcephaly severity score and the semi-automated method. The trimester of infection did not correlate with the semi-automated method. Neuropsychomotor development correlated with the severity classification based on the radiologic readings and semi-automated method; the more severe the imaging scores, the lower the neuropsychomotor developmental scores. CONCLUSION: These severity classification methods can be used to evaluate severity of microcephaly and possible association with developmental consequences. The semi-automated methods thus provide an alternative for predicting severity of microcephaly based on only one MRI sequence.

Using LC and Hierarchical Cluster Analysis as Tools to Distinguish Timbó Collections into Two Deguelia Species: A Contribution to Chemotaxonomy.

The species Deguelia utilis and Deguelia rufescens var. urucu, popularly known as "timbó," have been used for many years as rotenone sources in insecticide formulations. In this work, a method was developed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system, and results were analyzed using hierarchical cluster analysis (HCA). By quantifying the major rotenoids of these species, it was possible to establish a linear relation between them. The ratio between the concentrations of rotenone and deguelin for D. utilis is approximately 1:0.8, respectively, while for D. rufescens var. urucu it is 2:1. These results may help to distinguish these species contributing to their taxonomic identification.

Heart failure with preserved ejection fraction: emerging drug strategies.

Approximately half of heart failure patients have a normal ejection fraction, a condition designated as heart failure with preserved ejection fraction (HFpEF). This heart failure subtype disproportionately affects women and the elderly and is commonly associated with other cardiovascular comorbidities, such as hypertension and diabetes. HFpEF is increasing at a steady rate and is predicted to become the leading cause of heart failure within a decade. HFpEF is characterized by impaired diastolic function, thought to be due to concentric remodeling of the heart along with increased stiffness of both the extracellular matrix and myofilaments. In addition, oxidative stress and inflammation are thought to have a role in HFpEF progression, along with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling. Surprisingly a number of clinical studies have failed to demonstrate any benefit of drugs effective in heart failure with systolic dysfunction in HFpEF patients. Thus, HFpEF is one of the largest unmet needs in cardiovascular medicine, and there is a substantial need for new therapeutic approaches and strategies that target mechanisms specific for HFpEF. This conclusion is underscored by the recently reported disappointing results of the RELAX trial, which assessed the use of phosphodiesterase-5 inhibitor sildenafil for treating HFpEF. In animal models, endothelial nitric oxide synthase activators and If current inhibitors have shown benefit in improving diastolic function, and there is a rationale for assessing matrix metalloproteinase 9 inhibitors and nitroxyl donors. LCZ696, a combination drug of angiotensin II receptor blocker and neprilysin inhibitor, and the aldosterone receptor antagonist spironolactone are currently in clinical trial for treating HFpEF. Here we present an overview of the etiology and diagnosis of HFpEF that segues into a discussion of new therapeutic approaches emerging from basic research and drugs currently in clinical trial that primarily target diastolic dysfunction or imbalanced ventricular-arterial coupling.

Computerized working memory training for hypertensive individuals with executive function impairment: a randomized clinical trial.

Background: Hypertension is associated with working memory (WM) impairment. However, the benefits of Cogmed WM training for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed's effects on the WM performance of hypertensive individuals with executive function (EF) impairment. Methods: We included 40 hypertensive patients (aged 40-70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive 10 weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were verbal memory, visuospatial ability, executive function, global cognition, and the neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Results: Cogmed did not show a significant effect on WM or any other cognitive outcome post-training. However, under the WM-low load and WM-high load conditions of the fMRI, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analyses) and left inferior frontal lobe (PP analysis) in comparison to the control group. Conclusion: The Cogmed showed no effects on the WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting a more efficient neuronal activity after training.

Higher Perceived Stress as an Independent Predictor for Lower Use of Emotion-Focused Coping Strategies in Hypertensive Individuals.

Introduction: Individuals with high scores of perceived stress (PS) are more likely to develop arterial hypertension (AH) than those with low levels of stress. In addition to this, AH and stress are both independent risk factors for executive function (EF) impairment and worse quality of life (QoL). Therefore, strategies to control and cope with emotional stress are of paramount importance. However, less is known about the association of PS with EF, QoL, and coping in individuals with hypertension. This study aimed to evaluate the association of PS with EF performance, coping strategies use, and QoL in a sample of hypertensive patients. Methods: We assessed a group of 45 hypertensive individuals (mean age = 58.42 ± 8.9 years, 71.11% female). The EF evaluation was: Frontal Assessment Battery; Controlled Oral Word Association Test-FAS; Letter-Number Sequencing subtest from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III); Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test. The type and frequency of coping strategies used were measured by the Brief Coping with Experienced Problems Scale (Brief-COPE). The World Health Organization Quality of Life Questionnaire Bref (WHOQOL-bref) was applied to measure QoL. The associations of the PS with EF performance, coping strategies, and QoL were investigated using univariate and multiple linear regression models adjusted for age, sex, education, systolic pressure, and depression symptoms. Results: In the multivariate analyses, higher PS was an independent predictor for a lower frequency of emotion-focused strategy use (ß = -0.23; p = 0.03). However, PS was not significantly related to EF and Qol in this sample. The lower the PS, the greater the use of emotion-focused coping. Conclusion: Hypertensive individuals with high PS use less frequently positive emotion-focused coping strategies.

CDC25B Inhibition by Menadione: A Potential New Therapeutical Approach.

Gastric cancer (GC) is the fifth most common type of tumor and the third leading cause of cancer death worldwide. The evolution of gastric carcinogenesis is still poorly understood and, for this reason, preclinical research protocols were established that included the development of gastric cancer cell lines and the establishment of models of gastric carcinogenesis in non-human primates such as Sapajus apella. A comprehensive literature search was performed in relevant databases such as PubMed, ResearchGate, and Google Scholar to identify studies related to the topic. After an in-depth study of these reports, significant data were collected and compiled under appropriate headings. The main result of the studies carried out by the group on GC is the demonstration of the MYC gene overexpression as a common phenomenon in stomach carcinogenesis. Furthermore, we revealed that reducing the expression of the CDC25B gene, regulated by the MYC protein, is a therapeutic strategy against stomach tumors. This review article reveals preclinical evidence that treatment with menadione in experimental models of gastric tumorigenesis, in vivo and in vitro, inhibits the action of the phosphatase CDC25B and, consequently, prevents cell proliferation, invasion, and migration.

Metabolomics Reveals a 26-Membered Macrolactone Produced by Endophytic Colletotrichum spp. from Alcatrazes Island, Brazil.

Comparative metabolomics analysis of nonphytotoxic endophytic Colletotrichum spp. isolated from Anthurium alcatrazense endemic to Alcatrazes island (Brazil) and phytopathogenic Colletotrichum spp. isolated from the mainland of Brazil revealed significant differences in chemical composition. Examination of endophytic Colletotrichum spp. from Alcatrazes island led to the discovery of a 26-member macrolactone, colletotrichumolide (1), containing a phosphatidyl choline side chain. Further examination of the phytopathogenic strains from the mainland identified a family of phytopathogenic metabolites not present in the nonpathogenic island-derived strains, suggesting that geographical isolation could influence the secondary metabolism of fungal strains.

Route learning performance: is it a hippocampus function?

INTRODUCTION: In temporal lobe epilepsy (TLE), about 30% of the patients do not achieve adequate pharmacologic control of refractory crises, and surgery becomes an alternative. In ablative interventions, neuropsychologic testing of memory is a crucial step. However, evaluations of the right hippocampal functions have not been consistent. AIM: To assess the hippocampal function in remote orientation and visuospatial memory in patients with refractory temporal epilepsy. METHODS: A controlled study of patients with left (LTLE) or right (RTLE) TLE. The subjects were submitted to a neuropsychologic evaluation through the Route Learning Test and the Childhood Home Test in the preoperative period. The statistical analysis was performed using the Kruskal-Wallis, analysis of variance, χ, and Mann-Whitney U tests. RESULTS: There was no significant difference in performance in the remote visuospatial memory (as measured by the Childhood Home Test) across the groups (LTLE, RTLE, and control). Concerning the spatial orientation memory, however, there was a significant difference between the LTLE and controls as compared with the RTLE group (P<0.001), the latter showing a poorer performance. CONCLUSIONS: The study suggests that spatial orientation memory relies on the integrity of the right hippocampus. Nevertheless, further studies are necessary to confirm this hypothesis.

Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon.

PURPOSE: Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon. METHODS: The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs). RESULTS: The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of FPGS (p = 0.001; OR 3.40; CI 95% 1.65-7.00 and p = 0.006; OR 4.63; CI 95% 1.56-13.72, respectively) and the rs9524885 of ABCC4 (p = 0.023; OR 2.74; CI 95% 1.14-6.65 and p = 0.024; OR 5.36; IC 95% 1.24-23.11, respectively) genes. The rs760370 in the SLC29A1 gene (p = 0.009; OR 6.71; CI 95% 1.16-8.21) and the rs1801133 in the MTHFR toxicity (p = 0.023; OR 3.09; CI 95% 1.16-8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction. CONCLUSION: Four polymorphisms of the ABCC4, FPGS, SLC29A1, and MTHFR genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.

Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle-brachial index.

INTRODUCTION: Peripheral arterial disease, as measured by the ankle-brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. AIM: To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. METHOD: The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). RESULTS: Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. CONCLUSION: This study found an independent association between functional performance and ECF in an elderly population including low ABI individuals, showing that, in elderly populations with functional impairment, ECF may also be impaired.