Associação de Fatores de Risco Cardiovascular e Polimorfismo de APOE com Mortalidade em Idosos Longevos: Uma Coorte de 21 Anos

Background:Knowledge of environmental and genetic factors for healthy aging in elderly people is controversial. In addition to this evidence, few studies have been designed for this population.Objectives:To investigate the relationship between the most frequent apolipoprotein E (APOE) genotypes and mortality in very elderly individuals living in a community and to evaluate survival according to cardiovascular risk factors.Methods:A sample of 74 elderly individuals aged ≥ 80 years, from the Veranópolis Project cohort, was selected for APOE genotyping. At baseline, anthropometric variables, glucose and lipid levels, blood pressure, and lifestyle variables (smoking, alcohol consumption, and physical activity) were collected. The Bayer Activities of Daily Living Scale was applied to their caregivers. Total study follow-up was 21 years. Two-sided p < 0.05 was considered statistically significant.Results:There was no association between APOE genotypes and mortality. However, the risk of death in elderly smokers was 2.30 times higher (hazard ratio [HR], 95% CI 1.01 to 5.24); in individuals with diabetes, it was 3.95 times higher (HR, 95% CI 1.27 to 12.30) than in individuals without diabetes. Subjects who practiced vigorous physical activity had a 51% reduction in risk of death (HR = 0.49, 95% CI 0.27 to 0.88). For an increase of 1 mmHg in systolic blood pressure, there was a 2% reduction (HR = 0.98, 95% CI 0.97 to 0.99) in risk of death.Conclusion:In this sample population, APOE genotypes were not associated with mortality. However, classic cardiovascular risk factors may be important for overall mortality in the very elderly.     

Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

In order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin‐2,4‐dione derivatives, 1′‐[4‐(4‐(o‐methoxyphenyl)‐piperazin‐1‐yl)butyl]‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione ( 3 ) and its salt ( 4 ) with rhodanine‐3‐acetic acid ( RA ) were prepared and investigated by X‐ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T‐lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro. The molecular geometry, intermolecular interactions, and crystal packing of base and acid forms of 3 were analyzed to see, if conformational changes influence the biological activities. The geometry of 2‐methoxyphenylpiperazine and 5‐spirofluorenehydantoin moieties was compared with other crystal structures containing these fragments. Our results indicated a very potent inhibitory action on ABCB1 pump, and significant cytotoxic and antiproliferative properties of 3 in T‐lymphoma, even more potent in the case of multidrug resistance cells. Furthermore, the compound 3 converted into the salt 4 of inactive acid ( RA ) has maintained both, the efflux pump inhibitory and antiproliferative activities, showing strong synergism with doxorubicin. A comparison of geometry of 3 in both crystal structures ( 3 and 4 ) shows a significant difference in the arrangement of piperazine ring with respect to the aliphatic linker.     

A prospective study of maternal,fetal and neonatal deaths in low- and middle-income countries

Objective

To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths.

Methods

A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum.

Findings

Between 2010 and 2012, 214 070 of 220 235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100 000 live births, ranging from 69 per 100 000 in Argentina to 316 per 100 000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97–11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26–5.67) and 7-day (RR: 3.94; 95% CI: 2.74–5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54–9.77).

Conclusion

Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.     

Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells

Brain metastasis is a major cause of morbidity and mortality in patients with breast cancer. Our previous studies indicated that Stat3 plays an important role in brain metastasis. Here, we present evidence that Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells. Furthermore, inhibition of Stat3 by WP1066 decreased the incidence of brain metastases and increased survival in a preclinical model of breast cancer brain metastasis. WP1066 inhibited Stat3 activation in tumor-associated endothelial cells, reducing their infiltration and angiogenesis. WP1066 also inhibited breast cancer cell invasion. Our results indicate that WP1066 can inhibit tumor angiogenesis and brain metastasis mediated by Stat3 in endothelial and tumor cells.     

Are TNC gene variants associated with anterior cruciate ligament rupture susceptibility?

Objectives

To investigate the role of inter-individual variations in a particular glycoprotein, TNC, and its potential contribution to anterior cruciate ligament (ACL) injury susceptibility in Polish Caucasian participants. ACL rupture is one of the most prevalent and severe knee injury that predominantly occurs during sports participation, primarily via a non-contact mechanism. Several polymorphisms in genes encoding glycoproteins either independently or as allelic combinations, modulate the risk of musculoskeletal soft tissue injuries. Specifically, the TNC rs1330363 (C > T), rs2104772 (T > A) and rs13321 (G > C) variants, independently or in haplotype combinations, were analysed in this context.

Microdialysis technique as a monitoring system for acute complications of diabetes

Abstract:  The objective of the study was to establish the quasi-continuous courses, using microdialysis technique, of glucose, lactate, and glycerol concentrations in interstitial fluid of abdominal adipose tissue during the standard treatment of acute diabetes complications. Clinical studies were carried out on 31 diabetic patients during the initial 48 h of the treatment. In all but two obese female patients with hyperglycemic hyperosmolar state (HHS) did glucose concentration in perfusion fluid (PF) reflect concentration in capillary blood. The recovery of glucose correlated with patients' body mass index ( r  = 0.55). It was significantly higher in lean and overweight patients (91 ± 15%) than in obese patients (55 ± 31%). The course of lactate concentration in PF coincided with the course in venous blood (2.1 ± 0.3 mmol/L vs. 2.0 ± 0.5 mmol/L, P  = 0.35). Glycerol concentration was 267 ± 41 µmol/L and 133 ± 40 µmol/L in PF and venous blood, respectively ( P  = 0.004). The study indicated that microdialysis may be an effective tool to monitor concentration of different metabolites in interstitial fluid of the adipose tissue during treatment of the acute complications of diabetes. Applicability of the technique in the monitoring of HHS, especially in obese female patients, needs further investigation.     

Influence of Magnetic Field on the Distribution of the Ferromagnetic Component in Centrifugally Cast Ceramic-Metal Gradient Composites

The main aim of the investigation was to determine the impact of the content of nickel and the content of slurry on the nature of the microstructure and physical properties of the final products. In the study, six types of slurries were examined and prepared, differing in both the amounts of content of Ni metallic phase particles (5 vol.%, 10 vol.%, and 20 vol.%) and the amount of content of solid content in the prepared slurries (35 vol.%, and, 50 vol.%). The centrifugal slip casting (CSC) method in a magnetic field was used to fabricate the composites. This technique allowed the production of high-density ZrO₂-Ni composites after sintering. Composites containing 50 vol.% of the solid content were characterized by a relative density equal to 99%. Applying the magnetic field allows controlling the distribution of the ferromagnetic phase (Ni) in the ceramic matrix (ZrO₂). Based on the results obtained, it was found that the nature of the composites obtained is influenced by the rheological properties of the slurries, depending on their composition. The applicability of the CSC in the magnetic field technique for the production of the composite is characterized by a gradient in the distribution of components on the longitudinal section and has been proved. Based on the obtained results, a model for shaping the microstructure of composites with a longitudinal section was proposed. This work enabled a better understanding of creating microstructures in materials fabricated by centrifugal slip casting in a magnetic field.