Don't lose sight of the importance of the individual in effective falls prevention interventions

Falls remain a major public health problem, despite strong growth in the research evidence of effective single and multifactorial interventions, particularly in the community setting. A number of aspects of falls prevention require individual tailoring, despite limitations being reported regarding some of these, including questions being raised regarding the role of falls risk screening and falls risk assessment. Being able to personalise an individual's specific risk and risk factors, increase their understanding of what interventions are likely to be effective, and exploring options of choice and preference, can all impact upon whether or not an individual undertakes and sustains participation in one or more recommendations, which will ultimately influence outcomes. On all of these fronts, the individual patient receiving appropriate and targeted interventions that are meaningful, feasible and that they are motivated to implement, remains central to effective translation of falls prevention research evidence into practice.     

Novel mutations in CYP21 detected in individuals with hyperandrogenism

We studied the functional and structural consequences of two novel missense mutations in CYP21 found in women with hyperandrogenism. The women were predicted to carry mutations by hormonal evaluation, but did not display any of the genotypes commonly associated with congenital adrenal hyperplasia. In one woman the novel mutation V304M was found in homozygous form. After expression in COS-1 cells the mutated enzyme was found to have a residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme. The V304M variant thus represents the sixth known missense mutation associated with nonclassical disease. A normal degradation pattern for this mutant enzyme indicates that the missense mutation is of functional, rather than structural, importance. The other mutation, G375S, was detected in a young woman with signs of hyperandrogenism, in heterozygous form together with P453S, a mutation known to cause nonclassical congenital adrenal hyperplasia (her genotype was G375S+P453S/wild type). This novel variant almost completely abolished enzyme activity; conversion was 1.6% and 0.7% of normal for 17-hydroxyprogesterone and progesterone, respectively. These results underline the importance of genetic evaluation and counseling in hyperandrogenic women who are predicted to carry congenital adrenal hyperplasia-causing mutations by biochemical tests. It also supports the idea that the heterozygous carrier state for CYP21 mutations can be associated with symptoms of androgen excess in certain susceptible individuals.     

Lysine induces lipid and protein damage and decreases reduced glutathione concentrations in brain of young rats

The present work investigated the in vitro effects of lysine on important parameters of oxidative stress in cerebral cortex of young rats. Our results show that lysine significantly induced lipid peroxidation, as determined by increase of thiobarbituric acid-reactive substances and chemiluminescence levels, as well as protein oxidative damage since carbonyl formation and sulfhydryl oxidation were enhanced by this amino acid. Furthermore, the addition of free radical scavengers significantly prevented lysine-induced lipid oxidative damage, suggesting that free radicals were involved in this effect. Lysine also significantly diminished glutathione levels in cortical supernatants, decreasing, therefore, the major brain antioxidant defense. Finally, lysine markedly oxidized a glutathione commercial solution in a medium devoid of brain supernatants, indicating that it behaved as a direct acting oxidant. The present data indicate that lysine induces oxidative stress in cerebral cortex of young rats. Therefore, it is presumed that this pathomechanism may be involved at least in part in the neurological damage found in patients affected by disorders with hyperlysinemia.     

Visual deficits and cognitive assessment of multiple sclerosis: confounder,correlate, or both?

Journal of Neurology - The relationship between visual impairment and cognitive performance in multiple sclerosis (MS) remains poorly understood. To determine associations between visual acuity and...     

Efeitos Agudos do Nitrato Dietético na Pressão Central e Desempenho Cardíaco em Hipertensos: Estudo Cruzado,Randomizado e Placebo-Controlado

BackgroundThe diet’s inorganic nitrate (NO₃^–) may provide a physiological substrate for reducing nitrate (NO₂^–) to NO independent of the endothelium. Studies suggest that inorganic NO₃^–has beneficial effects on cardiovascular health.ObjectiveThis study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO₃^–) on blood pressure and endothelial function in treated hypertensive patients.MethodsA randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05.ResultsThe mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046).ConclusionsThe acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.