Association of Alzheimer's disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study

BACKGROUND: Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially Ginkgo biloba extracts are prescribed for a number of symptoms, particularly memory impairment, in elderly patients. It is postulated that because of its pharmacological actions, this treatment could prevent the decline of cognitive function, but no studies have been published to date to test its efficacy in prevention of Alzheimer's disease. The potential association between use of C4A treatments, in particular EGb 761 (standardized Ginkgo biloba extracts), and dementia of the Alzheimer type was investigated. METHODS: A case-control study was nested in a cohort of 1462 community-dwelling elderly women aged over 75 years. Sixty-nine women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal. This study involved women whose cognitive function was evaluated at baseline by use of Pfeiffer's test and whose medication history was taken. The onset of cognitive impairment was investigated over a 7-year follow-up period. In order to study the factors associated with the onset of dementia, the data concerning women with a score of > or = 8 on Pfeiffer's test at inclusion, indicating normal cognitive function, were analyzed. RESULTS: A multivariate analysis including potential confounding factors showed that fewer women who developed Alzheimer's dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio = 0.31, 95% confidence interval = 0.12-0.82, p =.018). Figures for EGb 761 alone were similar but did not reach statistical significance (odds ratio = 0.38, 95% confidence interval = 0.08-1.76, p =.22). CONCLUSION: These results suggest that C4A treatment may reduce the risk of developing Alzheimer's dementia in elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To establish a causal relationship, these findings have to be confirmed with prospective studies.     

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

Purpose

Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods

The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results

Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r ² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r ² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion

Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.     

A comparison of two modalities of stereotactic body radiation therapy for peripheral early-stage non-small cell lung cancer: results of a prospective French study

Objectives:This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC).Methods:From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife^®. Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization.Results:2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife^® (p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) (p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] (p = 0.0831) using Linac and Cyberknife^® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events (n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged.Conclusions:No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife^®.Advances in knowledge:This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife^®. No significant difference in efficiency or toxicity was shown in this situation.     

Perforated diverticulitis of the sigmoid colon causing a subcutaneous emphysema

INTRODUCTION

Although diverticular disease of the colon is frequent, perforated diverticulitis causing subcutaneous emphysema is a uncommon entity. We wish to present this extremely rare case of perforated colonic diverticulum in the subcutaneous tissue, which is the first one that we have encountered in our practice, along with the accompanying diagnostic and therapeutic issues and a review of the literature.

PRESENTATION OF CASE

We report the case of an 83-year-old man who admitted to the emergency room due to an abdominal subcutaneous emphysema. Physical examination revealed a severe subcutaneous emphysema especially in the left iliac fossa and abdominal pain. An urgent contrast enhanced abdominal CT scan showed multiple diverticula in the sigmoid colon and multiple air bubbles in the subcutaneous tissue. The exploratory laparotomy identified a perforation of diverticular in subcutaneous tissue. Forty centimeters of colon were resected. The subcutaneous emphysema resolved without specific treatment. The postoperative period was uncomplicated.

DISCUSSION

Subcutaneous emphysema of anterior abdomen wall is an obvious physical sign but its etiology is complex to determine and may be potentially lethal. The pathophysiological mechanism involved is the emergence of a pressure gradient between the peritoneum and surrounding structures, causing rupture of the anterior abdominal wall, allowing gas from a perforation to diffuse along tissue planes.

CONCLUSION

This physical sign may be of especial value in elderly patient groups amongst whom perforation may be less clinically obvious. General surgeons should bear in mind this rare complication of colonic diverticulosis.     

Feminized Behavior and Brain Gene Expression in a Novel Mouse Model of Klinefelter Syndrome

Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM versus XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM versus XYM and not XXM versus XYM. Genes that are both feminized and unique to XXYM versus XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of KS and may aid our understanding of sex differences in brain and behavior.     

Timing of clamping and factors associated with iron stores in full-term newborns

OBJECTIVE

To analyze the impact of timing of clamping and obstetric, biological and socioeconomic factors on the iron stores of full-term newborns.

METHODS

Cross-sectional study between October 2011 and July 2012 in which hematological parameters were evaluated for newborns in Viçosa, MG, Southeastern Brazil. It involved collecting 7 mL of umbilical cord blood from 144 full-term not underweight newborns. The parameters investigated were complete blood count, serum iron, ferritin and C-reactive protein. The time of umbilical cord clamping was measured using a digital timer without interfering in the procedures of childbirth. The birth data were collected from Live Birth Certificates and other information was obtained from the mother through a questionnaire applied in the first month postpartum. Analysis of multiple linear regression was then used to estimate the influence of biological, obstetrics and socioeconomic factors on the ferritin levels at birth.

RESULTS

The median ferritin was 130.3 µg/L (n = 129, minimum = 16.4; maximum = 420.5 µg/L), the mean serum iron was 137.9 μg/dL (n = 144, SD = 39.29) and mean hemoglobin was 14.7 g/dL (n = 144, SD = 1.47). The median time of cord clamping was 36 seconds, ranging between 7 and 100. The bivariate analysis detected an association between ferritin levels and color of the child, timing clamping of 60 seconds, type of delivery, the presence of gestational diabetes and per capita family income. In multivariate analysis, the variables per capita income, number of antenatal visits and length at birth accounted for 22.0% of variation in ferritin levels.

CONCLUSIONS

Iron stores at birth were influenced by biological, obstetric and social characteristics. Tackling anemia should involve creating policies aimed at reducing social inequalities, improving the quality of antenatal care, as well as implementing a criterion of delayed clamping of the umbilical cord within the guidelines of labor.     

Neighborhood contextual characteristics and leisure-time physical activity: Pró-Saúde Study

OBJECTIVE

To estimate the association between neighborhood contextual variables and leisure-time physical activity.

METHODS

Data were analyzed for 2,674 adults from Rio de Janeiro, RJ, Southeastern Brazil, participating in the longitudinal study in 1999. Leisure-time physical activity in the two preceding weeks was assessed dichotomously. Sex, age, income, education and marital status were analyzed as individual variables. Neighborhood contextual characteristics were the social development index, the Theil index and the proportion of the area occupied by parks, squares and gardens, categorized in quintiles. The unadjusted and adjusted odds ratios and 95% confidence intervals were estimated using multilevel logistic regression.

RESULTS

The prevalence of leisure-time physical activity was higher in residents in neighborhoods with higher indices of social development (between 32.3% and 53.1%) and a greater proportion of parks, squares and gardens (between 35.8% and 53.1%). Regarding the social development index, the adjusted odds ratios for physical activity were 1.22 (95%CI 0.93;1.61), 1.44 (95%CI 1.09;1.89), 1.75 (95%CI 1.31;2.34) and 2.25 (95%CI 1.70;3.00) for residents in neighborhoods in the second, third, fourth and fifth quintiles, respectively, compared with residents in neighborhoods in the first quintile. The odds ratios for the proportion of parks, squares and gardens were 0.90 (95%CI 0.69;1.19), 1.41 (95%CI 1.04;1.90), 1.63 (95%CI 1.24;2.14) and 1.05 (95%CI 0.80;1.38) for residents in neighborhoods in the second, third, fourth and fifth quintiles. After adjusting for the other variables, only the social development index continued to be associated with leisure-time physical activity, with odds ratios of 1.41 (95%CI 1.02;1.95); 1.54 (95%CI 1.12;2.12); 1.65 (95%CI 1.14;2.39) and 2.13 (95%CI 1.40;3.25) for residents in neighborhoods in the second, third, fourth and fifth quintiles.

CONCLUSIONS

Leisure-time physical activity was more common in residents in neighborhoods with higher social development indices. No association was observed between access to leisure areas and income inequality.     

Quality of life instruments used in mental health research: Properties and utilization

Quality of life (QoL) assessment is increasingly used in mental health. Multiple instruments exist, but the conditions for choosing one instrument over another for purposes of a specific study are not clear. We performed a systematic review to identify the QoL instruments used in mental health. The instruments were systematically described regarding their intrinsic properties (e.g., generic v. disease-specific) and their characteristics of utilization in studies (e.g., study objectives). Using cluster analyses, we investigated the existence of similar instruments with respect to each of these sets of characteristics and studied potential links between instruments' intrinsic properties and their characteristics of utilization. We included 149 studies in which 56 distinct instruments were used. Similarities were found among instruments in terms of their intrinsic properties as well as their characteristics of utilization, leading to the construction of four clusters of instruments in each case. However, no relevant links were identified between instruments' intrinsic properties and their characteristics of utilization, suggesting that the choice of QoL instruments did not depend on their properties. A consensus about common QoL instruments must be reached to facilitate the choice of instruments, the comparison of results and thus to have an impact on clinical and policy decision-making.