Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

Cancer survival in the elderly: Effects of socio-economic factors and health care system features (ELDCARE project)

The purpose of the ELDCARE project is to study differences in cancer survival for elderly patients by country, taking into account the socio-economic conditions and the characteristics of health care systems at the ecological level. Fifty-three European cancer registries, from 19 countries, participating in the EUROCARE 3 programme, collected information to compute relative survival on patients aged 65-84 years, diagnosed over the period 1990-1994. National statistics offices provided the macro-economic and labour force indicators (gross domestic product, total health expenditure, and proportion of people employed in the agriculture sector) as well as the features of national health care systems. Survival for several of the cancer sites had high positive Pearson's correlations (r) with the affluence indicators (usually r > 0.7), but survival for the poor prognosis cancers (lung, ovary, stomach) and for cervix uteri was not so well correlated. Among the medical resources considered, the number of computed tomography scanners was the variable most related to survival in the elderly; the number of total health practitioners in the country did not show any relationship. Survival was related to the marital status of elderly women more strongly than for men and younger people. The highest correlations of survival with the percentage of married elderly women in the population were for cancers of the rectum (r = 0.79) and breast (r = 0.66), while survival correlated negatively with the proportion of widows for most cancers. Being married or widowed is for elderly people, in particular elderly women, an important factor influencing psychological status, life habits and social relationships. Social conditions could play a major role in determining health outcomes, particularly in the elderly, by affecting access to health care and delay in diagnosis

Breast cancer survival in the US and Europe: a CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment

Impatto a breve termine dell\u2019inquinamento dell\u2019aria nelle citt\ue0 coperte dalla sorveglianza epidemiologica EpiAir2. [Short-term impact of air pollution among Italian cities covered by the EpiAir2 project].

Abstract OBJECTIVES: to estimate the short-term impact of air pollutants on adult population of 23 Italian cities on the calendar period 2006- 2009 as part of the EpiAir2 project. DESIGN, MATERIALS AND METHODS: for each city, the short-term impact of air pollution on mortality was estimated. In particular, it was calculated the number of deaths attributable to particulate matter levels (PM10 and PM2.5) exceeding different thresholds deriving from the European Union legislation and the World Health Organization guidelines (PM10: 20 and 40 \ub5g/m(3), reduction of 20% up to 20 \ub5g/m(3) and more than 35 days per year with daily average above 50 \ub5g/m(3); PM2.5: 10, 18 and 25 \ub5g/m(3), reduction of 20% up to 18 \ub5g/m(3)). The impact evaluation was done combining the effect estimates of air pollutant, the observed mortality level and the air pollution concentration measured by the ambient monitors. Regarding effects, the posterior city-specific distributions arising from a Bayesian metanalysis was employed. Uncertainty around the impact estimates was obtained by Monte Carlo methods. RESULTS: overall, in the 23 cities considered in the present study attributable deaths to short-term effects of PM10 concentrations above 20 \ub5g/m(3) as annual average and of PM2.5 concentrations above 10 \ub5g/m(3) on the period 2006-2009 was respectively 0.9% (assuming independence among cities the 80% credibility interval is 0.4-1.4) and 0.8% (80%CrI 0.2-1.3) of natural mortality. The impact was larger for the cities of the river Po valley, the Florence area and the large conurbations of Rome, Naples and Palermo: considering PM10 1.0% (80%CrI 0.4-1.5) vs. 0.4% (80%CrI 0.2-0.7) of natural deaths among the other cities in the study. Pollution reduction actions as prescribed by the European Union legislation, i.e. a 20% reduction up to 20 \ub5g/m(3) for PM10 and up to 18 \ub5g/m(3) for PM2.5, would have saved, over all the cities covered by this study, 42% and 51% of all attributable deaths, respectively. CONCLUSIONS: during the study period, air pollution exposure was responsible for a relevant impact on mortality in the enrolled cities. Policies based on percent reduction of PM10 and PM2.5 as prescribed by the European Union could substantially reduce the short term impact on population mortality

Analysis of mortality and hospitalization in patients with dementia.

mortality and hospitalization in patients with dementi

Childhood Cancer Survival Trends in Europe: A EUROCARE Working Group Study.

Abstract PURPOSE: EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe. PATIENTS AND METHODS: Survival in 44,129 children diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated. RESULTS: For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms' tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt's lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year. CONCLUSION: These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase

Yearly variations of demographic indices and mortality data in Italy from 1901 to 2008 as related to the caloric intake.

The aim of the present study was to evaluate, by Join Point regression method, the yearly variations in demographic indices and mortality data in Italy from 1901 to 2008, as related to the caloric intake. The relationships between mortality and caloric intake were studied by time series. The results showed that, from 1901 to 2008, the Italian population grew from 32.5 to 59.6 millions; the live births rates decreased from 31.8 to 10.1\u2030 (males) and from 33.3 to 9.0\u2030 (females); the infant mortality rates fell from 184.1 to 3.7\u2030 (males) and from 149.4 to 3.2\u2030 (females); males and females gained 35.7 and 40.6 years in life expectancy at birth, respectively. In 1901 the 61% of deaths occurred in the youngest, whereas in 2008 the elderly accounted for the 80%. In 1901, in terms of age-adjusted data, other and undefined causes overcame the specific causes of death, whose rank was: respiratory, digestive, infectious, cardiovascular, cerebrovascular, cancers, accidents, endocrine, and nervous system diseases. In 2008, undefined causes ranked 3rd (males) and 4th (females), while cancers became the leading cause of death, followed by cardiovascular, cerebrovascular, accidental, respiratory, endocrine, digestive, nervous system, and infectious diseases. The caloric intake showed a negative correlation with all-cause mortality, infant mortality, and mortality for a number of specific causes. These patterns reflect the progress in average nutritional status, lifestyle quality, socioeconomic level, and hygienic conditions