Effect of oxidized cholesterol on age-associated changes to immune parameters in spleen lymphocytes and peritoneal exudate cells derived from rats

The effects of oxidized cholesterol on immune parameters were examined by using spleen lymphocytes and peritoneal exudate cells (PEC) derived from 5-week- (Young) and 9-month-old (Adult) rats. The immunoglobulin (Ig) G and IgM production was inhibited by oxidized cholesterol in the rats of both ages when lymphocytes were exposed to 30 micrograms/ml of oxidized cholesterol for 24 hr. The intracellular IgA level was also lowered by 30 micrograms/ml of oxidized cholesterol, irrespective of age. In contrast, IgE production was significantly increased by the addition of 30 micrograms/ml of oxidized cholesterol in only young lymphocytes. Moreover, oxidized cholesterol enhanced the intracellular histamine accumulation in only adult PEC, although the total histamine level produced by PEC was similar in the rats of both ages. These results thus suggest the possibility that oxidized cholesterol can have different effects on the age-related modulation of immune functions such as Igs production and histamine release.

Age above 60 years is not a negative predictive factor for combined antiviral therapy with pegylated interferon alpha and ribavirin in hepatitis C patients

Background: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral hepatitis C therapy. However, elderly patients often show relevant fibrosis or cirrhosis which is a known negative predictive factor, making it difficult to interpret age as an independent predictive factor. Methods: From the framework of the Swiss hepatitis C cohort (SCCS), we collected data from 545 antiviral hepatitis C therapies, including data from 67 hepatitis C patients ≥ 60 y who had been treated with PEG-interferon and ribavirin. We analyzed host factors (age, gender, fibrosis, haemoglobin, depression, earlier hepatitis C treatment), viral factors (genotype, viral load) and treatment course (early virological response, end of treatment response, SVR). Generalised estimating equations (GEE) regression modelling was used for the primary end point (SVR), with age ≥ 60 y and < 60 y as independent variable and gender, presence of cirrhosis, genotype, earlier treatment and viral load as confounders. SVR was analysed in young and elderly patients after matching for these confounders. Additionally, classification tree analysis was done in elderly patients using these confounders. Results: SVR analyzed in 545 patients was 55%. In genotype 1/4, SVR was 42.9% in 259 patients < 60 y and 26.1% in 46 patients ≥ 60 y. In genotype 2/3, SVR was 74.4% in 215 patients < 60 y and 84% in 25 patients ≥ 60 y. However, GEE model showed that age had no influence on achieving SVR (Odds ratio 0.91). Confounders influenced SVR as known from previous studies (cirrhosis, genotype 1/4, previous treatment and viral load >600'000 IE/ml as negative predictive factors). When young and elderly patients were matched (analysis in 59 elderly patients), SVR was not different in these patient groups (54.2% and 55.9%, resp.; p=0.795 in binomial test). The classification tree-derived best criterion for SVR in elderly patients was genotype, with no further criteria relevant for predicting SVR in genotype 2/3. In patients with genotype 1/4, further criteria were presence of cirrhosis and low viral load <600'000 IE/ml in non-cirrhotic patients. Conclusions: Age is not a relevant predictive factor for achieving SVR, when confounders were taken into account. In terms of effectiveness of antiviral therapy, age does not play a major role and should not be regarded as relevant negative predictive factor. Since life expectancy in Switzerland at age 60 is more than 22 y, hepatitis C therapy is reasonable in elderly patients with known relevant fibrosis or cirrhosis, because interferon-based hepatitis C therapy improves survival and reduces carcinogenesis.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME)

Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. AIMS: (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. METHODS: Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. RESULTS: Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. CONCLUSION: Age is a factor that should be considered when biological limit values are developed.

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Gastrointestinal malformations: impact of prenatal diagnosis on gestational age at birth.

The aim of the study was to analyse the degree to which gestational age (GA) has been shortened due to prenatal diagnosis of gastrointestinal malformations (GIM). The data source for the study was 14 population-based registries of congenital malformations (EUROCAT). All liveborn infants with GIMs and without chromosomal anomalies, born 1997-2002, were included. The 14 registries identified 1047 liveborn infants with one or more GIMs (oesophageal atresia, duodenal atresia, omphalocele, gastroschisis and diaphragmatic hernia). Median GA at birth was lower in prenatally diagnosed cases for all five malformations, although not statistically significant for gastroschisis. There was little difference in median birthweight by GA for the pre- and postnatally diagnosed infants. The difference in GA at birth between prenatally and postnatally diagnosed infants with GIMs is enough to increase the risk of mortality for the prenatally diagnosed infants. Clinicians need to balance the risk of early delivery against the benefits of clinical convenience when making case management decisions after prenatal diagnosis. Very few studies have been able to show benefits of prenatal diagnosis of congenital malformations for liveborn infants. This may be because the benefits of prenatal diagnosis are outweighed by the problems arising from a lower GA at birth.

Influence of sex and age on T3 receptors and T3 concentration in the pituitary gland of the rat: consequences on TSH secretion.

A reduced secretion of thyroid hormones with age has been documented in humans and animals with no substantial increase in TSH secretion, which may be indicative of an age-related impairment of the pituitary sensitivity to the negative control exerted by thyroid hormones. We have evaluated in rats the influence of sex and age on pituitary T3 nuclear receptors--known to be determinant in the regulation of TSH secretion--as well as on T3 concentration in the pituitary gland. As regards sex, the density of T3 receptors and the concentration of T3 in pituitary gland and plasma were greater in females than in males whereas pituitary and plasma TSH concentrations were less. As for age, the density of T3 receptors was greater in old male rats than in young ones with no changes in pituitary T3 and plasma TSH concentrations. In old female rats in contrast, there was no significant increase in T3 receptors but pituitary T3 was less and plasma TSH greater than in young female rats. In both sexes plasma thyroid hormones and pituitary TSH were reduced with age whereas TSH response to TRH was not altered. These results illustrate sex and age differences in pituitary T3 receptors and pituitary T3 concentration as well as in TSH secretion. In young animals of both sexes an inverse correlation is observed between the density of pituitary T3 receptors and plasma TSH. In contrast, in old animals the absence of this correlation is suggestive of an age-related impairment of T3 action on the thyrotrophs or of changes pertaining to other factors modulating TSH secretion.

A longitudinal study of environmental tobacco smoke exposure in children: parental self reports versus age dependent biomarkers

Background: Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.Methods: The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay. Results: At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.Conclusion: We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.

Swiss Democracy on the Web 2010 : Society and Politics in a Connected Age

The rapid adoption of online media like Facebook, Twitter or Wikileaks leaves us with little time to think. Where is information technology taking us, our society and our democratic institutions ? Is the Web replicating social divides that already exist offline or does collaborative technology pave the way for a more equal society ? How do we find the right balance between openness and privacy ? Can social media improve civic participation or do they breed superficial exchange and the promotion of false information ? These and lots of other questions arise when one starts to look at the Internet, society and politics. The first part of this paper gives an overview of the social changes that occur with the rise of the Web. The second part serves as an overview on how the Web is being used for political participation in Switzerland and abroad. Le développement rapide de nouveaux médias comme Facebook, Twitter ou Wikileaks ne laisse que peu de temps à la réflexion. Quels sont les changements que ces technologies de l'information impliquent pour nous, notre société et nos institutions démocratiques ? Internet ne fait-il que reproduire des divisions sociales qui lui préexistent ou constitue-t-il un moyen de lisser et d'égaliser ces mêmes divisions ? Comment trouver le bon équilibre entre transparence et respect de la vie privée ? Les médias sociaux permettent-ils de stimuler la participation politique ou ne sont-ils que le vecteur d'échanges superficiels et de fausses informations ? Ces questions, parmi d'autres, émergent rapidement lorsque l'on s'intéresse à la question des liens entre Internet, la société et la politique. La première partie de ce cahier est consacrée aux changements sociaux générés par l'émergence et le développement d'Internet. La seconde fait l'état des lieux de la manière dont Internet est utilisé pour stimuler la participation politique en Suisse et à l'étranger.

Smoking and adolescence: Exploring tobacco consumption and related attitudes in three different age groups in Switzerland

The present study constitutes an investigation of tobacco consumption, related attitudes and individual differences in smoking or non-smoking behaviors in a sample of adolescents of different ages in the French-speaking part of Switzerland. We investigated three school-age groups (7th-grade, 9th-grade, and the second-year of high school) for differences in attitude and social and cognitive dimensions. We present both descriptive and inferential statistics. On an inferential level, we present a binary logistic regression-based model predicting risk of smoking. The resulting model most importantly suggests a strong relationship between smoking and alcohol consumption (both regular and sporadic). We interpret this result in terms of both the impact of the actual campaigns and the cognitive processes associated with adolescence.

Younger age as a bad prognostic factor in patients with carcinoma of the cervix.

OBJECTIVE: To verify the influence of age on the prognosis of cervix carcinoma. STUDY DESIGN: Five hundred and sixty eight patients treated for a FIGO stage IB-IVA with radical irradiation in the Centre Hospitalier Universitaire Vaudois of Lausanne were subdivided according to the following age categories: < or = 45, 46-60, 61-69 and >70 years. Taking the 46-60 years age group as the reference, the hazard ratios (HR) of death and corresponding 95% confidence intervals (95% CI) were estimated by means of a Cox multivariate analysis. RESULTS: The 5-year survival rates were, respectively, 57%, 67%, 60% and 45%. For the youngest women the risk of death was significantly increased (HR = 2.00, 95% CI [1.32-3.00]) and was even more accentuated in advanced stages. CONCLUSION: Age under 45 years is a bad prognostic factor in carcinoma of the cervix.

Alpine tectonic evolution of a Jurassic subduction-accretionary complex: Deformation, kinematics and 40Ar/39Ar age constraints on the Mesozoic low-grade schists of the Circum-Rhodope Belt in the eastern Rhodope-Thrace region, Bulgaria-Greece

Deformation of the Circum-Rhodope Belt Mesozoic (Middle Triassic to earliest Lower Cretaceous) low-grade schists underneath an arc-related ophiolitic magmatic suite and associated sedimentary successions in the eastern Rhodope-Thrace region occurred as a two-episode tectonic process: (i) Late Jurassic deformation of arc to margin units resulting from the eastern Rhodope-Evros arc-Rhodope terrane continental margin collision and accretion to that margin, and (ii) Middle Eocene deformation related to the Tertiary crustal extension and final collision resulting in the closure of the Vardar ocean south of the Rhodope terrane. The first deformational event D-1 is expressed by Late Jurassic NW-N vergent fold generations and the main and subsidiary planar-linear structures. Although overprinting, these structural elements depict uniform bulk north-directed thrust kinematics and are geometrically compatible with the increments of progressive deformation that develops in same greenschist-facies metamorphic grade. It followed the Early-Middle Jurassic magmatic evolution of the eastern Rhodope-Evros arc established on the upper plate of the southward subducting Maliac-Meliata oceanic lithosphere that established the Vardar Ocean in a supra-subduction back-arc setting. This first event resulted in the thrust-related tectonic emplacement of the Mesozoic schists in a supra-crustal level onto the Rhodope continental margin. This Late Jurassic-Early Cretaceous tectonic event related to N-vergent Balkan orogeny is well-constrained by geochronological data and traced at a regional-scale within distinct units of the Carpatho-Balkan Belt. Following subduction reversal towards the north whereby the Vardar Ocean was subducted beneath the Rhodope margin by latest Cretaceous times, the low-grade schists aquired a new position in the upper plate, and hence, the Mesozoic schists are lacking the Cretaceous S-directed tectono-metamorphic episode whose effects are widespread in the underlying high-grade basement. The subduction of the remnant Vardar Ocean located behind the colliding arc since the middle Cretaceous was responsible for its ultimate closure, Early Tertiary collision with the Pelagonian block and extension in the region caused the extensional collapse related to the second deformational event D-2. This extensional episode was experienced passively by the Mesozoic schists located in the hanging wall of the extensional detachments in Eocene times. It resulted in NE-SW oriented open folds representing corrugation antiforms of the extensional detachment surfaces, brittle faulting and burial history beneath thick Eocene sediments as indicated by 42.1-39.7 Ma Ar-40/Ar-39 mica plateau ages obtained in the study. The results provide structural constraints for the involvement components of Jurassic paleo-subduction zone in a Late Jurassic arc-continental margin collisional history that contributed to accretion-related crustal growth of the Rhodope terrane. (C) 2011 Elsevier Ltd. All rights reserved.

Age over 40 years increases the failure rate of non-operative management of blunt splenic injuries

Objective: Non-operative management (NOM) of blunt splenic injuries (BSI) is nowadays considered the standard treatment. The study aimed to determine the criteria applied for NOM and to identify risk factors for its failure. Methods: Review of all adult patients with BSI treated at the University Hospital Bern, Switzerland, between 2000 and 2008. Results: There were 206 patients (146 men, 70·9%) with a mean age of 38·2 ± 19·1 years and an Injury Severity Score of 30·9 ± 11·6. The American Association for the Surgery of Trauma classification of the splenic injury was: grade I, n=43 (20·9%); grade II, n=52 (25·2%); grade III, n=60 (29·1%); grade IV, n=42 (20·4%) and grade V, n=9 (4·4%). 47 patients (22·8%) required immediate surgery. Five or more units of red cell transfusions (P<0·001), Glasgow Coma Scale<11 (P=0·009) and age ≥55 years (P=0·038) were associated with primary operative management (OM). 159 patients (77·2%) qualified for NOM, which was successful in 89·9% (143/159). The overall splenic salvage rate was 69·4% (143/206). Multivariate analysis found age ≥40 years to be the only factor independently related to the failure of NOM (P=0·001). Conclusion: Advanced age is associated with an increased failure rate ofNOM in patients with BSI.

Right Hepatectomy in Patients over 70 Years of Age: An Analysis of Liver Function and Outcome.

BACKGROUND: As a consequence of the increase in life expectancy, hepatobiliary surgeons have to deal with an emerging aged population. We aimed to analyze the liver function and outcome after right hepatectomy (RH) in patients over 70 years of age. METHODS: From January 2006 to December 2009, we prospectively collected data of 207 consecutive elective hepatectomies. In patients who had RH, cardiac risk was assessed by a dedicated preoperative workup. Liver failure (LF) was defined by the "fifty-fifty" criteria at postoperative day 5 (POD) and morbidity by the Clavien-Dindo classification. Liver function tests (LFTs) and short-term outcome were retrospectively analyzed in patients over (elderly group, EG) and younger (young group, YG) than 70 years of age. RESULTS: Eighty-seven consecutive RH were performed during the study period. Indication for surgery included 90 % malignancy in 47 % of patients requiring preoperative chemotherapy. ASA grade > 2 (44 vs. 16 %, p = 0.027), ischemic heart disease (17 vs. 5 %, p = 0.076), and preoperative cardiac failure (26 vs. 2 %, p < 0.001) were more frequent in the EG (n = 23) than in the YG (n = 64). Both groups were similar regarding rates of normal liver parenchyma, chemotherapy and intraoperative parameters. The overall morbidity rates were comparable, but the serious complication (grades III-V) rate was relatively higher in the EG (39 vs. 25 %, p = 0.199), particularly in patients with diabetes mellitus (100 vs. 29 %, p = 0.04) and those who had additional nonhepatic surgery (67 vs. 35 %, p = 0.110) and transfusions (44 vs. 30 %, p = 0.523). The 90-day mortality rate was similar (9 % in the EG vs. 3 % in the YG, p = 0.28) and was related to heart failure in the EG. LFTs showed a similar trend from POD 1 to 8, and patients ≥70 years of age had no liver failure. CONCLUSIONS: Age ≥70 years alone is not a contraindication to RH. However, major morbidity is particularly higher in the elderly with diabetes. This high-risk group should be closely monitored in the postoperative course. Liver function is not altered in the elderly patient after RH.