Determinants of hepatitis A vaccine immunity in a cohort of human immunodeficiency virus-infected children living in Switzerland

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4(+) T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4(+) T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed.

Regional Differences in Living Standards in Eastern European Countries - Changes During the Transition

This research aimed to discover how differences in living standards between regional units changed during the period of transformation from 1990 to 1995 in Poland, the Slovak Republic, the Czech Republic and Hungary. The standard of living was measured by the so-called Living Standard Index (LSI), a composite taxonomic measure. Fixed reference points make it possible to compare the standard of living in regional administrative units and to study its dynamics. The analysis was country-specific, since the lists of variable were not fully identical for all the countries studied. The main tools used were LSI variability measures (mainly variance and standard deviation). By identifying trend patterns in the characteristics of LSIs, it was possible to compare the different countries. It was found that * differences in living standards between regional units have been decreasing during the transformation in Poland and in the Czech Republic. In the latter this process is slow and smooth, while in Poland there was a relatively sharp decline which then stopped entirely in 1994 * the only country with increasing differences between regions is Hungary and these differences are growing at a constant rate * the lowest level of regional differences in the LSI was found in Poland, followed by the Slovak Republic and the Czech Republic * the regional differences in Hungary are almost twice as high as in the Czech Republic

The chironomid-temperature relationship: expression in nature and palaeoenvironmental implications

Fossils of chironomid larvae (non-biting midges) preserved in lake sediments are well-established palaeotemperature indicators which, with the aid of numerical chironomid-based inference models (transfer functions), can provide quantitative estimates of past temperature change. This approach to temperature reconstruction relies on the strong relationship between air and lake surface water temperature and the distribution of individual chironomid taxa (species, species groups, genera) that has been observed in different climate regions (arctic, subarctic, temperate and tropical) in both the Northern and Southern hemisphere. A major complicating factor for the use of chironomids for palaeoclimate reconstruction which increases the uncertainty associated with chironomid-based temperature estimates is that the exact nature of the mechanism responsible for the strong relationship between temperature and chironomid assemblages in lakes remains uncertain. While a number of authors have provided state of the art overviews of fossil chironomid palaeoecology and the use of chironomids for temperature reconstruction, few have focused on examining the ecological basis for this approach. Here, we review the nature of the relationship between chironomids and temperature based on the available ecological evidence. After discussing many of the surveys describing the distribution of chironomid taxa in lake surface sediments in relation to temperature, we also examine evidence from laboratory and field studies exploring the effects of temperature on chironomid physiology, life cycles and behaviour. We show that, even though a direct influence of water temperature on chironomid development, growth and survival is well described, chironomid palaeoclimatology is presently faced with the paradoxical situation that the relationship between chironomid distribution and temperature seems strongest in relatively deep, thermally stratified lakes in temperate and subarctic regions in which the benthic chironomid fauna lives largely decoupled from the direct influence of air and surface water temperature. This finding suggests that indirect effects of temperature on physical and chemical characteristics of lakes play an important role in determining the distribution of lake-living chironomid larvae. However, we also demonstrate that no single indirect mechanism has been identified that can explain the strong relationship between chironomid distribution and temperature in all regions and datasets presently available. This observation contrasts with the previously published hypothesis that climatic effects on lake nutrient status and productivity may be largely responsible for the apparent correlation between chironomid assemblage distribution and temperature. We conclude our review by summarizing the implications of our findings for chironomid-based palaeoclimatology and by pointing towards further avenues of research necessary to improve our mechanistic understanding of the chironomid-temperature relationship.

Synthesis and two-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 in living cells

The synthesis of a photolabile derivative of inositol-1,4,5-trisphosphate (IP3) is described. This new caged second messenger (6-ortho-nitroveratryl)-IP3 (6-NV-IP3) has an extinction coefficient of 5000 M(-1) cm(-1) at 350 nm, and a quantum yield of photolysis of 0.12. Therefore, 6-NV-IP3 is photolyzed with UV light about three times more efficiently than the widely used P(4(5))-1-(2-nitrophenyl)ethyl-caged IP3 (NPE-IP3). 6-NV-IP3 has a two-photon cross-section of about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two-photon excitation in living cells at modest power levels. Using near-IR light (5 mW, 710 nm, 80 MHz, pulse-width 70 fs), we produced focal bursts of IP3 in HeLa cells, as revealed by laser-scanning confocal imaging of intracellular Ca2+ concentrations. Therefore, 6-NV-IP3 can be used for efficient, subcellular photorelease of IP3, not only in cultured cells but also, potentially, in vivo. It is in the latter situation that two-photon photolysis should reveal its true forte.

The nitrodibenzofuran chromophore: a new caging group for ultra-efficient photolysis in living cells

Photochemical uncaging of bio-active molecules was introduced in 1977, but since then, there has been no substantial improvement in the properties of generic caging chromophores. We have developed a new chromophore, nitrodibenzofuran (NDBF) for ultra-efficient uncaging of second messengers inside cells. Photolysis of a NDBF derivative of EGTA (caged calcium) is about 16-160 times more efficient than photolysis of the most widely used caged compounds (the quantum yield of photolysis is 0.7 and the extinction coefficient is 18,400 M(-1) cm(-1)). Ultraviolet (UV)-laser photolysis of NDBF-EGTA:Ca(2+) rapidly released Ca(2+) (rate of 20,000 s(-1)) and initiated contraction of skinned guinea pig cardiac muscle. NDBF-EGTA has a two-photon cross-section of approximately 0.6 GM and two-photon photolysis induced localized Ca(2+)-induced Ca(2+) release from the sarcoplasmic recticulum of intact cardiac myocytes. Thus, the NDBF chromophore has great promise as a generic and photochemically efficient protecting group for both one- and two-photon uncaging in living cells.

Health risk appraisal in older people 1: are older people living alone an "at-risk" group?

BACKGROUND: In the UK, population screening for unmet need has failed to improve the health of older people. Attention is turning to interventions targeted at 'at-risk' groups. Living alone in later life is seen as a potential health risk, and older people living alone are thought to be an at-risk group worthy of further intervention. AIM: To explore the clinical significance of living alone and the epidemiology of lone status as an at-risk category, by investigating associations between lone status and health behaviours, health status, and service use, in non-disabled older people. Design of study: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal in older people. SETTING: Four group practices in suburban London. METHOD: Sixty per cent of 2641 community-dwelling non-disabled people aged 65 years and over registered at a practice agreed to participate in the study; 84% of these returned completed questionnaires. A third of this group, (n = 860, 33.1%) lived alone and two-thirds (n = 1741, 66.9%) lived with someone else. RESULTS: Those living alone were more likely to report fair or poor health, poor vision, difficulties in instrumental and basic activities of daily living, worse memory and mood, lower physical activity, poorer diet, worsening function, risk of social isolation, hazardous alcohol use, having no emergency carer, and multiple falls in the previous 12 months. After adjustment for age, sex, income, and educational attainment, living alone remained associated with multiple falls, functional impairment, poor diet, smoking status, risk of social isolation, and three self-reported chronic conditions: arthritis and/or rheumatism, glaucoma, and cataracts. CONCLUSION: Clinicians working with independently-living older people living alone should anticipate higher levels of disease and disability in these patients, and higher health and social risks, much of which will be due to older age, lower educational status, and female sex. Living alone itself appears to be associated with higher risks of falling, and constellations of pathologies, including visual loss and joint disorders. Targeted population screening using lone status may be useful in identifying older individuals at high risk of falling.

Asthma in young south Asian women living in the United Kingdom: the importance of early life

BACKGROUND: Studies of immigrants suggest that the environment during fetal life and duration of residence in the host country might influence the development of asthma. Little is known about the importance of the timing of the exposure in the host country and whether migrants might be especially vulnerable in certain age windows. OBJECTIVE: We compared the reported prevalence of asthma between young white and south Asian women in the United Kingdom, and investigated associations with country of birth and age at immigration. METHODS: A questionnaire on atopic disorders was posted to 2380 south Asian and 5796 white young mothers randomly sampled in Leicestershire. Data on ethnicity were also available from maternity records. Data were analysed using multivariable logistic regression and a propensity score approach. Results The reported prevalence of asthma was 10.9% in south Asian and 21.8% in white women. South Asian women who migrated to the United Kingdom aged 5 years or older reported less asthma (6.5%) than those born in the United Kingdom or who migrated before age 5 (16.0%), with an adjusted odds ratio of 0.38 [95% Confidence Interval 0.23-0.64, P<0.001]. For those who migrated aged over 5 years, the prevalence did not alter with the duration of residence in the United Kingdom. Current exposure to common environmental risk factors had relatively little effect on prevalence estimates. CONCLUSION: These data from a large population-based study support the hypothesis that early life environmental factors influence the risk of adult asthma.

Fluorescent annexin A1 reveals dynamics of ceramide platforms in living cells

Upon its genesis during apoptosis, ceramide promotes gross reorganization of the plasma membrane structure involving clustering of signalling molecules and an amplification of vesicle formation, fusion and trafficking. The annexins are a family of proteins, which in the presence of Ca(2+), bind to membranes containing negatively charged phospholipids. Here, we show that ceramide increases affinity of annexin A1-membrane interaction. In the physiologically relevant range of Ca(2+) concentrations, this leads to an increase in the Ca(2+)sensitivity of annexin A1-membrane interaction. In fixed cells, using a ceramide-specific antibody, we establish a direct interaction of annexin A1 with areas of the plasma membrane enriched in ceramide (ceramide platforms). In living cells, the intracellular dynamics of annexin A1 match those of plasmalemmal ceramide. Among proteins of the annexin family, the interaction with ceramide platforms is restricted to annexin A1 and is conveyed by its unique N-terminal domain. We demonstrate that intracellular Ca(2+)overload occurring at the conditions of cellular stress induces ceramide production. Using fluorescently tagged annexin A1 as a reporter for ceramide platforms and annexin A6 as a non-selective membrane marker, we visualize ceramide platforms for the first time in living cells and provide evidence for a ceramide-driven segregation and internalization of membrane-associated proteins.