Effective exposure to solar UV in building workers: influence of local and individual factors.

Excessive exposure to solar UV light is the main cause of skin cancers in humans. UV exposure depends on environmental as well as individual factors related to activity. Although outdoor occupational activities contribute significantly to the individual dose received, data on effective exposure are scarce and limited to a few occupations. A study was undertaken in order to assess effective short-term exposure among building workers and characterize the influence of individual and local factors on exposure. The effective exposure of construction workers in a mountainous area in the southern part of Switzerland was investigated through short-term dosimetry (97 dosimeters). Three altitudes, of about 500, 1500 and 2500 m were considered. Individual measurements over 20 working periods were performed using Spore film dosimeters on five body locations. The postural activity of workers was concomitantly recorded and static UV measurements were also performed. Effective exposure among building workers was high and exceeded occupational recommendations, for all individuals for at least one body location. The mean daily UV dose in plain was 11.9 SED (0.0-31.3 SED), in middle mountain 21.4 SED (6.6-46.8 SED) and in high mountain 28.6 SED (0.0-91.1 SED). Measured doses between workers and anatomical locations exhibited a high variability, stressing the role of local exposure conditions and individual factors. Short-term effective exposure ranged between 0 and 200% of ambient irradiation, indicating the occurrence of intense, subacute exposures. A predictive irradiation model was developed to investigate the role of individual factors. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure, and were also found to account more than altitude on the total variance of effective daily exposures. Targeted sensitization actions through professional information channels and specific prevention messages are recommended. Altitude outdoor workers should also benefit from preventive medical examination.

Expression pattern of sirtuins in innate immune cells and influence of Sirtuin 1/2 inhibition on innate immune responses to Toll-like receptor ligands and to infection

Purpose/Objective: The family of histone deacetylases comprises 18 members in mammals, among which seven sirtuins (SIRT1-7). Sirtuins are NADP-dependent enzymes that have been involved in the control of cell metabolism, proliferation and survival. The expression pattern of sirtuins and their influence on host response to microbial infection remain largely unknown. The aim of the study was to analyze the expression of SIRT1-7 and to address the effects of SIRT1/2 inhibition on innate immune responses in vitro and in vivo.. Materials and methods: in vitro: Bone marrow (BM), BM-derived macrophages (BMDMs) and dendritic cells (BMDCs) and RAW 264.7 and J774.1 macrophage cell lines were stimulated for 0, 2, 6 and 18 h with LPS, Pam3CSK4 and CpG ODN. SIRT1-7 mRNA was quantified by real time-PCR. TNF was measured by ELISA. In vivo: BALB/c mice were challenged with LPS (350 lg i.p.) with or without a SIRT1/2 inhibitor. Blood and organs were collected after 0, 1, 4, 8 and 24 h to quantify SIRT1-7 and TNF. Mortality was assessed daily. Results: Bone marrow, macrophages and DCs express, in order of abundance, SIRT2 > > SIRT1, SIRT3 and SIRT6 > SIRT4, SIRT5 and SIRT7. Microbial products decrease the expression of all sirtuins except SIRT6 in a time dependent manner in BMDMs (0_24 h). SIRT2 is the most expressed sirtuin also in the liver, kidney (together with SIRT3) and spleen. Upon LPS challenge, SIRT1, SIRT3, SIRT4 and SIRT7 mRNA levels decrease in the liver (from 4 h to 24 h), whereas SIRT1-7 mRNA levels decrease within 1 h in both kidney and spleen. Pharmacological inhibition of SIRT1/2 decreases TNF production by macrophages stimulated with LPS, Pam3CSK4 and CpG ODN (n = 6; P < 0.001). In agreement, prophylactic treatment with a SIRT1/2 inhibitor decreases TNF production (n = 8; P = 0.04) and increases survival (n = 13, P = 0.03) of mice challenged with LPS. Conclusions: Sirtuins are expressed in innate immune cells. Inhibition of SIRT1/2 activity decreases cytokine production by macrophages and protects from endotoxemia, suggesting that sirtuin inhibitors may represent novel adjunctive therapy for treating inflammatory disorders such as sepsis.

Importance of TNF-alpha in the course of acute infection with Trypanosoma cruzi: influence of its inhibition by pentoxifylline treatment

Infection of C3H/He mice with the Peruvian strain of Trypanosoma cruzi (Biodeme type I, Z2b), a macrophagotropic strain, determined severe parasitism of macrophages, necrosis of the spleen, and high host mortality. In the present study, pentoxifylline (PTX), an inhibitor of TNF-alpha was investigated on its action upon splenic necrosis, parasitemia and host survival. Immunohistochemical data suggested the importance of this cytokine in parasite destruction and decreasing of parasitemia, although paradoxically contributing to the high mortality of infected mice. Necrotic lesions involving several organs, specially the heart, in acute Chagas disease, are important aggravating factors, increasing cardiac morbidity. Advantage of inhibiting TNF-alpha action was herein investigated. Infected mice were divided into two groups: untreated (n = 24), and PTX treated mice (n = 25). PTX was administered in two daily doses of 30 mg/kg/bw, by intraperitoneal route. Normal controls either treated with PTX or saline were also included. Histopathology of the spleen and in situ immunolabeling of TNF-alpha, using anti-TNF-alpha monoclonal antibody, were performed. Necrotic areas were evaluated by morphometry. Mice treated with PTX showed a significant decrease of necrotic areas and diminution of TNF-alpha expression in spleen tissue, suggesting that PTX treatment could control TNF-alpha effects, and thus be used as an adjuvant in the treatment of acute Chagas' disease.

Influence of temperature and humidity on the biology of Triatoma mexicana (Hemiptera: Reduviidae: Triatominae) under laboratory conditions

Several biological parameters related to the Triatoma mexicana life-cycle were evaluated in this study. Three cohorts were maintained under different combinations of temperature and relative humidity (RH): 25ºC/50% RH; 25ºC/75% RH; and 30ºC/75% RH. Observed hatching rates varied from 49-57.5% whereas the average time of hatching varied from 19.5-22.7 days. In the three cohorts studied, the mean time-lapse between presentation of the blood meal and the beginning of feeding was less than 5 min in all instars; the mean feeding time was longer than 10 min in all the instars; the post-feed defecation delay was over 10 min in all the instars. Less than 50% of nymphs in each cohort completed the cycle and the average time from 1st instar nymph to adult was more than 255 days for the three cohorts. The number of blood meals before molt at each nymphal instar varied from 1-9. Our results appear to indicate a lack of influence of temperature and RH on the biological parameters of T. mexicana that were studied, which could reflect the adaptation capacity of this species. We also conclude that T. mexicana can not be considered an effective transmitter of Trypanosoma cruzi to human populations in areas where this species is currently present.

Embryonic development of Aedes aegypti (Diptera: Culicidae): influence of different constant temperatures

Despite its vector importance little attention is given to Aedes aegypti embryonic development. In this study, temperature influence on time course of Ae. aegypti larvae hatching and egg viability were evaluated. The dormancy state at the end of embryogenesis could be interrupted with a proper stimulus. Temperatures tested ranged between 12-36°C; the maximum temperature limit is 35°C and the minimum one is below 12°C. Egg viability between 16-31°C was above 80%. The definition of physiological embryonic parameters at this temperature range corroborates Ae. aegypti presence on tropical and subtropical world regions.

The influence of individual, social and physical environment factors on physical activity in the adult population in Andalusia, Spain

A person’s physical and social environment is considered as an influencing factor in terms of rates of engagement in physical activity. This study analyses the influence of socio-demographic, physical and social environmental factors on physical activity reported in the adult population in Andalusia. This is a cross-sectional study using data collected in the Andalusia Health Survey in 1999 and 2003. In addition to the influence of the individual’s characteristics, if there are no green spaces in the neighbourhood it is less likely that men and women will take exercise (OR = 1.26; 95% CI = 1.13, 1.41). Likewise, a higher local illiteracy rate also has a negative influence on exercise habits in men (OR = 1.39; 95% CI = 1.21, 1.59) and in women (OR = 1.22; 95% CI = 1.07, 1.40). Physical activity is influenced by individuals’ characteristics as well as by their social and physical environment, the most disadvantaged groups are less likely to engage in physical activity

Ocular toxoplasmosis: the influence of patient age

The influence of patient age on various features of ocular toxoplasmosis has been a subject of study for many years. The age at which Toxoplasma gondii infection occurs in different populations is related to socioeconomic factors and studies suggest that ocular toxoplasmosis is a more severe disease at the extremes of age. The prevalence of ocular involvement is markedly different between individuals with congenital and those with post-natally acquired infections. Even among those with post-natally acquired infections, age influences the risk and timing of ocular involvement. The severity of toxoplasmic retinochoroiditis (in terms of lesion size, location and associated inflammation) is also affected by patient age at the time of initial infection or recurrence. The risk of recurrent toxoplasmic retinochoroiditis is influenced by age at the time of initial infection and age at most recent episode of active disease. Understanding of relationships between ocular toxoplasmosis and patient age is incomplete; evidence has often been indirect and in some cases conflicting. The influence of patient age on ocular toxoplasmosis should be studied in a systematic manner to provide a better understanding of disease mechanisms and to provide clinical information that can used to establish better strategies for disease treatment and prevention.

A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.

Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor.

INTRODUCTION The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF). METHODS We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined. RESULTS We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found. CONCLUSIONS HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.