Common infections and the role of burnout in a Dutch working population

OBJECTIVE: To determine if burnout is a risk factor for common cold, flu-like illness and gastroenteritis. METHODS: We conducted a prospective cohort study among 12,140 employees at baseline, using three consecutive self-administered questionnaires. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to define employees with burnout complaints (Level 1) and clinical burnout (Level 2). The cross-sectional relationship between burnout and the occurrence of common infections was assessed at baseline, using logistic regression analysis. Survival analysis with Cox regression was performed to study the longitudinal relationship between burnout and the subscales of the MBI-GS as risk factors for common infections. RESULTS: For both levels of burnout, an increased incidence of common infections was found at baseline. The largest effect was found for the relationship between burnout and gastroenteritis (OR: 1.86, CI: 1.57-2.21 for Level 1 and OR: 3.59, CI: 2.09-6.17 for Level 2). The longitudinal analyses showed comparable results, although less pronounced. The largest effect was again found for gastroenteritis (RR: 1.55, CI: 1.28-1.86 for Level 1 and RR: 2.09, CI: 1.09-3.98 for Level 2). For flu-like illness and common cold, we found smaller but significant effects at Level 1, but not at Level 2. The subscale "Exhaustion" was found to be the strongest predictor for infections at both levels of burnout. CONCLUSIONS: This study provides evidence for burnout as a risk factor for common infections in a large heterogeneous population. Taking into account that burnout or its subscales are not primary etiological agents for these common infections, the observed effects are large.     

Reduced thrombus cohesion in an ex vivo human model of arterial thrombosis induced by clopidogrel treatment: kinetics of the effect and influence of single and double loading-dose regimens

OBJECTIVE: To compare the effects of clopidogrel on ex vivo thrombogenesis with those on ADP-dependent platelet aggregation, and to compare single and double loading-dose regimens. METHODS AND RESULTS: Step 1: Volunteers (n=12) received clopidogrel 75 mg/day for 8 days. ADP-induced platelet aggregation was measured in platelet-rich plasma (PRP). Thrombogenesis was measured in an ex vivo model. Clopidogrel produced rapid platelet inhibition, increasing up to day 5. Maximal intensity of platelet aggregation correlated with density of platelet thrombus, surface of collagen covered by platelets and thrombus cross-sectional surface (p<0.001). Step 2: On day 1, volunteers (n=60) randomly received clopidogrel 75 mg, a single 300-mg loading dose or two 300-mg loading doses separated by a 12-h interval. On day 2, all volunteers received clopidogrel 75 mg. Both loading dose regimens enhanced platelet inhibition at all time points (p<0.03 vs. clopidogrel 75 mg). After 3 h, the antiplatelet effect of a loading dose was substantial, and the mean decrease in dense thrombus surface was greater in the loading-dose groups than in the 75 mg group (p=0.041 for the single loading dose). Ex vivo, there were no significant differences between loading-dose groups. CONCLUSIONS: Clopidogrel reduces arterial thrombus cohesion by an effect that correlates with inhibition of ADP-induced platelet aggregation. A single 300-mg loading dose provides a rapid onset of such an antithrombotic effect, which was more significant at 24 h with the double loading dose.     

Cancer mortality in workers exposed to dieldrin and aldrin: an update

This study was conducted to investigate the possible long-term health effects, in particular carcinogenic effects, of occupational exposure to the organochlorine insecticides dieldrin and aldrin. We updated an earlier cohort mortality study of 570 employees involved in the production of these insecticides. All of the employees had worked in the production plants between 1 January 1954 and 1 January 1970 and were followed for cause-specific mortality until 1 January 2001. Based on dieldrin levels in blood samples taken during the exposure period, available for 343 workers, individual estimates of the total intake of dieldrin were estimated for all individual subjects in the cohort. The estimated total intake ranged from 11 to 7755 mg of dieldrin, with an average of 737 mg. One hundred and seventy-one workers had died before 1 January 2001, compared with an expected number of 226.6, giving a standardized mortality ratio (SMR) of 75.6 [95% confidence interval (CI): 64.6-87.7]. This deficit in total mortality was mainly attributable to a deficit in cardiovascular disease mortality, but cancer mortality was also lower than expected. The observed number of deaths from rectal cancer was significantly higher than expected (SMR = 300.0; 95% CI: 109.5-649.3), but was most pronounced in the low-intake subgroup and appears to be unrelated to exposure to dieldrin and aldrin. This study reinforces the earlier findings that occupational exposure of workers to significant amounts of dieldrin and aldrin has not led to a higher cancer mortality than would be found in an unexposed population.     

Crystal structures of the vitamin D-binding protein and its complex with actin: structural basis of the actin-scavenger system

Actin is the most abundant protein in eukaryotic cells, but its release from cells into blood vessels can be lethal, being associated with clinical situations including hepatic necrosis and septic shock. A homeostatic mechanism, termed the actin-scavenger system, is responsible for the depolymerization and removal of actin from the circulation. During the first phase of this mechanism, gelsolin severs the actin filaments. In the second phase, the vitamin D-binding protein (DBP) traps the actin monomers, which accelerates their clearance. We have determined the crystal structures of DBP by itself and complexed with actin to 2.1 A resolution. Similar to its homologue serum albumin, DBP consists of three related domains. Yet, in DBP a strikingly different organization of the domains gives rise to a large actin-binding cavity. After complex formation the three domains of DBP move slightly to "clamp" onto actin subdomain 3 and to a lesser extent subdomain 1. Contacts between actin and DBP throughout their extensive 3,454-A(2) intermolecular interface involve a mixture of hydrophobic, electrostatic, and solvent-mediated interactions. The area of actin covered by DBP within the complex approximately equals the sum of those covered by gelsolin and profilin. Moreover, certain interactions of DBP with actin mirror those observed in the actin-gelsolin complex, which may explain how DBP can compete effectively with gelsolin for actin binding. Formation of the strong actin-DBP complex proceeds with limited conformational changes to both proteins, demonstrating how DBP has evolved to become an effective actin-scavenger protein.     

Systematic review of case reports concerning adults suffering from neutropenic enterocolitis

Introduction Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including solid and haematological malignancies or aplastic anaemia. Objective This review was aimed at evaluating overall NEC mortality rate, describing clinical diagnostic findings and therapeutical interventions reported in the literature and generating a hypothesis regarding factors influencing mortality and surgical intervention. Materials and Methods An advanced search was made in Medline, Embase, Lilacs and Google. Additional strategies included manual search of specific journals. Reports were considered if they described case definition, inclusion and exclusion criteria.Results. 275 cases were selected; 109 were from individual data and 40 from grouped data. Comparing data between case reports and case series revealed no significant differences related to mortatity, surgical intervention, sex or age. Higher mortality (χ²=7.51 p=0.006) was found in women (50%) compared to men (28%). No significant difference was found between antibiotic combinations and mortality (χ²=12.85 df 13 p=0.45). Mortality (χ²=3.89 df 1, p=0.049), surgical intervention (χ²=7.64 df 1, p=0.006) and duration of diarrhoea (χ²=4.71 df 1, p=0.045) were significantly different in 26.4% of individuals using antifungal agents; death occurred in 81% of patients! who did not receive such medication compared to 19% individuals reported as being treated with antifungal agents. Conclusion The current evidence suggests that antifungal agents should be used early in patients suffering from NEC. However, this hypothesis must be evaluated in multi-centric, randomised controlled trials.     

Inherited disorders of the IL-12-IFN-γ axis in patients with disseminated BCG infection

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN- axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN- circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN- receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12R1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN- circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN- circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.     

Evaluation of periapical lesion healing by correction of gray values

The purpose of this study was to compare two methods for evaluating periapical healing in humans: the periapical index (PAI) and a gray value correction method. Fifty human teeth with a periapical lesion were endodontically treated. Radiographs, with a special aluminum device, were taken postoperatively, after 3 months and after 6 months. The PAI was recorded at each period of time, and a Kruskall and Wallis test was performed to compare the three groups. After scanning, the size of the lesion and its gray value were recorded. The aluminum device allowed the gray values to be equalized. An analysis of variance followed by a Duncan test was performed to compare the three groups. The teeth that showed no sign of healing according to the PAI were separately analyzed by an analysis of variance and a Duncan test. The PAI (n = 50) showed signs of periapical healing over time (p < 0.01). The analysis of variance, based on gray value evaluation (n = 50), also showed signs of periapical healing over time (p < 0.002). The analysis of variance of teeth with the same PAI over time (n = 15 at 3 months, and n = 5 at 6 months), based on gray value evaluation showed statistically significant differences among the 3 groups (p < 0.02). These results show that the gray level correction method is powerful and may reduce the risks of false negative responses during assessment of treatment results or epidemiological studies.     

Enhancing and diminishing gene function in human embryonic stem cells

It is widely recognized that gain- and loss-of-function approaches are essential for understanding the functions of specific genes, and such approaches would be particularly valuable in studies involving human embryonic stem (hES) cells. We describe a simple and efficient approach using lipofection to transfect hES cells, which enabled us to generate hES cell lines expressing naturally fluorescent green or red proteins without affecting cell pluripotency. We used these cell lines to establish a means of diminishing gene function using small interfering (si)RNAs, which were effective at knocking down gene expression in hES cells. We then demonstrated that stable expression of siRNA could knock down the expression of endogenous genes. Application of these gain- and loss-of-function approaches should have widespread use, not only in revealing the developmental roles of specific human genes, but also for their utility in modulating differentiation.     

Impact of one year of shift work on cardiovascular disease risk factors

The purpose of the study was to investigate whether the reported increased cardiovascular disease risk in shift workers could be explained by changes in cardiovascular risk factors. In a cohort of 239 shift and 157 daytime workers, 1-year changes in biological and lifestyle cardiovascular risk factors were monitored between the start of a new job and 1 year later. Both body mass index and low-density lipoprotein/high-density lipoprotein cholesterol ratio decreased significantly in shift workers compared with daytime workers (body mass index change: -0.31 and +0.13 kg/m; low-density lipoprotein/high-density lipoprotein ratio change: -0.33 and -0.13 respectively). Cigarettes smoked per day increased significantly in shift compared with daytime workers (+1.42 and -1.03, respectively). Therefore, only for smoking, an unfavorable change was observed. This may explain, at most, only a part of the excess cardiovascular disease risk reported in shift workers.     

Distribution of the mRNAs encoding the thyrotropin-releasing hormone (TRH) precursor and three TRH receptors in the brain and pituitary of Xenopus laevis: effect of background color adaptation on TRH and TRH receptor gene expression

In amphibians, thyrotropin-releasing hormone (TRH) is a potent stimulator of alpha-melanotropin (alpha-MSH) secretion, so TRH plays a major role in the neuroendocrine regulation of skin-color adaptation. We have recently cloned a third type of TRH receptor in Xenopus laevis (xTRHR3) that has not yet been characterized in any other vertebrate species. In the present study, we have examined the distribution of the mRNAs encoding proTRH and the three receptor subtypes (xTRHR1, xTRHR2, and xTRHR3) in the frog CNS and pituitary, and we have investigated the effect of background color adaptation on the expression of these mRNAs. A good correlation was generally observed between the expression patterns of proTRH and xTRHR mRNAs. xTRHRs, including the novel receptor subtype xTRHR3, were widely expressed in the telencephalon and diencephalon, where two or even three xTRHR mRNAs were often simultaneously observed within the same brain structures. In the pituitary, xTRHR2 was expressed selectively in the distal lobe, and xTRHR3 was found exclusively in the intermediate lobe. Adaptation of frog skin to background illumination had no effect on the expression of proTRH and xTRHRs in the brain. In contrast, adaptation of the animals to a white background provoked an 18-fold increase in xTRHR3 mRNA concentration in the intermediate lobe of the pituitary. These data demonstrate that, in amphibians, the effect of TRH on alpha-MSH secretion is mediated through the novel receptor subtype xTRHR3.