Increased mortality in COPD among construction workers exposed to inorganic dust.

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.     

Increased nitric oxide in exhaled air after intake of a nitrate-rich meal

Exhaled and nasal NO (ENO, NNO) have been suggested as markers for inflammation in lower and upper respiratory tract respectively. It is still unknown how a number of factors, apart from airway inflammation, can influence NO levels. The aim of this study was to determine the effect of a nitrate-rich meal on ENO and NNO. Sixteen healthy subjects were observed during 1 week on normal diet before a nitrate-restricted diet was introduced in the next. On day 3 of the second week they were made to ingest a nitrate rich meal. ENO, NNO, plasma nitrate and plasma L-arginine were followed before the meal and afterwards for 3 h. ENO and NNO as well as plasma nitrate and plasma L-arginine were significantly elevated after the nitrate-rich meal. The median maximal increase of ENO and NNO was 47% and 13% respectively. We found a moderate but significant correlation between the rise in plasma nitrate and ENO (r(s)=0.57, P=0.027) but none between plasma nitrate and NNO (r(s)=-0.02, P=0.95). As nitrate in the diet seems to substantially influence the levels of ENO it is important either to restrict or register the intake of nitrate-rich food prior to measuring ENO.     

Down syndrome associated with father's age in Norway.

Records of births in Norway in 1967 to 1978 were examined for evidence of an increased risk of Down syndrome associated with older paternal age. From among some 685 000 total births with known maternal and paternal age, 693 cases of Down syndrome were reported to the Medical Birth Registry of Norway. The effect of paternal age was assessed by classifying fathers as young and old on the basis of several definitions. The effect of maternal age was removed by stratifying the data on single years of mothers' age. When fathers were considered young if they were less than or equal to 49 and old if they were less than or equal to 50, the analysis yielded a statistic for the test of a one-sided hypothesis which was significant at the 0.05 level. There appears to be an increase risk (perhaps 20 to 30%) of Down syndrome associated with older fathers, independent of maternal age effect. If this increase does in fact exist, it is much smaller than the increases in risk associated with advancing maternal age, and because older men contribute a relatively small proportion of total births their contribution to the communal burden of Down syndrome is quite small. However, the finding is of aetiological interest and is the first indication of a significant paternal age effect where control for maternal age has been stringent.     

The Dilemma of Occupational Rhinitis

Occupational rhinitis is a common heterogeneous group of inflammatory conditions in the nose, caused by exposure to airborne irritants and sensitizers in the occupational environment. The mechanism can be allergic, neurogenic or toxic.Data from several epidemiologic studies indicate that animal dander, organic dusts, latex and chemicals can cause occupational rhinitis, but because of methodological problems as well as weaknesses in the definition of occupational rhinitis, occupational exposure is probably an underestimated cause of rhinitis. The effect of rhinitis on the mental aspects of quality of life and substantial costs due to loss of productivity make it important to diagnose and treat occupational rhinitis. Diagnosis relies on a history of exposure, skin prick testing and, if possible, nasal provoacation. Avoidance of exposure, protective measures at the workplace and medical treatment, with agents such as second generation antihistamines and nasal corticosteroids, can make it possible to avoid progress of the disease from rhinitis to asthma. The efficacies of montelukast, a leukotrienne receptor antagonist, and omalizumab, an anti-immunoglobulin E monoclonal antibody in the treatment of occupational rhinitis are yet to be evaluated     

Flow disturbances generated by feeding and swimming zooplankton

Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r⁻³ to r⁻⁴) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r⁻¹ to r⁻²). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The “quiet” propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by “breast-stroke swimming.” Both produce rapidly attenuating flows. The more “noisy” swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk.Zooplankters move to feed, find food, and find mates, so moving is critical to the efficient execution of essential functions. However, moving comes at a predation risk: Swimming increases the predator encounter velocity (encounter rate increases with prey velocity to a power ≤1), and feeding and swimming generate fluid disturbances that may be perceived by rheotactic predators, thus increasing the predator’s detection distance (encounter rate increases with detection distance squared) (1–5). So, the advantages of moving and feeding must be traded off against the associated risks, and organisms should aim at moving and foraging in ways that reduce the predation risk and optimize the trade-off (6, 7). They may do so by moving in patterns that minimize encounter rates (8) and/or they may feed and propel themselves in ways that generate only small fluid disturbances (9). For example, theoretical models suggest that zooplankton that swim by a sequence of jumps may create a smaller fluid disturbance than similar-sized ones that swim smoothly (9), that a hovering zooplankter generates a larger fluid signal than one that cruises through the water (10, 11), and that a zooplankter moving at low Reynolds numbers will generate a relatively larger fluid signal than one moving at higher Reynolds numbers (11). Thus, motility patterns and propulsion modes may strongly influence predation risk and must be subject to strong selection pressure during evolution.Zooplankton span a huge taxonomic diversity and a large size range (from microns to centimeters) and their propulsion mechanisms vary substantially (12). Unicellular plankton may use one or more flagella or cilia, and the flagella may be smooth or plumose, which has implications for whether the cell is pulled or pushed by the beating flagellum (13). Ciliates may have the cilia rather evenly distributed on the cell surface or concentrated on certain parts of the cell, typically either anteriorly or as an equatorial band. Small animals may have an anterior “corona” of cilia (e.g., rotifers and many pelagic invertebrate larvae) to generate feeding currents and propulsion, or they may have beating or vibrating appendages that can be positioned anteriorly, ventrally, or laterally. The implications and potential adaptive value of this diversity of propulsion modes for feeding and survival are largely unexplored.Various idealized models, simplifying the swimming organisms to combinations of point forces acting on the water, have been used to describe the fluid disturbance generated by moving and feeding plankton. A self-propelled plankton is often described by a so-called stresslet (two oppositely directed point forces of equal magnitude), a hovering one by a stokeslet (a stationary point force), and a jumping animal by an impulsive stresslet (a stresslet working impulsively) (9, 11, 12). These highly idealized models yield very different predictions of the spatial attenuation of the fluid disturbance and, thus, of how far away the feeding and swimming animal can be detected. A few studies have compared observed flow patterns with those predicted from these simple models and in some cases found fair comparisons (4, 14–17). However, numerical simulations as well as observations of self-propelled microplankton have demonstrated that the distribution of propulsion forces, i.e., the position of flagella, cilia, or appendages on the (cell) body, may have a profound effect on the imposed fluid flow (18, 19). Also, most of the idealized models ignore the fact that swimming in most cases is unsteady, which leads to fluctuating flows at scales smaller than the Stokes length scale (ν/ω, where ν is the kinematic viscosity and ω is the beat frequency) (e.g., ref. 19). The simple, idealized models hitherto applied may be insufficient to represent the diverse propulsion modes observed in real organisms and to understand the associated trade-offs.Feeding and swimming are often part of the same process in zooplankton. Many zooplankton generate a feeding current that at the same time propels the animal through the water. In others, feeding and swimming are separate processes. For example, ambush feeding “sit-and-wait” zooplankters do not move as part of feeding but may swim to undertake vertical migration or to search for mates or patches of elevated food availability. Also, many of the plankton that generate a feeding current by vibrating appendages may in addition swim by using the same appendages in a different way (e.g., the nauplius larvae of most crustaceans) or by using other swimming appendages dedicated to propel themselves (most pelagic copepods and cladocerans).Whereas feeding and swimming may both compromise the survival of the organism, the trade-offs may be different. To get sufficient food, zooplankters need to daily clear a volume of water for prey that corresponds to about 10⁶ times their own body volume (20, 21) and hence, implicit in the feeding process is the need to examine or process large volumes of water. In contrast, dedicated swimming should translate the organism through the water as quietly as possible. Thus, we hypothesize that in microplankton, dedicated swimming produces flow fields that attenuate more readily and/or have a smaller spatial extension than the cases in which feeding and propulsion are intimately related.In this study we use particle image velocimetry (PIV) to describe the flow fields generated by micron- to millimeter-sized feeding and swimming zooplankton that use a variety of propulsion modes. We show that—across taxa and sizes—dedicated swimming produces flow fields with a much smaller spatial extension and a faster spatial attenuation than those produced by the plankton for which feeding and swimming are integrated, and we characterize the propulsion modes that minimize susceptibility to rheotactic predators.     

Clostridial toxins: sensing a target in a hostile gut environment

The current global outbreak of Clostridium difficile infection exemplifies the major public health threat posed by clostridial glucosylating toxins. In the western world, C. difficile infection is one of the most prolific causes of bacterial-induced diarrhea and potentially fatal colitis. Two pathogenic enterotoxins, TcdA and TcdB, cause the disease. Vancomycin and metronidazole remain readily available treatment options for C. difficile infection, but neither is fully effective as is evident by high clinical relapse and fatality rates. Thus, there is an urgent need to find an alternative therapy that preferentially targets the toxins and not the drug-resistant pathogen. Recently, we addressed these critical issues in a Nature Medicine letter, describing a novel host defense mechanism for subverting toxin virulence that we translated into prototypic allosteric therapy for C. difficile infection. In this addendum article, we provide a continued perspective of this antitoxin mechanism and consider the broader implications of therapeutic allostery in combating gut microbial pathogenesis.     

Tobacco smoking: a major risk factor for loss of teeth in three 70-year-old cohorts

Oral health was examined in a random sample of 1377 people in three 70-year-old cohorts studied within 5-yr intervals. During the studied period 1971-1983 the prevalence of toothlessness decreased from 52 to 34%. Toothlessness in men was more common in smokers, 48%, and ex-smokers, 32%, than in non-smokers, 20%. Eichner's index was used as a measurement of dental invalidity. This index showed a worse dental state among smokers and ex-smokers compared to non-smokers. Multivariate analyses indicated that tobacco smoking was a major independent risk factor for tooth loss in elderly men.