The Prevalence of Respiratory Symptoms in Irish Dairy Farmers.

Work-related respiratory disease is a significant risk in the farming community. We assessed respiratory symptoms using a validated work-related respiratory questionnaire in 126 dairy farmers (19-75 years; 91.3% male). The prevalence of cough symptoms was 34.4%. Thirty-seven farmers (29.4%) complained of upper airway symptoms while forty (31.7%) complained of eye problems. Cumulated symptoms scores did not indicate higher than normal rates of chronic lung disease. Only 10 farmers (7.9%) were taking medication for lung conditions. Only 7 (5.6%) were current smokers. The rate of respiratory symptoms did not relate to the herd size or the method of animal feeding used by the farmers. The incidence of respiratory symptoms remains high among Irish dairy farmers. While the exact reason for this is unknown it may be related to continuing work- related dust exposure.

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury.

The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans.

Methylation of the SKA2 (spindle and kinetochore-associated complex subunit 2) gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness and psychiatric phenotypes linked to suicide in trauma-exposed veterans. About 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. Of all, 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the cytosine-guanine locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated single nucleotide polymorphism (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD) and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylation(adj)). Specifically, DNA methylation(adj) was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylation(adj) and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylation(adj) of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

The prevalence of respiratory symptoms among mushroom workers in Ireland.

BACKGROUND: Respiratory conditions such as asthma, bronchitis, hypersensitivity pneumonitis and upper airways symptoms have been ascribed to fungal exposures. Mushroom workers may be at risk of these as a consequence. AIMS: To assess the prevalence of respiratory symptoms in mushroom workers. METHODS: A cross-sectional study assessed 4 weeks of respiratory symptoms among mushroom workers divided into four categories of exposure, using a self-administered respiratory questionnaire and spirometry. RESULTS: The population of 191 subjects was predominantly (66%) from Eastern Europe; 61% were women and 39% were under 30. It included 73 growers, 38 composters, 26 administrators and 52 packers. Among all workers, there was a high prevalence (67%) of one or more respiratory symptoms which did not appear to vary by age, gender, pack-years of smoking or duration of employment. There was a significant improvement in respiratory symptoms in workers during absence from the workplace (P < 0.001). Spirometry readings across all groups were within normal values. Symptom profiles suggest that as many as 22 workers had symptoms of airways disease; 18 (82%) of these were mushroom growers. Growers were significantly more likely to have symptoms consistent with airways disease than all other workers, odds ratio 9.2 (95% CI 3.0-28.4). CONCLUSIONS: There was a high prevalence of respiratory symptoms among mushroom workers. Mushroom growers may be at high risk of airways disease, possibly from fungal antigens or related exposures.

Metabolic rates, genetic constraints, and the evolution of endothermy.

The metabolic distinction between endotherms and ectotherms is profound. Whereas the ecology of metabolic rates is well studied, how endotherms evolved from their ectothermic ancestors remains unclear. The aerobic capacity model postulates that a genetic constraint between resting and maximal metabolism was essential for the evolution of endothermy. Using the multivariate breeders' equation, I illustrate how the (i) relative sizes of genetic variances and (ii) relative magnitudes of selection gradients for resting and maximal metabolism affect the genetic correlation needed for endothermy to have evolved via a correlated response to selection. If genetic variances in existing populations are representative of ancestral conditions, then the aerobic capacity model is viable even if the genetic correlation was modest. The analyses reveal how contemporary data on selection and genetic architecture can be used to test hypotheses about the evolution of endothermy, and they show the benefits of explicitly linking physiology and quantitative genetic theory.

Isochromosome of a deleted 20q: a rare but recurrent chromosome abnormality in myelodysplastic syndromes.

Interstitial deletion of the long arm of chromosome 20, as the sole abnormality, is commonly observed in myeloid malignancies, including myeloproliferative disorder, myelodysplastic syndrome, and acute myeloid leukemia. The breakpoints of the deletion are typically located in the region 20q11.2 approximately q13.3, although smaller deletions within this region have also been reported. We present here 4 patients with myelodysplastic syndrome with an isochromosome of the deleted long arm of chromosome 20: ider(20)(q10)del(20)(q11q13). Fluorescence in situ hybridization studies were performed on the bone marrow samples from these patients to prove the identity of this unusual chromosome abnormality.

The quantitative genetics of maximal and basal rates of oxygen consumption in mice.

A positive genetic correlation between basal metabolic rate (BMR) and maximal (VO(2)max) rate of oxygen consumption is a key assumption of the aerobic capacity model for the evolution of endothermy. We estimated the genetic (V(A), additive, and V(D), dominance), prenatal (V(N)), and postnatal common environmental (V(C)) contributions to individual differences in metabolic rates and body mass for a genetically heterogeneous laboratory strain of house mice (Mus domesticus). Our breeding design did not allow the simultaneous estimation of V(D) and V(N). Regardless of whether V(D) or V(N) was assumed, estimates of V(A) were negative under the full models. Hence, we fitted reduced models (e.g., V(A) + V(N) + V(E) or V(A) + V(E)) and obtained new variance estimates. For reduced models, narrow-sense heritability (h(2)(N)) for BMR was <0.1, but estimates of h(2)(N) for VO(2)max were higher. When estimated with the V(A) + V(E) model, the additive genetic covariance between VO(2)max and BMR was positive and statistically different from zero. This result offers tentative support for the aerobic capacity model for the evolution of vertebrate energetics. However, constraints imposed on the genetic model may cause our estimates of additive variance and covariance to be biased, so our results should be interpreted with caution and tested via selection experiments.

Comparison of metabolisable energy values of different foodstuffs determined in ostriches and poultry.

Apparent (AMEn) and true (TMEn) metabolisable energy values, corrected for nitrogen retention, of wheat bran, saltbush (Atriplex nummularia), common reed (Phragmites australis), lupins, soyabean oil cake meal (SBOCM), sunflower oil cake meal (SFOCM) and fishmeal were compared in 7 successive trials using 12 mature South African Black ostriches and 10 adult Australorp cockerels per ingredient. TMEn values of 11.91, 7.09, 8.67, 14.61, 13.44, 10.79 and 15.13 MJ/kg for wheat bran, saltbush, common reed, lupins, SBOCM, SFOCM and fishmeal, respectively, were found for ostriches in comparison to lower (P<0.05) values of 8.55, 4.50, 2.79, 9.40, 9.04, 8.89 and 13.95 MJ/kg for cockerels. The higher (P<0.05) ME values for ostriches confirm that the ostrich is capable of digesting foodstuffs, especially those with high fibre concentrations such as drought-resistant fodders, more effectively than poultry. Plant protein sources could make a considerable energy contribution to diets for ostriches. It is concluded that it is essential to use energy values of foodstuffs determined using ostriches and not extrapolated values derived from poultry in diet formulation for ostriches.

Genetic variation and correlations between genotype and locomotor physiology in outbred laboratory house mice (Mus domesticus).

Laboratory strains of house mice (Mus domesticus) are increasingly used as model organisms in evolutionary physiology, so information on levels of genetic variation is important. For example, are levels of genetic variation comparable to those found in populations of wild house mice? We studied allozymes to estimate genetic variation in outbred Hsd:ICR mice, which have been used in several studies with evolutionary emphasis. The physiological significance of allozyme variation remains obscure. Several workers have reported relationships between multi-locus heterozygosity and metabolic traits, but endotherms have not been studied. Therefore, we also measured mice for basal metabolic rate (BMR), maximal oxygen consumption during forced treadmill exercise (VO2max), and 12 other traits related to locomotor physiology, before genotyping them for 10 allozyme loci. Four of these loci were polymorphic, all were in Hardy-Weinberg equilibrium, and inbreeding coefficients were not significantly different from zero. Average heterozygosities were 11%, similar to values reported for wild populations of house mice. Fourteen percent of the associations between single-locus genotype and physiological traits were statistically significant. Multi-locus heterozygosity was not significantly related to VO2max, but was positively correlated with BMR, a result opposite to the negative correlation between standard metabolic rate and heterozygosity reported in many ectotherms. Therefore, the proposed mechanisms for the effect of multi-locus heterozygosity on metabolic rate in ectotherms may not apply to endotherms.

Effects of dietary quality on basal metabolic rate and internal morphology of European starlings (Sturnus vulgaris).

European starlings (Sturnus vulgaris) were fed either a low- or high-quality diet to test the effects of dietary quality on basal metabolic rate (BMR) and internal morphology. Basal metabolic rate did not differ significantly between the two dietary groups, but internal morphology differed greatly. Starlings fed the low-quality diet had heavier gastrointestinal tracts, gizzards, and livers. Starlings fed the high-quality diet had heavier breast muscles. Starlings on the low-quality diet maintained mass, while starlings on the high-quality diet gained mass. Dry matter digestibility and energy digestibility were lower for starlings fed the low-quality diet, and their food and water intake were greater than starlings on the high-quality diet. The lack of dietary effect on BMR may be the result of increased energy expenditure of digestive organs paralleling a reduction of energy expenditure of organs and tissues not related to digestion (i.e., skeletal muscle). This trade-off in energy allocation among organs suggests a mechanism by which organisms may alter BMR in response to a change in seasonal variation in food availability.

Research note: a comparison of metabolisable energy values of lucerne and barley between young and mature ostriches.

Apparent and true metabolisable energy (ME) values, corrected for zero nitrogen retention, of lucerne and barley were compared in balance studies between young (six months old, 50 to 60 kg BW) and mature (30 months old, 110 to 120 kg BW) ostriches. Birds were housed in individual metabolism crates and excreta collection were performed over a five day period after an adaptation period of seven days. Apparent metabolisable energy, corrected for zero nitrogen retention, (AMEN) of 9.17 +/- 0.251 MJ/kg (lucerne) and 14.24 +/- 0.136 MJ/kg (barley) for young ostriches do not differ (P > 0.05) from values of 8.97 +/- 0.226 MJ/kg (lucerne) and 14.21 +/- 0.134 MJ/kg (barley) obtained for mature ostriches. Also no significant differences occurred between true metabolisable energy, corrected for zero nitrogen retention, (TMEN) values of 9.16 +/- 0.450 MJ/kg (lucerne) and 13.94 +/- 0.390 MJ/kg (barley) for young ostriches and 9.26 +/- 0.412 MJ/kg (lucerne) and 13.92 +/- 0.316 MJ/kg (barley) for mature ostriches. It is concluded that similar AMEN and TMEN values of feedstuffs would be suitable in ostrich diet formulation for age groups older than six months.

A comparative study between mature ostriches (Struthio camelus) and adult cockerels with regard to the true and apparent digestibilities of amino acids.

1. A study was conducted to compare apparent and true digestibility of amino acids in a high protein experimental diet between young ostriches (7 months of age) and cockerels. 2. A mean value for true digestibility of amino acids (TAAD) of 0.837 +/- 0.0073 (range 0.780 to 0.862) was derived for ostriches, compared with a mean value of 0.795 +/- 0.0258 (range 0.723 to 0.825) for cockerels. 3. True retention of dietary protein was 0.646 +/- 0.0114 and 0.609 +/- 0.0643 for ostriches and cockerels respectively. 4. Results in the present study produced evidence that the method for determining metabolisable energy values of ingredients for ostriches is also suitable for measuring the digestibility of amino acids. 5. It was concluded that accurate diet formulation for ostriches requires the assessment of amino acid digestibilities for individual ingredients, because values derived from poultry would underestimate digestibilities for ostriches.

A comparative study between mature ostriches (Struthio camelus) and adult cockerels with respect to true and apparent metabolisable energy values for maize, barley, oats and triticale.

1. In three successive trials with cockerels and mature ostrich males the apparent and true metabolisable energy values, corrected for nitrogen retention (AMEn and TMEn) were determined by a balance method for malting barley, oats, triticale and yellow maize. All these ingredients were used as sole dietary components with the exception of triticale for ostriches which was diluted with 440 g/kg lucerne meal. The balance trial lasted for 5 d after an adaption period of 7 d for ostriches, and 3 d after an adaption period of one day for cockerels. 2. AMEn values for cockerels of malting barley, oats, triticale and maize were 11.6, 10.48, 11.44 and 14.42 MJ/kg respectively. Significantly higher values of 14.21, 12.65, 12.60 and 14.89 MJ/kg were determined for malting barley, oats, triticale and maize for ostriches. 3. TMEn values determined by regression yielded values in ostriches of 13.92, 12.27, 13.21 and 15.22 MJ/kg for malting barley, oats, triticale and maize respectively. The corresponding TMEn values in cockerels were 11.33, 10.63, 11.82 and 14.07 MJ/kg. 4. The ostrich is capable of utilising fibre more efficiently than poultry. The higher energy values observed for the various ingredients also indicated that the non-starch polysaccharides such as beta-glucans and arabinoxylans in the more fibrous energy sources had little if any effect on the available energy of these ingredients as found with poultry. 5. The potential of ostriches to utilise the more fibrous energy sources like barley, oats and triticale allows for their economical use in diet formulation. This possibility may result in markedly lower food costs for ostriches.

Elastin and collagen remodeling in emphysema. A scanning electron microscopy study.

The relationship between elastin degradation and emphysema is well known. Recent evidence suggests that a complex process of pulmonary remodeling occurs within the emphysematous lung. The aim of this study was to assess the extent of extracellular matrix remodeling in emphysema by ultrastructural examination of elastin and collagen templates in an animal model of emphysema and in human emphysematous lungs. Emphysema was induced in rats by the intratracheal administration of porcine pancreatic elastase. Human lung samples were obtained at surgical resection for lung carcinoma. Emphysema was confirmed morphometrically and quantitated using the mean linear intercept. Matching sections were treated with sodium hydroxide and formic acid to expose collagen and elastin templates, respectively. Scanning electron microscopy with stereo-pair imaging allowed three-dimensional visualization of the exposed templates. In emphysematous lungs from both sources, sheets of elastin were disrupted and perforated with multiple fenestrations. In elastase-induced emphysema, this disintegration was accompanied by a marked increase in thickness of collagen fibrils, which contrasted with the fine fibrillar network of control lungs. Similarly, a pattern of thickened fibrils and disorganized deposition of collagen was observed in human lungs. In conclusion, these findings support the novel concept of increased collagen deposition and aberrant collagen remodeling in the pathogenesis of emphysema.

Response to long-term selection for egg production in laying hens.

1. A White Leghorn line was selected for part-record hen-housed number of eggs from 1962 to 1990. Genetic changes were estimated as deviations from its unselected control line. 2. Over the first 10 generations with selection almost exclusively for number of eggs to the age of 273 d, all traits, except rate of mortality, showed significant changes. Regressions per year were: 273 d production, 3.07 eggs; 497 d production, 5.18 eggs; production from 274 to 497 d, 2.43 eggs; age at first egg, -2.33 d; mean weight of first 10 eggs, -0.82 g; body weight at 497 d, -19.02 g and rate of mortality, 0.19%. 3. Over the rest of the period increasing selection pressure for egg weight has been applied. This resulted in positive changes for this trait and no or small negative changes in egg number. 4. In general, heritabilities and genetic correlations did not change over the period of selection. The heritability of the main trait of selection, production to 273 d was 0.19 +/- 0.04 and heritabilities of egg size traits about 0.50. 5. The genetic correlation between egg production to 273 d and mean weight of first 10 eggs was estimated as -0.37 +/- 0.06 but from the observed response a realised genetic correlation of -0.97 was calculated.

Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis.

BACKGROUND: DNA released by degenerating inflammatory neutrophils contributes to mucous plugging of airways in patients with cystic fibrosis. Neutrophil elastase, a major effector of tissue destruction in the lungs of patients with cystic fibrosis, is a highly cationic molecule which is bound and inhibited by negatively charged polyanions such as mucin and DNA in purulent sputum. Thus, the solubilisation of DNA in the airways by aerosolised recombinant DNase may remove a source of neutrophil elastase inhibition, effectively increasing elastase load. The aim of this study was to assess the effect of rhDNase therapy on neutrophil elastase load in patients with cystic fibrosis. METHODS: Blood and sputum were collected from 15 patients with cystic fibrosis before initiation of nebulised DNase therapy and at 12 weeks following therapy. The long term effects of continuous rhDNase administration were evaluated at 52 weeks for 11 of these patients. Plasma was analysed for neutrophil elastase, interleukin (IL)-8 and neutrophil elastase in complex with alpha 1-protease inhibitor (alpha 1PI). Sputum was assessed for neutrophil elastase, IL-8, and active elastase. At each visit spirometric measurements were carried out. RESULTS: Sputum elastase activity decreased at 12 weeks and was maintained at 52 weeks when a decline in total plasma elastase was also observed. Although, as expected, there was a correlation between plasma levels of total elastase and neutrophil elastase/alpha 1PI complex, the decrease in the levels of the complex at 52 weeks did not reach statistical significance. CONCLUSIONS: This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.

Lung injury in patients following thoracotomy.

BACKGROUND: Postoperative lung injury is a recognised complication of thoracotomy for which there are few data regarding incidence and outcome. METHODS: In a case controlled study the notes of all adult patients who developed acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) following thoracotomy between 1991 and 1994 were examined and classified according to the guidelines of the American Thoracic Society/European Respiratory Society for ALI/ARDS. The predictive value of a routine preoperative assessment and duration of anaesthesia in determining those patients most likely to develop ALI/ARDS was assessed. RESULTS: Between 1991 and 1994 231 lobectomies, 103 pneumonectomies, and 135 wedge resections and segmentectomies were performed. The overall incidence of lung injury was 5.1%; 17 patients developed ARDS (two survived) and seven developed ALI (five survived). There was no significant difference compared with case matched controls in preoperative spirometric values, arterial oxygen tension (PaO2), or duration of anaesthesia. None of these parameters was useful in predicting those patients most likely to develop lung injury. CONCLUSION: Lung injury after thoracotomy is associated with a high mortality. Conventional parameters for preoperative assessment do not predict those patients most likely to develop ALI/ARDS in these circumstances.