Genetic correlations of milk fatty acid contents predicted from milk mid-infrared spectra in New Zealand dairy cattle.

The objective of this study was to estimate genetic correlations among milk fatty acid (FA) concentrations in New Zealand dairy cattle. Concentrations of each of the most common FA, expressed as a percentage of the total FA, were determined by gas chromatography on a specific cohort of animals. Using this data set, prediction equations were derived using mid-infrared (MIR) spectroscopy data collected from the same samples. These prediction equations were applied to a large data set of MIR measurements in 34,141 milk samples from 3,445 Holstein-Friesian, 2,935 Jersey, and 3,609 crossbred Holstein-Friesian × Jersey cows, sampled an average of 3.42 times during the 2007-2008 season. Data were analyzed using univariate and bivariate repeatability animal models. Heritability of predicted FA concentration in milk fat ranged from 0.21 to 0.42, indicating that genetic selection could be used to change the FA composition of milk. The de novo synthesized FA (C6:0, C8:0, C10:0, C12:0, and C14:0) showed strong positive genetic correlations with each other, ranging from 0.24 to 0.99. Saturated FA were negatively correlated with unsaturated (-0.93) and polyunsaturated (-0.84) FA. The saturated FA were positively correlated with milk fat yield and fat percentage, whereas the unsaturated FA were negatively associated with fat yield and fat percentage. Our results indicate that bovine milk FA composition can be changed through genetic selection using MIR as a phenotypic proxy.

Chronic obstructive pulmonary disease (COPD) in Spain and the different aspects of its social impact: a multidisciplinary opinion document.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached.

Soccer players' fitting perception of different upper boot materials.

The present study assessed the influence of upper boot materials on fitting perception. Twenty players tested three soccer boots only differing in the upper boot material (natural calf leather, natural kangaroo leather and synthetic leather). Players reported fitting perception and preference on specific foot areas using a perceived fitting scale. Ratings were averaged for every foot area. Repeated measures ANOVA was used to analyze the differences between boots. The kangaroo leather boots were perceived tighter and closer to the preferred fitting in general fitting, metatarsals area and instep area. The synthetic leather boots were perceived as the loosest and as the most distant boot from the preferred fitting in medial front area and instep area. In conclusion, the type of upper boot material influences the fitting perception of soccer players. The kangaroo leather was the material whose fitting was perceived closest to the players fitting preference.

Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial.

BACKGROUND: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. METHODS: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). RESULTS: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). INTERPRETATION: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions.

Genotoxic exposure: novel cause of selection for a functional ΔN-p53 isoform.

The p53 gene is frequently mutated in cancers and it is vital for cell cycle control, homeostasis and carcinogenesis. We describe a novel p53 mutational spectrum, different to those generally observed in human and murine tumors. Our study shows a high prevalence of nonsense mutations in the p53 N terminus of 2-acetylaminofluorene (2-AAF)-induced urinary bladder tumors. These nonsense mutations forced downstream translation initiation at codon 41 of Trp53, resulting in the aberrant expression of the p53 isoform ΔN-p53 (or p44). We propose a novel mechanism for the origination and the selection for this isoform. We show that chemical exposure can act as a novel cause of selection for this truncated protein. In addition, our data suggest that the occurrence of ΔN-p53 accounts, at least in mice, for a cancer phenotype. We also show that gene expression profiles of embryonic stem (ES) cells carrying the ΔN-p53 isoform in a p53-null background are divergent from p53 knockout ES cells, and therefore postulate that ΔN-p53 itself has functional transcriptional properties.

A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections.

In this study the efficacy and cost-effectiveness of i.v. ceftriaxone 1 g once daily (CTX) was compared with standard i.v. antibiotic treatment (STD) for lower respiratory tract infections (LRTI). STD was given according to the guidelines of the American Thoracic Society and consisted of either cefuroxime 1500 mg three times daily (q8h), amoxicillin/clavulanic acid 1200 mg q8h or ceftriaxone 2 g once daily; each with or without a macrolide. After a minimum of 5 days i.v. therapy, patients could be switched to oral therapy. One hundred patients were enrolled in the study; 52 patients received CTX and 48 STD. Groups were comparable with respect to demographic and baseline characteristics. Seventy patients had a confirmed diagnosis of pneumonia. Twenty-nine patients had a severe type I exacerbation of chronic bronchitis. In one patient the diagnosis of LRTI could not be confirmed. In approximately 50% of the patients a microbiological diagnosis could be made. The most important isolated pathogens from sputum and blood were (positive blood cultures in brackets): Streptococcus pneumoniae 14 (9) and Haemophilus influenzae 16. Mean duration of i.v. therapy was 7.4 days in both groups. Average duration of hospitalisation was 15.0 days for CTX patients and 15.9 days for STD patients. Overall cure and improvement rate at the end of treatment was 47 (90%) for patients receiving ceftriaxone 1 g compared to 37 (77%) for patients receiving standard therapy. Pathogens were eradicated or presumed to be eradicated in 84% of the CTX patients and in 76% of the STD patients. Mean total costs per treatment were lower for CTX than for STD treatment: NLG 169 versus 458. These results show, that i.v. ceftriaxone 1 g once daily is as effective as standard therapy in the treatment of LRTI and that its use reduces treatment costs, in view of the multiple daily dosing regimens of most standard therapies.

Characterization of molecular and catalytic properties of intact and truncated human 17beta-hydroxysteroid dehydrogenase type 2 enzymes: intracellular localization of the wild-type enzyme in the endoplasmic reticulum.

Human 17beta-hydroxysteroid dehydrogenase (17HSD) type 2 is a widely distributed enzyme that primarily converts the highly active 17beta-hydroxysteroids to their inactive keto forms. In the present study, full-length human 17HSD type 2 was localized in the endoplasmic reticulum using a double immunofluorescence labeling technique. As a consequence of its strong membrane interaction, full-length human 17HSD type 2 could not be solubilized as a biologically active form in vitro. However, by deleting the first 29 amino acids from the N-terminus, we were able to purify a catalytically active enzyme from the cytosolic fraction of Sf9 insect cells. Biochemical and catalytic properties of the purified truncated human 17HSD type 2 protein confirm its suitability for structure-function analyses of the enzyme. Both intact and truncated 17HSD type 2 enzymes efficiently catalyzed the oxidation of estradiol, testosterone, dihydrotestosterone, androstenediol, and 20alpha-dihydroprogesterone. The oxidation of estradiol brought about by human 17HSD type 2 was effectively inhibited by several other steroidal compounds, such as 2-hydroxyestradiol, 5beta-androstan-3alpha,17beta-diol, 5alpha-androstan-3alpha,17beta-diol, and 5alpha-androstan-3beta,17beta-diol. The broad substrate specificity of human 17HSD type 2 together with its predominant oxidative activity and intracellular location, as observed in this study, indicate the physiological role of the enzyme to be primarily an inactivator of highly active 17beta-hydroxysteroids.

Child pedestrian injuries in the Cape metropolitan area--final results of a hospital-based study.

Over a 12-month period 430 children under 14 years of age presented to Red Cross War Memorial Children's Hospital in Cape Town having been injured as pedestrians, and 106 children who died from such injuries were registered at the regional state mortuary. Information about the circumstances surrounding injury was obtained from the parents or guardians of all children reporting to hospital and 48 (45.3%) of the fatalities. Analysis of results revealed a strong relationship between pedestrian injury and children playing or running errands in residential areas during daylight hours, particularly in the later part of the afternoon. Only 24.3% of all children were supervised by an adult at the time of injury. The pattern of behaviour described must be acknowledged in the planning of future road safety measures. The inconsistency of parental supervision highlights the need to include adults in educational and awareness campaigns.

Secondary effects of prolonged intestinal obstruction on the enteric nervous system in the rat.

Motility disturbances following prolonged intestinal obstruction have been attributed to secondary effects. This study aimed to demonstrate the effects of incomplete obstruction on the enteric nervous system (ENS) of a rat model. Surgical placement of a nonstrangulating ligature encircling the distal bowel was performed in 41 freshly weaned rats. Anesthetic protocol included Ketamine, ether, or Xylazine (an alpha 2-adrenergic agonist). Histological evaluation was by ganglion cell morphology, histochemical staining for acetylcholinesterase (AChE) and tyrosine hydroxylase (TOH) immunocytochemistry. Forty-one freshly weaned LE rats were divided into controls (8), sham procedures (8), intestinal obstruction (16), and a group of rats with colonic biopsy performed prior to and following experimental obstruction (9). The rats were sacrificed at periods varying between 14 and 45 days post experimental obstruction (median survival, 27 days). Histological changes included elongation of ganglion cells and a decrease in the number per 5-mm slide in obstructed animals. No other obstruction specific differences were detected. A significant (P < .01) increase in AChE in the submucous plexus was recorded in Xylazine-anesthetized animals. No obstruction-specific effects could be demonstrated in the ENS, suggesting that prolonged obstruction without ischemia does not result in any significant alterations in the ENS. Pharmacological stimulation of the alpha 2-adrenergic receptor appeared to result in an increase in AChE. This mechanism may help to explain a possible role for the adrenergic system in the increased AChE levels in affected bowel in patients with Hirschsprung's disease.

Road traffic collisions involving children as pedestrians. Provisional results of a hospital-based study.

In December 1990 a study was undertaken at Red Cross Children's Hospital to examine the circumstances surrounding pedestrian injuries in children under the age of 13. The provisional results, based on the first 154 parental interviews, are reported here. There is a strong correlation between pedestrian injury and children playing or running errands in residential areas during day-light hours, particularly in the late afternoon. Lack of adult supervision may be an important factor. The relevance of these findings to future road safety strategies is discussed.