A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses

Background: Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. Conclusions: Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1: 75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population

Conservative treatment in patients with an acute lumbosacral radicular syndrome: design of a randomised clinical trial [ISRCTN68857256]

BACKGROUND: The objective is to present the design of randomised clinical trial (RCT) on the effectiveness of physical therapy added to general practitioners management compared to general practitioners management only in patients with an acute lumbosacral radicular syndrome (also called sciatica). METHODS/DESIGN: Patients in general practice diagnosed with an acute (less than 6 weeks) lumbosacral radicular syndrome and an age above 18 years are eligible for participation. The general practitioners treatment follows their clinical guideline. The physical therapy treatment will consist of patient education and exercise therapy. The primary outcome measure is patients reported global perceived effect. Secondary outcome measures are severity of complaints, functional status, health status, fear of movement, medical consumption, sickness absence, costs and treatment preference. The follow-up is 52 weeks. DISCUSSION: Treatment by general practitioners and physical therapists in this study will be transparent and not a complete "black box". The results of this trial will contribute to the decision of the general practitioner regarding referral to physical therapy in patients with an acute lumbosacral radicular syndrome

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Seropositive Camel Handlers in Kenya

Middle East respiratory syndrome (MERS) is a respiratory disease caused by a zoonotic coronavirus (MERS-CoV). Camel handlers, including slaughterhouse workers and herders, are at risk of acquiring MERS-CoV infections. However, there is limited evidence of infections among camel handlers in Africa. The purpose of this study was to determine the presence of antibodies to MERS-CoV in high-risk groups in Kenya. Sera collected from 93 camel handlers, 58 slaughterhouse workers and 35 camel herders, were screened for MERS-CoV antibodies using ELISA and PRNT. We found four seropositive slaughterhouse workers by PRNT. Risk factors amongst the slaughterhouse workers included being the slaughterman (the person who cuts the throat of the camel) and drinking camel blood. Further research is required to understand the epidemiology of MERS-CoV in Africa in relation to occupational risk, with a need for additional studies on the transmission of MERS-CoV from dromedary camels to humans, seroprevalence and associated risk factors

The role of parental achievement goals in predicting autonomy-supportive and controlling parenting

Although autonomy-supportive and controlling parenting are linked to numerous positive and negative child outcomes respectively, fewer studies have focused on their determinants. Drawing on achievement goal theory and self-determination theory, we propose that parental achievement goals (i.e., achievement goals that parents have for their children) can be mastery, performance-approach or performance-avoidance oriented and that types of goals predict mothers' tendency to adopt autonomy-supportive and controlling behaviors. A total of 67 mothers (aged 30-53 years) reported their goals for their adolescent (aged 13-16 years; 19.4 % girls), while their adolescent evaluated their mothers' behaviors. Hierarchical regression analyses showed that parental performance-approach goals predict more controlling parenting and prevent acknowledgement of feelings, one autonomy-supportive behavior. In addition, mothers who have mastery goals and who endorse performance-avoidance goals are less likely to use guilt-inducing criticisms. These findings were observed while controlling for the effect of maternal anxiety

Efficient cationic ring-opening polymerization of diverse cyclic imino ethers: unexpected copolymerization behavior

The recently developed fast microwave-assisted cationic ring-opening polymerization procedure for 2-oxazolines seems to be ideally suited for slower polymerizing cyclic imino ether monomers. In this study we report the effect of the cyclic imino ether structure on the polymerization rate under exactly the same microwave-assisted conditions revealing that indeed less reactive cyclic imino ethers, including 2-oxazines as well as 4- and 5-substituted 2-oxazolines, can be polymerized to at least 50% conversion for the slowest monomer, namely 5-methyl-2-butyl-2-oxazoline, within 10 h. In addition, the copolymerization behavior of 4-ethyl-2-butyl-2-oxazoline with 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline unexpectedly revealed faster incorporation of the less reactive 4-ethy1-2-buty1-2-oxazoline monomer compared to 2-phenyl-2-oxazoline due to the increased bulk of the latter monomer amplifying the sterical hindrance for polymerization onto the 4-ethyl-2-butyl-2-oxazolinium propagating species

Nebulized antithrombin limits bacterial outgrowth and lung injury in Streptococcus pneumoniae pneumonia in rats

Introduction Disturbed alveolar fibrin turnover is a cardinal feature of severe pneumonia. Clinical studies suggest that natural inhibitors of coagulation exert lung-protective effects via anticoagulant and possibly also anti-inflammatory pathways. Intravenous infusion of the natural anticoagulants increases the risk of bleeding. Local administration may allow for higher treatment dosages and increased local efficacy while at the same time reducing the risk of bleeding. We evaluated the effect of nebulized anticoagulants on pulmonary coagulopathy and inflammation in a rat model of Streptococcus pneumoniae pneumonia. Methods In this randomized controlled in vivo laboratory study rats were challenged intratracheally with S. pneumoniae, inducing pneumonia, and randomized to treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin or danaparoid, by means of nebulization. Results S. pneumoniae infection increased pulmonary levels of thrombin-antithrombin complexes and fibrin degradation products. All nebulized anticoagulants significantly limited pulmonary coagulopathy. None of the agents except danaparoid resulted in changes in systemic coagulopathy. Treatment with plasma-derived AT reduced outgrowth of S. pneumoniae and histopathologic damage in lungs. In vitro experiments confirmed outgrowth was reduced in bronchoalveolar lavage fluid (BALF) from rats treated with plasma-derived AT compared with placebo. Neutralizing of cationic components in BALF diminished the inhibitory effects on bacterial outgrowth of BALF, suggesting a role for cationic antimicrobial proteins. Conclusions Nebulization of anticoagulants attenuates pulmonary coagulopathy during S. pneumoniae pneumonia in rats while only danaparoid affects systemic coagulation. Nebulized plasma-derived AT reduces bacterial outgrowth and exerts significant lung-protective effect

Design of the Verbiest trial: cost-effectiveness of surgery versus prolonged conservative treatment in patients with lumbar stenosis

Background: Degenerative changes of lumbar spine anatomy resulting in the encroachment of neural structures are often regarded progressive, ultimately necessitating decompressive surgery. However the natural course is not necessarily progressive and the efficacy of a variety of nonsurgical interventions has also been described. At present there is insufficient data to compare surgical and nonsurgical interventions in terms of their relative benefit and safety. Previous attempts failed to provide clear clinical recommendations or to distinguish subgroups that substantially benefit from a certain treatment strategy. We present the design of a randomized controlled trial on (cost-) effectiveness of surgical decompression versus prolonged conservative treatment in patients with neurogenic intermittent claudication caused by lumbar stenosis. Methods/Design. The aim of the Verbiest trial is to evaluate the effectiveness of prolonged conservative treatment compared to decompressive surgery. The study is a multi-center randomized controlled trial with two parallel groups design. Patients (age over 50) presenting

Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis

1427 E 60TH ST, CHICAGO, USA, IL, 60637-295

Radiostereometry and new prostheses

Optimising joint reconstruction management in arthritis and bone tumour patient