501 research outputs found
An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders
Background: Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named the NM-CGH array, revealed pathogenic copy number variation (CNV) in the genes for nebulin (NEB) and tropomyosin 3 (TPM3), as well as recurrent CNVs in the segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In the light of this knowledge, we have designed and validated an extended CGH array, which includes a selection of 187 genes known to cause neuromuscular disorders (NMDs). Objective: Our aim was to develop a reliable method for CNV detection in genes related to neuromuscular disorders for routine mutation detection and analysis, as a much-needed complement to sequencing methods. Methods: We have developed a novel custom-made 4×180 k CGH array for the diagnostics of NMDs. It includes the same tiled ultra-high density coverage of the 12 known or putative NM genes as our 8×60 k NM-CGH-array but also comprises a selection of 175 additional genes associated with NMDs, including titin (TTN), at a high to very high coverage. The genes were divided into three coverage groups according to known and potential pathogenicity in neuromuscular disorders. Results: The array detected known and putative CNVs in all three gene coverage groups, including the repetitive regions of NEB and TTN. Conclusions: The targeted neuromuscular disorder 4×180 k array-CGH (NMD-CGH-array v1.0) design allows CNV detection for a broader spectrum of neuromuscular disorders at a high resolution. © 2018 - IOS Press and the authors. All rights reserved.Peer reviewe
Dynamics of serum antibodies to and load of porcine circovirus type 2 (PCV2) in pigs in three finishing herds, affected or not by postweaning multisystemic wasting syndrome
Background: Despite that PMWS commonly affects pigs aged eight to sixteen weeks; most studies of PMWS have been conducted during the period before transfer to finishing herds. This study focused on PCV2 load and antibody dynamics in finishing herds with different PMWS status.
Methods: Sequentially collected blood samples from 40 pigs in each of two Swedish (A and B) and one Norwegian (C) finishing herds were analysed for serum PCV2-load and -antibodies and saliva cortisol. The two Swedish herds differed in PMWS status, despite receiving animals from the same sow pool (multi-site production). However, the PMWS-deemed herd (A) had previously also received pigs from the spot market. ResultsThe initial serum PCV2 load was similar in the two Swedish herds. In herd A, it peaked after two weeks in the finishing herd and a high number of the pigs had serum PCV2 levels above 10(7) per ml. The antibody titres increased continually with exception for the pigs that developed PMWS, that had initially low and then declining antibody levels. Pigs in the healthy herd B also expressed high titres of antibodies to PCV2 on arrival but remained at that level throughout the study whereas the viral load steadily decreased. No PCV2 antibodies and only low amounts of PCV2 DNA were detected in serum collected during the first five weeks in the PMWS-free herd C. Thereafter a peak in serum PCV2 load accompanied by an antibody response was recorded. PCV2 from the two Swedish herds grouped into genotype PCV2b whereas the Norwegian isolate grouped into PCV2a. Cortisol levels were lower in herd C than in herds A and B.
Conclusions: The most obvious difference between the Swedish finishing herds and the Norwegian herd was the time of infection with PCV2 in relation to the time of allocation, as well as the genotype of PCV2. Clinical PMWS was preceded by low levels of serum antibodies and a high load of PCV2 but did not develop in all such animals. It is notable that herd A became affected by PMWS after errors in management routine, emphasising the importance of proper hygiene and general disease-preventing measures
The paradox of public acceptance of bike sharing in Gothenburg
Bike sharing is one of the most promising urban planning interventions to facilitate an all-necessary transition towards a more sustainable transport paradigm. Regardless of the fact that hundreds of schemes run in more than 50 countries worldwide, bike sharing is still moderately investigated by research. This paper reports on a primarily quantitative study of 558 responses that was set to frame attitudes reflecting public acceptance towards the rapidly expanding bike-sharing scheme in Gothenburg (Styr & Ställ), in an attempt to identify the ‘formula for success’. The respondents generally believed that Styr & Ställ is a pro-environmental, inexpensive and healthy transport mode, which complements the city’s public transport services and promotes a more human-friendly identity for Gothenburg.
Even the respondents that self-reported a small (or no) likelihood to use bike sharing were positive towards the scheme. This means that they recognise that bike sharing has a significant pro-social potential and is not a system favouring a particular road-user segment over others that might not be interested or able to use it. The fact that the majority of the respondents do not Bike sharing is one of the most promising urban planning interventions to facilitate an all-necessary transition
towards a more sustainable transport paradigm. Regardless of the fact that hundreds of schemes run in more than 50 countries worldwide, bike sharing is still moderately investigated by research. This paper reports on a primarily
quantitative study of 558 responses that was set to frame attitudes reflecting public acceptance towards the rapidly expanding bike-sharing scheme in Gothenburg (Styr & Ställ), in an attempt to identify the ‘formula for success’. The respondents generally believed that Styr & Ställ is a pro-environmental, inexpensive and healthy transport mode, which complements the city’s public transport services and promotes a more human-friendly identity for Gothenburg. Even the respondents that self-reported a small (or no) likelihood to use bike sharing were positive towards the scheme. This means that they recognise that bike sharing has a significant pro-social potential and is not a system favouring a particular road-user segment over others that might not be interested or able to use it. The fact that the majority of the respondents do not use the scheme and yet its popularity is still vast indicates that there is much potential for more use in real terms
The index herd with PMWS in Sweden: Presence of serum amyloid A, circovirus 2 viral load and antibody levels in healthy and PMWS-affected pigs
Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2
Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene
We report the first family with a dominantly inherited mutation of the nebulin gene (NEB). This 100kb in-frame deletion encompasses NEB exons 14-89, causing distal nemaline/cap myopathy in a three-generation family. It is the largest deletion characterized in NEB hitherto. The mutated allele was shown to be expressed at the mRNA level and furthermore, for the first time, a deletion was shown to cause the production of a smaller mutant nebulin protein. Thus, we suggest that this novel mutant nebulin protein has a dominant-negative effect, explaining the first documented dominant inheritance of nebulin-caused myopathy. The index patient, a young man, was more severely affected than his mother and grandmother. His first symptom was foot drop at the age of three, followed by distal muscle atrophy, slight hypomimia, high-arched palate, and weakness of the neck and elbow flexors, hands, tibialis anterior and toe extensors. Muscle biopsies showed myopathic features with type 1 fibre predominance in the index patient and nemaline bodies and cap-like structures in biopsies from his mother and grandmother. The muscle biopsy findings constitute a further example of nemaline bodies and cap-like structures being part of the same spectrum of pathological changes. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe
Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty: A randomized double-blind study involving 48 patients
Direct and indirect transmission of four Salmonella enterica serotypes in pigs
<p>Abstract</p> <p>Background</p> <p>Feed-borne spread of <it>Salmonella </it>spp. to pigs has been documented several times in recent years in Sweden. Experiences from the field suggest that feed-associated serotypes might be less transmittable and subsequently easier to eradicate from pig herds than other serotypes more commonly associated to pigs. Four <it>Salmonella </it>serotypes were selected for experimental studies in pigs in order to study transmissibility and compare possible differences between feed-assoociated (<it>S </it>Cubana and <it>S </it>Yoruba) and pig-associated serotypes (<it>S </it>Derby and <it>S </it>Typhimurium).</p> <p>Methods</p> <p>Direct contact transmission was studied in four groups of pigs formed by six 10-week-old salmonella negative pigs commingled with two fatteners excreting one of the four salmonella serotypes. Indirect transmission was studied by putting six 10-week-old salmonella negative pigs in each of four salmonella contaminated rooms. Each room had previously housed a group of pigs, excreting one of the four selected serotypes.</p> <p>All pigs were monitored for two weeks with respect to the faecal excretion of salmonella and the presence of serum antibodies. At the end of the trial, eight samples from inner tissues and organs were collected from each pig at necropsy.</p> <p>Results</p> <p>In the four direct transmission groups, one pig shed <it>Salmonella </it>(Cubana) at one occasion. At necropsy, <it>S </it>Typhimurium was isolated from one pig.</p> <p>In the indirect transmission groups, two pigs in the Yoruba room and one pig in each of the other rooms were excreting detectable levels of <it>Salmonella </it>once during the study period of two weeks. At necropsy, <it>S </it>Derby was isolated from one of six pigs in the Derby room and <it>S </it>Typhimurium was isolated from four of the six pigs in the Typhimurium room.</p> <p>No significant serological response could be detected in any of the 48 pigs.</p> <p>Conclusions</p> <p>These results show that all four selected serotypes were able to be transmitted in at least one of these field-like trials, but the transmission rate was low in all groups and no obvious differences between feed-associated and pig-associated serotypes in the transmission to naïve pigs and their subsequent faecal shedding were revealed. However, the post mortem results indicated a higher detection of <it>S </it>Typhimurium in the ileocecal lymph nodes of pigs introduced into a contaminated environment in comparison with the other three serotypes.</p
Reduced hospital stay, morphine consumption, and pain intensity with local infiltration analgesia after unicompartmental knee arthroplasty: A randomized double–blind study of 40 patients
Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively
Actin Nemaline Myopathy Mouse Reproduces Disease, Suggests Other Actin Disease Phenotypes and Provides Cautionary Note on Muscle Transgene Expression
Mutations in the skeletal muscle α-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G) of ACTA1 (identified in a severe nemaline myopathy patient) fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT) muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ∼30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC) fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations
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