Preclinical studies using large animal models play an intergral part in translational research. For this study, our objectives were: to develop and validate arthroscopic approaches to four ...compartments of the stifle joint as determined via the gross and arthroscopic anatomy of the cranial and caudal aspects of the joint.
Cadaveric hindlimbs (n = 39) were harvested from mature ewes. The anatomy was examined by tissue dissection (n = 6), transverse sections (n = 4), and computed tomography (n = 4). The joint was arthroscopically explored in 25 hindlimbs.
A cranio-medial portal was created medial to the patellar ligament. The cranio-lateral portal was made medial to the extensor digitorum longus tendon. The medial femoral condyle was visible, as well as the cranial cruciate ligament, caudal cruciate ligament and both menisci with the intermeniscal ligament. Valgus stress improved visibility of the caudal horn of the medial meniscus and tibial plateau. To explore the caudal compartments, a portal was created 1 cm proximal to the most caudal aspect of the tibial condyle. Both femoral condyles, menisci, caudal cruciate ligament, the popliteal tendon and the menisco-femoral ligament were visible. The common peroneal nerve and popliteal artery and vein are vulnerable structures to injury during arthroscopy.
The arthroscopic approach developed in this research is ideal to evaluate the ovine stifle joint.
The triple tibial osteotomy (TTO) is a technique which combines the features of tibial tuberosity advancement and wedge osteotomy for the treatment of complete and partial cruciate ligament injuries ...in dogs. In this paper, the technique is described and the results of a prospective study of 64 consecutive cases are presented. TTO provided a satisfactory clinical outcome in a very high percentage of cases. The technique is relatively easy to learn and has a low post-operative complication rate.
The objective of this study was to evaluate the accuracy of ultrasonographic diagnosis of lesions in the canine stifle associated with cranial cruciate ligament rupture. Thirteen dogs that had a ...diagnosis of cranial cruciate ligament rupture were included in this prospective clinical study. Two ultrasonographers who were unaware of specific historical and clinical data performed the sonography with a high frequency (8-16 MHz) linear transducer. Surgical treatment of the affected stifle was performed within two days of ultrasonography by a surgeon who was unaware of the ultrasonographic findings. The lesions observed during ultrasonography and arthrotomy were compared at the completion of the study. Visualisation of the superficial tendons (quadriceps and long digital extensor) and ligaments (patellar ligament, collateral ligaments) of the stifle using ultrasonography was excellent. However, the detection of deep stifle ligaments (cranial cruciate ligament and caudal cruciate ligament) was extremely difficult to perform using ultrasonography. For cranial cruciate ligament rupture, the sensitivity for ultrasonographic diagnosis was 15.4%. For meniscal lesions, the sensitivity, specificity, positive and negative predictive values for ultrasonographic diagnosis were 82%, 93%, 90% and 88% respectively. High frequency ultrasonography is a non-invasive method for accurately and efficiently detecting superficial ligaments, tendons and meniscal lesions associated with cranial cruciate ligament rupture in the stifle of non-sedated dogs.
A seven-year-old Labrador Retriever dog was presented with the complaint of chronic left hindlimb lameness. A diagnosis of partial rupture of the left cranial cruciate ligament with concurrent ...cranio-medial synovial cyst formation was made. This cystic structure was assumed to be communicating with the stifle joint. There was no evidence of a meniscal tear, but superficial fibrillation of the axial border was present. Surgical excision of the cyst with concurrent treatment of the cranial cruciate ligament deficiency by tibial tuberosity advancement was performed with a successful outcome. Whilst commonly encountered in humans, synovial cysts are uncommon in dogs. To the authors' knowledge this is the first reported case of synovial cyst formation in the stifle of a dog.
The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to ...restore the function of Phe508del CFTR protein in patients with cystic fibrosis.
We evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV
).
VX-659-tezacaftor-ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659-tezacaftor-ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659-tezacaftor-ivacaftor resulted in significant mean increases in the percentage of predicted FEV
through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del-MF genotypes; in patients with the Phe508del-Phe508del genotype already receiving tezacaftor-ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV
. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised improved in both patient populations.
Robust in vitro activity of VX-659-tezacaftor-ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del-MF or Phe508del-Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455 .).
The genome of bluetongue virus type 20 consists of 10 segments of double-stranded RNA each of which contains unique sequences as determined by oligonucleotide mapping. The 10 polypeptide products of ...the virus genome were detected in virus-infected cells, and in pulse--chase experiments there was no secondary cleavage of the primary gene products. Using stringent conditions for RNA--RNA reassociation, no significant homology could be detected between the genomes of bluetongue type 20 isolated in Australia and representative serotypes isolated in other geographic regions. The results suggest sequence divergence between geographically isolated viruses and not the recent introduction of a bluetongue virus into Australia.
The occurrence of the rare but potentially fatal neuroleptic malignant syndrome must be considered by the surgeon treating a patient who develops hyperthermia, mental abnormalities, autonomic ...instability, and muscle rigidity after exposure to phenothiazines or other neuroleptic drugs. The dopamine agonist bromocriptine appears to be the treatment of choice in adults and seemed to be effective and well tolerated in our patient. Although the syndrome cannot be prevented, recognition is crucial, since effective general and specific therapy is available. Differentiating neuroleptic malignant syndrome from malignant hyperthermia allows early appropriate treatment with bromocriptine.
Archaea represent a significant fraction of Earth's biodiversity, yet they remain much less well understood than Bacteria. Gene surveys, a few metagenomic studies, and some single-cell sequencing ...projects have revealed numerous little-studied archaeal phyla. Certain lineages appear to branch deeply and may be part of a major phylum radiation. The structure of this radiation and the physiology of the organisms remain almost unknown.
We used genome-resolved metagenomic analyses to investigate the diversity, genomes sizes, metabolic capacities, and potential roles of Archaea in terrestrial subsurface biogeochemical cycles. We sequenced DNA from complex sediment and planktonic consortia from an aquifer adjacent to the Colorado River (USA) and reconstructed the first complete genomes for Archaea using cultivation-independent methods. To provide taxonomic context, we analyzed an additional 151 newly sampled archaeal sequences. We resolved two new phyla within a major, apparently deep-branching group of phyla (a superphylum). The organisms have small genomes, and metabolic predictions indicate that their primary contributions to Earth's biogeochemical cycles involve carbon and hydrogen metabolism, probably associated with symbiotic and/or fermentation-based lifestyles.
The results dramatically expand genomic sampling of the domain Archaea and clarify taxonomic designations within a major superphylum. This study, in combination with recently published work on bacterial phyla lacking cultivated representatives, reveals a fascinating phenomenon of major radiations of organisms with small genomes, novel proteome composition, and strong interdependence in both domains.
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