Radiographic assessment of the skeletons of Dolly and other clones finds no abnormal osteoarthritis.

Our recent report detailing the health status of cloned sheep concluded that the animals had aged normally. This is in stark contrast to reports on Dolly (first animal cloned from adult cells) whose diagnoses of osteoarthritis (OA) at 5½ years of age led to considerable scientific concern and media debate over the possibility of early-onset age-related diseases in cloned animals. Our study included four 8-year old ewes derived from the cell line that gave rise to Dolly, yet none of our aged sheep showed clinical signs of OA, and they had radiographic evidence of only mild or, in one case, moderate OA. Given that the only formal record of OA in Dolly is a brief mention of a single joint in a conference abstract, this led us to question whether the original concerns about Dolly's OA were justified. As none of the original clinical or radiographic records were preserved, we undertook radiographic examination of the skeletons of Dolly and her contemporary clones. We report a prevalence and distribution of radiographic-OA similar to that observed in naturally conceived sheep, and our healthy aged cloned sheep. We conclude that the original concerns that cloning had caused early-onset OA in Dolly were unfounded.

Healthy ageing of cloned sheep.

The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental long-term health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7-9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5-and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals.

MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C.

MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal(-/-) mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection. Altered expression of occludin, Zonula occludens-1, and claudin-3 in intestinal epithelia from Mal(-/-) mice suggest that Mal regulates tight junction formation, which may in part contribute to intestinal integrity. Mal interacted with several protein kinase C (PKC) isoforms in a Caco-2 model of intestinal epithelia and inhibition of Mal or PKC increased permeability and bacterial invasion via a paracellular route, while a pan-PKC inhibitor increased susceptibility to oral infection in mice. Mal signaling is therefore beneficial to the integrity of the intestinal barrier during infection.

Clinical audit for the tibial tuberosity advancement procedure: establishing the learning curve and monitoring ongoing performance for the tibial tuberosity advancement procedure using the cumulative summation technique.

OBJECTIVES: To quantitatively assess the learning curve for the tibial tuberosity advancement (TTA) procedure performed by a single surgeon using the cumulative summation (CUSUM) technique and to determine if surgeon performance remained under control (i.e. within specified quality boundaries) after the learning curve had been climbed. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n = 122) with cranial cruciate ligament deficient stifles (n = 167). METHODS: Records of all dogs that had a TTA procedure performed by the same surgeon were reviewed. Cases were included if the following information was available: weight, breed, date of surgery, presence of partial or full cruciate rupture, meniscal pathology, occurrence and description of postoperative complications and treatment with a minimum of 12 months follow-up. Patients were excluded if they had a concurrent illness. Major complications were defined as those requiring revision surgery. The CUSUM technique was used to determine the time taken for the surgeon to reach a pre-defined level of competency and to monitor ongoing performance. RESULTS: Major complications occurred in 15 out of 167 procedures (9%) within 12 months of TTA surgery. The complication rate decreased as surgical experience was gained with the technique, however the learning curve continued until the 22nd procedure. Thereafter, despite the target complication rate being re-set at a lower level, the surgeon's performance remained acceptable, i.e. within the revised quality boundary. CLINICAL SIGNIFICANCE: The CUSUM technique was used for clinical audit, to determine the learning curve for the TTA procedure for a single surgeon, and to monitor ongoing performance. An experienced general practitioner had a learning curve of 22 procedures and complication rates were within the published ranges.

Succinate is an inflammatory signal that induces IL-1ß through HIF-1α.

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1ß but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1ß as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1ß production during inflammation.

A retrospective study of tibial plateau translation following tibial plateau levelling osteotomy stabilisation using three different plate types.

OBJECTIVE: To retrospectively evaluate mediolateral translation of the proximal tibial segment (tibial plateau) after tibial plateau levelling osteotomy (TPLO), stabilised with three types of plate. METHOD: Pre- and postoperative radiographs of 79 dogs that had TPLO surgery using three different types of plates were reviewed. Two plate types incorporated non-locking screws: Slocum (22 cases) and Orthomed Delta (33 cases) plates. The third plate type incorporated locking screws: Synthes TPLO Locking Compression Plate (LCP) (24 cases). The radiographs were viewed by three Diplomate surgeons who were blinded to the type of implant used. Medial or lateral translation of the proximal tibial plateau relative to the tibial diaphysis was assessed and measured at the lateral tibial cortex at the osteotomy site. RESULTS: Mean lateral translation of the tibial plateau was significantly greater when using the Synthes TPLO LCP with locking screws (+2.1 mm) compared to the non-locking Slocum (+0.4 mm) or Orthomed Delta (0.0 mm) plates. CLINICAL SIGNIFICANCE: The use of the Synthes TPLO LCP will maintain a malalignment of the tibial plateau. Accurate alignment of the tibial plateau must be ensured prior to application of the Synthes TPLO LCP.

A 3.90 V iron-based fluorosulphate material for lithium-ion batteries crystallizing in the triplite structure.

Li-ion batteries have empowered consumer electronics and are now seen as the best choice to propel forward the development of eco-friendly (hybrid) electric vehicles. To enhance the energy density, an intensive search has been made for new polyanionic compounds that have a higher potential for the Fe²âº/Fe³âº redox couple. Herein we push this potential to 3.90 V in a new polyanionic material that crystallizes in the triplite structure by substituting as little as 5 atomic per cent of Mn for Fe in Li(Fe(1-δ)Mn(δ))SO4F. Not only is this the highest voltage reported so far for the Fe²âº/Fe³âº redox couple, exceeding that of LiFePO4 by 450 mV, but this new triplite phase is capable of reversibly releasing and reinserting 0.7-0.8 Li ions with a volume change of 0.6% (compared with 7 and 10% for LiFePO4 and LiFeSO4F respectively), to give a capacity of ~125 mA h g⁻¹.

Retrospective study of Achilles mechanism disruption in 45 dogs.

Forty-five cases of canine Achilles mechanism disruption were reviewed, mostly involving medium-sized dogs, among which dobermanns, labradors and border collies were most commonly represented. Most cases were acute in onset (66.7 per cent), and were usually closed injuries (75.6 per cent). In the majority of cases, the damage involved all tendons (26.7 per cent), all tendons except the superficial digital flexor tendon (22.2 per cent), or the gastrocnemius alone (20 per cent). Damage most commonly occurred at the tendo-osseous junction (60 per cent), with injury occurring less commonly at the musculotendinous junction (20 per cent) or in the body of the tendon (13.3 per cent). A plantigrade posture was not predictive of involvement of specific tendons, but was more likely if the injury involved the musculotendinous junction. The most common method of treatment was a primary tendon repair using polydioxanone suture in a locking-loop pattern, with placement of a temporary calcaneotibial screw and cast. The outcome was not significantly influenced by whether the injury was open or closed, the duration of the injury, the tendons involved, or the method of repair. Complications were recorded in 16 cases (35 per cent), of which 10 were minor and six major. Complications were significantly more likely if the damage involved the body of the tendon. Long-term follow-up was available for 19 dogs; the outcome of surgery was considered to be good to excellent in 18 dogs.

Owners' observations of domestic cats after limb amputation.

Questionnaires were distributed to owners of cats that had undergone limb amputation in the UK, through 1000 veterinary clinics or publications relating to companion cats, or online. Between July 2009 and February 2010, responses were received relating to 234 cats, and data for 204 of these were included in subsequent analyses. The responses received provided data on signalment, aetiology, quality of life, behavioural changes and pain observed in cats after partial or total amputation of a limb. Young male domestic shorthair cats were over-represented in the sample; the most common reason for amputation was a fractured bone, and the hindlimb was almost twice as likely to be amputated as the forelimb. Although 89 per cent of the cats received analgesics/anti-inflammatories after discharge, the owners of 35 per cent of the animals observed some signs of pain during recovery. Eighty-nine per cent of the cats were thought to have regained a 'normal' quality of life as defined by the owner and 94 per cent of the owners stated that they would agree with the decision to amputate the affected limb in a pet if faced with the same decision again.

Diagnostic accuracy of positive contrast computed tomography arthrography for the detection of injuries to the medial meniscus in dogs with naturally occurring cranial cruciate ligament insufficiency.

OBJECTIVE: To assess the usefulness of computed tomography arthrography of the stifle in diagnosing meniscal tears in dogs with cranial cruciate ligament insufficiency. METHODS: A prospective clinical study was performed. Dogs were included if they had evidence of cranial cruciate ligament insufficiency or persistent or recurrent lameness following surgery for cranial cruciate ligament insufficiency. Dogs were sedated for a computed tomography scan of the affected stifle, orientated in the dorsal plane. A survey computed tomography scan was followed by a computed tomography arthrogram. A stifle arthrotomy was performed, and the surgical findings were recorded. The computed tomography scans were reviewed by three blinded reviewers, and the results were compared to the surgical findings. RESULTS: Twenty-one computed tomography arthrograms from 20 dogs were included. At surgery, damage to the medial meniscus was identified in 14 stifles. Initial interpretation of computed tomography arthrography images was 57 to 64 per cent sensitive and 71 to 100 per cent specific for diagnosing medial meniscal injuries. Interpretation of the images on retrospective analysis was 71 per cent sensitive and 100 per cent specific, with an accuracy of 0.857. CLINICAL SIGNIFICANCE: The accuracy of stifle computed tomography arthrography for the diagnosis of tears to the medial meniscus was found to be good. It is a minimally invasive and repeatable technique, which does not require general anaesthesia or specialist training to obtain the images. The ability to reliably diagnose meniscal injury without the need for surgery may be advantageous, particularly in dogs which had previously had surgery for cranial cruciate ligament insufficiency.

Cross-sectional study to evaluate radiological parameters in hallux rigidus.

BACKGROUND: Hallux rigidus (HR) is a common condition with X-rays used to evaluate its pathology, grade joint changes and to inform treatment. METHOD: A cross-sectional study was undertaken to evaluate radiological foot parameters in HR. In 110 subjects (180 feet) aged 18-70 years (mean 52 years) standard weight-bearing X-rays were examined using dorsal plantar and lateral views. RESULTS: Seventy (64%) subjects had bilateral HR and 73 (66%) were female. The mean onset of HR (denoted by first metatarsophalangeal (MTP) joint restriction/pain) was 44 (14-68 years) years and median HR duration was 6 years (1-33 years). Flat or chevron-shaped metatarsal heads presented in 131 (73%) feet and a history of first MTP joint trauma in 22% (74% of whom had unilateral HR). In 74% of feet hallux abductus interphalangeus angle (HAI degrees) was greater than normal (< or =10 degrees). Correlations between first MTP joint narrowing and sclerosis (r=0.76, p=0.01) and increased HAI degrees and first MTP joint narrowing (r=0.34, p=0.01) was found. The mean hallux equinus angle of 11 degrees was outside the normal range (16-18 degrees). Abnormal sesamoid morphology presented in 117 (65%) feet (30% irregular or hypertrophic). Proximal sesamoid displacement was greater than that seen in non-HR. Metatarsus primus elevatus was within normal range (< or =8 mm) in 160 (89%) feet. The first metatarsal was longer than the second metatarsal in 66 (37%) feet although the first metatarsal was longer than the third metatarsal in 131 (73%) feet and may be responsible for altered forefoot function in HR. CONCLUSIONS: HR was associated with female gender, bilateral involvement, older age groups, flat or chevron-shaped metatarsal head, longer proximal phalanx, increased HAI degrees and a first metatarsal longer than the third metatarsal. For radiological parameters to be considered valid for inclusion in a classification of HR their content validity needs to be established by formal research.

Hallux rigidus: a cross-sectional study to evaluate clinical parameters.

BACKGROUND: Hallux rigidus (HR) is a common condition with history and physical examination used to help evaluate pathology, grade clinical changes and to inform treatment. METHOD: A cross-sectional study was undertaken to evaluate the demographics of and clinical parameters encountered in HR. In 110 subjects (180 feet) aged 18-70 years (mean 52 years) a standardized history and physical examination was undertaken. Clinical parameters associated with HR were evaluated. The Foot Health Status Questionnaire (FHSQ) was used to measure health-related quality-of-life dimensions. RESULTS: Seventy (64%) subjects had bilateral HR and 73 (66%) were female. Mean HR onset was 44 (14-68 years) years and median HR duration 6 years (1-33 years). A history of 1st MTPJ trauma presented in 22% of subjects; 74% of whom had unilateral HR. Eighty-four (47%) feet had pes planus based on a positive Foot Posture Index. A correlation between pes planus and 1st MTPJ pain was found (r=0.84, p=0.05). In 74% of feet, hallux abductus interphalangeus angle (HAI degrees ) was greater than normal (< or =10 degrees ). A correlation between HAI and reduced 1st MTPJ ROM was found (r=0.92, p=0.05). Second toe length was the same as the hallux in 111 feet (62%). A correlation between valgus hallucal rotation and 1st MTP joint pain in HR was found (r=.78, p=.05). A positive relationship was found between 2nd toe length and 1st MTPJ pain (p=0.001<0.05). A correlation between hallucal interphalangeal joint (IPJ) hyperextension and 1st MTPJ pain was found (r=0.78, p=0.01). A positive relationship was found between lesser MTPJ pain and supination at propulsion (p<0.001). There was no evidence of Achilles tendon contracture. The FHSQ results concur with clinical findings. CONCLUSIONS: HR was associated with female gender, bilateral involvement, older age groups, increased HAI degrees, 2nd toe length similar to hallux, hallucal IPJ hyperextension, lesser MTP joint pain, flat foot and certain gait alterations. HR was not associated with Achilles tendon tightness or footwear. The content validity of clinical parameters of HR needs to be established by formal research prior to their inclusion in a classification of HR.

Necrotising fasciitis with sub-periosteal Streptococcus canis infection in two puppies.

Necrotising fasciitis is an uncommon and potentially devastating disease which has been infrequently reported in animals. This brief communication describes an unusual presentation of necrotising fasciitis in two immature Bull Terriers. Both animals were admitted with a history of minimal trauma yet rapidly progressive, localising, disproportionate pain. Streptococcus canis was cultured from sub-periosteal fluid-filled pockets surrounding the femur in both cases.

A comparison of outcomes following tibial plateau levelling osteotomy and cranial tibial wedge osteotomy procedures.

The objective of this study was to determine whether clinical outcomes were superior and complication rates were lower in dogs that had had a cranial cruciate ligament rupture treated by tibial plateau levelling osteotomy (TPLO), compared to those dogs that had been treated using the original cranial tibial wedge osteotomy (CTWO) procedure. Thirty-seven client-owned dogs with cranial cruciate ligament rupture were included in the study: 19 dogs underwent a TPLO procedure, and 18 dogs underwent a CTWO procedure. The study was retrospective, with the data being obtained from medical records and a review of radiographs. The long-term outcome was assessed by means of an owner questionnaire using a visual analogue scale. For the majority of factors that were reviewed, there was not a significant difference in outcome between the dogs that had a TPLO or those that had undergone a CTWO. All of the dogs showed a rapid return to weight bearing after surgery, and at the six week re-examination, the majority of the dogs did not have any pain on stifle palpation. They displayed a good stifle range of motion and significantly lower lameness scores than those prior to surgery. The complication rates did not differ between the procedures, however, within this small sample of dogs, complications following a CTWO were more likely to require revision surgery.

Individual patient data meta-analysis of randomized controlled trials of community occupational therapy for stroke patients.

BACKGROUND AND PURPOSE: Trials of occupational therapy for stroke patients living in the community have varied in their findings. It is unclear why these discrepancies have occurred. METHODS: Trials were identified from searches of the Cochrane Library and other sources. The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) score at the end of intervention. Secondary outcome measures included the Barthel Index or the Rivermead ADL (Personal ADL), General Health Questionnaire (GHQ), Nottingham Leisure Questionnaire (NLQ), and death. Data were analyzed using linear or logistic regression with a random effect for trial and adjustment for age, gender, baseline dependency, and method of follow-up. Subgroup analyses compared any occupational therapy intervention with control. RESULTS: We included 8 single-blind randomized controlled trials incorporating 1143 patients. Occupational therapy was associated with higher NEADL scores at the end of intervention (weighted mean difference [WMD], 1.30 points, 95% confidence intervals [CI], 0.47 to 2.13) and higher leisure scores at the end of intervention (WMD, 1.51 points; 95% CI, 0.24 to 2.79). Occupational therapy emphasizing activities of daily living (ADL) was associated with improved end of intervention NEADL (WMD, 1.61 points; 95% CI, 0.72 to 2.49) and personal activities of daily living (odds ratio [OR], 0.65; 95% CI, 0.46 to 0.91), but not NLQ. Leisure-based occupational therapy improved end of intervention NLQ (WMD, 1.96 points; 95% CI, 0.27 to 3.66) but not NEADL or PADL. CONCLUSIONS: Community occupational therapy significantly improved personal and extended activities of daily living and leisure activity in patients with stroke. Better outcomes were found with targeted interventions.

Fracture of the proximal tibial epiphysis and tuberosity in 10 dogs.

Ten dogs were presented with fractures of the proximal tibial epiphysis and tuberosity. All dogs had a cranioproximal-caudodistal angulation of the tibial plateau. Six dogs had marked caudal displacement of the proximal tibial epiphysis, five of which had also sustained fractures of the proximal fibula. The estimated mean angle of inclination of the tibial plateau of affected limbs was 45.8 +/- 9.6 degrees, which was significantly greater (P<0.0005) than the estimated mean angle of the normal contralateral limb 26.2 +/- 6.6 degrees. The mean angle of inclination of the tibial plateau of dogs with fibular fractures (n=5) was not significantly different from dogs without fibular fractures (n=5) (P>0.25). Five dogs were treated conservatively and five were treated by three different methods of surgical repair. Surgically treated dogs had significantly greater preoperative tibial plateau angles (P<0.05). All dogs regained full limb usage, regardless of the method of treatment chosen.

Preliminary study of joint disease in poultry by the analysis of synovial fluid.

Samples of synovial fluid and synovial membrane were obtained from the hock joints of several groups of broilers, including lame birds and two strains of broilers raised on different feeding regimens and given different drug treatments (carprofen or placebo). There were more significant differences between the groups on the basis of the analysis of the synovial fluid samples than the synovial membrane samples. Experimental birds fed ad libitum had the highest median red blood cell counts and median ghost cell counts of all of the groups, but there were no differences between the groups in the thickness of the synovial lining cell layer or the degree of cellular infiltrate in the synovial membrane. The synovial fluid from the broilers and lame birds fed ad libitum was more turbid, suggestive of intra-articular pathology, and the large numbers of heterophils in samples from the lame birds indicated an inflammatory arthropathy. The birds fed ad libitum which were treated with carprofen had more cells in the synovial fluid than the birds given the placebo. A large number of the samples of synovial fluid from the ad libitum-fed broilers contained blood.

Hypothalamic neuropeptide Y mRNA is increased after feed restriction in growing broilers.

As part of an approach to uncover the brain mechanisms underlying the regulation of energy balance in broiler chickens, we investigated the possible role of neuropeptide Y (NPY). The NPY gene expression was measured in the hypothalamus of birds from a standard Ross male line and a Ross relaxed line. Both lines are derived from the same founder stock, but the relaxed line has not been selected for rapid growth since 1976. Birds of each line consumed feed either ad libitum or according to a standard commercial restricted feeding program. All groups of birds were killed at an average body weight of 2.4 kg. The NPY mRNA levels were significantly increased (P < 0.0001) in feed-restricted birds of both lines relative to ad libitum controls. No significant differences were detected between the lines. These results show that NPY gene expression in the broiler hypothalamus is sensitive to changes in energetic status, as it is in mammals. However, the maintenance of selection pressure for high growth rate is not associated with altered hypothalamic NPY mRNA levels in the ad libitum or restricted state.