Causes of pleural effusions in horses resident in the UK

Pleural effusions (PE) reportedly occur most commonly secondary to bacterial pneumonia with neoplastic effusions contributing a minority of cases. The majority of reports originate from the USA and Australia, where long distance transport of horses, a recognised risk factor, may occur more frequently than in the UK. Anecdotally, a greater proportion of horses with PE are diagnosed with neoplasia in the UK than has been reported. The aim of this retrospective study was to describe the causes of PE in horses in the UK, and to identify markers that can help differentiate between septic and neoplastic causes of PE. Medical records from 4 equine hospitals in the UK were searched for horses diagnosed with PE. Information recorded included case background, admission physical examination and biochemical findings, and characteristics of the effusion (volume, cell count, total protein [TP] concentration). A total of 69 horses were identified, with 26 (38%) diagnosed with a neoplastic effusion. The remainder were categorised as septic, including 14/43 (32.5%) that had a history of international transport. Horses with septic effusions were significantly younger (8 vs. 13 years; P = 0.001) and had significantly smaller volumes of pleural fluid drained at admission (9.8 l vs. 32.2 l; P<0.001). Horses with septic PE had a significantly higher rectal temperature (38.6°C vs. 38.2°C; P = 0.03), fibrinogen concentration (7.8 g/l vs. 5.3 g/l; P = 0.01) and serum amyloid A concentration (230 mg/l vs. 59 mg/l; P = 0.02) than those with neoplastic effusions. Significantly higher pleural fluid cell count and TP concentration were identified in horses with septic PE (63.9 × 109/l vs. 8.6 × 109/l; P<0.001; 57.5 g/l vs. 35.9 g/l; P = 0.04). These results suggest that in the UK, neoplastic effusions account for a greater proportion of PE than previously reported. A large volume of PE in an older horse with a low cell count and relatively low TP concentration should increase the index of suspicion of neoplasia

Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype.

In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors

Optical and Magnetic Resonance Characterization of Point Defects in Lithium Niobate and Lithium Tantalate

Physic

Adhesion-contractile balance in myocyte differentiation

Tissue cells generally pull on their matrix attachments and balance a quasi-static contractility against adequate adhesion, but any correlation with and/or influence on phenotype are not yet understood. Here, we begin to demonstrate how differentiation state couples to actomyosin-based contractility through adhesion and substrate compliance. Myotubes are differentiated from myoblasts on collagen-patterned coverslips that allow linear fusion but prevent classic myotube branching. Postfusion, myotubes adhere to the micro-strips but lock into a stress fiber-rich state and do not differentiate significantly further. In contrast, myotubes grown on top of such cells do progress through differentiation, exhibiting actomyosin striations within one week. A compliant adhesion to these lower cells is suggested to couple to contractility and accommodate the reorganization needed for upper cell striation. Contractility is assessed in these adherent cells by mechanically detaching one end of the myotubes. All myotubes, whether striated or not, shorten with an exponential decay. The cell-on-cell myotubes relax more, which implies a greater contractile stress. The non-muscle myosin II inhibitor blebbistatin inhibits relaxation for either case. Myotubes in culture are thus clearly prestressed by myosin II, and this contractility couples to substrate compliance and ultimately influences actomyosin striation

Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin.

IntroductionDysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf-/- ) mice.MethodsMuscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf-/- and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice.ResultsMuscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf-/- muscles.DiscussionWe conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies

Purposeful Pedaling: Analyzing MS 150 Participant Behavior

Purpose – The purpose of this paper is to explore factors affecting participant awareness, attraction, and attachment to the National Multiple Sclerosis Society’s (NMSS) MS 150 PGA Tour Cycle to the Shore charitable bike ride utilizing the Psychological Continuum Model (PCM) developed by Funk and James. In addition, the authors sought to outline variables sport organizations can use to predict donor behavior. Design/methodology/approach – Data for this project were derived from an electronic survey distributed to race participants and was analyzed in SPSS® software. Regression analysis was employed. Findings – The findings support previous research employing the PCM; wherein social situational variables have the greatest influence on the relational significance of hedonic and dispositional needs in attraction and attachment to sporting events. The work supports the inclusion of communities as an additional attachment outcome. Practical implications – In all, 92 percent of riders were informed about the event through word of mouth (WOM) marketing, highlighting the importance this promotional technique in the awareness stage of the PCM. NMSS would be well served by capitalizing on the power of WOM. Originality/value – The research provides insight into predictors of fundraising efficacy. In terms of fundraising effectiveness, participants with four or more years of participation were six times more likely than first-year riders to raise $1,000 or more

Overexpression of SERCA1a in the \u3cem\u3emdx\u3c/em\u3e Diaphragm Reduces Susceptibility to Contraction-Induced Damage

Although the precise pathophysiological mechanism of muscle damage in dystrophin-deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne muscular dystrophy patients and mouse models of dystrophin deficiency exhibit extensive abnormalities of calcium homeostasis, which we hypothesized would be mitigated by increased expression of the sarcoplasmic reticulum calcium pump. Neonatal adeno-associated virus gene transfer of sarcoplasmic reticulum ATPase 1a to the mdx diaphragm decreased centrally located nuclei and resulted in reduced susceptibility to eccentric contraction-induced damage at 6 months of age. As the diaphragm is the mouse muscle most representative of human disease, these results provide impetus for further investigation of therapeutic strategies aimed at enhanced cytosolic calcium removal

Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice

Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration–regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. Because insulin-like growth factor I (IGF-I) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-I in mdx muscle could preserve muscle function in the diseased state. In transgenic mdx mice expressing mIgf-I (mdx:mIgf+/+), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mIgf+/+ mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin