Despite lost contractility, a sub-population of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation

J Neuropathol Exp Neurol. 2009 Dec;68(12):1256-68. A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility. Squecco R, Carraro U, Kern H, Pond A, Adami N, Biral D, Vindigni V, Boncompagni S, Pietrangelo T, Bosco G, Fanò G, Marini M, Abruzzo PM, Germinario E, Danieli-Betto D, Protasi F, Francini F, Zampieri S. Source Interuniversitary Institute of Myology, Chieti, Italy. Abstract To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties and electrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation: 1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lost nerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in response to rehabilitation strategies developed based on empirical clinical observations. PMID: 19915489 [PubMed - indexed for MEDLINE

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep

Cystic Echinococcosis (CE) is a near-cosmopolitan parasitic zoonosis that causes economic losses in many regions of the world. This parasitic infection can be regarded as an emerging or re-emerging disease causing considerable losses in livestock production. CE is produced by the larval cystic stage (hydatid) of the dog parasite Echinococcus granulosus. After infective eggs are ingested, cysts develop mainly in lungs and liver of humans and animals (sheep, cattle, pigs, horses, etc). Infected people may require surgery and/or Albendazole-based chemotherapy. In this study, we evaluated the effects of Oxfendazole alone (an antiparasitic drug used in animals), Oxfendazole plus Praziquantel, and Albendazole plus Praziquantel against hydatid cysts in sheep over 4 to 6 weeks of treatment. All of the treatments in this study were efficacious in killing the larval stages and, therefore, in minimizing the risk of a dog acquiring new infections (taenias). These treatment schemes can be added to control measures in animals and eventually could be used for the treatment of human infection. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans

A proposed quantitative methodology for the evaluation of the effectiveness of Human Element, Leadership and Management (HELM) training in the UK

In 2006, a review of maritime accidents found that non-technical skills (NTSs) are the single largest contributing factor towards such incidents. NTSs are composed of both interpersonal and cognitive elements. These include things such as situational awareness, teamwork, decision making, leadership, management and communication skills. In a crisis situation, good NTSs allow a deck officer to quickly recognise that a problem exists and then harness the resources that are at their disposal to safely and efficiently bring the situation back under control. This paper has two aims. The first is to develop a methodology which will enable educators to quantitatively assess the impact of Maritime and Coastguard Agency (MCA)-approved Human Element, Leadership and Management (HELM) training on deck officer’s NTSs with a view to identifying further training requirements. The second is to determine whether the HELM training provided to develop the NTSs of trainee deck officers is fit for purpose. To achieve these aims, a three-phase approach was adopted. Initially, a taxonomy for deck officer’s NTSs is established, behavioural markers are identified and the relative importance of each attribute is calculated using the analytical hierarchy process (AHP). Subsequently, a set of scenarios were identified for the assessment of deck officer’s NTSs in a ship bridge simulator environment. A random selection of students that have completed the Chief Mate (CM) programme was performed, and data regarding their NTS-related performance in the scenarios was collected. Finally, the collected data was fed into the evidential reasoning (ER) algorithm, utility values were produced and, having established these values, the effectiveness of the HELM training that the students have received was then evaluated

Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer

Alteration in transforming growth factor-β signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

<p>Abstract</p> <p>Background</p> <p>Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia.</p> <p>Methods</p> <p>A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics.</p> <p>Results</p> <p>The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%).</p> <p>Conclusion</p> <p>These findings may have clinical implications for risk-based antimicrobial treatment strategies.</p

Unforgettable film music: The role of emotion in episodic long-term memory for music

<p>Abstract</p> <p>Background</p> <p>Specific pieces of music can elicit strong emotions in listeners and, possibly in connection with these emotions, can be remembered even years later. However, episodic memory for emotional music compared with less emotional music has not yet been examined. We investigated whether emotional music is remembered better than less emotional music. Also, we examined the influence of musical structure on memory performance.</p> <p>Results</p> <p>Recognition of 40 musical excerpts was investigated as a function of arousal, valence, and emotional intensity ratings of the music. In the first session the participants judged valence and arousal of the musical pieces. One week later, participants listened to the 40 old and 40 new musical excerpts randomly interspersed and were asked to make an old/new decision as well as to indicate arousal and valence of the pieces. Musical pieces that were rated as very positive were recognized significantly better.</p> <p>Conclusion</p> <p>Musical excerpts rated as very positive are remembered better. Valence seems to be an important modulator of episodic long-term memory for music. Evidently, strong emotions related to the musical experience facilitate memory formation and retrieval.</p