Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects

Introduction: A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether g-loop dysfunction contributes to AMI in people with knee joint OA. Methods: Fifteen subjects with knee joint OA and 15 controls with no history of knee joint pathology participated in this study. Quadriceps and hamstrings peak isometric torque (Nm) and electromyography (EMG) amplitude were collected before and after 20 minutes of 50 Hz vibration applied to the infrapatellar tendon. Between-group differences in pre-vibration torque were analysed using a one-way analysis of covariance, with age, gender and body mass (kg) as the covariates. If the g-loop is intact, vibration should decrease torque and EMG levels in the target muscle; if dysfunctional, then torque and EMG levels should not change following vibration. One-sample t tests were thus undertaken to analyse whether percentage changes in torque and EMG differed from zero after vibration in each group. In addition, analyses of covariance were utilised to analyse between-group differences in the percentage changes in torque and EMG following vibration. Results: Pre-vibration quadriceps torque was significantly lower in the OA group compared with the control group (P = 0.005). Following tendon vibration, quadriceps torque (P < 0.001) and EMG amplitude (P ≤0.001) decreased significantly in the control group but did not change in the OA group (all P > 0.299). Hamstrings torque and EMG amplitude were unchanged in both groups (all P > 0.204). The vibration-induced changes in quadriceps torque and EMG were significantly different between the OA and control groups (all P < 0.011). No between-group differences were observed for the change in hamstrings torque or EMG (all P > 0.554). Conclusions: g-loop dysfunction may contribute to AMI in individuals with knee joint OA, partially explaining the marked quadriceps weakness and atrophy that is often observed in this population

Feeding-associated gene expression in sheep scab mites (Psoroptes ovis)

The mite Psoroptes ovis is the causative agent of sheep scab. Although not usually fatal, the disease can spread rapidly and is a serious animal welfare concern. Vaccine development against ectoparasites has primarily focussed on two sources of candidate vaccine antigens – “exposed” antigens that are secreted in saliva during feeding on a host and “concealed” antigens that are usually expressed in the parasite gut and may be involved in digestion. Here, we sought to identify genes encoding proteins important for mite feeding and digestion by a subtractive suppressive hybridisation approach comparing mRNA transcript abundance in “fed” and “starved” mites. The study identified a variety of genes which are up-regulated by feeding mites. These included group 1, 5, 7 and 13 allergens including the previously described cysteine protease Pso o 1. In addition, numerous novel genes were identified here including some encoding potential salivary gland proteins and others encoding proteins which may facilitate feeding such as a serum opacity factor. An olfactory receptor-like protein was identified in the starved mite population which may help the mite to identify a host

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Evaluation of Three Automated Genome Annotations for Halorhabdus utahensis

Genome annotations are accumulating rapidly and depend heavily on automated annotation systems. Many genome centers offer annotation systems but no one has compared their output in a systematic way to determine accuracy and inherent errors. Errors in the annotations are routinely deposited in databases such as NCBI and used to validate subsequent annotation errors. We submitted the genome sequence of halophilic archaeon Halorhabdus utahensis to be analyzed by three genome annotation services. We have examined the output from each service in a variety of ways in order to compare the methodology and effectiveness of the annotations, as well as to explore the genes, pathways, and physiology of the previously unannotated genome. The annotation services differ considerably in gene calls, features, and ease of use. We had to manually identify the origin of replication and the species-specific consensus ribosome-binding site. Additionally, we conducted laboratory experiments to test H. utahensis growth and enzyme activity. Current annotation practices need to improve in order to more accurately reflect a genome's biological potential. We make specific recommendations that could improve the quality of microbial annotation projects

Political Contest and Oppositional Voices in Postconflict Democracy:The Impact of Institutional Design on Government–Media Relations

The media are considered to play a crucial democratic role in the public sphere through representing political issues to the public (Gelders et al. 2007); facilitating deliberation, public opinion formation and political participation (Habermas 1989); acting as the 'watchdog' of powerful societal institutions (Norris 2000); and in assisting in the development of civil society in politically fragile and divided contexts (Taylor 2000). Journalists are expected to perform their news reporting within the framework of public interest values, such as objectivity, impartiality, public service, autonomy, and a critical questioning of power (Street 2001). Yet, it is acknowledged that political, cultural, organisational, economic, and relational factors affect this journalistic ideal (Davis 2010). In deeply divided, post-conflict societies, ethno-political antagonisms are fundamental to almost all aspects of civic life, yet there is limited research into how government-media relations operate in such contexts. Most media-politics studies focus on Western majoritarian parliamentary or presidential systems - that is, any system that has clear ‘winners’ and ‘losers’ after elections - and where institutional factors are considered, the focus is largely on how party systems impact on journalism (e.g. Çarkoğlu et al. 2014; Hallin and Mancini 2004; Sheafer and Wolfsfeld 2009). This focus however, neglects important institutional variables, such as mandatory coalition, proportionality and special cross-community voting arrangements, which pertain in more constitutionally complex democracies and which may have a significant impact on media-politics relations

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty