Bisphosphonates attenuate age-related muscle decline in Caenorhabditis elegans

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Age-related muscle decline (sarcopenia) associates with numerous health risk factors and poor quality of life. Drugs that counter sarcopenia without harmful side effects are lacking, and repurposing existing pharmaceuticals could expedite realistic clinical options. Recent studies suggest bisphosphonates promote muscle health; however, the efficacy of bisphosphonates as an anti-sarcopenic therapy is currently unclear. METHODS: Using Caenorhabditis elegans as a sarcopenia model, we treated animals with 100 nM, 1, 10, 100 and 500 μM zoledronic acid (ZA) and assessed lifespan and healthspan (movement rates) using a microfluidic chip device. The effects of ZA on sarcopenia were examined using GFP-tagged myofibres or mitochondria at days 0, 4 and 6 post-adulthood. Mechanisms of ZA-mediated healthspan extension were determined using combined ZA and targeted RNAi gene knockdown across the life-course. RESULTS: We found 100 nM and 1 μM ZA increased lifespan (P  0.05), whereas 100 and 500 μM ZA were larval lethal. ZA (1 μM) significantly improved myofibrillar structure on days 4 and 6 post-adulthood (83 and 71% well-organized myofibres, respectively, vs. 56 and 34% controls, P  0.05). Life/healthspan was extended through knockdown of igdb-1/FNDC5 (635 ± 10 vs. 523 ± 10% population activity AUC in gene knockdown vs. untreated controls, P  0.05]. Conversely, let-756/FGF21 and sir-2.2/SIRT-4 were dispensable for ZA-induced healthspan [630 ± 6 vs. 523 ± 10% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, P < 0.01 (let-756/FGF21) and 568 ± 9 vs. 523 ± 10%, P < 0.05 (sir-2.2/SIRT-4)]. CONCLUSIONS: Despite lacking an endoskeleton, ZA delays Caenorhabditis elegans sarcopenia, which translates to improved neuromuscular function across the life course. Bisphosphonates might, therefore, be an immediately exploitable anti-sarcopenia therapy

Elective high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: an individual patient data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Despite the considerable amount of evidence from randomized controlled trials and meta-analyses, uncertainty remains regarding the efficacy and safety of high-frequency oscillatory ventilation as compared to conventional ventilation in the early treatment of respiratory distress syndrome in preterm infants. This results in a wide variation in the clinical use of high-frequency oscillatory ventilation for this indication throughout the world. The reasons are an unexplained heterogeneity between trial results and a number of unanswered, clinically important questions. Do infants with different risk profiles respond differently to high-frequency oscillatory ventilation? How does the ventilation strategy affect outcomes? Does the delay – either from birth or from the moment of intubation – to the start of high-frequency oscillation modify the effect of the intervention? Instead of doing new trials, those questions can be addressed by re-analyzing the individual patient data from the existing randomized controlled trials.</p> <p>Methods/Design</p> <p>A systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of the original individual data from each infant included in each randomized controlled trial addressing this question.</p> <p>The study objective is to estimate the effect of high-frequency oscillatory ventilation on the risk for the combined outcome of death or bronchopulmonary dysplasia or a severe adverse neurological event. In addition, it will explore whether the effect of high-frequency oscillatory ventilation differs by the infant's risk profile, defined by gestational age, intrauterine growth restriction, severity of lung disease at birth and whether or not corticosteroids were given to the mother prior to delivery. Finally, it will explore the importance of effect modifying factors such as the ventilator device, ventilation strategy and the delay to the start of high-frequency ventilation.</p> <p>Discussion</p> <p>An international collaborative group, the PreVILIG Collaboration (Prevention of Ventilator Induced Lung Injury Group), has been formed with the investigators of the original randomized trials to conduct this systematic review. In the field of neonatology, individual patient data meta-analysis has not been used previously. Final results are expected to be available by the end of 2009.</p

Timescales of Massive Human Entrainment

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

Factor Structure of the Neurocognitive Tests: An Application of the Confirmative Factor Analysis in Stabilized Schizophrenia Patients

The purpose of the present study was to identify the factor structure of neurocognitive tests used on schizophrenia patients by using the confirmative factor analysis, and to assess the factor score differences of schizophrenia patients and healthy controls. Comprehensive neurocognitive tests were administered to stabilized schizophrenia patients (N=114) and healthy controls (N=120). In the results of factor analyses on patients, the multifactorial-6-factor model, which included the speed of processing, working memory, verbal learning and memory, visual learning and memory, attention/vigilance, and reasoning/problem solving as suggested by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), showed the better goodness of fit than any of the other models tested. And assessing the group differences of factor scores, we found the patients performed worse than the controls in all factors, but the result showed meaningful variations of impairments across the cognitive factors. Our study identifies the six major domains with multifactorial structure of cognitive abilities in schizophrenia patients and confirms the distinctive impairment patterns of each cognitive domain. These results may have utility in better understanding the pathology of schizophrenia as well as in genetic studies

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Genome-wide analysis identifies a role for common copy number variants in specific language impairment

An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with population controls, suggesting that CNVs may contribute to SLI risk. A similar trend was observed in first-degree relatives regardless of affection status. The increased burden found in our study was not driven by large or de novo events, which have been described as causative in other neurodevelopmental disorders. Nevertheless, de novo CNVs might be important on a case-by-case basis, as indicated by identification of events affecting relevant genes, such as ACTR2 and CSNK1A1, and small events within known micro-deletion/-duplication syndrome regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs of the independent cases identified significant overrepresentation of acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC proteins as compared with controls. Taken together, our data suggest that the majority of the risk conferred by CNVs in SLI is via common, inherited events within a ‘common disorder–common variant’ model. Therefore the risk conferred by CNVs will depend upon the combination of events inherited (both CNVs and SNPs), the genetic background of the individual and the environmental factors

The clinical relevance of PCL index on the reconstruction of anterior cruciate ligament with hamstring tendon autograft

The posterior cruciate ligament index (PCL index) has been reported as a diagnostic and prognostic marker for anterior cruciate ligament (ACL) reconstruction. The clinical relevance of PCL index on the reconstruction of ACL with hamstring tendon autograft has not been described in the literature. The objective of this study is to evaluate the importance of the PCL index as a marker of anatomic reconstruction and of functional improvement of patients undergoing ACL reconstruction with HT autograft. Twenty-four patients were submitted to ACL reconstruction with HT autograft. The PCL index was assessed by magnetic resonance imaging before and after surgery. The functional evaluation was performed through the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form© and Knee Society Knee Scoring System© (IKS). Patients presented a significant positive variation of the PCL index, IKDC and IKS scores. There is no significant correlation between PCL index variation and IKDC and IKS scores (p > 0.05). Unlike other studies reporting a relationship between the PCL index, control of rotational kinematics, and functional improvement in patients undergoing ACL reconstruction with bone-patellar tendon-bone autograft, this study does not demonstrate this association. There is evidence in this study to show that the PCL index may be used as an anatomic reconstructive marker of ACL but not to predict the clinical outcome in this type of reconstruction.(undefined

A finer grained approach to psychological capital and work performance

Purpose Psychological capital is a set of personal resources comprised by hope, efficacy, optimism, and resilience, which previous research has supported as being valuable for general work performance. However, in today’s organizations, a multidimensional approach is required to understanding work performance, thus, we aimed to determine whether psychological capital improves proficiency, adaptivity, and proactivity, and also whether hope, efficiency, resilience, and optimism have a differential contribution to the same outcomes. Analyzing the temporal meaning of each psychological capital dimension, this paper theorizes the relative weights of psychological capital dimensions on proficiency, adaptivity, and proactivity, proposing also that higher relative weight dimensions are helpful to cope with job demands and perform well. Methodology Two survey studies, the first based on cross-sectional data and the second on two waves of data, were conducted with employees from diverse organizations, who provided measures of their psychological capital, work performance, and job demands. Data was modeled with regression analysis together with relative weights analysis. Findings Relative weights for dimensions of psychological capital were supported as having remarkable unique contributions for proficient, adaptive, and proactive behavior, particularly when job demands were high. Originality/Value We concluded that organizations facing high job demands should implement actions to enhance psychological capital dimensions; however, those actions should focus on the specific criterion of performance of interest