Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans.

UNLABELLED: Antiviral RNA-mediated silencing (RNA interference [RNAi]) acts as a powerful innate immunity defense in plants, invertebrates, and mammals. In Caenorhabditis elegans, RNAi is systemic; i.e., RNAi silencing signals can move between cells and tissues. Furthermore, RNAi effects can be inherited transgenerationally and may last for many generations. Neither the biological relevance of systemic RNAi nor transgenerational RNAi is currently understood. Here we examined the role of both pathways in the protection of C. elegans from viral infection. We studied the Orsay virus, a positive-strand RNA virus related to Nodaviridae and the first and only virus known to infect C. elegans. Immunity to Orsay virus infection requires the RNAi pathway. Surprisingly, we found that genes required for systemic or transgenerational RNAi did not have a role in antiviral defense. Furthermore, we found that Orsay virus infection did not elicit a systemic RNAi response even when a target for RNAi was provided by using transgenes. Finally, we show that viral siRNAs, the effectors of RNAi, are not inherited to a level that provides any significant resistance to viral infection in the next generation. We conclude that systemic or transgenerational RNAi does not play a role in the defense against natural Orsay virus infection. Furthermore, our data suggest that there is a qualitative difference between experimental RNAi and antiviral RNAi. Our data are consistent with a model of systemic and transgenerational RNAi that requires a nuclear or germ line component that is lacking in almost all RNA virus infections. IMPORTANCE: Since its discovery in Caenorhabditis elegans, RNAi has proven a valuable scientific tool in many organisms. In C. elegans, exogenous RNAi spreads throughout the organism and can be passed between generations; however, there has been controversy as to the endogenous role(s) that the RNAi pathway plays. One endogenous role for which spreading both within the infected organism and between generations would be advantageous is a role in viral defense. In plants, antiviral RNAi is systemic and the spread of RNAi between cells provides protection against subsequent viral infection. Here we investigated this by using the only naturally occurring virus known to infect C. elegans, Orsay virus, and surprisingly found that, in contrast to the exogenous RNAi pathway, the antiviral RNAi response targeted against this virus does not spread systemically throughout the organism and cannot be passed between generations. These results suggest that there are differences between the two pathways that remain to be discovered

Sex differences in the influence of body mass index on anatomical architecture of brain networks.

Background/objectivesThe brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters.Subjects/methodsStructural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age.ResultsIn both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions.ConclusionsIn individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology

a pilot randomized controlled trial

Objectives: Our primary aim of this pilot study was to test feasibility of the planned design, the interventions (education plus telephone coaching), and the outcome measures, and to facilitate a power calculation for a future randomized controlled trial to improve adherence to recovery goals following hip fracture. Design: This is a parallel 1:1 randomized controlled feasibility study. Setting: The study was conducted in a teaching hospital in Vancouver, BC, Canada. Participants: Participants were community-dwelling adults over 60 years of age with a recent hip fracture. They were recruited and assessed in hospital, and then randomized after hospital discharge to the intervention or control group by a web-based randomization service. Treatment allocation was concealed to the investigators, measurement team, and data entry assistants and analysts. Participants and the research physiotherapist were aware of treatment allocation. Intervention: Intervention included usual care for hip fracture plus a 1-hour in-hospital educational session using a patient- centered educational manual and four videos, and up to five postdischarge telephone calls from a physiotherapist to provide recovery coaching. The control group received usual care plus a 1-hour in-hospital educational session using the educational manual and videos. Measurement: Our primary outcome was feasibility, specifically recruitment and retention of participants. We also collected selected health outcomes, including health- related quality of life (EQ5D-5L), gait speed, and psychosocial factors (ICEpop CAPability measure for Older people and the Hospital Anxiety and Depression Scale). Results: Our pilot study results indicate that it is feasible to recruit, retain, and provide follow-up telephone coaching to older adults after hip fracture. We enrolled 30 older adults (mean age 81.5 years; range 61–97 years), representing a 42% recruitment rate. Participants excluded were those who were not community dwelling on admission, were discharged to a residential care facility, had physician-diagnosed dementia, and/or had medical contraindications to participation. There were 27 participants who completed the study: eleven in the intervention group, 15 in the control group, and one participant completed a qualitative interview only. There were no differences between groups for health measures. Conclusion: We highlight the feasibility of telephone coaching for older adults after hip fracture to improve adherence to mobility recovery goals

“everything in one place”

Purpose: To describe older adults’ perspectives on a new patient education manual for the recovery process after hip fracture. Materials and methods: The Fracture Recovery for Seniors at Home (FReSH) Start manual is an evidence- based manual for older adults with fall-related hip fracture. The manual aims to support the transition from hospital to home by facilitating self- management of the recovery process. We enrolled 31 community-dwelling older adults with previous fall-related hip fracture and one family member. We collected data using a telephone-based questionnaire with eight five-point Likert items and four semi-structured open-ended questions to explore participants’ perceptions on the structure, content, and illustration of the manual. The questionnaire also asked participants to rate the overall utility (out of 10 points) and length of the manual. We used content analysis to describe main themes from responses to the open-ended interview questions. Results: Participants’ ratings for structure, content, and illustrations ranged from 4 to 5 (agree to highly agree), and the median usefulness rating was 9 (10th percentile: 7, 90th percentile: 10). Main themes from the content analysis included: ease of use and presentation; health literacy; illustration utility; health care team delivery; general impression, information support from hospital to home; emotional and decision-making support; and the novelty of the manual. Conclusion: The FReSH Start manual was perceived as comprehensive in content and acceptable for use with older adults post-fall- related hip fracture. Participants expressed a need for delivery and explanation of the manual by a health care team member

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals

Living between languages: The politics of translation in Leila Aboulela’s Minaret and Xiaolu Guo’s A Concise Chinese-English Dictionary for Lovers

This is the author's final draft post-refereeing as published in The Journal of Commonwealth Literature 2012 47: 207 DOI:10.1177/0021989412440433. The online version of this article can be found at: http://jcl.sagepub.com/content/47/2/20

Effectiveness and cost effectiveness of pharmacist input at the ward level: a systematic review and meta-analysis

Background Pharmacists play important role in ensuring timely care delivery at the ward level. The optimal level of pharmacist input, however, is not clearly defined. Objective To systematically review the evidence that assessed the outcomes of ward pharmacist input for people admitted with acute or emergent illness. Methods The protocol and search strategies were developed with input from clinicians. Medline, EMBASE, Centre for Reviews and Dissemination, The Cochrane Library, NHS Economic Evaluations, Health Technology Assessment and Health Economic Evaluations databases were searched. Inclusion criteria specified the population as adults and young people (age >16 years) who are admitted to hospital with suspected or confirmed acute or emergent illness. Only randomised controlled trials (RCTs) published in English were eligible for inclusion in the effectiveness review. Economic studies were limited to full economic evaluations and comparative cost analysis. Included studies were quality-assessed. Data were extracted, summarised. and meta-analysed, where appropriate. Results Eighteen RCTs and 7 economic studies were included. The RCTs were from USA (n=3), Sweden (n=2), Belgium (n=2), China (n=2), Australia (n=2), Denmark (n=2), Northern Ireland, Norway, Canada, UK and Netherlands. The economic studies were from UK (n=2), Sweden (n=2), Belgium and Netherlands. The results showed that regular pharmacist input was most cost effective. It reduced length-of-stay (mean= -1.74 days [95% CI: -2.76, -0.72], and increased patient and/or carer satisfaction (Relative Risk (RR) =1.49 [1.09, 2.03] at discharge). At £20,000 per quality-adjusted life-year (QALY)-gained cost-effectiveness threshold, it was either cost-saving or cost-effective (Incremental Cost Effectiveness Ratio (ICER) =£632/ QALY-gained). No evidence was found for 7-day pharmacist presence. Conclusions Pharmacist inclusion in the ward multidisciplinary team improves patient safety and satisfaction and is cost-effective when regularly provided throughout the ward stay. Research is needed to determine whether the provision of 7-day service is cost-effective.Peer reviewe