Depression, anxiety, pain and quality of life in people living with chronic hepatitis C: A systematic review and meta-analysis

Objectives: Individuals infected with hepatitis C virus (HCV) can develop extrahepatic conditions which may have a significant impact on life expectancy and quality of life. We conducted a systematic review to assess the causal relationship between HCV and extrahepatic conditions and the impact of HCV upon health-related quality of life of people in the UK. / Methods: HCV advocacy groups identified conditions that they thought most important to research, and the perspectives of various stakeholders informed the scope of the review. A comprehensive literature search of a range of electronic databases and websites was undertaken. Screening, quality assessment and data extraction were conducted using specialist software. The key criterion for inclusion in a synthesis was a study’s testing of the association between HCV and either quality of life or conditions specified as important by advocacy groups: depression, anxiety or painful conditions. Other criteria relating to study populations, measures and matching of study groups were also applied. Two reviewers assessed included studies, with disagreements resolved by a third reviewer where necessary. Studies were assessed for methodological quality using standardised appraisal tools. Metaanalyses were performed. Based on the consistency and sufficiency of research evidence, the findings were graded as strong, promising, tentative or inconclusive. / Results: 71 studies were included in the review’s syntheses. All studies were judged to be at a moderate or high risk of bias. Only two UK studies met our inclusion criteria. / Quality of life: Evidence from 22 studies indicates that people with HCV have worse quality of life than ‘general’ or ‘healthy’ populations; meta-analysis of nine studies indicated\ud that the physical (PCS) and mental health (MCS) domains of quality of life on the Health-Related Quality of Life Scale were both statistically and clinically worse among HCV-infected people (PCS: MD 5.54, 95% CI 3.73-7.35, MCS: MD 3.81, 95% CI 1.97-5.64). Evidence from seven included studies suggests that people co-infected with HCV and HIV have worse quality of life than individuals with HIV only; metaanalysis of five studies indicated that both the physical and mental health domains of quality of life were significantly worse among people who were co-infected (PCS: MD 2.57, 95% CI 1.08-4.06, MCS: MD 1.88, 95% CI 0.06-3.69). / Depression and anxiety: Evidence from 22 studies indicates that depression and anxiety are more severe, and depression is more common among people with HCV compared to those without it. Meta-analysis of 12 studies identified the severity of depression in people with HCV to be significantly greater than in those without HCV (Mean difference 0.98, 95% CI 0.43-1.53). Meta-analysis of nine studies identified the severity of clinical anxiety to be significantly greater among people with HCV (Mean difference 0.47, 95% CI 0.09-0.86). Meta-analysis of seven studies identified participants with HCV to be approximately three times more likely to be depressed compared to those without HCV (OR 2.77, 95% CI 1.62-4.74). No statistically significant evidence that anxiety is more common among people with HCV was found. / Pain: Evidence was appraised from 26 studies on painful conditions. A meta-analysis of four studies indicates that people with HCV are 17% more likely to suffer from arthralgia than those without HCV (RR 1.17, 95% CI 1.04-1.31). A meta-analysis of five studies suggested that people with HCV are significantly more likely to suffer from fibromyalgia; key differences across the studies in terms of the health status (co-morbidities) of HCV patients and comparison groups mean it is not possible to quantify the increased risk attributable to HCV. Other studies, including those on arthritis, were not amenable to meta-analysis. / Conclusions: Evidence suggests an association between HCV infection and depression, anxiety, fibromyalgia, arthralgia and health-related quality of life. However, the evidence was graded as ‘promising’ or ‘tentative’ rather than ‘strong’. More high-quality research on the association between HCV and these conditions is needed

Polarization squeezing of intense pulses with a fiber Sagnac interferometer

We report on the generation of polarization squeezing of intense, short light pulses using an asymmetric fiber Sagnac interferometer. The Kerr nonlinearity of the fiber is exploited to produce independent amplitude squeezed pulses. The polarization squeezing properties of spatially overlapped amplitude squeezed and coherent states are discussed. The experimental results for a single amplitude squeezed beam are compared to the case of two phase-matched, spatially overlapped amplitude squeezed pulses. For the latter, noise variances of -3.4dB below shot noise in the S0 and the S1 and of -2.8dB in the S2 Stokes parameters were observed, which is comparable to the input squeezing magnitude. Polarization squeezing, that is squeezing relative to a corresponding polarization minimum uncertainty state, was generated in S1.Comment: v4: 2 small typos corrected v3: misc problems with Tex surmounted - mysteriously missing text returned to results - vol# for Korolkova et al. PRA v2: was a spelling change in author lis

A pulsed source of continuous variable polarization entanglement

We have experimentally demonstrated polarization entanglement using continuous variables in an ultra-short pulsed laser system at telecommunication wavelengths. Exploiting the Kerr-nonlinearity of a glass fibre we generated a polarization squeezed pulse with S2 the only non-zero Stokes parameter thus S1 and S3 being the conjugate pair. Polarization entanglement was generated by interference of the polarization squeezed field with a vacuum on a 50:50 beam splitter. The two resultant beams exhibit strong quantum noise correlations in S1 and S3. The sum noise signal of S3 was at the respective shot noise level and the difference noise signal of S1 fell 2.9dB below this value

Evaluation of a graded exercise test to determine peak fat oxidation in individuals with low cardiorespiratory fitness:Estimating maximal capacity for fat oxidation

The maximal capacity to utilise fat (peak fat oxidation [PFO]) may have implications for health and ultra-endurance performance, and is commonly determined by incremental exercise tests employing 3-minute stages. However, 3-minute stages may be insufficient to attain steady-state gas kinetics, compromising test validity. We assessed whether 4-minute stages produce steady-state gas exchange and reliable PFO in adults with V̇O2peakThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Exercise strategies to protect against the impact of short-term reduced physical activity on muscle function and markers of health in older men:study protocol for a randomised controlled trial

BACKGROUND: Muscles get smaller and weaker as we age and become more vulnerable to atrophy when physical activity is reduced or removed. This research is designed to investigate the potentially protective effects of two separate exercise strategies against loss in skeletal muscle function and size, and other key indices of health, following 14 days of reduced physical activity in older men. METHODS: Three groups of 10 older men (aged 65–80 years) will undertake 2 weeks of reduced activity by decreasing daily steps from more than 3500 to less than 1500 (using pedometers to record step count). Two of the three groups will then undertake additional exercise interventions, either: 4 weeks of progressive resistance training prior to the step-reduction intervention (PT-group), or home-based ‘exercise snacking’ three times per day during the step-reduction intervention (ES-group). The third group undertaking only the step-reduction intervention (control) will provide a comparison against which to assess the effectiveness of the protective exercise strategies. Pre and post step-reduction assessments of muscle function, standing balance, anthropometry and muscle architecture will be taken. Pre and post step-reduction in postprandial metabolic control, resting systemic inflammation, adipose inflammation, oxidative stress, immune function, sleep quality, dietary habits, and quality of life will be measured. The stress response to exercise, and signalling protein and gene expression for muscle protein synthesis and breakdown following an acute bout of exercise will also be assessed pre and post step-reduction. Rates of muscle protein synthesis and adipose triglyceride turnover during the step-reduction intervention will be measured using stable isotope methodology. All participants will then undertake 2 weeks of supervised resistance training with the aim of regaining any deficit from baseline in muscle function and size. DISCUSSION: This study aims to identify exercise strategies that could be implemented to protect against loss of muscle power during 2 weeks of reduced activity in older men, and to improve understanding of the way in which a short-term reduction in physical activity impacts upon muscle function and health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02495727 (Initial registration: 25 June 2015

Store-Operated Ca2+ Entry (SOCE) and Purinergic Receptor-Mediated Ca2+ Homeostasis in Murine bv2 Microglia Cells: Early Cellular Responses to ATP-Mediated Microglia Activation

Microglia activation is a neuroinflammatory response to parenchymal damage with release of intracellular metabolites, e.g., purines, and signaling molecules from damaged cells. Extracellular purines can elicit Ca(2+)-mediated microglia activation involving P2X/P2Y receptors with metabotropic (P2Y) and ionotropic (P2X) cell signaling in target cells. Such microglia activation results in increased phagocytic activity, activation of their inflammasome and release of cytokines to sustain neuroinflammatory (so-called M1/M2 polarization). ATP-induced activation of ionotropic P2X4 and P2X7 receptors differentially induces receptor-operated Ca(2+) entry (ROCE). Although store-operated Ca(2+) entry (SOCE) was identified to modulate ROCE in primary microglia, its existence and role in one of the most common murine microglia cell line, BV2, is unknown. To dissect SOCE from ROCE in BV2 cells, we applied high-resolution multiphoton Ca(2+) imaging. After depleting internal Ca(2+) stores, SOCE was clearly detectable. High ATP concentrations (1 mM) elicited sustained increases in intracellular [Ca(2+)]i whereas lower concentrations (≤100 μM) also induced Ca(2+) oscillations. These differential responses were assigned to P2X7 and P2X4 activation, respectively. Pharmacologically inhibiting P2Y and P2X responses did not affect SOCE, and in fact, P2Y-responses were barely detectable in BV2 cells. STIM1S content was significantly upregulated by 1 mM ATP. As P2X-mediated Ca(2+) oscillations were rare events in single cells, we implemented a high-content screening approach that allows to record Ca(2+) signal patterns from a large number of individual cells at lower optical resolution. Using automated classifier analysis, several drugs (minocycline, U73122, U73343, wortmannin, LY294002, AZ10606120) were tested on their profile to act on Ca(2+) oscillations (P2X4) and sustained [Ca(2+)]i increases. We demonstrate specific drug effects on purinergic Ca(2+) pathways and provide new pharmacological insights into Ca(2+) oscillations in BV2 cells. For example, minocycline inhibits both P2X7- and P2X4-mediated Ca(2+)-responses, and this may explain its anti-inflammatory action in neuroinflammatory disease. As a technical result, our novel automated bio-screening approach provides a biomedical engineering platform to allow high-content drug library screens to study neuro-inflammation in vitro

On the development of rod-based models for pneumatically actuated soft robot arms: A five-parameter constitutive relation

While soft robots have many attractive features compared to their hard counterparts, developing tractable models for these highly deformable, nonlinear, systems is challenging. In a recent paper, the authors published a non-classic, five-parameter constitutive relation for a rod-based model of a widely used, pneumatically actuated soft robot arm. It is natural to ask if the complexity of the relation can be eliminated by redesigning the actuator? To this end, finite element models and experimental results are used to further explore the five-parameter constitutive relation. For multiple designs of the pneumatically actuated soft robot arm, we are able to demonstrate how finite element models can be employed in place of experiments to specify the constitutive relations and how the relations are scalable by actuator length and applied pressure. Our primary result is the finding that the five-parameter constitutive relation is germane to pneumatically actuated soft robot arms and the parameters for this relation can be determined by three finite element simulations

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this

A leaky umbrella has little value:evidence clearly indicates the serotonin system is implicated in depression

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this