The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers

This is the author accepted manuscript. The final version is available on open access from the American Physiological Society via the DOI in this recordAlthough the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration (i.e. pharmacologically lowering circulating non-esterified fatty acid (NEFA) availability) on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age 22±1 years, BMI 24.0±0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n=9) or acipimox (ACI; 250 mg Olbetam; n=9) ingestion four times daily. Before and after immobilization, whole-body glucose disposal rate (GDR), forearm glucose uptake (FGU, i.e. muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinaemic-hyperaminoacidaemic-euglycaemic clamp conditions using forearm balance and L-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups; more so in ACI (from 53±8 to 12±5 µmol·min-1) than PLA (from 52±8 to 38±13 µmol·min-1; P<0.05). In ACI only, and in contrast to our hypothesis, fasting arterialised NEFA concentrations were elevated to 1.3±0.1 mmol·L-1 post-immobilization (P<0.05), and fasting forearm NEFA balance increased ~4-fold (P=0.10). Forearm phenylalanine net balance decreased following immobilization (P<0.10), driven by increased Ra (from 32±5 (fasting) and 21±4 (clamp) pre-immobilization to 53±8 and 31±4 post-immobilization; P<0.05) while Rd was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.Wellcome TrustNational Institute of Agin

Glycaemia as a sign of the viability of the foetuses in the last days of gestation in dairy goats with pregnancy toxaemia

Pregnancy toxaemia is one of the most common diseases affecting small ruminants in the last month of gestation. Nearly 80% of the foetal growth occurs in the last 6 weeks of gestation. Fat goats and goats carrying twins and triplets are at greater risk. Pregnancy toxaemia is characterized by metabolic acidosis, hypoglycaemia and ketonaemia and a very high mortality rate. In our study five does with pregnancy toxaemia showed a marked hyperglycaemia (12.4 ± 5.4 mmol/L). Although our findings are based on a small population sample (10 goats), we nonetheless postulate that hyperglycaemia could be explained by the death of the foetuses. Caesarian surgery was performed on four of the five does with hyperglycaemia (HG does). In the fifth, kidding was induced. In this group, two does had two dead foetuses, two had three dead foetuses and one does had four foetuses, only one of which was alive. Caesarian surgery was performed on all five does with hypoglycaemia (LG does). Four does of the LG group had three foetuses and one had two foetuses, all alive. The HG doe had lower rectal temperatures, lower sodium and higher urea nitrogen (BUN) in the blood when compared with the LG does. As the condition of affected does may deteriorate quickly, the results of the present study suggest that in the last days of pregnancy goats with pregnancy toxaemia and concurrent hypoglycaemia should be considered for caesarian surgery

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

Anticipatory nausea in cyclical vomiting

BACKGROUND: Cyclical Vomiting Syndrome (CVS) is characterised by discrete, unexplained episodes of intense nausea and vomiting, and mainly affects children and adolescents. Comprehending Cyclical Vomiting Syndrome requires awareness of the severity of nausea experienced by patients. As a subjective symptom, nausea is easily overlooked, yet is the most distressing symptom for patients and causes many behavioural changes during attacks. CASE PRESENTATION: This first-hand account of one patient's experience of Cyclical Vomiting Syndrome shows how severe nausea contributed to the development of anticipatory nausea and vomiting (ANV), a conditioned response frequently observed in chemotherapy patients. This conditioning apparently worsened the course of the patient's disease. Anticipatory nausea and vomiting has not previously been recognised in Cyclical Vomiting Syndrome, however predictors of its occurrence in oncology patients indicate that it could complicate many cases. CONCLUSION: We suggest a model whereby untreated severe and prolonged nausea provokes anxiety about further cyclical vomiting attacks. This anxiety facilitates conditioning, thus increasing the range of triggers in a self-perpetuating manner. Effective management of the nausea-anxiety feedback loop can reduce the likelihood of anticipatory nausea and vomiting developing in other patients

Giant cervicothoracic extradural arachnoid cyst: case report

The pathogenesis, etiology, and treatment of the spinal arachnoid cyst have not been well established because of its rarity. A 57-year-old male was presented with spastic quadriparesis predominantly on the left side. His radiological examination showed widening of the cervical spinal canal and left neural foramina due to a cerebrospinal fluid - filled extradural cyst that extended from C2 to T2 level. The cyst was located left anterolaterally, compressing the spinal cord. Through a C4–T2 laminotomy, the cyst was excised totally and the dural defect was repaired. Several features of the reported case, such as cyst size, location, and clinical features make it extremely unusual. The case is discussed in light of the relevant literature

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

Impact of a mobile phone and web program on symptom and functional outcomes for people with mild-to-moderate depression, anxiety and stress: a randomised controlled trial.

Background Mobile phone-based psychological interventions enable real time self-monitoring and self-management, and large-scale dissemination. However, few studies have focused on mild-to-moderate symptoms where public health need is greatest, and none have targeted work and social functioning. This study reports outcomes of a CONSORT-compliant randomised controlled trial (RCT) to evaluate the efficacy of myCompass, a self-guided psychological treatment delivered via mobile phone and computer, designed to reduce mild-to-moderate depression, anxiety and stress, and improve work and social functioning. Method Community-based volunteers with mild-to-moderate depression, anxiety and/or stress (N= 720) were randomly assigned to the myCompass program, an attention control intervention, or to a waitlist condition for seven weeks. The interventions were fully automated, without any human input or guidance. Participants’ symptoms and functioning were assessed at baseline, post-intervention and 3-month follow-up, using the Depression, Anxiety and Stress Scale and the Work and Social Adjustment Scale. Results Retention rates at post-intervention and follow-up for the study sample were 72.1% (n= 449) and 48.6% (n= 350) respectively. The myCompass group showed significantly greater improvement in symptoms of depression, anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase (between-group effect sizes ranged from d= .22 to d= .55 based on the observed means). Symptom scores remained at near normal levels at 3-month follow-up. Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up. Conclusions The myCompass program is an effective public health program, facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems

Quantifying Child Mortality Reductions Related to Measles Vaccination

Background: This study characterizes the historical relationship between coverage of measles containing vaccines (MCV) and mortality in children under 5 years, with a view toward ongoing global efforts to reduce child mortality. Methodology/Principal Findings: Using country-level, longitudinal panel data, from 44 countries over the period 1960–2005, we analyzed the relationship between MCV coverage and measles mortality with (1) logistic regressions for no measles deaths in a country-year, and (2) linear regressions for the logarithm of the measles death rate. All regressions allowed a flexible, non-linear relationship between coverage and mortality. Covariates included birth rate, death rates from other causes, percent living in urban areas, population density, per-capita GDP, use of the two-dose MCV, year, and mortality coding system. Regressions used lagged covariates, country fixed effects, and robust standard errors clustered by country. The likelihood of no measles deaths increased nonlinearly with higher MCV coverage (ORs: 13.8 [1.6–122.7] for 80–89% to 40.7 [3.2–517.6] for ≥95%), compared to pre-vaccination risk levels. Measles death rates declined nonlinearly with higher MCV coverage, with benefits accruing more slowly above 90% coverage. Compared to no coverage, predicted average reductions in death rates were −79% at 70% coverage, −93% at 90%, and −95% at 95%. Conclusions/Significance: 40 years of experience with MCV vaccination suggests that extremely high levels of vaccination coverage are needed to produce sharp reductions in measles deaths. Achieving sustainable benefits likely requires a combination of extended vaccine programs and supplementary vaccine efforts