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Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.
- Jessica C. Ralston, Kathleen A.J. Mitchelson, Gina M. Lynch, Tam T.T. Tran, Conall R. Strain, Yvonne M. Lenighan, Elaine B. Kennedy, Fiona C. McGillicuddy, Paul W. O'Toole, Helen M. Roche
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E92
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Reduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.
Needle Thoracostomy for Patients with Prolonged Transport Times: A Case-control Study
- Lori Weichenthal, Desiree Hansen Crane, Luke Rond, Conal Roche
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- Journal:
- Prehospital and Disaster Medicine / Volume 30 / Issue 4 / August 2015
- Published online by Cambridge University Press:
- 08 July 2015, pp. 397-401
- Print publication:
- August 2015
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Introduction
The use of prehospital needle thoracostomy (NT) is controversial. Some studies support its use; however, concerns exist regarding misplacement, inappropriate patient selection, and iatrogenic injury. Even less is known about its efficacy in situations where there is a delay to definitive care.
Hypothesis/AimTo determine any differences in survival of patients who underwent NT in the setting of prolonged versus short transport times, and to describe differences in mechanisms and complications between the two groups.
MethodsThis was a retrospective, matched, case-control study of trauma patients in a four county Emergency Medical Service (EMS) system from April 1, 2007 through April 1, 2013. This system serves an urban, rural, and wilderness catchment area. A prehospital database was queried for all patients in whom NT was performed, identifying 182 patients. When these calls were limited to those with prolonged transport times, the search was narrowed to 32 cases. A matched control group, based on age and gender, with short transport times was then created as a comparison. Data collected from prehospital and hospital records included: demographics; mechanism of injury; call status; response to NT; and final outcome. Univariate and multivariate analyses were conducted, as appropriate, to assess the primary outcome of survival and to further elucidate the descriptive data.
ResultsThere was no difference in survival between the case and control groups, either when evaluated with univariate (34% vs 25%; P=.41) or multivariate (odds ratio=0.99; 95% CI, 0.96-1.02; P=.57) analyses. Blunt trauma was the most common mechanism in both groups, but penetrating trauma was more common in the control group (30% vs 9%; P=.003). Patients in the control group were also more likely to have no vital signs on initial assessment (62% vs 31%; P=.003). More patients in the case group were described as having clinical improvement after NT (34% vs 19%; P=.03). No complications of NT were reported in either group.
ConclusionsThere was no significant difference in survival between patients with prolonged versus short transport times who underwent NT. Patients with prolonged transport times were more likely to have sustained blunt trauma, have vital signs on EMS arrival, and to have clinical improvement after NT.
,Weichenthal L ,Crane DH ,Rond L .Roche C Needle Thoracostomy for Patients with Prolonged Transport Times: A Case-control Study . Prehosp Disaster Med.2015 ;30 (4 ):1 –5 .
Prevalence and clinical correlates of depression in the acute phase of first episode schizophrenia
- Eric Roche, Mary Clarke, Stephen Browne, Niall Turner, Orflaith McTuige, Moaayad Kamali, Anthony Kinsellla, Conall Larkin, John L Waddington, Eadbhard O'Callaghan
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- Journal:
- Irish Journal of Psychological Medicine / Volume 27 / Issue 1 / March 2010
- Published online by Cambridge University Press:
- 13 June 2014, pp. 15-18
- Print publication:
- March 2010
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Background: Reported rates of depression in schizophrenia vary considerably.
Objective: To measure the prevalence of depression in a first episode sample of people with schizophrenia.
Methods: All referrals with a first episode of schizophrenia diagnosed using SCID interviews were assessed pre-discharge and again six months later. We used the Calgary Depression Scale for Schizophrenia (CDSS) and Positive and Negative Syndrome Scale (PANSS) to assess the severity of symptoms.
Results: Pre-discharge, 10.4% of the sample met CDSS criteria for depression. According to the PANSS depression (PANSS -D) subscale, 3% of patients were depressed, with a mean score of 7.48 (SD = 2.97). Only 3% of patients pre-discharge were found to be depressed on both the CDSS and the PANSS-D. Six months later 6.5% were depressed according to the CDSS. However none reached depression criteria according to the PANSS-D. The CDSS correlated with PANSS-D both pre-discharge and at follow-up. Feelings of depression and self-deprecation were the most common symptoms at baseline and follow-up. The CDSS was unrelated to negative symptoms at both stages. A lifetime history of alcohol abuse increased the risk for depression.
Conclusion: Rates of depression in this sample were low. The CDSS appears to discriminate between depression and negative symptoms. Like the general population, alcohol misuse is a risk factor for depression in first episode schizophrenia.