LOCAL IgA-MEMORY RESPONSE TO BACTERIAL ANTIGENS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72248/1/j.1749-6632.1983.tb26912.x.pd

Role of interferon‐γ and inflammatory monocytes in driving colonic inflammation during acute Clostridium difficile infection in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136491/1/imm12700.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136491/2/imm12700_am.pd

The role of Gr‐1+ cells and tumour necrosis factor‐α signalling during Clostridium difficile colitis in mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110845/1/imm12425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110845/2/imm12425-sup-0001-FigS1-2.pd

Interleukin‐22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110834/1/imm12414.pd

A Type 1 Diabetes Genetic Risk Score Can Identify Patients With GAD65 Autoantibody-Positive Type 2 Diabetes Who Rapidly Progress to Insulin Therapy

This is the author accepted manuscript. The final version is available from American Diabetes Association via the DOI in this record.Objective Progression to insulin therapy in clinically diagnosed type 2 diabetes is highly variable. GAD65 autoantibodies (GADA) are associated with faster progression, but their predictive value is limited. We aimed to determine if a Type 1 Diabetes Genetic Risk Score (T1DGRS) could predict rapid progression to insulin treatment over and above GADA testing. Research Design and Methods We examined the relationship between T1DGRS, GADA (negative or positive) and rapid insulin requirement (within 5 years) using Kaplan-Meier survival analysis and Cox regression in 8,608 participants with clinical type 2 diabetes (onset >35 years, treated without insulin for ≥6 months). T1DGRS was analyzed both continuously (as standardized scores) and categorized based on previously reported centiles of a type 1 diabetes population (50th (high)). Results In GADA positive participants (3.3%), those with higher T1DGRS progressed to insulin more quickly: Probability of insulin requirement at five years [95% CI]: 47.9%[35.0%,62.78%] (high T1DGRS) vs 27.6%[20.5%,36.5%] (medium T1DGRS) vs 17.6%[11.2%,27.2%] (low T1DGRS), p=0.001. In contrast T1DGRS did not predict rapid insulin requirement in GADA negative participants (p=0.4). In Cox regression analysis with adjustment for age of diagnosis, BMI and cohort, T1DGRS was independently associated with time to insulin only in the presence of GADA: hazard ratio per SD increase 1.48 (1.15,1.90), p=0.002. Conclusions A Type 1 Diabetes Genetic Risk Score alters the clinical implications of a positive GADA test in patients with clinical type 2 diabetes, and is independent of and additive to clinical features.The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) was funded by The Wellcome Trust (084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT program. GADA assessment in GoDARTS and DCS was funded by EU Innovative Medicines Initiative 115317 (DIRECT), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013), and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in kind contribution. The DCS cohort was partially funded by the Netherlands Organization for Health Research and Development (Priority Medicines Elderly Programme 113102006). The Diabetes Alliance for Research in England (DARE) study was funded by the Wellcome Trust and supported by the Exeter NIHR Clinical Research Facility. The MASTERMIND study was funded by the UK Medical Research Council (MR/N00633X/) and supported by the NIHR Exeter Clinical Research Facility. The PRIBA study was funded by the National Institute for Health Research (U.K.) (DRF-2010-03-72) and supported by the NIHR Exeter Clinical Research Facility. B.M.S and A.T.H. are supported by the NIHR Exeter Clinical Research Facility. T.J.M. is a National Institute for Health Research Senior Clinical Senior Lecturer. E.R.P. is a Wellcome Trust New Investigator (102820/Z/13/Z). A.T.H. is a Wellcome Trust Senior Investigator and NIHR Senior Investigator. R.A.O is supported by a Diabetes UK Harry Keen Fellowship (16/0005529). A.G.J. is supported by an NIHR Clinician Scientist award (CS-2015-15-018)

Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial

Background: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. Methods: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L-leucine), or nothing (Control). In EXP1, participants (n=10, 68±5 years, mean±SD) consumed Bar, Gel or Control with appetite sensations and appetite-related hormonal responses monitored for one hour, followed by consumption of an ad libitum breakfast (ALB). In EXP2, participants (n=11, 69±5 years) ingested Bar, Gel or Control alongside an ALB. Results: In EXP1, EI at ALB was not different (P=0.674) between conditions (1179±566, 1254±511, 1206±550 kJ for the Control, Bar, and Gel respectively). However, total EI was significantly higher in the Bar and Gel compared to the Control after accounting for the energy content of the supplements (P<0.0005). Analysis revealed significantly higher appetite Area under the Curve (AUC) (P<0.007), a tendency for higher acylated ghrelin AUC (P=0.087), and significantly lower pancreatic polypeptide AUC (P=0.02) in the Control compared with the Bar and Gel. In EXP2, EI at ALB was significantly higher (P=0.028) in the Control (1282±513 kJ) compared to the Bar (1026±565 kJ) and Gel (1064±495 kJ). However, total EI was significantly higher in the Bar and Gel after accounting for the energy content of the supplements (P<0.007). Conclusions: Supplementation with either the Bar or Gel increased total energy intake whether consumed one hour before or during breakfast. This may represent an effective nutritional means for addressing protein and total energy deficiencies in older women

University student engagement inventory (USEI): psychometric properties

Academic engagement describes students’ investment in academic learning and achievement and is an important indicator of students’ adjustment to university life, particularly in the first year. A tridimensional conceptualization of academic engagement has been accepted (behavioral, emotional and cognitive dimensions). This paper tests the dimensionality, internal consistency reliability and invariance of the University Student Engagement Inventory (USEI) taking into consideration both gender and the scientific area of graduation. A sample of 908 Portuguese first-year university students was considered. Good evidence of reliability has been obtained with ordinal alpha and omega values. Confirmatory factor analysis substantiates the theoretical dimensionality proposed (second-order latent factor), internal consistency reliability evidence indicates good values and the results suggest measurement invariance across gender and the area of graduation. The present study enhances the role of the USEI regarding the lack of consensus on the dimensionality and constructs delimitation of academic engagement.Jorge Sinval received funding from the William James Center for Research, Portuguese Science Foundation (FCT UID/PSI/04810/2013). Leandro S. Almeida and Joana R. Casanova received funding from CIEd – Research Centre on Education, projects UID/CED/1661/2013 and UID/CED/1661/2016, Institute of Education, University of Minho, through national funds of FCT/MCTES-PT. Joana R. Casanova received funding from the Portuguese Science Foundation (FCT) as a Doctoral Grant, under grant agreement number SFRH/BD/117902/2016.info:eu-repo/semantics/publishedVersio

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome