Season and vitamin D status are independently associated with glucose homeostasis in pregnancy

Background: Vitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism.Methods: This is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks' gestation) and late pregnancy (28 weeks' gestation). Season of first antenatal visit was categorised as extended winter (November–April) or extended summer (May–October). Multiple linear regression models, adjusted for confounders, were used for analysis.Results: Those who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P < 0.001). Compared to those who attended their first antenatal visit during extended summer, extended winter was associated with increased HOMA-IR in early-pregnancy (46.7%) and late pregnancy (53.7%), independent of 25OHD <30 nmol/L and confounders. Early pregnancy 25OHD <30 nmol/L and extended winter were independently associated with significantly higher fasting glucose in late pregnancy (B = 0.15 and 0.13, respectively).Conclusions: Women who attended their first antenatal visit during the months of extended winter were more likely to have raised insulin resistance in early pregnancy, which had a lasting association to 28 weeks, and was independent of 25OHD. Our novel findings imply that seasonal variation in insulin resistance may not be fully explained by differences in vitamin D status. This could reflect circannual rhythm or seasonal lifestyle behaviours, and requires further exploration.Trial registration: ISRCTN registry, ISRCTN54392969, date of registration: 22/04/2009, retrospectively registered

Stable isotope profile (C, N, O, S) of Irish raw milk: Baseline data for authentication

Grass-based milk production is a major contributor to Irish agricultural output. The study characterized the Irish milk pool using stable isotope ratio analysis of carbon, nitrogen, oxygen and sulphur. Authentic raw milk samples were collected from 50 farms on five occasions over 13 months. Mean values of −27.11, 6.79, −3.27 and 6.16‰ were obtained for δ13C, δ15N, δ18O and δ34S, respectively. δ13C values reflected a high level of grass input and values increased with increasing cereal concentrate feed input (P < 0.001). δ18O values were most negative in spring. There was a significant interaction between feed and season for δ13C and δ15N values (P < 0.05), with the impact of concentrate feeding most evident in spring. δ34S values were lowest at the highest level of concentrate input (P < 0.05). The isotopic values reported here describe the Irish milk pool and may offer the potential to discriminate Irish milk and dairy products from similar commodities from other countries

Expert by Experience involvement in Mental Health Nursing Education: The co-production of standards between Experts by Experience and Academics in Mental Health Nursing

Introduction: Involving people with lived experience of mental distress in mental health nursing education has gained considerable traction yet broader implementation remains ad-hoc and tokenistic. Effective involvement requires curricula be informed by lived experience of service use. Aim: To develop standards to underpin expert by experience involvement in mental health nursing education based on lived experience of service use. Methods: Phase one used qualitative descriptive methods, involving focus groups with service users (n=50) from six countries to explore perceptions of service user involvement in mental health nursing education. Phase two utilised these findings through consensus building to co-produce standards to support Experts by Experience involvement in mental health nursing education. Results: Three themes emerged in Phase one: enablers and barriers, practical and informational support, and emotional and appraisal support. These themes underpinned development of the standards, which reflect nine processes: induction and orientation, external supervision, supportive teamwork, preparation for teaching and assessing, 'intervision', mutual mentorship, pre and post debriefing, role clarity and equitable payment. Conclusions: These standards form the framework entitled; Standards for Co-production of Education (Mental Health Nursing) (SCo-PE [MHN]). Implications for Practice The standards aim to support implementation of Expert by Experience roles in mental health nursing education

A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI

A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting

Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer

Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function

Tumour Conditioned Media inhibits dendritic cell maturation, augments IL-10 while inhibiting IL-12p70 secretion induced by LPS.

<p>iDC (n = 6) were treated with TCM of 21 colorectal cancer patients for 4 hours before adding LPS; the cells were cultured for a further 18 hours. Levels of IL-10 and IL-12p70 secretion by the DCs were measured by ELISA. Statistical differences were determined by ANOVA. (A) Expression of the following maturation markers: CD80, CD54, CD86, HLA-DR, and CD83 were assessed by flow cytometry. One representative experiment of six is shown (B). The Fold Change in M.F.I. of each marker was calculated relative to unstimulated iDCs for cells treated with LPS or TCM+LPS. Statistical significance was calculated using the Wilcoxon signed rank test. (C). * <i>p<</i>0.05, ** <i>p</i><0.01, and *** <i>p</i><0.001.</p

Levels of CCL2, CXCL1, and CXCL5 in TCM correlate with CD83 expression and IL-12p70 secretion.

<p>Concentrations of CCL2, CXCL1, CXCL5 and VEGF in tumour conditioned media of 21 colorectal cancer patients were measured by ELISA. The concentrations of CCL2, CXCL1 and CXCL5 correlated with expression of CD83 on DCs treated with TCM (A). CCL2, CXCL1 and CXCL5 inversely correlated with secretion of IL-12p70 from dendritic cells treated with the TCM (B). The Spearman rank correlation test was used.</p

The combination of CXCL1 and VEGF inhibits LPS induced IL-12p70 secretion by DCs.

<p>iDCs (n = 5) were treated with a combination of recombinant CXCL1 (100ng/mL) and VEGF (20 ng/mL), 4 hours prior to the addition of LPS (1 µg/mL). The cells were then cultured for a further 18 hours and the levels of CD80, CD54, CD86, HLA-DR and CD83 were assessed by flow cytometry. Results are shown as fold-change in M.F.I. relative to untreated iDCs. Statistical significance was determined by Wilcoxon signed rank test (A). Supernatants were removed from the cells treated as described above and the concentration of IL-10 and IL-12p70 was determined by ELISA. Statistical significance was calculated by Mann-Whitney U test (B). * p<0.05, ** p<0.01.</p