An investigation of the effects of procalcitonin testing on antimicrobial prescribing in respiratory tract infections in an Irish university hospital setting: a feasibility study

Background: Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable. Methods: We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs. Results: A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P"0.012) and decreased length of hospital stay (median 7 versus 8 days, P"0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy. Conclusions: PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings

Variable Glycemic Responses to Intact and Hydrolyzed Milk Proteins in Overweight and Obese Adults Reveal the Need for Precision Nutrition

peer-reviewedBackground Dietary modifications can contribute to improved pancreatic β cell function and enhance glycemic control. Objectives The objectives of this study were as follows: 1) to investigate the potential of milk protein hydrolysates to modulate postprandial glucose response; 2) to assess individual responses; and 3) to explore the inter- and intraindividual reproducibility of the response. Methods A 14-d randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B) consumed in random order with a 2-d washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 men, 9 women) aged 50 ± 8 y with a body mass index (in kg/m2) of 30.2 ± 3.1 were recruited. Primary outcome was glucose levels assessed at 15-min intervals with the use of glucose monitors. Results Repeated-measures ANOVA revealed that for breakfast there was a significant difference across the 3 treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to casein hydrolysate B in comparison with intact caseinate (P = 0.039). However, despite this significant difference, further examination revealed that only 3 out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients were obtained for glucose response to study meals (intraclass correlation coefficient: 0.892 for breakfast with intact caseinate). The interindividual CVs were higher than the intraindividual CVs. Mean inter- and intraindividual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response; however, at an individual level only 3 participants were classified as responders, highlighting the need for precision nutrition. Exploration of high interindividual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach. This clinical trial was registered as ISRCTN61079365 (https://www.isrctn.com/).Food for Health Irelan

Variable glycemic responses to intact and hydrolysed milk proteins in overweight and obese adults reveal the need for precision nutrition

Background: Dietary modifications can contribute to improved pancreatic beta cell function and enhance glycemic control. Objective: The objectives of this study were to 1) investigate the potential of milk protein hydrolysates to modulate postprandial glucose response, 2) assess individual responses, 3) explore the inter and intra-individual reproducibility of the response. Methods: A 14-day randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B (CH-A and CH-B) consumed in random order with a 2-day washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 male/ 9 female) aged 50 ± 8 y with a body mass index of 30.2 ± 3.1 kg/m2 were recruited. Primary outcome was glucose levels assessed at 15 min intervals using glucose monitors. Results: Repeated measures-ANOVA revealed that for breakfast there was a significant difference across the three treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to CH-B in comparison to intact caseinate (P = 0.039). However, despite this significant difference further examination revealed that only three out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients (ICCs) were obtained for glucose response to study meals (ICC: 0.892 for breakfast with intact caseinate). The inter-individual coefficient of variations (CVs) were higher than intra-individual CVs. Mean inter- and intra-individual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion: Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response, however at an individual level only three participants were classified as responders, highlighting the need for precision nutrition. Exploration of high inter-individual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach.Enterprise IrelandFood for Health Irelan

Variable glycemic responses to intact and hydrolysed milk proteins in overweight and obese adults reveal the need for precision nutrition

Background: Dietary modifications can contribute to improved pancreatic beta cell function and enhance glycemic control. Objective: The objectives of this study were to 1) investigate the potential of milk protein hydrolysates to modulate postprandial glucose response, 2) assess individual responses, 3) explore the inter and intra-individual reproducibility of the response. Methods: A 14-day randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B (CH-A and CH-B) consumed in random order with a 2-day washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 male/ 9 female) aged 50 ± 8 y with a body mass index of 30.2 ± 3.1 kg/m2 were recruited. Primary outcome was glucose levels assessed at 15 min intervals using glucose monitors. Results: Repeated measures-ANOVA revealed that for breakfast there was a significant difference across the three treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to CH-B in comparison to intact caseinate (P = 0.039). However, despite this significant difference further examination revealed that only three out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients (ICCs) were obtained for glucose response to study meals (ICC: 0.892 for breakfast with intact caseinate). The inter-individual coefficient of variations (CVs) were higher than intra-individual CVs. Mean inter- and intra-individual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion: Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response, however at an individual level only three participants were classified as responders, highlighting the need for precision nutrition. Exploration of high inter-individual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach.Enterprise IrelandFood for Health Irelan

Factors related to beta-cell function

Aim: The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Methods: Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. Results: Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. Conclusions: Waist-to-hip ratio and RA index were identified as significant modulators of beta-cell function. The ability of the RA index to modulate insulin secretion was confirmed in mechanistic studies. Future work should identify strategies to alter the RA index.Department of Agriculture, Food and the MarineEnterprise IrelandEuropean Research CouncilScience Foundation Irelan

Assessing Hydrolyzed Gluten Content in Dietary Enzyme Supplements Following Fermentation

Partially digested gluten fragments from grains including wheat, rye, spelt and barley are responsible for triggering an inflammatory response in the intestinal tract of Celiac Disease (CD) and Non-Celiac Gluten Sensitive (NCGS) individuals. Fermentation is an effective method to metabolize gluten, with enzymes from bacterial or fungal species being released to help in this process. However, the levels of gluten in commercially available enzymes, including those involved in gluten fermentation, are unknown. In this study we investigated gluten levels in commercially available dietary enzymes combined with assessing their effect on inflammatory response in human cell culture assays. Using antibodies that recognize different gluten epitopes (G12, R5, 2D4, MloBS and Skerritt), we employed ELISA and immunoblotting methodologies to determine gluten content in crude gluten, crude gliadin, pepsin-trypsin digested gluten and a selection of commercially available enzymes. We further investigated the effect of these compounds on inflammatory response in immortalized immune and intestinal human cell lines, as well as in peripheral blood mononuclear cells (PBMCs) from coeliac individuals. All tested supplemental enzyme products reported a gluten concentration that was equivalent to or below 20 parts per million (ppm) as compared with an intact wheat reference standard and a pepsin-trypsin digested standard. Similarly, the inflammatory response to IL-8 and TNF-α inflammatory cytokines in mammalian cell lines and PBMCs from coeliac individuals to the commercial enzymes was not significantly different to 20 ppm of crude gluten, crude gliadin or pepsin-trypsin digested gluten. This combined approach provides insight into the extent of gluten breakdown in the fermentation process and the safety of these products to gluten-sensitive individuals

Sexual dimorphism, age, and fat mass are key phenotypic drivers of proteomic signatures

Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.Department of Agriculture, Food and the MarineEuropean CommissionFood for Health Irelan

A proteomic signature that reflects pancreatic beta-cell function.

AIM:Proteomics has the potential to enhance early identification of beta-cell dysfunction, in conjunction with monitoring the various stages of type 2 diabetes onset. The most routine method of assessing pancreatic beta-cell function is an oral glucose tolerance test, however this method is time consuming and carries a participant burden. The objectives of this research were to identify protein signatures and pathways related to pancreatic beta-cell function in fasting blood samples. METHODS:Beta-cell function measures were calculated for MECHE study participants who completed an oral glucose tolerance test and had proteomic data (n = 100). Information on 1,129 protein levels was obtained using the SOMAscan assay. Receiver operating characteristic curves were used to assess discriminatory ability of proteins of interest. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Replication of findings were achieved in a second human cohort where possible. RESULTS:Twenty-two proteins measured by aptamer technology were significantly associated with beta-cell function/HOMA-IR while 17 proteins were significantly associated with the disposition index (p ≤ 0.01). Receiver operator characteristic curves determined the protein panels to have excellent discrimination between low and high beta-cell function. Linear regression analysis determined that beta-endorphin and IL-17F have strong associations with beta-cell function/HOMA-IR, β = 0.039 (p = 0.005) and β = -0.027 (p = 0.013) respectively. Calcineurin and CRTAM were strongly associated with the disposition index (β = 0.005 and β = 0.005 respectively, p = 0.012). In vitro experiments confirmed that IL-17F modulated insulin secretion in the BRIN-BD11 cell line, with the lower concentration of 10 ng/mL significantly increasing glucose stimulated insulin secretion (p = 0.043). CONCLUSIONS:Early detection of compromised beta-cell function could allow for implementation of nutritional and lifestyle interventions before progression to type 2 diabetes

A systematic review of the psychobiological burden of informal caregiving for patients with dementia: Focus on cognitive and biological markers of chronic stress

As the physiological impact of chronic stress is difficult to study in humans, naturalistic stressors are invaluable sources of information in this area. This review systematically evaluates the research literature examining biomarkers of chronic stress, including neurocognition, in informal dementia caregivers. We identified 151 papers for inclusion in the final review, including papers examining differences between caregivers and controls as well as interventions aimed at counteracting the biological burden of chronic caregiving stress. Results indicate that cortisol was increased in caregivers in a majority of studies examining this biomarker. There was mixed evidence for differences in epinephrine, norepinephrine and other cardiovascular markers. There was a high level of heterogeneity in immune system measures. Caregivers performed more poorly on attention and executive functioning tests. There was mixed evidence for memory performance. Interventions to reduce stress improved cognition but had mixed effects on cortisol. Risk of bias was generally low to moderate. Given the rising need for family caregivers worldwide, the implications of these findings can no longer be neglected

Beta-cell function, resistin and adiponectin according to BMI categories.

<p>Beta-cell function, resistin and adiponectin according to BMI categories.</p