Androgen-responsive non-coding small RNAs extend the potential of HCG stimulation to act as a bioassay of androgen sufficiency

Background: It is unclear whether a short-term change in circulating androgens is associated with changes in the transcriptome of the peripheral blood mononuclear cells (PBMC). Aims & Methods: To explore the effect of hCG-stimulation on the PBMC-transcriptome, 12 boys with a median age (range) of 0.7yrs (0.3, 11.2) who received intramuscular hCG 1500u on 3 consecutive days as part of their investigations underwent transcriptomic array analysis on RNA extracted from peripheral blood mononuclear cells before and after hCG stimulation. Results: Median pre and post hCG testosterone for the overall group was 0.7nmol/l (<0.5,6) and 7.9nmol/l (<0.5, 31.5), respectively. Of the 12 boys, 3 (25%) did not respond to hCG stimulation with a pre and post median serum testosterone of <0.5nmol/l and <0.5nmol/l, respectively. When corrected for gene expression changes in the non-responders to exclude hCG effects, all 9 of the hCG responders consistently demonstrated a 20% or greater increase in the expression of piR-37153 and piR-39248, non-coding PIWI-interacting RNAs (piRNAs). In addition, of the 9 responders, 8, 6 and 4 demonstrated a 30%, 40% and 50% rise, respectively in a total of 2 further piRNAs. In addition, 3 of the responders showed a 50% or greater rise in the expression of another small RNA, SNORD5. On comparing fold change in serum testosterone with fold change in the above transcripts, a positive correlation was detected for SNORD5 (p=0.01). Conclusions: The identification of a dynamic and androgen-responsive PBMC-transcriptome extends the potential value of the hCG test for assessment of androgen sufficiency

Investigating the Mediating Role of Market Orientation between Internal Marketing and the Development of Entrepreneurial Orientation within Private Sports Clubs

Purpose–This studyexamines the role of market orientation in the relationship between internal marketing and entrepreneurial orientation within private sports clubs. Design/methodology/approach–The research is a descriptive-correlational study based on private sports clubs employees within Iran (Sanandaj). A theoretical model was developed based on the literature and tested using SPSS and PLS-SEM software. Findings– The findings indicate a positive relationship between internal marketing and employees’ entrepreneurial orientation. Market orientation has also played a positive mediating role in the relationship between internal marketing and entrepreneurial orientation. Originality/value– The results suggest a higher level of market orientation in the organization can increase teamwork and, consequently, entrepreneurship development among employees. This is important in sports clubs as employees have a significant role in the success of the sports club. Club employees’ satisfaction, generated through internal marketing, provides is a prerequisite for customer satisfaction. This therefore creates an environment supportive of entrepreneurial orientation in the club

The use of combined physiological parameters in the early recognition of the deteriorating acute medical patient

Background: Early warning scores (EWS) are widely used to allow early recognition of the deteriorating patient. We aimed to test their ability to predict major deterioration in medical patients. Methods: Two cohorts were prospectively identified who were admitted to an acute medical admissions unit and to the respiratory unit but not admitted to the intensive care unit (ICU): medical-non ICU and respiratory-non ICU groups. Two further cohorts were retrospectively identified that required ICU admission from these units (medical-ICU and respiratory-ICU groups). Discriminant analysis and receiver operating characteristic curves were used to discriminate between groups, and time relationships were analysed. Results: Heart rate (HR), respiratory rate (RR) and oxygen saturation (SaO2) were significantly higher in the medical-ICU group than the medical-non ICU group and significantly higher in the respiratory-ICU group than in the respiratorynon ICU group. Discriminant functions incorporating HR, RR and SaO2 performed at least as well as existing EWS systems in predicting ICU admission. Conclusions: Commonly used physiological parameters and existing EWS systems are useful at identifying sick patients. The discriminant functions described here appear to have a role in this setting but require validation in future studies

Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation : a systematic review and economic evaluation

Background The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the UK and worldwide. Before the onset of T2DM, there are two conditions characterised by blood glucose levels that are above normal but below the threshold for diabetes. If screening for T2DM in introduced, many people with impaired glucose tolerance (IGT) will be found and it is necessary to consider how they should be treated. The number would depend on what screening test was used and what cut-offs were chosen. Objective To review the clinical effectiveness and cost-effectiveness of non-pharmacological interventions, including diet and physical activity, for the prevention of T2DM in people with intermediate hyperglycaemia. Data sources Electronic databases, MEDLINE (1996–2011), EMBASE (1980–2011) and all sections of The Cochrane Library, were searched for systematic reviews, randomised controlled trials (RCTs) and other relevant literature on the effectiveness of diet and/or physical activity in preventing, or delaying, progression to T2DM.The databases were also searched for studies on the cost-effectiveness of interventions. Review methods The review of clinical effectiveness was based mainly on RCTs, which were critically appraised. Subjects were people with intermediate hyperglycaemia, mainly with IGT. Interventions could be diet alone, physical activity alone, or the combination. For cost-effectiveness analysis, we updated the Sheffield economic model of T2DM. Modelling based on RCTs may not reflect what happens in routine care so we created a ‘real-life’ modelling scenario wherein people would try lifestyle change but switch to metformin after 1 year if they failed. Results Nine RCTs compared lifestyle interventions (predominantly dietary and physical activity advice, with regular reinforcement and frequent follow-up) with standard care. The primary outcome was progression to diabetes. In most trials, progression was reduced, by over half in some trials. The best effects were seen in participants who adhered best to the lifestyle changes; a scenario of a trial of lifestyle change but a switch to metformin after 1 year in those who did not adhere sufficiently appeared to be the most cost-effective option. Limitations Participants in the RCTs were volunteers and their results may have been better than in general populations. Even among the volunteers, many did not adhere. Some studies were not long enough to show whether the interventions reduced cardiovascular mortality as well as diabetes. The main problem is that we know what people should do to reduce progression, but not how to persuade most to do it. Conclusion In people with IGT, dietary change to ensure weight loss, coupled with physical activity, is clinically effective and cost-effective in reducing progression to diabetes

Research gaps and future needs for allergen prediction in food safety

The allergenicity and protein risk assessments in food safety are facing new challenges. Demands for healthier and more sustainable food systems have led to significant advances in biotechnology, the development of more complex foods, and the search for alternative protein sources. All this has increased the pressure on the safety assessment prediction approaches anchored into requirements defined in the late 90's. In 2022, the EFSA's Panel on Genetically Modified Organisms published a scientific opinion focusing on the developments needed for allergenicity and protein safety assessments of new products derived from biotechnology. Here, we further elaborate on the main elements described in this scientific opinion and prioritize those development needs requiring critical attention. The starting point of any new recommendation would require a focus on clinical relevance and the development of a fit-for-purpose database targeted for specific risk assessment goals. Furthermore, it is imperative to review and clarify the main purpose of the allergenicity risk assessment. An internationally agreed consensus on the overall purpose of allergenicity risk assessment will accelerate the development of fit-for-purpose methodologies, where the role of exposure should be better clarified. Considering the experience gained over the last 25 years and recent scientific developments in the fields of biotechnology, allergy, and risk assessment, it is time to revise and improve the allergenicity safety assessment to ensure the reliability of allergenicity assessments for food of the future

The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

Mothers and their children�s health (MATCH): a study protocol for a population�based longitudinal cohort

Background: The quality of prenatal care is critical for the prevention of adverse pregnancy outcomes. However, according to the World Health Organization (WHO), only 64 of women worldwide have access to over four sessions of prenatal care throughout their pregnancy. Thus, studies that address factors affecting maternal and child health status before and after pregnancy are of immense importance. The primary aim of the mothers and their children�s health (MATCH) cohort study is to evaluate the effect of nutrition, sleep quality, and lifestyle on maternal and neonatal outcomes. Methods: A prospective cohort of > 2500 pregnant women in the first trimester (before 12 weeks� gestation) will be recruited at Arash Women�s Hospital in Tehran, Iran between February 2020 and August 2021. All eligible pregnant women will be followed from their first trimester of pregnancy until delivery at four time points and assessed through a series of in-person visits with interviewer-administered questionnaires and telephone interviews. Detailed data will be collected on maternal demographics, lifestyle, medical history, reproductive history, obstetric history, dietary intake, sleep pattern, blood specimens, and anthropometric measurements, alongside paternal demographics, lifestyle, and family history. The outcomes will include antenatal, peripartum, and postnatal maternal complications and infant growth and neurodevelopment. Discussion: The results of the MATCH cohort study will support the development of contextual interventions that can enhance antenatal, peripartum, and postnatal status, neonatal outcomes, and longevity mother and child. © 2021, The Author(s)