Cardiomyopathy in Offspring of Pregestational Diabetic Mouse Pregnancy

Purpose. To investigate cardiomyopathy in offspring in a mouse model of pregestational type 1 diabetic pregnancy. Methods. Pregestational diabetes was induced with STZ administration in female C57BL6/J mice that were subsequently mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day 18.5 and 6-week adolescent and 12-week adult stages. The size and number of cardiomyocyte nuclei and also the extent of collagen deposition within the hearts of diabetic and control offspring were assessed following cardiac tissue staining with either haematoxylin and eosin or Picrosirius red and subsequently quantified using automated digital image analysis. Results. Offspring from diabetic mice at embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei present compared to controls. These nuclei were also significantly smaller than controls. Collagen deposition was shown to be significantly increased in the hearts of diabetic offspring at the same age. No significant differences were found between the groups at 6 and 12 weeks. Conclusions. Our results from offspring of type 1 diabetic mice show increased myocardial collagen deposition in late gestation and have increased myocardial nuclear counts (hyperplasia) as opposed to increased myocardial nuclear size (hypertrophy) in late gestation. These changes normalize postpartum after removal from the maternal intrauterine environment

How do people with eating disorders experience the stigma associated with their condition? A mixed-methods systematic review

Background: Public opinion research shows that eating disorders (EDs) are a major target of stigmatisation. To understand the implications of this stigma, research investigating how stigma is experienced by individuals with EDs is critical. Aims: This paper aims to collate, evaluate and synthesise the extant empirical research illuminating how people with EDs experience the stigma associated with their condition. Method: A systematic mixed-methods literature search was performed. Articles that met a specified set of inclusion criteria underwent a quality assessment and thematic synthesis. Results: 29 articles were included in the review. Studies were mostly qualitative and of reasonable methodological quality. The literature was characterised by five research themes, illuminating (i) the nature and prevalence of stigma experienced, (ii) stigma in families, (iii) stigma in healthcare contexts, (iv) self-stigmatisation and illness concealment, and (v) stigma resistance. Conclusions: The reviewed research showed that people with EDs have extensive experience of stigma in diverse settings. They report that stigma has negative implications for their psychological wellbeing and likelihood of help-seeking. However, research also shows that people with EDs actively seek to resist and challenge stigma. The review identifies the outstanding gaps and weaknesses in this literature

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The Impact of Childhood Obesity on Inflammation, Innate Immune Cell Frequency, and Metabolic MicroRNA Expression

Background: Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined. Aims and Methods: The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression. Profiling was performed on peripheral blood from 29 obese and 20 nonobese children using real-time PCR, ELISA, and flow cytometry. Results: Fasting glucose was similar in both groups, but there was a higher degree of insulin resistance in obese subjects (homeostasis model of assessment for insulin resistance, 4.8 vs 0.84; P .001). Soluble CD163, a marker of macrophage polarization to a proinflammatory profile, was elevated in the obese compared to nonobese children (135 vs 105 ng/mL; P .03). Invariant natural killer T cells were reduced in the obese children (CD3 T cells, 0.31 vs 0.53%; P .001). Cytokine profiling revealed significantly elevated TNF- (6.7 vs 5.1 pg/mL; P .01) and leptin (1186 vs 432 pg/mL; P .001) and reduced adiponectin (884 vs 1321 pg/mL; P .001) in obese compared to nonobese children. Stimulation of peripheral blood mononuclear cells from obese children resulted in higher levels of IL-1 (2100 vs 1500 pg/mL; P .018). There was a 4-fold increase in expression of microRNA33a (P .001) and a 3-fold increase in microRNA33b (P .017) in obese children. Conclusion: Childhood obesity is associated with changes in immune cell frequency, inflammatory environment, and regulation of metabolic gene expression. These changes have been causally linked to the onset of metabolic disease in adulthood and suggest the future trajectory of obese children to the development of type 2 diabetes mellitus and premature cardiovascular diseas

Conceptual functional-by-design optimisation of the antioxidant capacity of trans-resveratrol, quercetin, and chlorogenic acid: application in a functional tea

Designing functional foods as delivery systems may become a tailored strategy to decrease the risk of non-communicable diseases. Therefore, this work aims to optimise a combination of t-resveratrol (RES), chlorogenic acid (CHA), and quercetin (QUE) based on antioxidant assays and develop a functional tea formulation enriched with the optimal polyphenol combination (OPM). Experimental results showed that the antioxidant capacity of these compounds is assay- and compound-dependent. A mixture containing 73% RES and 27% QUE maximised the hydroxyl radical scavenging activity and FRAP. OPM upregulated the gene expressions of heme oxygenase-1, superoxide dismutase, and catalase and decreased the reactive oxygen species generation in L929 fibroblasts. Adding OPM (100 mg/L) to a chamomile tea increased FRAP:39%, DPPH:59%; total phenolic content: 57%, iron reducing capacity: 41%, human plasma protection against oxidation: 67%. However, pasteurisation (63 ◦C/30 min) decreased only the DPPH. Combining technology, engineering, and cell biology was effective for functional tea design.</p