Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes. METHODS: We used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records. RESULTS: Median age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3-G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at -1.3 ml min-1 [1.73 m]-2 year-1 (interquartile range [IQR]: -2.2, -0.4). However, 14% experienced a more significant loss of at least 3 ml min-1 [1.73 m]-2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10-5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10-16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction. CONCLUSIONS: These data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR). METHODS: From the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min-1 [1.73 m]-2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others' prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min-1 [1.73] m-2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data. RESULTS: Seven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min-1 [1.73 m]-2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10-3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min-1 [1.73 m]-2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min-1 [1.73 m]-2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR. CONCLUSIONS/INTERPRETATION: A parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Psychological effects of outdoor activity in type 2 diabetes: a review.

Previous research has shown individuals living with type 2 diabetes are more likely to experience depression, anxiety and reduced quality of life (QoL) in comparison to those without the disease. Physical activity has been highlighted as an important factor in improving physiological and psychological parameters in this population. Previous systematic reviews have found mixed results regarding the effects of exercise on psychological problems. Green exercise is an emerging research area with mounting evidence demonstrating positive effects on mental health. Objectives of the current review investigated whether conducting physical activity in outdoor environments had any effect on psychological problems in individuals with type 2 diabetes. Methods such as PubMed, Medline, PsycINFO, Scopus, Cochrane library, CINAHL, SPORTDiscus and Google Scholar databases were searched. The databases were searched for articles which used an outdoor exercise intervention and investigated psychological problems in individuals with type 2 diabetes. Results from the 1467 retrieved articles, 4 studies were included in the systematic review, consisting of 231 participants. All four studies investigated QoL, one study looked at depression and one investigated general wellbeing. Mixed results were found regarding QoL, no significant effect was found for depression. However, general wellbeing was improved. Due to the limited number of studies eligible for inclusion and the heterogeneity of outcome measures, it was difficult to draw firm conclusions. This systematic review acts as a starting point for future investigations into the use of green exercise in improving the mental health of individuals living with type 2 diabetes. Registration: PROSPERO: CRD42018088212.

Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes.

BACKGROUND: The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes. METHODS: C-peptide was measured in an untimed serum sample in the SDRNT1BIO cohort of 6076 Scottish people with clinically diagnosed type 1 diabetes or latent autoimmune diabetes of adulthood. Risk scores at loci previously associated with type 1 and type 2 diabetes were calculated from publicly available summary statistics. RESULTS: Prevalence of detectable C-peptide varied from 19% in those with onset before age 15 and duration greater than 15 years to 92% in those with onset after age 35 and duration less than 5 years. Twenty-nine percent of variance in C-peptide levels was accounted for by associations with male gender, late age at onset and short duration. The SNP heritability of residual C-peptide secretion adjusted for gender, age at onset and duration was estimated as 26%. Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions. A risk score for type 1 diabetes based on the HLA DR3 and DQ8-DR4 serotypes was strongly associated with early age at onset and inversely associated with C-peptide persistence. For C-peptide but not age at onset, there were strong associations with risk scores for type 1 and type 2 diabetes that were based on SNPs in the HLA region but not accounted for by HLA serotype. CONCLUSIONS: Persistence of C-peptide secretion varies widely in people clinically diagnosed as type 1 diabetes. C-peptide persistence is influenced by variants in the HLA region that are different from those determining risk of early-onset type 1 diabetes. Known risk loci for diabetes account for only a small proportion of the genetic effects on C-peptide persistence.

Assessing prevalence of urinary incontinence in Scottish fitness instructors and experience of teaching pelvic floor muscle exercises: an online survey.

BACKGROUND: The aim of this study was to assess the prevalence of urinary incontinence in fitness instructors, experience of teaching pelvic floor muscle exercises (PFME), and attitudes to incorporating such exercises into classes. METHOD: An online survey was undertaken of fitness instructors working in Scotland based on the Urinary Incontinence Short Form (ICIQ-UI). RESULTS: The survey was at least partially completed by 106, of whom 73.6% (53/72) were female and 52.8% (38/72) were in the 35-54 years age group. Prevalence of UI was 28.2% (24/85), and severity based on ICIQ-UI scores was 'slight' 65.2% (15/23), or 'moderate' in 26.1% (6/23). Leakage of urine was associated with physical activity in 36% (9/25), of whom 31.8% (7/22) had not taken actions to reduce the impact, and 86.4% (19/22) had not sought professional advice or treatment. There was widespread willingness to incorporate PFME into classes if given appropriate training 86.1% (62/72), and 67.1% (49/73) would be happy to recommend a PFME app. CONCLUSION: A significant proportion of fitness instructors are in need of PFME and those who perform PFME do so at a level below that which is recommended. However, many have had some training on PFME or are willing to provide this.

Evaluation of Technology-Enhanced Learning Programs for Health Care Professionals: Systematic Review.

BACKGROUND: Technology-enhanced learning (TEL) programs are increasingly seen as the way in which education for health care professionals can be transformed, giving access to effective ongoing learning and training even where time or geographical barriers exist. Given the increasing emphasis on this mode of educational support for health care practitioners, it is vital that we can effectively evaluate and measure impact to ensure that TEL programs are effective and fit for purpose. This paper examines the current evidence base for the first time, in relation to the evaluation of TEL programs for health care professionals. OBJECTIVE: We conducted a systematic review of the current literature relating to the evaluation of TEL programs for health care professionals and critically appraised the quality of the studies. METHODS: This review employed specific search criteria to identify research studies that included evaluation of TEL for health care professionals. The databases searched included Medline Ovid, Cumulative Index of Nursing and Allied Health Literature Plus Advanced, Applied Social Sciences Index and Abstracts, ZETOC, Institute of Electrical and Electronics Engineers Explore Digital Library, Allied and Complementary Medicine, and Education Resources Information Center between January 2006 and January 2017. An additional hand search for relevant articles from reference lists was undertaken. Each of the studies identified was critically appraised for quality using the Crowe Critical Appraisal Tool. This approach produced a percentage total score for each study across specified categories. A proportion of the studies were independently assessed by an additional two reviewers. RESULTS: The review identified 21 studies that met the inclusion criteria. The studies included scored totals across eight categories within a range of 37%-95% and an average score of 68%. Studies that measured TEL using learner satisfaction surveys, or combined pretest and posttest knowledge score testing with learner satisfaction surveys, were found to be the most common types of TEL evaluations evident in the literature. The studies reviewed had low scores across reporting on ethical matters, design, and data collection categories. CONCLUSIONS: There continues to be a need to develop effective and standard TEL evaluation tools, and good quality studies that describe effective evaluation of TEL education for health care professionals. Studies often fail to provide sufficient detail to support transferability or direct future TEL health care education programs.

Service user preferences for diabetes education in remote and rural areas of the Highlands and Islands of Scotland.

INTRODUCTION: Diabetes prevalence in Scotland is 5.3%, with type 2 diabetes accounting for 86.7% of all cases in the National Health Service Highlands health board area and 85.7% in the Western Isles. Structured education is a key component in the management of this chronic disease. However, current group session models are less feasible in lower-population non-urban environments due to distance, participant numbers and access to appropriately trained healthcare professionals. Group sessions may also be a less attractive option in small communities, where people tend to have close day-to-day personal contact. This study assesses the access and delivery preferences of remote and rural service users in the Highlands and Western Isles to structured diabetes education programs. METHODS: The study used a mixed methods approach of focus groups and questionnaires with people with type 2 diabetes in the Highlands and Islands of Scotland. Both modes of participation were designed to explore perception of diabetes knowledge, diabetes education and use of technology. RESULTS: One-to-one delivery was the delivery method of choice; however, there was a preference for a digital approach over group education sessions. Service users expressed a strong desire to be able to learn at their own pace, when and where they wanted to, and with no requirement to travel. To address these requirements an online resource, providing access to both learning sessions and trusted sources of information, was the preferred mode of delivery. CONCLUSIONS: People with type 2 diabetes living in remote and rural areas of the Scottish Highlands and Islands who already use the internet are receptive to the use of digital technology for delivery of diabetes education and are interested in learning more about management of their condition through this medium. They believe that a technology approach will provide them with more control over the pace of learning, and where and when this learning can take place.

Endothelial cell oxidative stress in diabetes: a key driver of cardiovascular complications?

Atherothrombotic disease is a well-recognized complication of diabetes and is a major contributor to the high morbidity and mortality associated with diabetes. Although there is substantial evidence linking diabetes with cardiovascular disease, the specific effect of hyper- (or hypo-) glycaemia is less well understood. The present review focuses on the impact that glycaemic dysregulation has on respiratory function and ROS (reactive oxygen species) generation in the endothelial cells that are critical in preventing several key steps in the atherothrombotic process. Endothelial cells are particularly susceptible to ROS-mediated dysfunction not only because of reduced cell viability and increased senescence, but also because one of the major endothelium-derived factors that help to protect against atherosclerosis, nitric oxide, is rapidly deactivated by superoxide radicals.

Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status.

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.

Use of Continuous Glucose Monitoring in Non-ICU Hospital Settings for People With Diabetes: A Scoping Review of Emerging Benefits and Issues.

BACKGROUND: Evidence indicates that poor glycemic control is associated with increased morbidity and length of stay in hospital. There are a wide range of guidelines published, which seek to ensure safe and effective inpatient glycemic control in the hospital setting. However, the implementation of these protocols is limited in practice. In particular, the feasibility of "flash" and continuous glucose monitoring (CGM) remains untested on general wards. METHOD: Scoping Review. RESULTS: If used in the general ward hospital settings, CGM and flash glucose monitoring (FGM) systems could lead to improved glycemic control, decreased length of stay, and reduced risk of severe hypoglycemia or hyperglycemia. Potential problems include lack of experience with this technology and costs of sensors. Rapid analysis of glucose measurements can facilitate clinical decision making and therapy adjustment in the hospital setting. In addition, people with diabetes may be empowered to better self-manage their condition in hospital as they have direct access to their glucose data. CONCLUSIONS: More studies are required in which the feasibility, benefits and limitations of FGM and CGM in non-intensive care unit hospital settings are elucidated. We need evidence on which types of hospital wards might benefit from the introduction of this technology and the contexts in which they are less useful. We also need to identify the types of people who are most likely to find FGM and CGM useful for self-management and for which populations they have the most benefit in terms of clinical outcomes and length of stay.

Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes.

BACKGROUND: Platelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH). Clinical delivery of N-acetylcysteine (NAC), a biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NAC in vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes. METHODS: Blood samples (n = 13) were incubated (2 h, 37°C) with NAC (10-100 micromolar) in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry) was assessed, together with platelet GSH concentration (reduced and oxidized), antioxidant status, reactive oxygen species (ROS) generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO). RESULTS: At therapeutically relevant concentrations (10-100 micromolar), NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregation in vitro. Plasma NOx was enhanced by 30 micromolar NAC. CONCLUSIONS: Our results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.

Progression to unscheduled hospital admissions in people with diabetes: a qualitative interview study.

BACKGROUND: People with diabetes often have difficulty maintaining optimal blood glucose levels, risking progressive complications that can lead to unscheduled care. Unscheduled care can include attending emergency departments, ambulance callouts, out-of-hours care, and non-elective hospital admissions. A large proportion of non-elective hospital admissions involve people with diabetes, with significant health and economic burden. AIM: To identify precipitating factors influencing diabetes-related unscheduled hospital admissions, exploring potential preventive strategies to reduce admissions. DESIGN & SETTING: Thirty-six people with type 1 (n = 11) or type 2 (n = 25) diabetes were interviewed. They were admitted to hospital for unscheduled diabetes-related care across three hospitals in Scotland, Northern Ireland, and the Republic of Ireland. Participants were admitted for peripheral limb complications (n = 17), hypoglycaemia (n = 5), hyperglycaemia (n = 6), or for comorbidities presenting with erratic blood glucose levels (n = 8). METHOD: Factors precipitating admissions were examined using framework analysis. RESULTS: Three aspects of care influenced unscheduled admissions: perceived inadequate knowledge of diabetes complications; restricted provision of care; and complexities in engagement with self-care and help-seeking. Limited specialist professional knowledge of diabetes by staff in primary and community care, alongside inadequate patient self-management knowledge, led to inappropriate treatment and significant delays. This was compounded by restricted provision of care, characterised by poor access to services - in time and proximity - and poor continuity of care. Complexities in patient engagement, help-seeking, and illness beliefs further complicated the progression to unscheduled admissions. CONCLUSION: Dedicated investment in primary care is needed to enhance provision of and access to services. There should be increased promotion and earlier diabetes specialist team involvement, alongside training and use of technology and telemedicine, to enhance existing care.

Technology-enabled remote management of diabetes foot disease and potential for reduction in associated health costs: a pilot study.

Diabetes-related foot disease, particularly when associated with amputation, affects quality of life and has a significant impact on health care costs. A pilot study using enhanced technology to facilitate remote access and video conferencing from rural locations to the diabetes MDT through a new service pathway confirmed high levels of patient satisfaction with 89% of foot ulcers improved or stable and only two minor amputations. A health economic analysis suggested potential for significant cost savings if this was scaled up regionally. Further evaluation of an integrated pathway, impact on lower limb amputation rates and full health economic assessment is recommended.

Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications.

OBJECTIVE: To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.

2-arachidonyl glycerol activates platelets via conversion to arachidonic acid and not by direct activation of cannabinoid receptors.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: There are conflicting views in the literature as to whether cannabinoids have an impact on platelet activity and to what extent cannabinoid receptors are involved. This is an important issue to resolve because platelet effects of putative therapeutic cannabinoid inhibitors and stimulators will have an impact on their potential benefits and safety. WHAT THIS PAPER ADDS: The data presented in this manuscript clearly show that the endocannabinoid 2-arrachidonyl glycerol can activate platelet activity, but that the effects are mediated through an aspirin-sensitive pathway that is not affected by cannabinoid receptor antagonists or FAAH inhibition, but is abolished by MAGL inhibition. The findings question the role of cannabinoid receptors in platelet function and suggest that platelet function is unlikely to be directly affected by cannabinoid receptor antagonists, at least in the acute phase. AIMS: Cannabinoid receptor-1 (CB(1)) antagonists suppress appetite and induce weight loss. Direct antagonism of CB(1) receptors on platelets might be an additional benefit for CB(1) antagonists, but the role of CB(1) receptors in platelets is controversial. We tested the hypothesis that the endocannabinoid, 2-arachidonyl glycerol (2-AG), induces platelet aggregation by a COX-mediated mechanism rather than through CB(1) receptor activation, in blood obtained from healthy volunteers and patients with coronary artery disease receiving low dose aspirin. METHODS: Aggregatory responses to the cannabinoids 2-AG and Delta(9)-THC were examined in blood sampled from healthy volunteers (n= 8) and patients (n= 12) with coronary artery disease receiving aspirin using whole blood aggregometry. The effects of CB(1) (AM251) and CB(2) (AM630) antagonists, as well as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) inhibitors and aspirin on 2-AG-induced aggregation were also assessed. RESULTS: AM251 (100 nm-30 microm) had no effect on platelet aggregation induced by either ADP (P= 0.90) or thrombin (P= 0.86). 2-AG, but not Delta(9)-THC, induced aggregation. 2-AG-induced aggregation was unaffected by AM251 and AM630 but was abolished by aspirin (P < 0.001) and by the MAGL inhibitor, URB602 (P < 0.001). Moreover, the aggregatory response to 2-AG was depressed (by >75%, P < 0.001) in blood from patients with coronary artery disease receiving aspirin compared with that from healthy volunteers. CONCLUSIONS: 2-AG-mediated activation of platelets is via metabolism to arachidonic acid by MAGL, and not through direct action on CB(1) or CB(2) receptors, at least in the acute phase.

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System.

Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.

Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity.

N-Acetylcysteine (NAC) is a frequently used "antioxidant" in vitro, but the concentrations applied rarely correlate with those encountered with oral dosing in vivo. Here, we investigated the in vitro antioxidant and antiplatelet properties of NAC at concentrations (10-100 microM) that are achievable in plasma with tolerable oral dosing. The impact of NAC pretreatment (2 hours) on aggregation of platelets from healthy volunteers in response to thrombin and adenosine diphosphate and on platelet-derived nitric oxide (NO) was examined. NAC was found to be a weak reducing agent and a poor antioxidant compared with glutathione (reduced form) (GSH). However, platelets treated with NAC showed enhanced antioxidant activity and depression of reactive oxygen species generation associated with increases in intraplatelet GSH levels. An approximately 2-fold increase in NO synthase-derived nitrite was observed with 10 microM NAC treatment, but the effect was not concentration dependent. Finally, NAC significantly reduced both thrombin-induced and adenosine diphosphate-induced platelet aggregation. NAC should be considered a weak antioxidant that requires prior conversion to GSH to convey antioxidant and antithrombotic benefit at therapeutically relevant concentrations. Our results suggest that NAC might be an effective antiplatelet agent in conditions where increased oxidative stress contributes to heightened risk of thrombosis but only if the intraplatelet machinery to convert it to GSH is functional.

Does the Mode of Exercise Influence the Benefits Obtained by Green Exercise?

Green exercise studies have tended to use walking as a modality of exercise to establish benefits to mental health. Whether green exercise benefits translate into different forms of green exercise has been deemed an important research gap. A mixed-methods study design was used to compare psychological responses between two forms of green exercise; golf and walking. A total of 20 participants (10 in each group), with a range of ages and experience were recruited to take part in the study. Participants in the walking condition exhibited significantly greater levels of dissociative cognitions than golf condition participants. Consequently, only the walking condition significantly improved in a directed attention test. Results from the Exercise-Induced Feeling Inventory questionnaire found the walking condition demonstrated increases in all four subscales, whereas the golf condition showed no significant improvements. Based on the findings from the qualitative analysis, distinct differences were seen with regards to the perception of the environment. Participants in the golf condition noted natural elements as obstacles to effective performance, whereas the walking group noted natural stimuli as evoking positive feelings. In agreement with the Attention Restoration Theory, the current study demonstrates that the benefits of green exercise are somewhat reduced when greater levels of directed attention towards the activity are exhibited during green exercise.

What Motivates Participants to Adhere to Green Exercise?

There is a lack of research into green exercise which investigates and compares motivational drivers between the different types of outdoor activities. The current paper addressed this gap by classifying and comparing three types of green exercise: (i) Recreational physical activity, (ii) competitive sport, and (iii) outdoor adventure sport. Using a mixed methodological approach, the present study investigated the motivations for adhering to green exercise and directly compared the differences between these three forms of green exercise. Online questionnaires and face-to-face interviews were used to collect data. The results demonstrated that within all types of green exercise, enjoyment was the greatest motivator. Based on analysis of the qualitative materials, extrinsic motivators such as the environment, family, and friends were highlighted as key factors in beginning and continuing their activity. However, intrinsic motivators were also emphasised as more important in adherence to green exercise. Furthermore, as seen in other research, numerous psychological benefits were reported over time. The results of the study may act as a starting point in understanding how we may increase public engagement in green exercise by prompting participants to select a form of green exercise that best suits them based on their motivational profile.