pinecone/core-2020-05-10-deduplication huggingface dataset:
Rank acquisition in rhesus macaque yearlings following permanent maternal separation: The importance of the social and physical environment

Rank acquisition is a developmental milestone for young primates, but the processes by which primate yearlings attain social rank in the absence of the mother remain unclear. We studied 18 maternally reared yearling rhesus macaques (Macaca mulatta) that differed in their social and physical rearing environments. We found that early social experience and maternal rank, but not individual traits (weight, sex, age), predicted dominance acquisition in the new peer‐only social group. Yearlings also used coalitions to reinforce the hierarchy, and social affiliation (play and grooming) was likely a product, rather than a determinant, of rank acquisition. Following relocation to a familiar environment, significant rank changes occurred indicating that familiarity with a physical environment was salient in rank acquisition. Our results add to the growing body of literature emphasizing the role of the social and physical environment on behavioral development, namely social asymmetries among peers
Cortisol stress responses and children's behavioral functioning at school

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                  167027.pdf (publisher's version ) (Open Access)The present study investigated whether cortisol stress responses of 6-year-olds were associated with their behavioral functioning at school. Additionally, the moderating role of stress in the family environment was examined. To this end, 149 healthy children (Mage = 6.09 years; 70 girls) participated in an age-appropriate innovative social evaluative stress test. Saliva cortisol samples were collected six times during the stress test to calculate two indices of the cortisol stress response: cortisol stress reactivity and total stress cortisol. Teachers assessed children's internalizing, externalizing, and prosocial behaviors. Stress in the family environment was operationalized as maternally reported parenting stress. Results indicated a significant increase in cortisol concentrations in response to the stressor. No significant associations were found between cortisol stress responses and behavioral functioning at school and there was no evidence for moderation by maternal parenting stress. Potential theoretical and methodological explanations for these results are discussed.8 p
Building Brand Relationships Online: A Comparison of Two Interactive Applications

-This is the author's version of the article:"Building brand relationships online:A comparison of two interactive applications" Journal of Interactive Marketing, Volume 16, Issue 3, pages 17–34, Summer 2002.Due to its potential for interactive communication, the Internet is considered a promising tool for relationship marketing. In this study, two of the most common applications for interactive communication - personalized websites and customer communities - were experimentally compared for their ability to develop consumer-brand relationships as measured by the Brand Relationship Quality (BRQ) framework of Fournier (1998). Moreover, the moderating role of Internet experience was investigated
Profound defects in β-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP)

BACKGROUND: Few studies have measured the ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes. The Early Diabetes Intervention Programme (ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycaemia in screen-detected type 2 diabetes. In the Early Diabetes Intervention Programme, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycaemia over a 5-year period was not greater than that of placebo. However, there was an early glucose-lowering effect of the trial. The objective of the current secondary analysis was to describe β-cell function changes in response to glucose lowering.
METHODS: Participants were overweight adult subjects with screen-detected type 2 diabetes. β-cell function was measured using hyperglycaemic clamps and oral glucose tolerance testing. The primary outcome was the change in β-cell function from baseline to year 1, the time point where the maximal glucose-lowering effect was seen.
RESULTS: At baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, fasting plasma glucose (PG) and 2-h PG, there was no clinically significant improvement in the first-phase insulin response. Late-phase insulin responses declined despite beneficial glycaemic effects of interventions.
CONCLUSIONS: Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of β-cell function
Prevention and management of foot problems in diabetes: A summary guidance for daily practice 2015, based on the IWGDF Guidance Documents

In this 'Summary Guidance for Daily Practice', we describe the basic principles of prevention and management of foot problems in persons with diabetes. This summary is based on the International Working Group on the Diabetic Foot (IWGDF) Guidance 2015. There are five key elements that underpin prevention of foot problems: \ud
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(1) identification of the at-risk foot; \ud
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(2) regular inspection and examination of the at-risk foot; \ud
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(3) education of patient, family and healthcare providers; \ud
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(4) routine wearing of appropriate footwear, and; \ud
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(5) treatment of pre-ulcerative signs. \ud
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Healthcare providers should follow a standardized and consistent strategy for evaluating a foot wound, as this will guide further evaluation and therapy. The following items must be addressed: type, cause, site and depth, and signs of infection. There are seven key elements that underpin ulcer treatment: \ud
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(1) relief of pressure and protection of the ulcer; \ud
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(2) restoration of skin perfusion; \ud
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(3) treatment of infection; \ud
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(4) metabolic control and treatment of co-morbidity; \ud
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(5) local wound care; \ud
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(6) education for patient and relatives, and; \ud
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(7) prevention of recurrence. \ud
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Finally, successful efforts to prevent and manage foot problems in diabetes depend upon a well-organized team, using a holistic approach in which the ulcer is seen as a sign of multi-organ disease, and integrating the various disciplines involved
Prevention of foot ulcers in the at-risk patient with diabetes: A systematic review

Background\ud
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Prevention of foot ulcers in patients with diabetes is extremely important to help reduce the enormous burden of foot ulceration on both patient and health resources. A comprehensive analysis of reported interventions is not currently available, but is needed to better inform caregivers about effective prevention. The aim of this systematic review is to investigate the effectiveness of interventions to prevent first and recurrent foot ulcers in persons with diabetes who are at risk for ulceration. \ud
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Methods\ud
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The available medical scientific literature in PubMed, EMBASE, CINAHL and the Cochrane database was searched for original research studies on preventative interventions. Both controlled and non-controlled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers. \ud
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Results\ud
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From the identified records, a total of 30 controlled studies (of which 19 RCTs) and another 44 non-controlled studies were assessed and described. Few controlled studies, of generally low to moderate quality, were identified on the prevention of a first foot ulcer. For the prevention of recurrent plantar foot ulcers, multiple RCTs with low risk of bias show the benefit for the use of daily foot skin temperature measurements and consequent preventative actions, as well as for therapeutic footwear that demonstrates to relieve plantar pressure and that is worn by the patient. To prevent recurrence, some evidence exists for integrated foot care when it includes a combination of professional foot treatment, therapeutic footwear and patient education; for just a single session of patient education, no evidence exists. Surgical interventions can be effective in selected patients, but the evidence base is small. \ud
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Conclusion\ud
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The evidence base to support the use of specific self-management and footwear interventions for the prevention of recurrent plantar foot ulcers is quite strong, but is small for the use of other, sometimes widely applied, interventions and is practically nonexistent for the prevention of a first foot ulcer and non-plantar foot ulcer
A shift in priority in diabetic foot care and research: 75% of foot ulcers are preventable

Diabetic foot ulceration poses a heavy burden on the patient and the healthcare system, but prevention thereof receives little attention. For every euro spent on ulcer prevention, ten are spent on ulcer healing, and for every randomized controlled trial conducted on prevention, ten are conducted on healing. In this article, we argue that a shift in priorities is needed. For the prevention of a first foot ulcer, we need more insight into the effect of interventions and practices already applied globally in many settings. This requires systematic recording of interventions and outcomes, and well-designed randomized controlled trials that include analysis of cost-effectiveness. After healing of a foot ulcer, the risk of recurrence is high. For the prevention of a recurrent foot ulcer, home monitoring of foot temperature, pressure-relieving therapeutic footwear, and certain surgical interventions prove to be effective. The median effect size found in a total of 23 studies on these interventions is large, over 60%, and further increases when patients are adherent to treatment. These interventions should be investigated for efficacy as a state-of-the-art integrated foot care approach, where attempts are made to assure treatment adherence. Effect sizes of 75-80% may be expected. If such state-of-the-art integrated foot care is implemented, the majority of problems with foot ulcer recurrence in diabetes can be resolved. It is therefore time to act and to set a new target in diabetic foot care. This target is to reduce foot ulcer incidence with at least 75%
Sedentary behaviour as a new behavioural target in the prevention and treatment of type 2 diabetes

The file associated with this record is under a 12-month embargo from publication in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.Our modern day society encompasses an ecological niche in which sedentary behaviour, labour-saving devices and energy dense foods have become the new reference of living. We now spend more time sedentary, defined as sitting, than in all other activities combined. It has recently been confirmed that the consequences of our modern chair dependency are substantial and a direct contributing factor to the ever increasing epidemic of chronic diseases witnessed within industrialized environments. Epidemiological evidence - from both cross-sectional and prospective observational studies - has indicated that the time spent in sedentary behaviour is a distinct risk factor for several health outcomes, including type 2 diabetes mellitus, insulin resistance, all-cause and cardiovascular disease mortality, depression and some types of cancer. Importantly, these detrimental associations remain even after accounting for time spent in moderate-to-vigorous physical activity, with the strongest and most persistent associations seen between sedentary time and type 2 diabetes mellitus. Importantly, experimental studies have started to confirm the observational associations, with mounting evidence showing that breaking prolonged sitting time with light ambulation is an effective strategy for improving postprandial glucose regulation. Indeed, there is even emerging evidence showing that simply substituting sitting for standing regularly throughout the day may be of sufficient stimulus to improve glucose regulation. We highlight some of the key definitions, issues and evidence underpinning the link between sedentary behaviour and chronic disease in order to better inform clinicians and patients about the importance of incorporating reduced sitting time into type 2 diabetes mellitus management and prevention pathways. Copyright © 2016 John Wiley & Sons, Ltd.Peer-reviewedPost-prin
Diabetes, obesity and exercise in skeletal muscle : effects on gene expression and DNA methylation

Type 2 diabetes, obesity and depression are growing concerns for human health. Physical exercise is a known protective factor against these disorders, although the underlying mechanisms are incompletely understood. The studies in this thesis aim to increase the understanding of mechanisms controlling gene expression and DNA methylation in the context of type 2 diabetes, obesity and exercise.



TWIST1 and TWIST2 proteins play an important role in embryonic muscle development, inflammation and tumor metabolism. We demonstrated that Twist1 or Twist2 overexpression in mature skeletal muscle favors glycolysis and increases the expression of pro-inflammatory cytokines. Gene expression of TWIST1 and TWIST2 is unaltered by obesity, type 2 diabetes or exercise training.



Decreased circulating kynurenine levels are associated with resistance to depression. Kynurenine is transformed into kynurenic acid by kynurenine aminotransferases (KATs). Exercise training and PGC1α induce expression of KATs in skeletal muscle. We report that a single bout of exercise acutely decreased plasma kynurenine, while concomitantly increasing kynurenic acid in both type 2 diabetic and healthy subjects. Exercise-induced changes in kynurenine metabolism were independent of mRNA expression of the KATs. Kynurenine levels correlated with body mass index, suggesting kynurenine metabolism may link obesity and depression.



Exercise and diet affect skeletal muscle insulin sensitivity and DNA methylation. Using genome-wide approaches, we unraveled the effect of exercise on the skeletal muscle methylome. Training and high-fat diet, but not in vitro contraction, lead to epigenetic changes in the promoter of Sprouty RTK Signaling Antagonist 1 (Spry1), a gene involved in muscle stem cell quiescence. We found DNA methylation of Spry1 increased binding of nuclear proteins to the promoter.



Insulin is a metabolic and growth promoting hormone. Using genome-wide approaches, we unraveled the effect of insulin on the skeletal muscle methylome. We observed that insulin treatment of skeletal muscle in vitro increased DNA methylation of the death-associated protein Kinase 3 (DAPK3). Conversely, DAPK3 DNA methylation was reduced in type 2 diabetic subjects compared to controls. A glucose challenge further decreased DAPK3 methylation suggesting that additional factors in the systemic milieu may affect DAPK3 DNA methylation.



Collectively, our results indicate that TWIST proteins affect skeletal muscle metabolism and inflammation. We provide a potential mechanism for the anti-depressive effects of exercise and shed new light on the complex interplay between metabolic conditions, skeletal muscle and DNA methylation. We provide a new insight in the protective effect of exercise or the pathophysiology of type 2 diabetes and obesity, opening opportunities for improvements in the management and treatment of metabolic diseases
A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin

BACKGROUND: This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. METHODS: Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RESULTS: RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). CONCLUSIONS: Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control.Peer-reviewedPublisher Versio
Temporal trends in quality of primary care for patients with type 2 diabetes mellitus: a population-based retrospective cohort study after implementation of a quality improvement initiative

Background: This study examined whether temporal trends exist in treatment of patients with type 2 diabetes (T2D) and quality of diabetes care after implementation of quality improvement initiative in primary care setting.  Methods: We conducted a population-based retrospective cohort study of 202,284 patients with T2D who were routinely managed in primary care clinics. We examined the change over time and the variability between clinics in quality-of-care from Hospital Authority administrative data over a five-year period (2009-2013), and used multilevel logistic regression to adjust for patient and clinic characteristics. Observational period was partitioned in five calendar years. Ten quality-of-care criteria were selected: adherence to seven process of care criteria (HbA1c test, renal function test, full lipid profile, urine protein analysis, retinal screening, lipid-lowering agent prescriptions among patients with hypercholesterolaemia, and ACEI/ARB prescriptions among patients with microalbuminuria) and three outcome of care criteria (HbA1c≤7%, BP≤130/80mmHg, LDL-C≤2.6mmol/L). Variability of standards between clinics was assessed using intra-cluster correlation coefficients.  Results: Characteristics of Patients with T2D managed in primary care changed substantially during the observational period, with increasing age and usage of insulin, longer duration of diabetes but improved metabolic profiles (all P-trend<0.001). Performance rates of the seven process and three clinical outcome of care criteria increased remarkably over time (all P-trend<0.001). Variations in retinal screening delivery between clinics was considerable, albeit decreasing over time.  Conclusions: Coinciding with implementation of quality improvement initiative, quality of diabetes care improved significantly in the past 5 years, in part attributable to benefits of integrated multidisciplinary diabetes management
Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin-1 and endothelial dysfunction in streptozotocin treated rats

This is the peer reviewed version of the following article: Yousif A. Shamsaldeen, Rosemary Ugur, Christopher D. Benham, and Lisa A. Lione, ???Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin???1, and endothelial dysfunction in streptozotocin treated rats???, Diabetes Metabolism Research and Reviews, e2995, March 2018, which has been published in final form at https://doi.org/10.1002/dmrr.2995. Under embargo until 22 February 2019. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Background: Diabetes is a complex progressive disease characterised by chronic hyperglycaemia and dyslipidaemia associated with endothelial dysfunction. Oxidised LDL (Ox-LDL) is elevated in diabetes and may contribute to endothelial dysfunction. The aim of this study was to relate the serum levels of Ox-LDL with endothelial dysfunction in streptozotocin (STZ)-diabetic rats and to further explore the changes in endothelial nitric oxide synthase (eNOS) and caveolin-1 (CAV-1) expression in primary aortic endothelial cells (ECs). Methods: Diabetes was induced with a single intraperitoneal injection of STZ in male Wistar rats. During the hyperglycaemic diabetes state serum lipid markers, aortic relaxation and aortic ECs eNOS and CAV-1 protein expression was measured. Results: Elevated serum Ox-LDL (STZ 1486 ?? 78.1 pg/ml vs control 732.6 ?? 160.6pg/ml, p<0.05) was associated with hyperglycaemia (STZ 29 ?? 0.9 mmol/L vs control: 7.2 ?? 0.2 mmol/L, p<0.001) and hypertriglyceridemia (STZ 9.0 ?? 1.5 mmol/L vs control: 3.0 ?? 0.3 mmol/L, p<0.01) in diabetic rats. A significant reduction was observed in STZ-diabetic aortic endothelial cell eNOS and CAV-1 of 40% and 30% respectively, accompanied by a compromised STZ-diabetic carbachol-induced vasodilation (STZ 29.6 ?? 9.3% vs control 77.2 ?? 2.5%, p<0.001). Conclusions: The elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats may contribute to diabetic endothelial dysfunction, possibly through downregulation of endothelial CAV-1 and eNOS
Anti-CD38 autoantibodies in type? diabetes.

International audienceHuman diabetes mellitus comprises two main clinical entities: type 1 and type 2 diabetes. While type 1 diabetes is autoimmune in origin, type 2 diabetes is due to a decreased sensitivity to insulin action (so-called insulin resistance) associated with impaired beta cell function. However, it is becoming increasingly clear that there is a certain overlap between these two diseases. While some degree of insulin resistance is present in type 1 diabetic patients, markers of beta cell autoimmunity (either primary or secondary) can frequently be detected in type 2 diabetic subjects. In this scenario, anti-CD38 autoantibodies (aAbs) have been described in both type 1 and type 2 diabetic patients. Contrary to the other known islet aAbs, anti-CD38 autoantibodies are more prevalent in long-standing than in new-onset type 1 diabetes, and more prevalent in type 2 than in type 1 diabetes. Moreover, anti-CD38 aAbs are endowed with unique stimulatory properties on Ca(2+) mobilization and insulin secretion. These observations suggest that autoimmunity may be both the cause and consequence of beta cell dysfunction, in either case imposing a further toll for the control of glucose homeostasis