Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Impaired hypoglycaemia awareness in type 1 diabetes:lessons from the lab

Hypoglycaemia remains the most common metabolic adverse effect of insulin and sulfonylurea therapy in diabetes. Repeated exposure to hypoglycaemia leads to a change in the symptom complex that characterises hypoglycaemia, culminating in a clinical phenomenon referred to as impaired awareness of hypoglycaemia (IAH). IAH effects approximately 20–25% of people with type 1 diabetes and increases the risk of severe hypoglycaemia. This review focuses on the mechanisms that are responsible for the much higher frequency of hypoglycaemia in people with diabetes compared with those without, and subsequently how repeated exposure to hypoglycaemia leads to the development of IAH. The mechanisms that result in IAH development are incompletely understood and likely to reflect changes in multiple aspects of the counterregulatory response to hypoglycaemia, from adaptations within glucose and non-glucose-sensing cells to changes in the integrative networks that govern glucose homeostasis. Finally, we propose that the general process that incorporates many of these changes and results in IAH following recurrent hypoglycaemia is a form of adaptive memory called ‘habituation’

Genetic influences on the insulin response of the beta cell to different secretagogues

Aims/hypothesis: The aim of the present study was to estimate the heritability of the beta cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine. Methods: This was a twin-family study that included 54 families from the Netherlands Twin Register. The participants were healthy twin pairs and their siblings of the same sex, aged 20 to 50 years. Insulin response of the beta cell was assessed by a modified hyperglycaemic clamp with additional GLP-1 and arginine. Insulin sensitivity index (ISI) was assessed by the euglycaemic-hyperinsulinaemic clamp. Multivariate structural equation modelling was used to obtain heritabilities and the genetic factors underlying individual differences in BMI, ISI and secretory responses of the beta cell. Results: The heritability of insulin levels in response to glucose was 52% and 77% for the first and second phase, respectively, 53% in response to glucose+GLP-1 and 80% in response to an additional arginine bolus. Insulin responses to the administration of glucose, glucose+GLP-1 and glucose+GLP-1+arginine were highly correlated (0.62<r<0.79). Heritability of BMI and ISI was 74% and 60% respectively. The genetic factors that influenced BMI and ISI explained about half of the heritability of insulin levels in response to the three secretagogues. The other half was due to genetic factors specific to the beta cell. Conclusions/interpretation: In healthy adults, genetic factors explain most of the individual differences in the secretory capacity of the beta cell. These genetic influences are partly independent from the genes that influence BMI and ISI. © 2009 Springer-Verlag

Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

Table S2. Spearman correlation of the expression of four glycolytic enzymes in a cohort of 380 ovarian cancers. Spearman rho correlation values (top value) along with the respective adjusted P value (bottom value) of statistically significant correlations thresholded at FDR P < 0.01 are summarised. (DOCX 21 kb

The portal of Neviaser: a valid option for antegrade nailing of humerus fractures

Introduction: The objective of this retrospective non-randomized study was to evaluate the portal of Neviaser (PN) as an alternative approach in antegrade humeral nailing. Methods: The surgical approach for the straight antegrade intramedullary nail (SAIN) was either the anterolateral delta-split (group 2, n = 79) or the portal of Neviaser (group 3, n = 27). Length of surgery and time of radiation were extracted from charts. Patients stabilized using the PN were followed for a clinical and radiological exam. At follow-up we evaluated the DASH (Disability of the Arm, Shoulder and Hand) and CMS (Constant-Murley Score). Results: Between 10.2015 and 12.2018 191 proximal and diaphyseal humeral fractures were operated using either an angular stable extramedullary device (group 1, PHILOS®, n = 85) or a straight humeral nail (MultiLoc®, n = 106). Time of radiation and intervention followed a normal distribution. The mean length of surgery was 172.9 min (SD 91.5) in group 1, 121.5 min (SD 54.1) in group 2 and 96.4 min (SD 33.7) in group 3 (p < 0.01). Time of radiation was significantly different with 1.1 min (SD 0.6: group 1), 3.1 min (SD 1.6: group 2) and 2.9 min (SD 1.7: group 3) (p < 0.01). After a mean interval of 21.5 months (range 6–43 months) 14 / 27 patients of group 3 were available for a clinical and radiological follow-up. The mean DASH in group 3 was 25, the CMS reached 70. The age and sex weighted CMS mean value was 96%. Forward flexion was 131°, abduction 125°. The ratio of strength affected versus non-affected side was 4.4: 6.2 kg. Conclusions: The portal of Neviaser is a feasible and safe approach and is an alternative to the anterolateral delta-split. Length of surgery and time of radiation were significantly shorter. Level of evidence: IV

Variation in care and outcome for fragile hip fracture patients: a European multicentre study benchmarking fulfilment of established quality indicators

PURPOSE Despite the availability of clinical guidelines for hip fracture patients, adherence to these guidelines is challenging, potentially resulting in suboptimal patient care. The goal of this study was (1) to evaluate and benchmark the adherence to recently established quality indicators (QIs), and (2) to study clinical outcomes, in fragile hip fracture patients from different European countries. METHODS This observational, cross-sectional multicenter study was performed in 10 hospitals from 9 European countries including data of 298 consecutive patients. RESULTS A large variation both within and between hospitals were seen regarding adherence to the individual QIs. QIs with the lowest overall adherence rates were the administration of systemic steroids (5.4%) and tranexamic acid (20.1%). Indicators with the highest adherence rates (above 95%) were pre-operative (99.3%) and post-operative haemoglobin level assessment (100%). The overall median time to surgery was 22.6 h (range 15.7-42.5 h). The median LOS was 9.0 days (range 5.0-19.0 days). The most common complications were delirium (23.2%) and postsurgical constipation (25.2%). CONCLUSION The present study shows large variation in the care for fragile patients with hip fractures indicating room for improvement. Therefore, hospitals should invest in benchmarking and knowledge-sharing. Large quality improvement initiatives with longitudinal follow up of both process and outcome indicators should be initiated

“To work, or not to work, that is the question” – Recent trends and avenues for research on presenteeism

This position paper brings together recent and emerging developments in the field of presenteeism. A critical synthesis of the evidence is needed due to persisting conceptual and methodological challenges as well as the increased volume of research in the field. This paper integrates emerging evidence and critical thinking into three areas: (1) concept, (2) measurement and methodological issues, and (3) the context of presenteeism. First, due to the variety of existing definitions, competing understandings, as well as the notion of positive presenteeism, it is important to reconsider the notion of presenteeism. Second, it is important to reflect on the measurement of the act of presenteeism and the productivity loss associated with that. Third, following the call to investigate presenteeism in specific contexts, it is important to explain the social, occupational, cross-cultural aspects, as well as the contemporary workplace changes. Based on this critical synthesis, we conclude by identifying recommendations for future research on presenteeism.info:eu-repo/semantics/acceptedVersio

Self-Control and Adverse “Drinking” Consequences

Most research on adverse alcohol consequences such as problems with health, work, and relationships focuses only on alcohol use itself as a cause of these outcomes. However, Gottfredson and Hirschi’s (1990) self-control theory holds that alcohol use and these negative outcomes are likely to have a common cause–low self-control. Tests of hypotheses derived from self-control theory show that self-control predicts negative drinking consequences better than combined measures of alcohol dependence and frequency and quantity of drinking. This suggests that various forms of risk–taking behavior and negative outcomes can be conceptualized as indicators of underlying levels of self-control