Implementation of Analytical Fatigue Models Into Opensim to Predict the Effects of Fatigue on Anterior Cruciate Ligament Loading

The anterior cruciate ligament (ACL) provides stability to the knee joint while performing activities such as a side step cut. Neuromuscular fatigue, a reduction in muscle force producing capabilities, alters lower extremity mechanics while performing a side step cut and may increase the risk of ACL injury, particularly in females. Musculoskeletal modeling allows for the measurement of muscle forces, which are difficult to measure in-vivo. Therefore, musculoskeletal modeling, may improve our understanding of the effects of neuromuscular fatigue on muscle force production and loading of the ACL. Therefore, the purpose of this study was to develop a musculoskeletal model which incorporated two analytical fatigue models by Tang et al. (2005) and Xia et al. (2008). These fatigue models were used to determine the effects of neuromuscular fatigue on muscle force production and ACL loading at various levels of fatigue (i.e. 10%, 25%, 50%, 75% and 90%) and were validated by comparing these results with experimental data. Six recreationally active females performed five anticipated side step cuts both before and after an isolated hamstrings fatigue protocol using the right lower extremity. Root mean square (RMS) differences were calculated between both fatigue models and the experimental hamstrings muscle force 1.91 N·kg-1 and 1.88 N·kg-1, for RMSTang and RMSXia, respectively. Despite similar RMS differences, the Xia et al. (2008) model was selected for analysis of fatigue as this model utilized general input parameters. The total quadriceps and hamstrings muscle forces demonstrated significant decreases (p0.05) due to fatigue. The limited number of participants in this study suggested an underpowered study and may help explain the lack of significance in various dependent variables including peak ACL loading. Using the model developed in this study can aid researchers in understanding the effects of fatigue on risk of ACL injury in order to develop better training programs in order to reduce the risk of injury

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial

Introduction People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. Methods and analysis A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. Ethics and dissemination The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. Trial registration number ISRCTN 61215213

Supporting self-management after attending a structured education programme: a qualitative longitudinal investigation of type 1 diabetes patients’ experiences and views

Background: Structured education programmes for patients with diabetes and other chronic conditions are being widely adopted. However, follow-up studies suggest that course graduates may struggle to sustain the self-care practices taught on their courses over time. This study explored the support needs of patients with type 1 diabetes after attending a structured education programme promoting an empowerment approach and training in use of flexible intensive insulin therapy, a regimen now widely advocated and used to manage this condition. The objective was to inform future support offered to course graduates. Methods: Repeat, in-depth interviews with 30 type 1 diabetes patients after attending Dose Adjustment for Normal Eating (DAFNE) courses in the UK, and six and 12 months later. Data were analysed using an inductive, thematic approach. Results: While the flexible intensive insulin treatment approach taught on DAFNE courses was seen as a logical and effective way of managing one’s diabetes, it was also considered more technically complex than other insulin regimens. To sustain effective disease self-management using flexible intensive insulin treatment over time, patients often expected, and needed, on-going input and support from health care professionals trained in the approach. This included: help determining insulin dose adjustments; reassurance; and, opportunities to trouble-shoot issues of concern. While some benefits were identified to receiving follow-up support in a group setting, most patients stated a preference or need for tailored and individualised support from appropriately-trained clinicians, accessible on an ‘as and when needed’ basis. Conclusions: Our findings highlight potential limitations to group-based forms of follow-up support for sustaining diabetes self-management. To maintain the clinical benefits of structured education for patients with type 1 diabetes over time, course graduates may benefit from and prefer ongoing, one-to-one support from health care professionals trained in the programme’s practices and principles. This support should be tailored and personalised to reflect patients’ specific and unique experiences of applying their education and training in the context of their everyday lives, and could be the subject of future research

Recent Updates on Type 1 Diabetes Mellitus Management for Clinicians

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia

Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation

Defects in WDR72 (WD repeat‐containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72‐knockout/lacZ‐knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild‐type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin‐associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle‐ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.We generated knockout mice lacking the ability to make WDR72. Deletion of WDR72 caused retention of degraded enamel proteins within the mineral layer and significantly reduced mineralization. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Interactome analysis of WDR72 protein revealed potential involvement in ameloblastic endocytosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112233/1/mgg3143.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112233/2/mgg3143-sup-0001-SuppInfo.pd

Disruption of LRRK2 Does Not Cause Specific Loss of Dopaminergic Neurons in Zebrafish

Mutations in LRRK2 are genetically linked to Parkinson's disease (PD) but its normal biological function is largely unknown. Sheng et al. recently reported that deletion of the WD40 domain of LRRK2 in zebrafish specifically causes PD-like loss of neurons and behavior defect. However, our similar early study and recent confirming experiments using the same reagents reported by Sheng et al. failed to reproduce the phenotype of the loss of dopaminergic neurons, although the mRNA of LRRK2 was molecularly disrupted. Our study suggests that function of LRRK2 and its usefulness to generate zebrafish PD model needs further evaluation

Metabolic control in a nationally representative diabetic elderly sample in Costa Rica: patients at community health centers vs. patients at other health care settings

<p>Abstract</p> <p>Background</p> <p>Costa Rica, like other developing countries, is experiencing an increasing burden of chronic conditions such as diabetes mellitus (DM), especially among its elderly population. This article has two goals: (1) to assess the level of metabolic control among the diabetic population age ≥ 60 years old in Costa Rica, and (2) to test whether diabetic elderly patients of community health centers differ from patients in other health care settings in terms of the level of metabolic control.</p> <p>Methods</p> <p>Data come from the project CRELES, a nationally representative study of people aged 60 and over in Costa Rica. This article analyzes a subsample of 542 participants in CRELES with self-reported diagnosis of diabetes mellitus. Odds ratios of poor levels of metabolic control at different health care settings are computed using logistic regressions.</p> <p>Results</p> <p>Lack of metabolic control among elderly diabetic population in Costa Rica is described as follows: 37% have glycated hemoglobin ≥ 7%; 78% have systolic blood pressure ≥ 130 mmHg; 66% have diastolic blood pressure ≥ 80 mmHg; 48% have triglycerides ≥ 150 mg/dl; 78% have LDL ≥ 100 mg/dl; 70% have HDL ≤ 40 mg/dl. Elevated levels of triglycerides and LDL were higher in patients of community health centers than in patients of other clinical settings. There were no statistical differences in the other metabolic control indicators across health care settings.</p> <p>Conclusion</p> <p>Levels of metabolic control among elderly population with DM in Costa Rica are not that different from those observed in industrialized countries. Elevated levels of triglycerides and LDL at community health centers may indicate problems of dyslipidemia treatment among diabetic patients; these problems are not observed in other health care settings. The Costa Rican health care system should address this problem, given that community health centers constitute a means of democratizing access to primary health care to underserved and poor areas.</p

Clinical effectiveness of a brief educational intervention in Type 1 diabetes:results from the BITES (Brief Intervention in Type 1 diabetes, Education for Self-efficacy) trial

AIMS: Intensive 5-day educational interventions for people with Type 1 diabetes have shown improved outcomes in a number of European studies. The aim was to assess the effectiveness of a brief (2.5 days) psycho-educational intervention. METHODS: Our randomized trial in a secondary-care setting had 54 and 60 participants allocated to intervention and control groups, respectively. Primary outcomes were HbA(1c) and severe hypoglycaemia. Secondary outcomes were blood pressure, weight, height, lipids and psychometric profile. RESULTS: HbA(1c) showed no statistically significant change at 3 months [difference = 0.01, 95% confidence interval (CI) –0.23, 0.26, P = 0.92], 6 months (difference = –0.06, 95% CI –0.32, 0.20, P = 0.67) and 12 months (difference = 0.01, 95% CI –0.30, 0.32, P = 0.94). Incidence of severe hypoglycaemia (per patient per year) in the intervention group (0.41) and control group (0.48) was not statistically different. Treatment satisfaction improved at 3 months (difference = 9.4, 95% CI 5.2, 13.6, P = 0.0005), 6 months (difference = 10.4, 95% CI 6.0, 14.8, P = 0.0005) and 12 months (difference = 7.1, 95% CI 2.1, 12.1, P = 0.006). The ‘Managing psychological aspects’ and ‘Setting and achieving goals’ dimensions of the Diabetes Empowerment Scale also showed significant improvement at 3, 6 and 12 months. Diabetes Knowledge Test, Illness Perception Questionnaire, Hypoglycaemia Fear Scale and Short Form 36 showed no significant change. CONCLUSIONS: This brief intervention had no significant impact on HbA(1c) or severe hypoglycaemia, but improved diabetes treatment satisfaction and patient empowerment. Current Controlled Trials ISRCTN75807800

Practical steps to improving the management of type 1 diabetes: recommendations from the Global Partnership for Effective Diabetes Management

The Diabetes Control and Complications Trial (DCCT) led to considerable improvements in the management of type 1 diabetes, with the wider adoption of intensive insulin therapy to reduce the risk of complications. However, a large gap between evidence and practice remains, as recently shown by the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, in which 30-year rates of microvascular complications in the ‘real world’ EDC patients were twice that of DCCT patients who received intensive insulin therapy. This gap may be attributed to the many challenges that patients and practitioners face in the day-to-day management of the disease. These barriers include reaching glycaemic goals, overcoming the reality and fear of hypoglycaemia, and appropriate insulin therapy and dose adjustment. As practitioners, the question remains: how do we help patients with type 1 diabetes manage glycaemia while overcoming barriers? In this article, the Global Partnership for Effective Diabetes Management provides practical recommendations to help improve the care of patients with type 1 diabetes