High Prevalence of Microvascular Complications in Adults With Type 1 Diabetes and Newly Diagnosed Celiac Disease

Objective: The implications of celiac disease (CD) in adult patients with type 1 diabetes are unknown, with respect to diabetes-related outcomes including glycemic control, lipids, microvascular complications, quality of life, and the effect of a gluten-free diet (GFD). We identified CD in adults with type 1 diabetes and investigated the effect of a GFD on diabetes-related complications. Research design and methods: This was a case-control study conducted at a U.K. teaching hospital. Patients with type 1 diabetes aged >16 years (n = 1,000) were assessed for CD. HbA1c, lipid profile, quality of life, retinopathy stage, nephropathy stage, and degree of neuropathy before and after 1 year on a GFD were assessed. Results: The prevalence of CD was 33 per 1,000 subjects (3.3% [95% CI 2.3–4.6]). At diagnosis of CD, adult type 1 diabetic patients had worse glycemic control (8.2 vs. 7.5%, P = 0.05), lower total cholesterol (4.1 vs. 4.9, P = 0.014), lower HDL cholesterol (1.1 vs. 1.6, P = 0.017), and a higher prevalence of retinopathy (58.3 vs. 25%, P = 0.02), nephropathy (41.6 vs. 4.2%, P = 0.009), and peripheral neuropathy (41.6 vs. 16.6%, P = 0.11). There was no difference in quality of life (P > 0.1). After 1 year on a GFD, only the lipid profile improved overall, but in adherent individuals HbA1c and markers for nephropathy improved. Conclusions: Adults with undetected CD and type 1 diabetes have worse glycemic control and a higher prevalence of retinopathy and nephropathy. Treatment with a GFD for 1 year is safe in adults with type 1 diabetes and does not have a negative impact on the quality of life. Long-term microvascular and neurologic complications are responsible for major morbidity and mortality in type 1 diabetes (1). Intensive glycemic control reduces these complications and improves quality of life (1). Even patients with good glycemic control have complications, suggesting that other factors increase the risk (2). Coexisting medical problems may be a confounding factor when managing glycemic control (2). The association between celiac disease (CD) and type 1 diabetes was recognized over 30 years ago, particularly by pediatricians. The prevalence of CD in patients with adult type 1 diabetes has been reported as 1.8–8.4% (3–6). Despite a large number of prevalence studies, other important clinical factors have not been well investigated, including glycemic control, quality of life, microvascular complications, cardiac risk factors, and bone mineral density. Investigations of the effect of CD on glycemic control have been conflicting, with some studies showing improvement (7) and some deterioration (4,8) and others showing no effect (9). The difficulty in interpreting these studies is that most involve pediatric populations and are small, retrospective, and uncontrolled, leaving this question unanswered. There have been no quality-of-life assessments before and after the diagnosis of CD to assess the impact of the diagnosis and a subsequent gluten-free diet (GFD) (3). Adapting to a GFD with the restrictions of a diabetic diet may negatively impact quality of life. Peripheral neuropathy affects up to 30% of patients with adult type 1 diabetes and is a major cause of morbidity (1). Neuropathy is associated with both type 1 diabetes and CD; therefore, patients with both conditions may have a higher prevalence (10,11). In gluten-sensitive neuropathy, the pathophysiological changes lie in the humoral immune response, and a GFD seems to be beneficial (12,13). There are no studies examining neuropathy in patients with type 1 diabetes and CD or the effect of a GFD. One study examined whether CD may contribute to autonomic neuropathy in a cohort of patients with type 1 diabetes. They found no difference in the prevalence of positive antibodies in patients with and without autonomic neuropathy (14). Two previous studies have examined the effect of CD on diabetic nephropathy but were conflicting (15,16). There are currently no studies examining the prevalence of retinopathy in individuals with both type 1 diabetes and CD. Recent data in nondiabetic CD cohorts have shown a reduced risk of ischemic heart disease, possibly attributed to lower cholesterol levels and a lower prevalence of hypertension (17). Reduced bone mineral density has been associated with both CD and type 1 diabetes, but there are little data on people with both conditions (18). The aim of our study was to identify undetected CD in adult patients with type 1 diabetes and investigate the effect on diabetes-related complications before and after a GFD

NASA technology utilization survey on composite materials

NASA and NASA-funded contractor contributions to the field of composite materials are surveyed. Existing and potential non-aerospace applications of the newer composite materials are emphasized. Economic factors for selection of a composite for a particular application are weight savings, performance (high strength, high elastic modulus, low coefficient of expansion, heat resistance, corrosion resistance,), longer service life, and reduced maintenance. Applications for composites in agriculture, chemical and petrochemical industries, construction, consumer goods, machinery, power generation and distribution, transportation, biomedicine, and safety are presented. With the continuing trend toward further cost reductions, composites warrant consideration in a wide range of non-aerospace applications. Composite materials discussed include filamentary reinforced materials, laminates, multiphase alloys, solid multiphase lubricants, and multiphase ceramics. New processes developed to aid in fabrication of composites are given

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial

OBJECTIVES: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT. RESEARCH DESIGN AND METHODS: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL). RESULTS: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01). CONCLUSIONS: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success. TRIAL REGISTRATION NUMBER: ISRCTN21335883

Incident analysis report

This document presents information about a fire that occurred in January 1996 at Lawrence Livermore National Laboratory. This fire was caused by the spontaneous combustion of 100% fuming nitric acid. Topics discussed include: Summary of the incident; technical background; procedural background; supervision; previous incidents with 100% fuming nitric acid; and judgment of potential hazards

Constitutive regulation of the glutamate/aspartate transporter EAAT1 by Calcium-Calmodulin-Dependent Protein Kinase II

Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1, respectively, in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al. 2013), the molecular mechanism underlying this regulation is unknown. Here, we use a heterologous expression model to explore CaMKII regulation of EAAT1 and EAAT2. In transiently transfected HEK293T cells, pharmacological inhibition of CaMKII (using KN-93 or tat-CN21) reduces [3 H]-glutamate uptake in EAAT1 without altering EAAT2-mediated glutamate uptake. While over-expressing the Thr287Asp mutant to enhance autonomous CaMKII activity had no effect on either EAAT1 or EAAT2-mediated glutamate uptake, over-expressing a dominant-negative version of CaMKII (Asp136Asn) diminished EAAT1 glutamate uptake. SPOTS peptide arrays and recombinant glutathione S-transferase-fusion proteins of the intracellular N- and C-termini of EAAT1 identified two potential phosphorylation sites at residues Thr26 and Thr37 in the N-terminus. Introducing an Ala (a non-phospho mimetic) at Thr37 diminished EAAT1-mediated glutamate uptake, suggesting that the phosphorylation state of this residue is important for constitutive EAAT1 function. Our study is the first to identify a glutamate transporter as a direct CaMKII substrate and suggests that CaMKII signaling is a critical driver of constitutive glutamate uptake by EAAT1

Escape from Vela X

While the Vela pulsar and its associated nebula are often considered as the archetype of a system powered by a {approx} 10{sup 4} year old isolated neutron star, many features of the spectral energy distribution of this pulsar wind nebula are both puzzling and unusual. Here we develop a model that for the first time relates the main structures in the system, the extended radio nebula (ERN) and the X-ray cocoon through continuous injection of particles with a fixed spectral shape. We argue that diffusive escape of particles from the ERN can explain the steep Fermi-LAT spectrum. In this scenario Vela X should produce a distinct feature in the locally-measured cosmic ray electron spectrum at very high energies. This prediction can be tested in the future using the Cherenkov Telescope Array (CTA). If particles are indeed released early in the evolution of PWNe and can avoid severe adiabatic losses, PWN provide a natural explanation for the rising positron fraction in the local CR spectrum

Lower gastrointestinal symptoms are associated with worse glycemic control and quality of life in type 1 diabetes mellitus

Objectives Lower gastrointestinal symptoms are not well characterized in people with type 1 diabetes, and the effects on quality of life and glycemic control are unknown. This study aimed to determine the prevalence of lower gastrointestinal symptoms and the effects on glycemic control and quality of life, and to investigate for underlying causes. Research design and methods This is a prospective, cohort study in secondary care. Patients with type 1 diabetes completed a gastrointestinal symptom questionnaire and the Short Form 36 V.2 quality of life questionnaire and had their hemoglobin A1c measured. Patients with diarrhea were offered reassessment and investigation as per the national guidelines. Controls without diabetes were used to compare symptom prevalence and quality of life scores. Results 706 with type 1 diabetes (mean age 41.9 years) and 604 controls (mean age 41.9 years) were enrolled. Gastrointestinal symptoms were significantly more frequent in type 1 diabetes compared with controls, in particular constipation (OR 2.4), diarrhea (OR 2.5), alternating bowel habit (OR 2.1), abdominal pain (OR 1.4), floating stools (OR 2.7), bloating (OR 1.4) and flatulence (OR 1.3) (all p<0.05). Previous pancreatitis was more frequent in type 1 diabetes (OR 4.6), but other gastrointestinal conditions were not. Gastrointestinal symptoms were associated with poorer glycemic control (p<0.01) and worse quality of life particularly in those with diarrhea. Investigation of those with diarrhea, including those with alternating bowel habit, (n=105), identified a cause in 72.3% with subsequent change in management. Conclusions Gastrointestinal symptoms are twice as common in type 1 diabetes and associated with poorer quality of life and glycemic control. Investigation of diarrhea in people with type 1 diabetes leads to a high yield of treatable conditions and a change in management in about three-quarters

Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines.

INTRODUCTION: Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS: A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS: Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines

Student perceptions of a healthy university

As complex environments within which individuals and populations operate, universities present important contexts for understanding and addressing health issues. The healthy university is an example of the settings approach, which adopts a whole system perspective, aiming to make places within which people, learn, live, work and play supportive to health and wellbeing. The UK Healthy Universities Network has formulated an online toolkit, which includes a self-review tool, intended to enable universities to assess what actions they need to take to develop as a healthy university. This paper presents findings from consultative research undertaken with students from universities in England, Scotland and Wales, which explored what they believe represents a healthy university. Methods Student surveys and focus groups were used to collect data across eleven universities in England, Scotland and Wales. A priori themes were used to develop our own model for a healthy university, and for the thematic coding phase of analysis. Findings A healthy university would promote student health and wellbeing in every aspect of its business from its facilities and environment through to its curriculum. Access to reasonably priced healthy food and exercise facilities were key features of a healthy university for students in this study. The Self Review Tool has provided a crucial start for universities undertaking the journey towards becoming a healthy university. In looking to the future both universities and the UK Healthy Universities Network will now need to look at what students want from their whole university experience, and consider how the Self Review Tool can help universities embrace a more explicit conceptual framework. Conclusion The concept of a healthy university that can tailor its facilities and supportive environments to the needs of its students will go some way to developing students who are active global citizens and who are more likely to value and prioritise health and wellbeing, in the short and long term through to their adult lives