Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD)

Designing and Implementing a Novel Graduate Program to Develop Transdisciplinary Leaders in Urban Sustainability

Urban settings, where \u3e50% of the world\u27s population resides, are increasingly faced with environmental challenges that threaten their sustainability. Aging infrastructure, water and air pollution, and increasing recognition of environmental injustices highlight the need for professionals to employ complex scientific reasoning across disciplines where they can effectively address the multifaceted issues of urban sustainability. Here we present an innovative model for preparing the next generation of public, private, and academic leaders to address complex problems in urban sustainability. Specifically, we outline the design and implementation of an integrated, adaptable graduate training program, with the goals of science leadership, curriculum relevancy, community impact, broader applicability, establishing a career development pathway in science, technology, engineering, and mathematics (STEM) programs, and program sustainability. This program addresses human-ecosystem challenges using a transdisciplinary approach to produce scientific products in partnership with local communities, businesses, industries, scientists, and policy makers, while providing a mechanism to understand and overcome contemporary societal and ecological challenges. Students receive rigorous training in their home disciplines, coupled with training across disciplinary lines and developmental experiences, to prepare them to communicate, collaborate, and innovate in a variety of contexts. Training success is evaluated across measurable competency domains including problem definition, research methods, communication, collaboration, and problem-solving. After 3 years the program expanded relationships across fields and professions, successfully established 18 internship opportunities with community partners, created a new dual-title PhD program open to students in five academic departments, and facilitated the coproduction of knowledge with external partners. This model bridges the gaps between research, education, and application, providing an integrated, rigorous graduate training program that fosters collaborative problem-solving between STEM graduate students and the broader community of professionals conducting sustainability work in a postindustrial urban setting

Dawn arrives at Ceres: Exploration of a small, volatile-rich world

On 6 March 2015, Dawn arrived at Ceres to find a dark, desiccated surface punctuated by small, bright areas. Parts of Ceres’ surface are heavily cratered, but the largest expected craters are absent. Ceres appears gravitationally relaxed at only the longest wavelengths, implying a mechanically strong lithosphere with a weaker deep interior. Ceres’ dry exterior displays hydroxylated silicates, including ammoniated clays of endogenous origin. The possibility of abundant volatiles at depth is supported by geomorphologic features such as flat crater floors with pits, lobate flows of materials, and a singular mountain that appears to be an extrusive cryovolcanic dome. On one occasion, Ceres temporarily interacted with the solar wind, producing a bow shock accelerating electrons to energies of tens of kilovolts

On the deflection of asteroids with mirrors

This paper presents an analysis of an asteroid deflection method based on multiple solar concentrators. A model of the deflection through the sublimation of the surface material of an asteroid is presented, with simulation results showing the achievable orbital deflection with, and without, accounting for the effects of mirror contamination due to the ejected debris plume. A second model with simulation results is presented analyzing an enhancement of the Yarkovsky effect, which provides a significant deflection even when the surface temperature is not high enough to sublimate. Finally the dynamical model of solar concentrators in the proximity of an irregular celestial body are discussed, together with a Lyapunov-based controller to maintain the spacecraft concentrators at a required distance from the asteroid

Closed-loop insulin delivery during pregnancy complicated by type 1 diabetes.

OBJECTIVE: This study evaluated closed-loop insulin delivery with a model predictive control (MPC) algorithm during early (12-16 weeks) and late gestation (28-32 weeks) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ten women with type 1 diabetes (age 31 years, diabetes duration 19 years, BMI 24.1 kg/m(2), booking A1C 6.9%) were studied over 24 h during early (14.8 weeks) and late pregnancy (28.0 weeks). A nurse adjusted the basal insulin infusion rate from continuous glucose measurements (CGM), fed into the MPC algorithm every 15 min. Mean glucose and time spent in target (63-140 mg/dL), hyperglycemic (>140 to ≥ 180 mg/dL), and hypoglycemic (140 mg/dL) was 7% (0-40%) in early and 0% (0-6%) in late pregnancy (P = 0.25) and hypoglycemic (<63 mg/dL) was 0% (0-3%) and 0% (0-0%), respectively (P = 0.18). Postprandial glucose control, glucose variability, insulin infusion rates, and CGM sensor accuracy were no different in early or late pregnancy. CONCLUSIONS: MPC algorithm performance was maintained throughout pregnancy, suggesting that overnight closed-loop insulin delivery could be used safely during pregnancy. More work is needed to achieve optimal postprandial glucose control.Diabetes UK (07/0003551), TCC (PDF/01/036), MRC (G0600717

Developing core sets for persons following amputation based on the International Classification of Functioning, Disability and Health as a way to specify functioning

Amputation is a common late stage sequel of peripheral vascular disease and diabetes or a sequel of accidental trauma, civil unrest and landmines. The functional impairments affect many facets of life including but not limited to: Mobility; activities of daily living; body image and sexuality. Classification, measurement and comparison of the consequences of amputations has been impeded by the limited availability of internationally, multiculturally standardized instruments in the amputee setting. The introduction of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in May 2001 provides a globally accepted framework and classification system to describe, assess and compare function and disability. In order to facilitate the use of the ICF in everyday clinical practice and research, ICF core sets have been developed that focus on specific aspects of function typically associated with a particular disability. The objective of this paper is to outline the development process for the ICF core sets for persons following amputation. The ICF core sets are designed to translate the benefits of the ICF into clinical routine. The ICF core sets will be defined at a Consensus conference which will integrate evidence from preparatory studies, namely: (a) a systematic literature review regarding the outcome measures of clinical trails and observational studies, (b) semi-structured patient interviews, (c) international experts participating in an internet-based survey, and (d) cross-sectional, multi-center studies for clinical applicability. To validate the ICF core sets field-testing will follow. Invitation for participation: The development of ICF Core Sets is an inclusive and open process. Anyone who wishes to actively participate in this process is invited to do so

Zaštitno djelovanje selenija protiv prekomjerne ekspresije apoptotskih gena povezanih s karcinomom u štakora izloženih o-krezolu

Cresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1 o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.Krezoli su monometilni derivati fenola koji se često rabe kao otapala te kao posrednici u proizvodnji dezinfekcijskih sredstava, mirisa, pesticida, boja i eksploziva. Otuda i njihova rasprostranjenost u okolišu. Opća je populacija izložena krezolima uglavnom putem zraka. U ovome se toksikološkom istraživanju ocijenilo djelovanje o-krezola, jednoga od tri krezolova izomera, na ekspresiju gena u tkivima jetre i prostate mužjaka štakora. Istraživanje je provedeno na 80 mužjaka, od kojih je 60 tijekom osam tjedana bilo izloženo o-krezolu (1,5 g kg-1, 5 g kg-1, odnosno 15 g kg-1) preko krmiva. Tri skupine štakora primale su uz o-krezol nadomjestak selenija u dozi od 0.1 mg kg-1 (Se, u obliku natrijeva selenita) radi ocjene njegove djelotvornosti protiv toksičnosti o-krezola. Kontrolna skupina nije primala ni o-krezol ni Se, dok je jedna skupina primala samo Se. Preživljenje je bilo podjednako u svih skupina životinja. Štakori izloženi najvišoj dozi o-krezola (15 g kg-1) imali su 16 % manju tjelesnu masu od kontrolne skupine na kraju ispitivanja, što može biti povezano s lošim okusom krmiva zbog primjese visoke doze o-krezola. S istekom osmotjednoga izlaganja o-krezolu životinje su eutanazirane te su prikupljeni uzorci tkiva jetre i prostate. Analiza m-RNA pokazala je značajno povišenu ekspresiju apoptotskih gena CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1 i PKCα, koji su povezani s nastankom karcinoma u skupinama štakora izloženim o-krezolu (5 g kg-1 i 15 g kg-1 u odnosu na kontrolu. Ova je prekomjerna ekspresija poništena u štakora koji su primali selenij. Još nisu jasni mehanizmi iza ovoga zaštitnog djelovanja, na što će odgovoriti buduća istraživanja

Community-based pre-pregnancy care programme improves pregnancy preparation in women with pregestational diabetes.

AIMS/HYPOTHESIS: Women with diabetes remain at increased risk of adverse pregnancy outcomes associated with poor pregnancy preparation. However, women with type 2 diabetes are less aware of and less likely to access pre-pregnancy care (PPC) compared with women with type 1 diabetes. We developed and evaluated a community-based PPC programme with the aim of improving pregnancy preparation in all women with pregestational diabetes. METHODS: This was a prospective cohort study comparing pregnancy preparation measures before and during/after the PPC intervention in women with pre-existing diabetes from 1 June 2013 to 28 February 2017. The setting was 422 primary care practices and ten National Health Service specialist antenatal diabetes clinics. A multifaceted approach was taken to engage women with diabetes and community healthcare teams. This included identifying and sending PPC information leaflets to all eligible women, electronic preconception care templates, online education modules and resources, and regional meetings and educational events. Key outcomes were preconception folic acid supplementation, maternal HbA1c level, use of potentially harmful medications at conception and gestational age at first presentation, before and during/after the PPC programme. RESULTS: A total of 306 (73%) primary care practices actively participated in the PPC programme. Primary care databases were used to identify 5075 women with diabetes aged 18-45 years. PPC leaflets were provided to 4558 (89.8%) eligible women. There were 842 consecutive pregnancies in women with diabetes: 502 before and 340 during/after the PPC intervention. During/after the PPC intervention, pregnant women with type 2 diabetes were more likely to achieve target HbA1c levels ≤48 mmol/mol (6.5%) (44.4% of women before vs 58.5% of women during/after PPC intervention; p = 0.016) and to take 5 mg folic acid daily (23.5% and 41.8%; p = 0.001). There was an almost threefold improvement in 'optimal' pregnancy preparation in women with type 2 diabetes (5.8% and 15.1%; p = 0.021). Women with type 1 diabetes presented for earlier antenatal care during/after PPC (54.0% vs 67.3% before 8 weeks' gestation; p = 0.003) with no other changes. CONCLUSIONS/INTERPRETATION: A pragmatic community-based PPC programme was associated with clinically relevant improvements in pregnancy preparation in women with type 2 diabetes. To our knowledge, this is the first community-based PPC intervention to improve pregnancy preparation for women with type 2 diabetes. DATA AVAILABILITY: Further details of the data collection methodology, individual clinic data and the full audit reports for healthcare professionals and service users are available from https://digital.nhs.uk/data-and-information/clinical-audits-and-registries/our-clinical-audits-and-registries/national-pregnancy-in-diabetes-audit