Microvascular complications of impaired glucose tolerance.

Journal ArticleImpaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both large- and small-vessel vascular complications, independent of a patient's progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known

Effects of serum and insulin-like growth factors on human neuroblastoma cell growth

Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides expressed in both developing and adult tissues. To examine the effects of IGFs on neuronal growth, we used SH-SY5Y neuroblastoma cells as an in vitro model of nervous system development. In the current study, we found that either IGF-I (0.1 to 10 nM), insulin (0.1 to 5 [mu]g/ml) or calf serum (0.1 to 3%) increased SH-SY5Y proliferation over a 3 day period in a dose dependent manner. In each case, treatment with anti-IGF-I receptor antibodies blocked cell proliferation. IGF-II mRNA levels correlated with SH-SY5Y cell density; subconfluent cells expressed high levels of IGF-II mRNA while low levels of IGF-II mRNA were present in confluent cells. Similarly, serum deprivation increased IGF-I receptor mRNA by 4-fold. Collectively, these results support the concept that an IGF/IGF-I receptor system at least partially mediates SH-SY5Y cell proliferation and suggests the importance of IGFs in regulating neuronal growth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30511/1/0000141.pd

Microvascular complications of impaired glucose tolerance. Perspectives in diabetes

Upośledzona tolerancja glukozy (IGT, impaired glucose tolerance) jest wskaźnikiem insulinooporności i czynnikiem predykcyjnym powikłań naczyniowych o charakterze makro- i mikroangiopatii, niezależnie od stopnia zaawansowania cukrzycy. U chorych z IGT istotnie zwiększa się ryzyko zgonu i chorobowości związane z zawałem serca, udarem mózgu i zmianami okluzyjnymi dużych naczyń. Upośledzona tolerancja glukozy jest bardziej wiarygodnym czynnikiem predykcyjnym chorób układu sercowo-naczyniowego niż nieprawidłowa glikemia na czczo prawdopodobnie dlatego, że jest lepszym miernikiem insulinooporności. Ponadto, IGT wykazuje niezależny związek z tradycyjnymi powikłaniami cukrzycy o charakterze mikroangiopatii, w tym również z retinopatią, nefropatią i polineuropatią, które są tematem niniejszego opracowania. Hamowanie zależnego od tlenku azotu rozszerzenia naczyń, uszkodzenie śródbłonka spowodowane zwiększonym uwalnianiem z adipocytów wolnych kwasów tłuszczowych i adipocytokin oraz uszkodzenia śródbłonka i komórek narządów docelowych spowodowane bezpośrednio przez zmiany metaboliczne przyczyniają się do powstania zmian naczyniowych. Wczesne wykrycie IGT pozwala wprowadzić ścisłą dietę i zwiększoną aktywność fizyczną, co, jak udowodniono, znacznie skuteczniej poprawia glikemię poposiłkową i spowalnia progresję cukrzycy niż farmakoterapia. Nie wiadomo jednak, w jakim stopniu takie działania mogą ograniczyć rozwój powikłań.Impaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both largeand small-vessel vascular complications, independent of a patient’s progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide- mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known

Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function

Background: Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan? (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology. Materials and Methods: Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants. Results: Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140359/1/dia.2015.0396.pd

Stringy Robinson-Trautman Solutions

A class of solutions of the low energy string theory in four dimensions is studied. This class admits a geodesic, shear-free null congruence which is non-twisting but in general diverging and the corresponding solutions in Einstein's theory form the Robinson-Trautman family together with a subset of the Kundt's class. The Robinson-Trautman conditions are found to be frame invariant in string theory. The Lorentz Chern-Simons three form of the stringy Robinson-Trautman solutions is shown to be always closed. The stringy generalizations of the vacuum Robinson-Trautman equation are obtained and three subclasses of solutions are identified. One of these subclasses exists, among all the dilatonic theories, only in Einstein's theory and in string theory. Several known solutions including the dilatonic black holes, the pp- waves, the stringy C-metric and certain solutions which correspond to exact conformal field theories are shown to be particular members of the stringy Robinson-Trautman family. Some new solutions which are static or asymptotically flat and radiating are also presented. The radiating solutions have a positive Bondi mass. One of these radiating solutions has the property that it settles down smoothly to a black hole state at late retarded times.Comment: Latex, 30 Pages, 1 Figure; to appear in Phys. Rev.

Surface-enhanced Raman scattering measurement from a lipid bilayer encapsulating a single decahedral nanoparticle mediated by an optical trap

We present a new technique for the study of model membranes on the length-scale of a single nanosized liposome. Silver decahedral nanoparticles have been encapsulated by a model unilamellar lipid bilayer creating nano-sized lipid vesicles. The metal core has two roles (i) increasing the polarizability of vesicles, enabling a single vesicle to be isolated and confined in an optical trap, and (ii) enhancing Raman scattering from the bilayer, via the high surface-plasmon field at the sharp vertices of the decahedral particles. Combined this has allowed us to measure a Raman fingerprint from a single vesicle of 50 nmdiameter, containing just ∼104 lipid molecules in a bilayer membrane over a surface area of <0.01 µm2, equivalent to a volume of approximately 1 zepto-litre. Raman scattering is a weak and inefficient process and previous studies have required either a substantially larger bilayer area in order to obtain a detectable signal, or the tagging of lipid molecules with a chromophore to provide an indirect probe of the bilayer. Our approach is fully label-free and bio-compatible and, in the future, it will enable much more localized studies of the heterogeneous structure of lipid bilayers and of membrane-bound components than is currently possible

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3′-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50–6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders

Does Gender Influence Colour Choice in the Treatment of Visual Stress?

Purpose Visual Stress (VS) is a condition in which words appear blurred, in motion, or otherwise distorted when reading. Some people diagnosed with VS find that viewing black text on white paper through coloured overlays or precision tinted lenses (PTLs) reduces symptoms attributed to VS. The aim of the present study is to determine whether the choice of colour of overlays or PTLs is influenced by a patient’s gender. Methods Records of all patients attending a VS assessment in two optometry practices between 2009 and 2014 were reviewed retrospectively. Patients who reported a significant and consistent reduction in symptoms with either overlay and or PTL were included in the analysis. Overlays and PTLs were categorized as stereotypical male, female or neutral colours based on gender preferences as described in the literature. Chi-square analysis was carried out to determine whether gender (across all ages or within age groups) was associated with overlay or PTL colour choice. Results 279 patients (133 males and 146 females, mean age 17 years) consistently showed a reduction in symptoms with an overlay and were included. Chi-square analysis revealed no significant association between the colour of overlay chosen and male or female gender (Chi-square 0.788, p = 0.674). 244 patients (120 males and 124 females, mean age 24.5 years) consistently showed a reduction in symptoms with PTLs and were included. Chi-square analysis revealed a significant association between stereotypical male/female/neutral colours of PTLs chosen and male/female gender (Chi-square 6.46, p = 0.040). More males preferred stereotypical male colour PTLs including blue and green while more females preferred stereotypical female colour PTLs including pink and purple. Conclusions For some VS patients, the choice of PTL colour is influenced not only by the alleviation of symptoms but also by other non-visual factors such as gender

The perceived impact of location privacy: A web-based survey of public health perspectives and requirements in the UK and Canada

<p>Abstract</p> <p>Background</p> <p>The "place-consciousness" of public health professionals is on the rise as spatial analyses and Geographic Information Systems (GIS) are rapidly becoming key components of their toolbox. However, "place" is most useful at its most precise, granular scale – which increases identification risks, thereby clashing with privacy issues. This paper describes the views and requirements of public health professionals in Canada and the UK on privacy issues and spatial data, as collected through a web-based survey.</p> <p>Methods</p> <p>Perceptions on the impact of privacy were collected through a web-based survey administered between November 2006 and January 2007. The survey targeted government, non-government and academic GIS labs and research groups involved in public health, as well as public health units (Canada), ministries, and observatories (UK). Potential participants were invited to participate through personally addressed, standardised emails.</p> <p>Results</p> <p>Of 112 invitees in Canada and 75 in the UK, 66 and 28 participated in the survey, respectively. The completion proportion for Canada was 91%, and 86% for the UK. No response differences were observed between the two countries. Ninety three percent of participants indicated a requirement for personally identifiable data (PID) in their public health activities, including geographic information. Privacy was identified as an obstacle to public health practice by 71% of respondents. The overall self-rated median score for knowledge of privacy legislation and policies was 7 out of 10. Those who rated their knowledge of privacy as high (at the median or above) also rated it significantly more severe as an obstacle to research (<it>P </it>< 0.001). The most critical cause cited by participants in both countries was bureaucracy.</p> <p>Conclusion</p> <p>The clash between PID requirements – including granular geography – and limitations imposed by privacy and its associated bureaucracy require immediate attention and solutions, particularly given the increasing utilisation of GIS in public health. Solutions include harmonization of privacy legislation with public health requirements, bureaucratic simplification, increased multidisciplinary discourse, education, and development of toolsets, algorithms and guidelines for using and reporting on disaggregate data.</p