Sodium glucose co-transporter-2 inhibitor-induced diabetic ketoacidosis following tooth extraction: improving awareness among dental practitioners.

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are a relatively new class of oral glucose lowering agents that improve glycaemic control and also provide significant cardiac and renal benefits. However, SGLT-2i use is associated with a small but significant increased risk of diabetic ketoacidosis (DKA) especially during periods of reduced oral intake such as following dental procedures, bowel preparation for colonoscopy, surgery and concurrent illness. In contrast with typical DKA, in many cases of SGLT2i-associated DKA, the blood glucose is normal or only slightly elevated, giving rise to the term euglycaemic DKA (euDKA). Patients with euDKA often present with non-specific symptoms. Moreover, their normal or only mildly elevated blood glucose levels might lead to delayed diagnosis and treatment and hence potentially life-threatening complications. Not only should patients taking an SGLT-2i be informed about the risk of euDKA, and be provided with SGLT-2i sick day management education, but clinicians should also be alert to this diagnosis.

Novel urchin-like FeCo oxide nanostructures supported carbon spheres as a highly sensitive sensor for hydrazine sensing application.

Herein, we successfully fabricated a novel nanostructure based on hierarchical urchin-like FeCo oxide supported carbon spheres (FeCo Oxide/CSs) via a two-step hydrothermal method followed by a simple annealing step at 300 °C under air. It was found that such urchin-like FeCo Oxide/CSs structure exhibited superior catalytic activity towards hydrazine oxidation to CSs, Fe Oxide/CSs, Co Oxide/CSs, and FeCo Hydroxide/CSs material. In this regard, the FeCo Oxide/CSs displayed a wide linear detection range of 0.1-516.6 µM, low detection limit of 0.1 µM, and long-term stability. The material also showed good selectivity towards hydrazine detection in the presence of various interferences, such as uric acid, ascorbic acid, urea, dopamine, Na+, SO42-, K+, and Cl-. The excellent sensing performance of the FeCo Oxide/CSs was assumed to the unique hierarchical urchin structure with the high density and uniformity of nano-sized FeCo Oxide nanoneedles, which produced massive electroactive sites and enhanced charge transfer ability. The achieved results implied that the FeCo Oxide/CSs may be a great candidate for sensitive hydrazine detection.

IGF-binding proteins.

Insulin-like growth factor-binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellular space, (ii) interaction with and modulation of other growth factor pathways including EGF, TGF-ß and VEGF, and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

Scaling of the mean and variance of population dynamics under fluctuating regimes.

Theoretical ecologists have long sought to understand how the persistence of populations depends on the interactions between exogenous (biotic and abiotic) and endogenous (e.g., demographic and genetic) drivers of population dynamics. Recent work focuses on the autocorrelation structure of environmental perturbations and its effects on the persistence of populations. Accurate estimation of extinction times and especially determination of the mechanisms affecting extinction times is important for biodiversity conservation. Here we examine the interaction between environmental fluctuations and the scaling effect of the mean population size with its variance. We investigate how interactions between environmental and demographic stochasticity can affect the mean time to extinction, change optimal patch size dynamics, and how it can alter the often-assumed linear relationship between the census size and the effective population size. The importance of the correlation between environmental and demographic variation depends on the relative importance of the two types of variation. We found the correlation to be important when the two types of variation were approximately equal; however, the importance of the correlation diminishes as one source of variation dominates. The implications of these findings are discussed from a conservation and eco-evolutionary point of view.

Diabetes is a major risk factor for mortality after lung transplantation.

Survival following lung transplant (LTx) remains significantly lower than after other solid organ transplants. Diabetes mellitus (DM) is a mortality risk factor not comprehensively studied in LTx recipients. Notably, neither the relation of time of DM onset to survival nor the actual causes of DM-associated excess mortality have been described. We determined DM status, DM diagnosis date and all-cause mortality in 386 consecutive adults who underwent LTx at our institution from January 1, 2001 to July 31, 2010. The relationship of DM to survival both as a categorical and time-dependent variable was studied. Fifty-three percent of patients had DM. Overall median survival was 5.2 (95% CI 3.8-6.6) years. At study end, 52% of patients had died, of whom 64% had DM. Estimated median survival was 10 years in patients without DM, 5.0 (3.3-6.8) years in patients with DM pre- and post-LTx and 4.3 (3.1-5.5) years in patients with new onset DM. As a time-dependent covariate, DM was the strongest risk factor for mortality, hazard ratio 3.96 (2.85-5.51). Bronchiolitis obliterans syndrome was the main cause of death in all patients surviving >90 days, but its incidence was not increased in patients with DM. Further studies are warranted to determine whether improved glycemic control could improve outcomes in LTx recipients.

Stereotactic radiosurgery for treatment of Cushing disease: an Australian experience.

Stereotactic radiation therapy has emerged as an alternative to conventional radiotherapy for treatment of Cushing disease. The aim of this study was to investigate the efficacy and safety of this treatment. Records of patients with Cushing disease treated with stereotactic radiation were reviewed. Seventeen patients underwent stereotactic radiosurgery. Ten achieved remission after a mean of 23 (95% confidence interval, 15-31) months, and two developed hormone deficiencies.

A high-resolution 15,000(Rad) radiation hybrid panel for the domestic cat.

The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first-generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000(Rad) radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000(Rad) RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000(Rad) RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons.

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models.

AIMS/HYPOTHESIS: We investigated the contribution of AGEs to the impairment of reverse cholesterol transport (RCT) variables in diabetic individuals and in two animal models of diabetic obesity and of renal impairment. METHODS: The capacity of plasma and HDL from 26 individuals with moderately controlled type 2 diabetes to support cholesterol efflux was compared with 26 age- and sex-matched individuals without diabetes. We also compared the rates of RCT in vivo in two animal models: db/db mice and mice with chronic renal failure. RESULTS: Diabetic individuals had characteristic dyslipidaemia and higher levels of plasma AGEs. The capacity of whole plasma, ApoB-depleted plasma and isolated HDL to support cholesterol efflux was greater for diabetic patients compared with controls despite their lower HDL-cholesterol levels. The capacity of plasma to support cholesterol efflux correlated with plasma levels of cholesteryl ester transfer protein and levels of ApoB, but not with levels of AGE. RCT was severely impaired in db/db mice despite elevated HDL-cholesterol levels and no change in AGE concentration, whereas RCT in uraemic mice was unaffected despite elevated AGE levels. CONCLUSIONS/INTERPRETATION: AGEs are unlikely to contribute significantly to the impairment of RCT in type 2 diabetes.

Hacia un uso adecuado de la telerradiología / Toward the appropriate use of teleradiology

La telerradiología no consiste en transmitir imágenes e información entre puntos distantes, sino en compartir conocimiento y trabajar en red. Facilita el acceso rápido a informes radiológicos y segundas opiniones; la teleconsulta entre médicos; la mejora de la asistencia a los pacientes; el acceso a sistemas complejos del posproceso y ayuda al diagnóstico; el apoyo a la investigación y la formación; el acercamiento de los servicios sanitarios aislados a las prestaciones continuadas o de mayor experiencia; la cobertura de 24 horas; y la promoción de la competencia entre los servicios de radiología. Los pacientes están mejor atendidos con una relación estrecha con el radiólogo. Pero la telerradiología no debe mermar la eficacia de un servicio clínico de radiología próximo al paciente. El control de los requerimientos legales, de los problemas clínico-asistenciales que puede generar y la adecuación de su uso para mejorar la salud de la población son la base de esta propuesta (AU)

Teleradiology involves much more than merely transmitting images and information between two points: teleradiology consists of sharing knowledge and working together in a network. It facilitates rapid access to radiological reports and second opinions, remote consulting among physicians, improved patient care, access to complex tools for postprocessing and computer-aided diagnosis, support for research and training projects, ties between isolated healthcare providers and busier or more experienced providers, 24-hour coverage, and competition among radiology departments. A close relation with the radiologist leads to better care. However, teleradiology should not have negative effects on the efficacy of the clinical radiology service that is closest to the patient. This article focuses on the legal requirements of teleradiology services and on the clinical problems that can arise in teleradiology settings, with the ultimate aim of ensuring the appropriate use of teleradiology to improve healthcare (AU)

[Toward the appropriate use of teleradiology]. / Hacia un uso adecuado de la telerradiología.

Teleradiology involves much more than merely transmitting images and information between two points: teleradiology consists of sharing knowledge and working together in a network. It facilitates rapid access to radiological reports and second opinions, remote consulting among physicians, improved patient care, access to complex tools for postprocessing and computer-aided diagnosis, support for research and training projects, ties between isolated healthcare providers and busier or more experienced providers, 24-hour coverage, and competition among radiology departments. A close relation with the radiologist leads to better care. However, teleradiology should not have negative effects on the efficacy of the clinical radiology service that is closest to the patient. This article focuses on the legal requirements of teleradiology services and on the clinical problems that can arise in teleradiology settings, with the ultimate aim of ensuring the appropriate use of teleradiology to improve healthcare.

Environmental fluctuations and level of density-compensation strongly affects the probability of fixation and fixation times.

The probability of, and time to, fixation of a mutation in a population has traditionally been studied by the classic Wright-Fisher model where population size is constant. Recent theoretical expansions have covered fluctuating populations in various ways but have not incorporated models of how the environment fluctuates in combination with different levels of density-compensation affecting fecundity. We tested the hypothesis that the probability of, and time to, fixation of neutral, advantageous and deleterious mutations is dependent on how the environment fluctuates over time, and on the level of density-compensation. We found that fixation probabilities and times were dependent on the pattern of autocorrelation of carrying capacity over time and interacted with density-compensation. The pattern found was most pronounced at small population sizes. The patterns differed greatly depending on whether the mutation was neutral, advantageous, or disadvantageous. The results indicate that the degree of mismatch between carrying capacity and population size is a key factor, rather than population size per se, and that effective population sizes can be very low also when the census population size is far above the carrying capacity. This study highlights the need for explicit population dynamic models and models for environmental fluctuations for the understanding of the dynamics of genes in populations.

Population viability analysis on domestic horse breeds (Equus caballus).

In this study, we performed a population viability analysis on 3 domestic horse breeds (Equus caballus) of Danish origin, namely, the Frederiksborg, the Knabstrupper, and the Jutland breeds. Because of their small population sizes, these breeds are considered endangered. The Vortex software simulation package was used for the population viability analysis. First, we investigated the future viability of these breeds based on present demographic and environmental parameters. Second, a sensitivity analysis revealed the most important variables for the viability of these breeds. Third, we examined management scenarios in which one of the studbooks was closed. According to the Vortex analysis, 2 of the breeds (Knabstrupper and Jutland) will persist for the next 200 yr, whereas the smaller breed (Frederiksborg) could become extinct within 40 yr. The sensitivity analyses indicated that the variables concerning reproduction of the mares had the greatest impact, with the number of mares actively breeding being the most influential on the population forecasts. The results suggest that closing the Knabstrupper studbooks can be done only if increasing the number of mares actively breeding counteracts the loss of genetic variation attributable to such a management strategy. It is recommended, based on these results, that the number of Frederiksborg and Knabstrupper mares actively breeding must be increased to approximately 30% in the 2 breeds that are presently using only 13%, while leaving the third (Frederiksborg ) at its present 30% level. Monitoring of the breeds in the future, however, may be exploited to adjust the breeding strategies. We suggest that the large amount of data required by Vortex makes it very useful for analyzing domestic animals because of the comprehensive data material often available. The results of this analysis accord with other studies on the Prezwalski horse, indicating robustness in the parameter sensitivity for horses.

Recombinant human thyroid-stimulating hormone (Thyrogen) in thyroid cancer follow up: experience at a single institution.

BACKGROUND: Recombinant human thyroid-stimulating hormone (Thyrogen; Genzyme Corporation, Cambridge, MA, USA) (rhTSH)-stimulated serum thyroglobulin (Tg) (stim-Tg) and (131)I whole-body scanning (WBS) have been reported to allow follow up of patients with thyroid cancer without the symptoms of thyroxine withdrawal and with equivalent diagnostic information to that obtained after thyroxine withdrawal. The aim of the study was to report results of rhTSH use at the Alfred Hospital, Melbourne, from 1999 to 2006 and in particular to examine the significance of detectable serum Tg after rhTSH in relation to thyroid cancer staging and to compare the sensitivity of rhTSH-stimulated serum Tg to whole-body (131)I scanning (WBS) in the detection of residual and recurrent thyroid cancer. METHODS: The study was a retrospective chart review. RESULTS: In 90 patients, rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to facilitate treatment with (131)I. In stages I and II cancer (n = 42), of three patients with stim-Tg 1-2 microg/L, none had identifiable disease, and the three patients who had stim-Tg >2 microg/L did not experience recurrent disease during follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim-Tg 1-2 microg/L had identifiable disease and 7 of 10 with stim-Tg >2 microg/L had identifiable disease. In Tg-positive, WBS-negative disease, further imaging identified persistent/recurrent disease. CONCLUSION: rhTSH was effective and safe in the management of thyroid cancer follow up for diagnosis of persistent/recurrent cancer and to enable (131)I treatment. In no case did rhTSH-stimulated WBS identify the presence of disease not also identified by raised basal Tg or stim-Tg. Therefore, in low risk cancer WBS may be omitted.

Roles profesionales en los servicios de radiología / No disponible

No disponible

The Tabby cat locus maps to feline chromosome B1.

The Tabby markings of the domestic cat are unique coat patterns for which no causative candidate gene has been inferred from other mammals. In this study, a genome scan was performed on a large pedigree of cats that segregated for Tabby coat markings, specifically for the Abyssinian (Ta-) and blotched (tbtb) phenotypes. There was linkage between the Tabby locus and eight markers on cat chromosome B1. The most significant linkage was between marker FCA700 and Tabby (Z = 7.56, theta = 0.03). Two additional markers in the region supported linkage, although not with significant LOD scores. Pairwise analysis of the markers supported the published genetic map of the cat, although additional meioses are required to refine the region. The linked markers cover a 17-cM region and flank an evolutionary breakpoint, suggesting that the Tabby gene has a homologue on either human chromosome 4 or 8. Alternatively, Tabby could be a unique locus in cats.

Intact theory of mind in TBI with behavioural disturbance.

Behavioural disturbance following TBI is common. Theory of mind(ToM) deficits have been noted in autism where difficulties with social interaction and communication are evident. It was hypothesised that TBI patients with behavioural disturbance would show deficits on ToM tasks independent of executive function. Twenty TBI patients with behavioural disturbance and 20 TBI patients without were assessed on verbal (stories) and non-verbal (cartoons) ToM tasks,standard psychometry, and measures of executive function.TBI patients were unimpaired on the ToM tasks. Both groups were unimpaired on standard tests of executive function (verbal fluency and trail making test) but were impaired on the Behavioural Assessment of Dysexecutive Syndrome (BADS). Groups did not differ significantly on these tests. It is concluded that ToM ability does not predict behavioural disturbance and may be independent of executive functioning.

The evolution of n-player cooperation-threshold games and ESS bifurcations.

An evolutionary game of individuals cooperating to obtain a collective benefit is here modelled as an n-player Prisoner's Dilemma game. With reference to biological situations, such as group foraging, we introduce a threshold condition in the number of cooperators required to obtain the collective benefit. In the simplest version, a three-player game, complex behaviour appears as the replicator dynamics exhibits a catastrophic event separating a parameter region allowing for coexistence of cooperators and defectors and a region of pure defection. Cooperation emerges through an ESS bifurcation, and cooperators only thrive beyond a critical point in cost-benefit space. Moreover, a repelling fixed point of the dynamics acts as a barrier to the introduction of cooperation in defecting populations. The results illustrate the qualitative difference between two-player games and multiple player games and thus the limitations to the generality of conclusions from two-player games. We present a procedure to find the evolutionarily stable strategies in any n-player game with cost and benefit depending on the number of cooperators. This was previously done by Motro [1991. Co-operation and defection: playing the field and the ESS. J. Theor. Biol. 151, 145-154] in the special cases of convex and concave benefit functions and constant cost.

Insulin-like growth factor binding protein-2 binding to extracellular matrix plays a critical role in neuroblastoma cell proliferation, migration, and invasion.

IGF binding proteins (IGFBPs) modulate IGF cellular bioavailability and may directly regulate tumor growth and invasion. We have previously shown that IGFBP-2 binds and localizes IGF-I to the pericellular matrix and have provided some evidence suggesting that the heparin binding domain (HBD) or the arginine-glycine-aspartic acid (RGD) integrin binding motif may be involved in these interactions. However, the precise mechanisms involved remain to be elucidated. We therefore mutated the HBD or RGD sequence of IGFBP-2 and investigated consequent effects on extracellular matrix (ECM) binding, IGF-induced proliferation, and migration of neuroblastoma cells. IGFBP-2 and its arginine-glycine-glutamic acid (RGE) mutant similarly bound ECM components, whereas binding of mutant HBD-IGFBP-2 to each of the ECM substrates was markedly reduced by 70-80% (P < 0.05). IGF-I (100 ng/ml) increased incorporation of 3H-thymidine in neuroblastoma SK-N-SHEP cells by approximately 30%, an effect blunted by exogenously added native or either mutant IGFBP-2. Overexpression of IGFBP-2 and its RGE mutant potently promoted SHEP cell proliferation (5-fold), whereas SHEP cell proliferation was negligible when HBD-IGFBP-2 was overexpressed. Addition or overexpression of IGFBP-2 and its RGE mutant potently (P < 0.05) enhanced SHEP cell migration/invasion through the ECM. However, overexpression of the HBD-IGFBP-2 mutant potently inhibited (50-60%) SHEP cell invasion through ECM. Thus, IGFBP-2, which binds to the ECM, enhances proliferation and metastatic behavior of neuroblastoma cells, functions that directly or indirectly use the HBD but not the integrin binding sequence. Our novel findings thus point to a key role for the HBD of IGFBP-2 in the control and regulation of neuroblastoma growth and invasion.

Fibroblast growth factor-2 over-rides insulin-like growth factor-I induced proliferation and cell survival in human neuroblastoma cells.

The insulin-like growth factor (IGF) system is a key regulator of cell growth, survival and differentiation, and these functions are co-modulated by other growth factors including fibroblast growth factor-2 (FGF-2). To investigate IGF/FGF interactions in neuronal cells, we employed neuroblastoma cells (SK-N-MC). In serum free conditions proliferation of the SK-N-MC cells was promoted by IGF-I (25 ng/ml), but blunted by FGF-2 (50 ng/ml). IGF-I-induced proliferation was abolished in the presence of FGF-2 even when IGF-I was used at 100 ng/ml. In addition to our previously described FGF-2 induced proteolytic cleavage of IGFBP-2, we found that FGF-2 increased IGFBP-6 levels in conditioned medium (CM) without affecting IGFBP-6 mRNA abundance. Modulation of IGFBP-2 and -6 levels were not significant mechanisms involved in the blockade of IGF-I action since the potent IGF-I analogues [QAYL]IGF-I and des(1-3)IGF-I (minimal IGFBP affinity) were unable to overcome FGF-2 inhibition of cell proliferation. FGF-2 treated cells showed morphological differentiation expressing the TUJ1 neuronal marker while cells treated with IGF-I alone showed no morphological change. When IGF-I was combined with FGF-2, however, cell morphology was indistinguishable from that seen with FGF-2 alone. FGF-2 inhibited proliferation and enhanced differentiation was also associated with a 70% increase in cell death. Although IGF-I alone was potently anti-apoptotic (60% decreased), IGF-I was unable to prevent apoptosis when administrated in combination with FGF-2. Gene-array analysis confirmed FGF-2 activation of the intrinsic and extrinsic apoptotic pathways and blockade of IGF anti-apoptotic signaling. FGF-2, directly and indirectly, overcomes the proliferative and anti-apoptotic activity of IGF-I by complex mechanisms, including enhancement of differentiation and apoptotic pathways, and inhibition of IGF-I induced anti-apoptotic signalling. Modulation of IGF binding protein abundance by FGF-2 does not play a significant role in inhibition of IGF-I induced mitogenesis.