493 research outputs found
A preliminary study on whether HbA1c levels can predict visual dependence for spatial orientation in asymptomatic Type 2 diabetic patients
Introduction: Diabetes-induced vestibular dysfunction has been commonly reported, and asymptomatic patients with type 2 diabetes display higher degrees of perceptual visual dependence for spatial orientation than healthy controls. This study aims to assess whether HbA1c can predict such visual dependence in the diabetic patients. Methods and Materials: Diabetic patients were divided into 2 groups: 22 subjects with âgoodâ (HbA1c < 7%) and 25 with âpoorâ (HbA1c â„
7%) glycemic control. Otolithic vestibular function was tested using the computerized rod-and-frame test (CRFT) and results
for the two diabetic groups were compared to 29 healthy controls. Results: When the frame was tilted, the diabetic group with âgoodâ glycemic control had largest positioning errors, with a significant difference only in comparison to the control group. The âgoodâ glycemic group exhibited larger degree of asymmetry under titled frame condition. Although HbA1c was not associated with vestibular asymmetry in any diabetic group, it was significantly associated with visual dependence in the âgoodâ glycemic group. During frame tilts, 10 diabetic patients had positioning errors above the reference range of 3.3°, 8 of which belonged to the âgoodâ glycemic diabetic group. Conclusions: Diabetes disease processes may affect vestibular symmetry during visuo-vestibular conflicts, even in asymptomatic diabetics within the recommended glycemic range. The weak correlations between HbA1c and CRFT parameters may indicate that HbA1c cannot fully predict visual dependence or asymmetry on the CRFT in patients with diabetes, and different glycemic disorders may affect vestibular dependent spatial orientation in diabetic patients
Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?
Mean terminal restriction fragment (TRF) lengths in white blood cells (WBCs) have been previously found to be associated with breast cancer. To assess whether this marker could be used as a test for breast cancer susceptibility in women, TRF length was measured in 72 treated female breast cancer patients and 1696 unaffected female controls between the ages of 45 and 77 from the Twin Research Unit at St Thomas' Hospital, as well as 140 newly diagnosed breast cancer cases and 108 mammographically screened unaffected controls from Guy's Hospital. Mean TRF was also tested for correlation with chromosome radiosensitivity and apoptotic response in the Guy's Hospital patients. After adjusting for age, smoking and body mass index, there was no significant difference in TRF lengths between the treated breast cancer patients and unaffected controls (P=0.71). A positive correlation between age-adjusted apoptotic response and mean TRF in newly diagnosed untreated breast cancer patients (P=0.008) was identified but no significant difference in TRF lengths between breast cancer patients and unaffected controls was detected (P=0.53). This suggests that TRF lengths in WBC, is not a marker of breast cancer susceptibility and does not vary significantly between affected women before and after treatment
The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells
Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humansâparticularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis.
<p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation.
<p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI.
<p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL
Responsible participation and housing: restoring democratic theory to the scene
Tensions between individual liberty and collective social justice characterise many advanced liberal societies. These tensions are reflected in the challenges posed for representative democracy both by participatory democratic practices and by the current emphasis on (so-called) responsible participation. Based on the example of âcommunityâ housing associations in Scotland, this paper explores these tensions. It is argued that the critique of responsibility may have been over-stated â that, in particular, âcommunityâ housing associations offer the basis for relatively more inclusive and effective processes of decision-making than council housing, which relies on the traditional processes and institutions of representative local government for its legitimacy
Competing Ultrafast Energy Relaxation Pathways in Photoexcited Graphene
For most optoelectronic applications of graphene a thorough understanding of
the processes that govern energy relaxation of photoexcited carriers is
essential. The ultrafast energy relaxation in graphene occurs through two
competing pathways: carrier-carrier scattering -- creating an elevated carrier
temperature -- and optical phonon emission. At present, it is not clear what
determines the dominating relaxation pathway. Here we reach a unifying picture
of the ultrafast energy relaxation by investigating the terahertz
photoconductivity, while varying the Fermi energy, photon energy, and fluence
over a wide range. We find that sufficiently low fluence ( 4
J/cm) in conjunction with sufficiently high Fermi energy (
0.1 eV) gives rise to energy relaxation that is dominated by carrier-carrier
scattering, which leads to efficient carrier heating. Upon increasing the
fluence or decreasing the Fermi energy, the carrier heating efficiency
decreases, presumably due to energy relaxation that becomes increasingly
dominated by phonon emission. Carrier heating through carrier-carrier
scattering accounts for the negative photoconductivity for doped graphene
observed at terahertz frequencies. We present a simple model that reproduces
the data for a wide range of Fermi levels and excitation energies, and allows
us to qualitatively assess how the branching ratio between the two distinct
relaxation pathways depends on excitation fluence and Fermi energy.Comment: Nano Letters 201
Dialectics and difference: against Harvey's dialectical post-Marxism
David Harvey`s recent book, Justice, nature and the geography of difference (JNGD), engages with a central philosophical debate that continues to dominate human geography: the tension between the radical Marxist project of recent decades and the apparently disempowering relativism and `play of difference' of postmodern thought. In this book, Harvey continues to argue for a revised `post-Marxist' approach in human geography which remains based on Hegelian-Marxian principles of dialectical thought. This article develops a critique of that stance, drawing on the work of Jacques Derrida, Gilles Deleuze and Felix Guattari. I argue that dialectical thinking, as well as Harvey's version of `post-Marxism', has been undermined by the wide-ranging `post-' critique. I suggest that Harvey has failed to appreciate the full force of this critique and the implications it has for `post-Marxist' ontology and epistemology. I argue that `post-Marxism', along with much contemporary human geography, is constrained by an inflexible ontology which excessively prioritizes space in the theory produced, and which implements inflexible concepts. Instead, using the insights of several `post-' writers, I contend there is a need to develop an ontology of `context' leading to the production of `contextual theories'. Such theories utilize flexible concepts in a multilayered understanding of ontology and epistemology. I compare how an approach which produces a `contextual theory' might lead to more politically empowering theory than `post-Marxism' with reference to one of Harvey's case studies in JNGD
Anti-nociceptive and desensitizing effects of olvanil on capsaicin-induced thermal hyperalgesia in the rat
Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanilâs anti-hyperalgesic effects were also investigated.
Methods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced thermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies of DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses. Statistical analysis used Studentâs t test or one way ANOVA followed by Dunnettâs post-hoctest as appropriate.
Results: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium concentrations [Ca2+]I in cultured DRG neurons. Olvanil was able to des ensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intra plantar injection of capsaicin (0.1, 0.3 and 1ÎŒg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1ÎŒg) produced no hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1ÎŒg) altered neither capsaicin-induced thermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1receptors.
Conclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizingTRPV1 channels in a CB 1 receptor-independent fashion. The results presented clearly support the potential for olvanil in the development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted side effects of capsaicin treatments
Smoking, self-regulation and moral positioning: a focus group study with British smokers from a disadvantaged community
Smoking in many Western societies has become a both moral aand health issue in recent years, but little is known about how smokers position themselves and regulate their behaviour in this context. In this article, we report the findings from a study investigating how smokers from an economically disadvantaged community in the East Midlands (UK) respond to concerns about the health impact of smoking on others. We conducted ten focus group (FG) discussions with mixed groups (by smoking status and gender; N = 58 participants) covering a range of topics, including smoking norms, self-regulation, and smoking in diverse contexts. We transcribed all FG discussions before analysing the data using techniques from discourse anlysis. Smokers in general positioned themselves as socially responsible smokers and morally upstanding citizens. This position was bolstered in two main ways: ‘everyday accommodation', whereby everyday efforts to accommodate the needs of non-smokers were referenced, and ‘taking a stand', whereby proactive interventions to prevent smoking in (young) others were cited. We suggest that smoking cessation campaigns could usefully be informed by this ethic of care for others
Activation and discovery of earth-abundant metal catalysts using sodium tert-butoxide
First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2Ï+2Ï] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis
Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis
Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man
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