bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is risk of diabetic retinopathy lower in Australia’s Greek‐born migrants?
Authors: Brazionis L. , Rowley K. , Itsiopoulos C. , O’Dea K. 
Published: April 2010

Diabet. Med. 27, 660–665 (2010)AbstractAim  The standardized cardiovascular disease death rate for the Greek population in Crete has increased since the 1960s, unlike the all‐cause and cardiovascular disease death rate for Australia’s Greek migrant population, which has remained paradoxically low. A small window of opportunity remains in which the vascular profile of this interesting atypical migrant population can be characterized. This study assessed whether ethnicity modulates the risk of diabetic retinopathy in Greek‐born migrants to Australia.Methods  The study design was a community‐based cross‐sectional study of diabetic retinopathy in 107 Greek‐born and Australian‐born men with Type 2 diabetes, aged 44–83 years. Diabetic retinopathy was assessed by mydriatic three‐field retinal photography.Results  Prevalence of diabetic retinopathy was lower in Greek‐born than in Australian‐born participants (22 and 37%, respectively). Despite having a higher mean systolic blood pressure level (148 vs. 137 mmHg), Greek‐born men had a significantly lower risk of diabetic retinopathy than Australian‐born men, after adjusting for age, duration of diabetes, glycated haemoglobin, systolic blood pressure, diastolic blood pressure, albumin to creatinine ratio, and total cholesterol and triglyceride levels [odds ratio 0.32 (0.10–0.99); r2 = 0.41, P = 0.047].Conclusion  Greek ethnicity may confer some protection against diabetic retinopathy to Australia’s Greek‐born migrants, an effect not explained by established risk factors for diabetic retinopathy. A small window of opportunity remains in which to elucidate the ethnicity‐related exposures that modulate vascular risk in this older migrant population.
Frequency of biochemical hypoglycaemia in adults with Type 1 diabetes with and without impaired awareness of hypoglycaemia: no identifiable differences using continuous glucose monitoring
Authors: Choudhary P. , Geddes J. , Freeman J. V. , Emery C. J. , Heller S. R. , Frier B. M. 
Published: April 2010

Diabet. Med. 27, 666–672 (2010)AbstractObjective  Impaired awareness of hypoglycaemia (IAH) is a major risk factor for severe hypoglycaemia in Type 1 diabetes. Although biochemical hypoglycaemia is asserted to be more frequent in IAH, this has not been estimated accurately. The aim of this study was to use Continuous Glucose Monitoring (CGM) to quantify hypoglycaemia in IAH and evaluate its use in identifying impaired awareness of hypoglycaemia.Methods  Ninety‐five patients with Type 1 diabetes were classified as having normal (n = 74) or impaired awareness (n = 21) using an established method of assessing hypoglycaemia awareness. Hypoglycaemia exposure was assessed prospectively over 9–12 months using weekly 4‐point capillary home blood glucose monitoring (HBGM), 5 days of CGM and prospective reporting of severe hypoglycaemia. The frequencies of biochemical and severe hypoglycaemia were compared in patients with normal and impaired awareness of hypoglycaemia.Results  Patients with impaired awareness had a 3‐fold higher incidence of severe hypoglycaemia than those with normal awareness [incidence rate ratio (IRR) 3.37 (95% CI 1.30–8.7); P = 0.01] and 1.6‐fold higher incidence of hypoglycaemia on weekly HBGM [IRR 1.63 (95% CI 1.09–2.44); P = 0.02]. No significant differences were observed with CGM [IRR for sensor glucose ≤ 3.0 mmol/l 1.47 (95% CI 0.91–2.39); P = 0.12; IRR for sensor glucose ≤ 2.2 mmol/l 1.23 (95% CI 0.76–1.98); P = 0.40].Conclusions  Patients with Type 1 diabetes with impaired awareness had a 3‐fold higher risk of severe hypoglycaemia and 1.6‐fold higher incidence of biochemical hypoglycaemia measured with weekly glucose monitoring compared with normal awareness, but 5 days of CGM did not differentiate those with impaired from those with normal awareness.
Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999–2004: a national health insurance data set study
Authors: Chang C. H. , Shau W. Y. , Jiang Y. D. , Li H. Y. , Chang T. J. , H.‐H. Sheu W. , Kwok C. F. , Ho L. T. , Chuang L. M. 
Published: April 2010

Diabet. Med. 27, 636–643 (2010)AbstractAim  To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan.Methods  A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999–2004. Adult patients aged ≥ 20 years old with prevalent and incident Type 2 diabetes were identified using ICD‐9‐CM diagnostic codes. Age‐specific and age‐direct‐standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression.Results  During the study years, the age‐standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and ≥ 80 years. The age‐standardized incidence rates of Type 2 diabetes per 1000 person‐years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20–1.42) for men and 1.04 (1.01–1.08) for women. The incidence trends for people aged ≥ 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001).Conclusions  This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999–2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20–40 years were most susceptible to higher incidence of Type 2 diabetes.
Ectopic expression of α‐synuclein affects the migration of neural stem cells in mouse subventricular zone
Authors: Tani Momo , Hayakawa Hideki , Yasuda Toru , Nihira Tomoko , Hattori Nobutaka , Mizuno Yoshikuni , Mochizuki Hideki 
Published: April 2010

J. Neurochem. (2010) 115, 854–863.Abstractα‐Synuclein (α‐syn) is a key protein in Parkinson’s disease (PD), and its abnormal accumulation is implicated only not in the loss of dopaminergic neurons in the substantia nigra but also in impairment of olfactory bulb (OB) in PD. Olfactory dysfunction could arise from these OB changes as an early symptom in PD. We reported previously the impairment of neuronal stem cell (NSC) proliferation in the subventricular zone, which is upstream of OB in PD models. Reduction of NSC generation could potentially lead to olfactory dysfunction, which is commonly associated with and precedes the motor symptoms by several years in PD. Here, we investigated neurosphere formation in vitro and migration of NSCs in vivo after transduction of α‐syn‐encoding retroviral vector to characterize the function of α‐syn in NSC. Over‐expression of α‐syn caused less effective formation of neurospheres and induced morphological changes. Fluorescence‐activated cell sorting showed diminished NSC cell cycle progression induced by over‐expression of α‐syn. Intriguingly, suppression of NSC migration along the rostral migratory stream was observed when the α‐syn‐encoding vector was directly injected into the subventricular zone of mice in vivo. These results indicate that α‐syn affects the generation of NSC and suggest that this protein could serve as a tool for the design of potentially useful therapy for PD patients.
Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors
Authors: Kim Do Young , Vallejo Johana , Rho Jong M. 
Published: April 2010

J. Neurochem. (2010) 114, 130–141.AbstractKetones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose‐dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre‐treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant‐induced PS recovery against the MRC II inhibitor 3‐nitropropionic acid (3‐NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3‐NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3‐NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation.
P2X1 receptor mobility and trafficking; regulation by receptor insertion and activation
Authors: Lalo Ulyana , Allsopp Rebecca C. , Mahaut‐Smith Martyn P. , Evans Richard J. 
Published: April 2010

J. Neurochem. (2010) 113, 1177–1187.AbstractP2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells P2X1 receptors C‐terminally tagged with enhanced green fluorescent protein (P2X1‐eGFP) were predominantly expressed at the cell surface. Following > 90% photo‐bleaching of P2X1‐eGFP within a 6 μm2 circle at the cell surface fluorescence recovery after photo‐bleaching (FRAP) was fit with a time constant of ∼60 s and recovered to ∼75% of pre‐bleach levels. Following activation of the P2X1 receptor with α,β‐methylene ATP the associated calcium influx doubled the FRAP recovery rate. The protein synthesis inhibitor cycloheximide had only a small effect on repeated FRAP and indicated a limited contribution of new P2X1 receptors to the FRAP. Inhibition of trafficking with brefeldin A reduced recovery and this effect could be reversed following receptor activation. In contrast, the dynamin inhibitor dynasore had no effect on FRAP under unstimulated conditions but reduced the level of recovery following agonist stimulation. In functional studies both brefeldin A and dynasore increased the recovery time from desensitisation. Taken together these studies demonstrate for the first time an important role of receptor recycling on P2X1 receptor responsiveness.
Enhancing the GLP‐1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells
Authors: Li Yazhou , Tweedie David , Mattson Mark P. , Holloway Harold W. , Greig Nigel H. 
Published: April 2010

J. Neurochem. (2010) 113, 1621–1631.AbstractIncreasing evidence suggests that glucagon‐like peptide‐1 (GLP‐1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP‐1 and associated underlying mechanisms, we over‐expressed the GLP‐1 receptor (GLP‐1R) on human neuroblastoma SH‐SY5Y cells to generate a neuronal culture system featuring enhanced GLP‐1R signaling. In GLP‐1R over‐expressing SH‐SY5Y (SH‐hGLP‐1R#9) cells, GLP‐1 and the long‐acting agonist exendin‐4 stimulated cell proliferation and increased cell viability by 2‐fold at 24 h at physiologically relevant concentrations. This GLP‐1R‐dependent action was mediated via the protein kinase A and phosphoinositide 3‐kinase signaling pathways, with the MAPK pathway playing a minor role. GLP‐1 and exendin‐4 pretreatment dose‐dependently protected SH‐hGLP‐1R#9 cells from hydrogen peroxide (H2O2)‐ and 6‐hydroxydopamine‐induced cell death. This involved amelioration of elevated caspase 3 activity, down‐regulation of pro‐apoptotic Bax and up‐regulation of anti‐apoptotic Bcl‐2 protein. In the presence of 6‐hydroxydopamine, GLP‐1’s ability to lower caspse‐3 activity was abolished with the phosphoinositide 3‐kinase inhibitor, LY2940002, and partly reduced with the protein kinase A inhibitor, H89. Hence, GLP‐1R mediated neurotrophic and anti‐apoptotic actions co‐contribute to the neuroprotective property of GLP‐1 in neuronal cell cultures, and reinforce the potential therapeutic value of GLP‐1R agonists in neurodegenerative disorders involving oxidative stress.
Susceptibility of brainstem to kindling and transfer to the forebrain
Authors: Lam Ann , Whelan Naomi , Corcoran Michael E. 
Published: April 2010

SummaryPurpose:  The kindling of seizures with stimulation of brainstem sites has been reported inconsistently in the literature. The characteristics of the kindling observed, involving high intensities of stimulation and immediate onset of generalized tonic–clonic convulsions, raise questions regarding the nature of kindling from these sites.Methods:  We implanted chronic electrodes in either the nucleus reticularis pontis oralis (RPO), mesencephalic reticular formation (MRF), dorsal periaqueductal gray (dPAG), or ventrolateral periaqueductal gray (vlPAG) in male Long‐Evans rats, with a recording electrode in the amygdala. Rats received conventional high‐frequency kindling stimulation once daily for 30 days. To test for transfer, we kindled the amygdala beginning 7 weeks after the last brainstem kindling trial.Results:  Tonic–clonic seizures were evoked by stimulation from all brainstem sites. Seizures were brief and were associated with characteristic low‐amplitude high‐frequency afterdischarge (AD). Kindling of the dPAG resulted in the development of classic AD and increased AD duration. Prior kindling of the dPAG facilitated subsequent kindling of the amygdala; however, no transfer was observed with prekindling of other brainstem sites.Discussion:  The variability in the response to kindling stimulation suggests that certain brainstem sites are resistant to kindling, whereas other sites are more susceptible to kindling but are still relatively resistant in comparison to sites in the forebrain. The development of classic AD in later trials of dPAG stimulation suggests that epileptogenesis can occur even in the initial absence of classic AD when low‐amplitude high‐frequency AD is present.
The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG‐PET
Authors: Wong Chong H. , Bleasel Andrew , Wen Lingfeng , Eberl Stefan , Byth Karen , Fulham Michael , Somerville Ernest , Mohamed Armin 
Published: April 2010

SummaryPurpose:  This study aims to map the temporal and extratemporal 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET)–defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome.Methods:  Sixty‐four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow‐up. Spatial preprocessing and statistical analysis on preoperative interictal FDG‐PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses.Results:  EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic‐–clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome.Discussion:  Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.
When is a postoperative seizure equivalent to “epilepsy recurrence” after epilepsy surgery?
Authors: Jehi Lara , Sarkis Rani , Bingaman William , Kotagal Prakash , Najm Imad 
Published: April 2010

SummaryPurpose:  Up to one‐half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy.Methods:  Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had ≥1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure‐free (no seizures for ≥1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis.Results:  After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2–3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05–8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13–7.30; p < 0.0001), and ipsilateral spikes on a 6‐months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10–3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness.Discussion:  Seizures will recur in most patients who present with their first postoperative event, with one‐third eventually regaining seizure‐freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.
Can changes in cortical excitability distinguish progressive from juvenile myoclonic epilepsy?
Authors: Badawy Radwa A.B. , Macdonell Richard A.L. , Jackson Graeme D , Berkovic Samuel F. 
Published: April 2010

SummaryPurpose:  We used transcranial magnetic stimulation (TMS) to investigate whether there were any characteristic cortical excitability changes in progressive myoclonic epilepsy (PME) compared to juvenile myoclonic epilepsy (JME).Methods:  Six patients with PME were studied. Motor threshold (MT) at rest and recovery curve analysis using paired‐pulse stimulation at a number of interstimulus intervals (ISIs) was determined. Results were compared to those of 9 patients with chronic refractory JME and 10 with chronic well‐controlled JME.Results:  PME showed a marked increase in cortical excitability at all the long ISIs (p < 0.01), compared to refractory JME (effect sizes ranging from 1.4 to 1.9) and well‐controlled JME (effect sizes ranging from 2.0 to 2.4). Significant differences at the short ISIs 2–5 ms were seen only on comparison with the well‐controlled group (p < 0.05, effect size 0.6, 0.7). There were no significant differences in MTs of PME compared to either JME groups.Conclusion:  Our findings demonstrate specific differences in cortical excitability using TMS between PME and those with JME, particularly at long latencies in the paired‐pulse paradigm, implicating a role for γ‐aminobutyric acid (GABA)B‐mediated networks.
Frameshift mutations of the ARX gene in familial Ohtahara syndrome
Authors: Kato Mitushiro , Koyama Norihisa , Ohta Masayasu , Miura Kiyokuni , Hayasaka Kiyoshi 
Published: April 2010

SummaryPurpose:  Ohtahara syndrome is one of the most severe and earliest forms of epilepsy and is frequently associated with brain malformations, such as hemimegalencephaly. Recently, longer expansion of the first polyalanine tract of ARX was found to be causative for Ohtahara syndrome without brain malformation, whereas premature termination mutations of ARX were found to cause severe brain malformations, such as lissencephaly or hydranencephaly. Both are designated as ARX‐related interneuronopathies.Methods:  We investigated the molecular basis of Ohtahara syndrome in two families, comprising six male patients in two generations demonstrating X‐linked inheritance.Results:  Novel frameshift mutations in the terminal exon of the ARX gene (Ala524fsX534 and E536fsX672) were identified in two patients (2 and 13 years, each) from both families. Two patients developed West syndrome, and one of these later developed Lennox‐Gastaut syndrome. Brain magnetic resonance imaging (MRI) of all patients showed no brain malformations in contrast to the patients with a premature termination mutation in other exons of ARX.Discussion:  The etiology of Ohtahara syndrome is heterogeneous; however, the molecular analysis of ARX should be considered in sporadic or familial male patients with Ohtahara syndrome.
Alteration of NMDA receptor–mediated synaptic interactions in the lateral amygdala associated with seizure activity in a mouse model of chronic temporal lobe epilepsy
Authors: Graebenitz Stéphanie , Lesting Jörg , Sosulina Ludmila , Seidenbecher Thomas , Pape Hans‐Christian 
Published: April 2010

SummaryPurpose:  Because results from both animal models and human temporal lobe epilepsy (TLE) have pointed to synaptic network alterations in the amygdala, we have tested the hypothesis that glutamatergic transmission in the lateral amygdala (LA) is critically involved.Methods:  Using the pilocarpine mouse model, LA slices were prepared ex vivo in the recurrent phase of TLE (Pilo group), and LA projection neurons (PNs) were recorded using patch‐clamp techniques. Intrinsic and synaptic properties of LA PNs were analyzed and compared with those in age‐matched saline‐injected controls.Results:  Only mild changes were observed in intrinsic properties of LA PNs, whereas both spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) were significantly increased in Pilo as compared to saline controls. This difference was sensitive to AP5, but persisted during action of NBQX, indicating mediation by N‐methyl‐d‐aspartate (NMDA) receptors. Moreover, these changes were associated with an increase in frequency but not amplitude of mEPSCs, indicative of a contribution of presynaptic mechanisms.Discussion:  In conclusion, dynamic changes seem to occur in glutamatergic transmission within the amygdala during TLE, to which a functional upregulation of presynaptic NMDA receptors in LA PNs makes a significant contribution.