GAD65 as a potential marker for cognitive performance in an adult population with prediabetes.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for cognitive dysfunction in aged populations. However, there are inconsistent reports about impaired fasting glucose or prediabetes as an independent risk factor for cognitive function. Glutamic acid decarboxylase 65 (GAD65) is the key enzyme responsible for γ-aminobutyric acid synthesis in the central nervous system. Antibodies against GAD65 (GAD65Abs) are not only detected in approximately 80% of early-onset type 1 DM, but also linked to several neurological disorders. AIM: This study aims to investigate the association between GAD65Ab titer levels and cognitive performance. In addition, we assessed the effect of GAD65Ab on cognitive function in adults with normal fasting glucose, prediabetes and DM. METHODS: A total of 328 subjects aged 49.10 ± 5.72 years were enrolled from the Third Health and Nutrition Examination Survey dataset. Cognitive performance was assessed by three computerized neurobehavioral tests, including the serial digit learning test, simple reaction time test (SRTT) and symbol-digit substitution test (SDST). RESULTS: Subjects with higher GAD65Ab titers had significantly poorer cognitive function in the SRTT and SDST (P < 0.05). Additionally, GAD65Ab was associated with cognitive decline in non-diabetic adults after adjusting for a number of relevant variables (P < 0.05 in both SRTT and SDST). CONCLUSIONS: These results indicate that GAD65Ab may be a potential marker for cognitive impairment in non-diabetic adults.

The association between septicemia and the risk of multiple sclerosis: a nationwide register-based retrospective cohort study in Taiwan.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. AIM: To evaluate the potential impact of septicemia on risk for MS. DESIGN: Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. METHODS: Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. RESULTS: Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P < 0.001) greater risk of developing MS than the matched group. In addition, higher severity of septicemia was associated with higher risk of developing MS (moderate: HR = 4.03, 95% CI: 2.53-6.45, P < 0.001; severe: HR = 11.1, 95% CI: 7.01-17.7, P < 0.001). Similar results also occurred in both male and female patients with septicemia (male: HR = 4.06, 95% CI: 2.17-7.58, P < 0.001; female: HR = 2.72, 95% CI: 1.79-4.11, P < 0.001). Patients without counterpart comorbidities had a significantly higher risk of MS than the controlled group (HR = 3.02, 95% CI: 2.10-4.35, P < 0.001). CONCLUSION: The results indicated septicemia is linked to an increased risk for MS. Aggressively preventing and treating septicemia may be warranted for one of precautionary strategies of MS.

Pre-stroke physical activity is associated with fewer post-stroke complications, lower mortality and a better long-term outcome.

BACKGROUND AND PURPOSE: Physical activity is associated with a reduced incidence of first-time stroke. However, few studies have examined the effect of pre-stroke physical activity on post-stroke complications and clinical outcomes. METHODS: A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre-stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure-time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups. RESULTS: The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post-stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post-stroke. CONCLUSION: Dedicated leisure-time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post-stroke complications, lower mortality and better outcomes.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

New-onset atrial fibrillation-related ischemic stroke occurring after hospital discharge in septicemia survivors.

BACKGROUND: Sepsis will induce stroke, new-onset atrial fibrillation (AF) increase ischemic stroke (IS) in in-hospitalization and long-term period after sepsis. Physicians must alert this condition and given suitable treatment. AIM: The associated of IS and new-onset AF in septicemia survivors after discharge have to be evaluated. DESIGN: The inpatient data was used of the Taiwan National Health Insurance Database (NHIRD) in 2010. We identified patients suffered their first occurrence of septicemia (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] is 038, 003.1, 036.1) and excluded less than 18 years old. Patients had AF (ICD-9-CM to 427.3×) during the same admission or after septicemia hospitalization discharged were defined as new-onset AF. The outcome was IS happened after septicemia discharge (ICD-9-CM as 433-437). METHODS: The factors related to IS after septicemia survival were established using multivariate logistic regression with forward stepwise selection. RESULTS: There were 1286 new-onset AF and 1026 IS happened after septicemia discharge. The crude odds ratio (OR) were 3.88 (95% confidence interval [C.I.]: 1.69-8.89) and 1.62 (95% C.I.: 1.14-2.3) in middle-aged and elderly septicemia survivors with new-onset AF induced IS. The risk of IS after septicemia survivors was noticed adjusted OR 1.74 (95% C.I.: 1.26-2.41) for new-onset AF. CONCLUSION: The middle-aged and elderly septicemia survivors suffered from new-onset AF had increased incidence of IS within three months. New-onset AF was a mediator factor of IS in septicemia survivors of Asian population.

Longitudinal MR imaging study in the prediction of ischemic susceptibility after cerebral hypoperfusion in rats: Influence of aging and hypertension.

Our previous study has shown that aging and hypertension may alter apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) and increase ischemic susceptibility in the non-ischemic rat brain. The present study wishes to further investigate whether aging and hypertension may influence cerebral diffusion/perfusion and increase ischemic susceptibility in the ischemic brain. Brain magnetic resonance (MR) imaging was examined 1day before and 1 and 7days after bilateral common carotid artery occlusion. Young and middle-aged normotensive Wistar-Kyoto rats and young and middle-aged spontaneously hypertensive rats (SHRs) were studied. Infarction occurred mainly in the parietal cortex and was larger in middle-aged SHRs than the other three groups (P<0.05). In pre-operation, ADC was higher and CBF was lower in middle-aged/hypertensive rats than young/normotensive rats (P<0.05). The ADC was higher in the parietal cortex of the rats with infarction at 7days when compared to the rats without infarction [receiver operating characteristic curve (ROC), P=0.001; binary logistic regression (BLR), P=0.006]. However, there was no difference in the hippocampus and thalamus. At day 1 post-operation, CBF reduced and ADC/CBF ratio elevated significantly in the parietal cortex of the rats with infarction when compared to the rats without infarction (CBF: ROC, P=0.002; BLR, P=0.017. ADC/CBF ratio: ROC, P=0.001; BLR, P=0.018). Our results demonstrated that pre-operation ADC and post-operation CBF and ADC/CBF ratio can be used as good MR markers in the prediction of ischemic susceptibility after cerebral hypoperfusion.

Spontaneous Early Recanalization after Acute Innominate Artery Thromboembolic Occlusion Secondary to Abrupt Aspirin and Statin Discontinuation: A Case Report.

Statin and antiplatelet drugs are widely used for prevention of ischaemic stroke and other cardiovascular diseases in high-risk patients. We report a rare case of a 49-year old man with a history of myocardial infarction and hyperlipidaemia who suffered an acute occlusion of his innominate artery (IA) accompanied by subclavian steal syndrome and cerebral infarction, on day seven after abrupt cessation of aspirin and statin, as confirmed by magnetic resonance and computed tomographic angiography of head and neck, and colour-coded Duplex ultrasonography (CCDU). Aspirin and atorvastatin were immediately re-started on admission. Spontaneous recanalization of IA was shown on repeat CCDU and digital subtraction angiography on day 10 after stroke onset. This case serves as a reminder that abrupt discontinuation of both aspirin and statin in patients with previous history of cardiovascular disease may increase the risk of ischaemic stroke.

Reversal of ophthalmic artery flow as a predictor of intracranial hemodynamic compromise: implication for prognosis of severe carotid stenosis.

BACKGROUND AND PURPOSE: High-grade cervical carotid stenosis (70-99%) or occlusion often accompanies reversed ophthalmic artery flow (ROAF), but its potential clinical significances remain poor understood. This study assessed ROAF and the related variables caused by carotid hemodynamic compromise in patients with unilateral severe cervical carotid stenosis. METHODS: The study consisted of 200 patients diagnosed as unilateral high-grade cervical carotid stenosis/occlusion using ultrasonography. The hemodynamic parameters of 152 patients, excluding 48 with cervical carotid occlusion, were compared based on the presence of ROAF. Out of 200 patients, 159 underwent brain magnetic resonance imaging and were analysed for risk factors impacting functional outcomes including ROAF. RESULTS: The patients (n = 48) with internal carotid artery occlusion had significantly higher incidence (62.5%) of ROAF compared with that of 25.0% in those patients (n = 152) with unilateral high-grade carotid stenosis (P < 0.001). In ROAF patients (n = 38) with the unilateral high-grade stenosis, a significant retrobulbar arteries hemodynamic difference was observed between the stenotic and non-stenotic vessels. The patients (n = 159) with history of stroke (P = 0.035), ROAF (P = 0.023) and intracranial stenosis (P < 0.001) exhibited significantly higher incidence of poor functional outcome compared with the corresponding control groups. In the same patients (n = 159), those with both cervical and intracranial stenosis showed sevenfold higher risk (OR, 7.60; 95% CI, 3.44-16.81) for ROAF than those with only cervical stenosis. CONCLUSIONS: ROAF may result from intracranial hemodynamic compromise. Patients with unilateral high-grade cervical carotid stenosis/occlusion in combination with intracranial stenosis appear to be a significant risk factor for poor functional outcome and increased incidence of ROAF.

Development of murine leukemia virus-based retroviral vectors with a minimum possibility of cis-activation.

The possibility of insertional mutagenesis in retroviral gene therapy can be reduced by using a vector lacking the enhancer sequence present in the U3 of the long-terminal repeats. However, such vectors suffer from many pitfalls. We attempted to improve a murine leukemia virus-based retroviral vector containing the enhancer-free U3, first by making it easier to construct a producer line and then by introducing the cellular RPL10 promoter as an internal promoter. The reverse orientation of the expression cassette of the transgene was found to give higher transducing titer and higher-level gene expression. The deletion analysis revealed that the 54-bp-long sequence of U3 (34 and 20 bp present at 5' and 3' extreme ends, respectively) was sufficient for the functions of retroviral vectors. The data from the in vitro cell culture assay indicated that the final construct, ROK, containing all these features, had little cis-activation activity, even if it was placed right upstream from the RNA start site of the neighboring gene. Our data suggested that the newly developed vector might provide increased safety, while still producing high viral titer from a stable producer line and high-level gene expression in various target cells including human CD34(+) stem cells.

Complex phylogeographic history of central African forest elephants and its implications for taxonomy.

BACKGROUND: Previous phylogenetic analyses of African elephants have included limited numbers of forest elephant samples. A large-scale assessment of mitochondrial DNA diversity in forest elephant populations here reveals a more complex evolutionary history in African elephants as a whole than two-taxon models assume. RESULTS: We analysed hypervariable region 1 of the mitochondrial control region for 71 new central African forest elephants and the mitochondrial cytochrome b gene from 28 new samples and compare these sequences to other African elephant data. We find that central African forest elephant populations fall into at least two lineages and that west African elephants (both forest and savannah) share their mitochondrial history almost exclusively with central African forest elephants. We also find that central African forest populations show lower genetic diversity than those in savannahs, and infer a recent population expansion. CONCLUSION: Our data do not support the separation of African elephants into two evolutionary lineages. The demographic history of African elephants seems more complex, with a combination of multiple refugial mitochondrial lineages and recurrent hybridization among them rendering a simple forest/savannah elephant split inapplicable to modern African elephant populations.

Bipaddled radial forearm flap for the reconstruction of bilateral buccal defects in oral submucous fibrosis.

Oral submucous fibrosis can result in progressive closure of the mouth. A total of 10 patients with advanced oral submucous fibrosis were surgically treated. The procedure consisted of (1) release of all the intraoral fibrotic tissue, (2) masticatory muscle myotomy and coronoidotomy, and (3) reconstruction with a bipaddled radial forearm flap. Preoperative mouth opening was 0-5mm (mean 2.3mm). The intraoperative mouth opening was 12-20mm (mean 16 mm) after submucous release, and 32-42 mm (mean 35.5mm) after further release via myotomy and coronoidotomy. The proximal flap included one perforator in four patients and two perforators in the remaining six patients. The flaps were 8-9 cm in length and 2-2.5 cm in width. Nine flaps survived uneventfully. Arterial thrombosis was noted in one flap, which was successfully salvaged. Temporomandibular joint subluxation developed in one patient. Two patients needed flap revision due to bulkiness. The postoperative mouth opening was 18-38 mm (mean 28.2mm) after a mean of 21 months' follow-up, and the mean increase was 25.9 mm. A bipaddled radial forearm flap, using a single donor site, can cover two separate buccal defects after release of oral submucosal fibrosis and obviate the need for a second free flap.

A polymorphism of MS4A2 (- 109T > C) encoding the beta-chain of the high-affinity immunoglobulin E receptor (FcepsilonR1beta) is associated with a susceptibility to aspirin-intolerant asthma.

BACKGROUND AND OBJECTIVE: The MS4A2 gene, the beta chain of the high-affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The beta-chain of FcepsilonR1 enhances receptor maturation and signal transduction capacity, leading to the release of proinflammatory mediators and cytokines that can exacerbate the symptom of asthma. This study was performed to evaluate whether two genetic polymorphisms of the FcepsilonR1beta gene (FcepsilonR1beta-109T > C and FcepsilonR1beta E237G) are associated with aspirin-intolerant asthma (AIA). The MS4A2 gene polymorphisms (FcepsilonR1beta-109T > C and FcepsilonR1beta E237G) were determined by SNP-IT assays in patients with AIA (N = 164), aspirin-tolerant asthma (ATA, N = 144) and normal controls (NC, N = 264) recruited from a Korean population. RESULTS: The genotype frequencies of FcepsilonR1beta-109T > C and E237G polymorphisms were not significantly associated with the pathogenesis of AIA. However, FcepsilonR1beta-109T > C polymorphism was significantly associated with the presence of specific IgE to Staphylococcal enterotoxin B (SEB); the number of subjects carrying both homozygous TT genotype of FcepsilonR1beta-109T > C and specific IgE to SEB was significantly higher in the AIA group when compared with the other control groups (P = 0.01, odds ratio (OR) = 7.723, 95% confidence interval (CI) = 1.327-39.860 for AIA vs. ATA; P = 0.02, OR = 6.364, 95% CI = 1.149 approximately 35.229 for AIA vs. NC). In addition, luciferase reporter assays also showed that the FcepsilonR1beta-109T allele was associated with higher promoter activity of MS4A2 in both RBL-2H3 and A549 cell lines. CONCLUSION: FcepsilonR1beta-109T > C polymorphism may increase expression of MS4A2 by mast cells, leading to enhanced release of proinflammatory mediators in the asthmatic airway, contributing to increased susceptibility to AIA.

The general picture of supportive health environments for persons with intellectual disabilities among 121 disability welfare institutions in Taiwan.

BACKGROUND: Little information is available on the provision of supportive health environments for persons with intellectual disabilities (ID) in institutions. The aim of this study was to present an overview of supportive environments for health in institutions in Taiwan. METHODS: A cross-sectional survey was conducted to examine the perceptions of 121 Taiwanese Institutional Directors on their setting's implementation of supportive healthy physical, social, and economic environments. RESULTS: Analyses showed that first-aid kits (97.5%) and medicine cabinets (85.5%) were the most common health facilities in institutions. Seventy-three per cent of institutions had set up specific areas to be used for rehabilitation practice, while only 43.1% thought their rehabilitation equipment/devices adequate for their real needs. Eighty-eight per cent of institutions implemented health promotion plans for people with ID, while 76.6% had appropriated specific health promotion plans. Sixty-three institutions (52.1%) reported employment of skilled nurses to serve people with ID, and these institutions showed statistically significant differences in implementation of each health facility. CONCLUSIONS: The present paper is the first to analyze supportive environments for health in disability institutions in Taiwan. An important focus of future research will be the extension of the present findings to consider the appropriateness of each area of supportive environments for improving the quality of institutional care for people with ID.

Engineering the splice acceptor for improved gene expression and viral titer in an MLV-based retroviral vector.

We have recently developed a retroviral vector that contains a splice acceptor from the human EF1-alpha gene and drives a significantly higher level of gene expression than other well known murine leukemia virus-based vectors. However, one downside of this vector is that viral titer significantly varies depending on the packaging lines used. Results from Northern blot analysis indicated that in certain cell lines the genomic transcript containing the packaging signal sequence was too efficiently spliced to the subgenomic RNA, resulting in low levels of genomic RNA and thus leading to a low viral titer. We tested the possibility of overcoming this problem by introducing mutations around the splice acceptor sequence in such a way that a delicate balance was maintained between the splicing efficiency (which determines the level of gene expression) and the amount of genomic transcript (which influences viral titer). After mutational analysis, one such mutant was found to meet this requirement. The newly constructed vector containing the engineered splice acceptor could indeed drive higher levels of expression in many therapeutic genes than other control vectors, without significantly compromising viral titer.