Glutamic acid decarboxylase and islet antigen 2 antibody profiles in people with adult-onset diabetes mellitus: a comparison between mixed ethnic populations in Singapore and Germany.

AIM: To gain insight into the presence of islet cell autoimmunity in an ethnic Asian compared with a white European population. METHODS: For this cross-sectional study we recruited people with adult-onset diabetes (age of diagnosis 20-60 years), at tertiary referral centres in Germany (n=1020) and Singapore (n=1088). Glutamic acid decarboxylase and islet antigen 2 antibodies were measured according to Islet Autoantibody Standardization Program protocols. RESULTS: The prevalence of glutamic acid decarboxylase antibody positivity was 13.9% (95% CI 12.1-16.0; P<0.001) in the white European cohort compared with 6.8% (95% CI 5.5-8.4; P<0.001) in the Asian cohort. Glutamic acid decarboxylase antibody positivity was 11.4% (95% CI 7.7-16.6) in Indian, 6.0% (95% CI 3.6-9.9) in Malay and 5.8% (95% CI 4.3-7.7; P<0.001) in Chinese participants. In the white European participants, the prevalence of islet antigen 2 antibody positivity was 7.8% (95% CI 6.4-9.4) compared with 14.8% (95% CI 12.8-17.0; P<0.001) in the Asian cohort as a whole, and among the three ethnicities in the Asian cohort it was 12.4% (95% CI 8.6-17.7) in Indian, 16.8% (95% CI 12.6-22.2) in Malay and 15.7% (95% CI 13.2-18.6) in Chinese participants. Double antibody positivity was seen in 5.7% (95% CI 4.5-7.1) of white European participants compared with 1.6% (95% CI 1.0-2.5; P<0.01) of Asian participants. In the white European cohort, those who were glutamic acid decarboxylase autoantibody-positive had a lower BMI than those who were autoantibody-negative, but this trend was absent in the Asian cohort. CONCLUSIONS: A marked prevalence of islet cell autoimmunity was observed in people with adult-onset diabetes. While glutamic acid decarboxylase antibodies were more frequent in the European cohort, islet antigen 2 antibody positivity was highest in the three ethnic groups in Singapore, suggesting ethnic-specific differences in antibody profiles.

Low Barrier Carbon Induced CO Dissociation on Stepped Cu.

Using x-ray photoelectron spectroscopy we observe the breaking of the strong interatomic bond in molecular CO at low temperature on a stepped Cu surface. Since the electronic structure of Cu does not allow for the splitting of CO at such low temperatures it suggests that there may be a less obvious pathway for the process. Through x-ray photoelectron spectroscopy we can clearly identify products associated with the dissociation of CO and the subsequent formation of stable graphitic carbon on the surface. However, the dissociation of CO can be inhibited when the stepped Cu surface is kept clean from surface carbon. These observations imply that the reaction is driven by the presence of small amounts of weakly bound carbon at the surface. Density-functional theory calculations confirm that carbon atoms on a stepped Cu surface indeed are the preferred adsorption sites for CO, which increases the stabilization of CO on the surface and weakens the C-O bond. This results in the breaking of the C-O bond at the step edge via the Boudouard reaction (2CO(ads)→C(ads)+CO(2)) with a barrier of 0.71 eV.

Strong Influence of Coadsorbate Interaction on CO Desorption Dynamics on Ru(0001) Probed by Ultrafast X-Ray Spectroscopy and Ab Initio Simulations.

We show that coadsorbed oxygen atoms have a dramatic influence on the CO desorption dynamics from Ru(0001). In contrast to the precursor-mediated desorption mechanism on Ru(0001), the presence of surface oxygen modifies the electronic structure of Ru atoms such that CO desorption occurs predominantly via the direct pathway. This phenomenon is directly observed in an ultrafast pump-probe experiment using a soft x-ray free-electron laser to monitor the dynamic evolution of the valence electronic structure of the surface species. This is supported with the potential of mean force along the CO desorption path obtained from density-functional theory calculations. Charge density distribution and frozen-orbital analysis suggest that the oxygen-induced reduction of the Pauli repulsion, and consequent increase of the dative interaction between the CO 5σ and the charged Ru atom, is the electronic origin of the distinct desorption dynamics. Ab initio molecular dynamics simulations of CO desorption from Ru(0001) and oxygen-coadsorbed Ru(0001) provide further insights into the surface bond-breaking process.

Aqueous solution/metal interfaces investigated in operando by photoelectron spectroscopy.

We describe a new in operando approach for the investigation of heterogeneous processes at solid/liquid interfaces with elemental and chemical specificity which combines the preparation of thin liquid films using the meniscus method with standing wave ambient pressure X-ray photoelectron spectroscopy [Nemsák et al., Nat. Commun., 5, 5441 (2014)]. This technique provides information about the chemical composition across liquid/solid interfaces with sub-nanometer depth resolution and under realistic conditions of solution composition and concentration, pH, as well as electrical bias. In this article, we discuss the basics of the technique and present the first results of measurements on KOH/Ni interfaces.

One-dimensional corrugation of the h-BN monolayer on Fe(110).

We report on a new nanopatterned structure represented by a single atomic layer of hexagonal boron nitride (h-BN) forming long periodic waves on the Fe(110) surface. The growth process and the structure of this system are characterized by X-ray absorption (XAS), core-level photoemission spectroscopy (CL PES), low-energy electron microscopy (LEEM), microbeam low-energy electron diffraction (µLEED), and scanning tunneling microscopy (STM). The h-BN monolayer on Fe(110) is periodically corrugated in a wavy fashion with an astonishing degree of long-range order, periodicity of 2.6 nm, and the corrugation amplitude of ∼0.8 Å. The wavy pattern results from a strong chemical bonding between h-BN and Fe in combination with a lattice mismatch in either [111] or [111] direction of the Fe(110) surface. Two primary orientations of h-BN on Fe(110) can be observed corresponding to the possible directions of lattice match between h-BN and Fe(110), with approximately equal area of the boron nitride domains of each orientation.

Treatment of articulatory dysfunction in Parkinson's disease using repetitive transcranial magnetic stimulation.

BACKGROUND AND PURPOSE: Neuroimaging has demonstrated that improved speech outcomes in Parkinson's Disease (PD) subsequent to behavioural treatment approaches are associated with increased activity in the motor and pre-motor cortex. High-frequency repetitive transcranial magnetic stimulation (rTMS) is capable of modulating cortical activity and has been reported to have significant benefit to general motor function in PD. It is possible that high-frequency rTMS may also have beneficial outcomes on speech production in PD. METHODS: High-frequency (5 Hz) rTMS was applied to 10 active stimulation and 10 sham placebo patients for 10 min/day (3000 pulses), for 10 days and speech outcome measures and lingual kinematic parameters recorded at baseline and 1 week, 2 and 12 months post-stimulation. RESULTS: The findings demonstrated positive treatment-related changes observed in the active rTMS group when compared to the sham placebo control group at 2 and 12 months post-stimulation in speech intelligibility, communication efficiency ratio, maximum velocity of tongue movements and distance of tongue movements. CONCLUSION: The results support the use of high-frequency rTMS as a therapeutic tool for the treatment of articulatory dysfunction in PD.

The pathology of 'scale drop syndrome' in Asian seabass, Lates calcarifer Bloch, a first description.

This is the first pathological description of 'scale drop syndrome' (SDS) in Asian seabass, Lates calcarifer Bloch. Cumulative mortality was estimated at 40-50%. The vasculitis in all major organs including the skin and associated tissue necrosis was distinctive. The dermis overlying scale beds was often necrotic and associated with scale loss. Necrosis of splenic ellipsoids, renal glomeruli and choroid rete glands of eye were further hallmarks of a disease with systemic vascular involvement. The brain was not spared vascular damage, and the resulting multifocal encephalomalacia probably accounts for the spiral swimming behaviour in some affected fish. Other lesions included accentuated hepatic lobulation and gastric gland necrosis. Nuclear chromatin margination and karyolysis in hepatocytes, renal tubular epithelium and gastric and intestinal epithelium suggest specific targeting of cells. Basophilic cytoplasmic inclusions were present in spleen, kidney, liver, heart and choroid rete, but they were not prominent. Using transmission electron microscopy, two morphological forms of virions were observed: single- and double-enveloped hexagonal virions. Based on size and morphology, these virions resemble iridovirus or herpesvirus. The cause of SDS is unknown, but the pathological changes, especially the vasculitis, suggest an infectious aetiology, possibly viral.

Impact of oxygen coadsorption on intercalation of cobalt under the h-BN nanomesh.

The process of penetration of cobalt atoms through the h-BN nanomesh on Rh(111) is investigated with both spectroscopic and microscopic techniques. It is discovered that oxygen coadsorption can drastically modify the physical properties and behavior of the deposited Co clusters upon postannealing. In the absence of oxygen, Co forms small nanoparticles in the pores (bonding parts) of the h-BN nanomesh, which start to agglomerate at elevated temperatures without any considerable intercalation. However, even a tiny amount of coadsorbed oxygen reduces cobalt agglomeration and greatly promotes its intercalation and trapping under h-BN. The oxygen exposure necessary for a complete intercalation of 1-2 monolayers of Co is very low, and the formation of oxidic species can be easily avoided. The nanomesh structure remains intact upon intercalating submonolayer amounts of Co, while further intercalation gradually distorts and finally destroys the periodic corrugation. Fortunately, this process is not accompanied by damaging the h-BN sheet itself, and the original structure can be restored by removing Co upon annealing at higher temperatures.

Inhibition of West Nile virus replication in cells stably transfected with vector-based shRNA expression system.

In this study, the efficacies of short hairpin RNAs (shRNAs) targeting different regions of West Nile virus (WNV) strain Sarafend genome were investigated. Short hairpin RNAs targeting Capsid, NS2B and NS4B genes were cloned into pSilencer 3.1-H1 neo and designated as pshCapsid, pshNS2B and pshNS4B, respectively. Vero cells that were positively transfected were selected for creating stable cell lines expressing shRNAs constitutively. These cells were subjected to West Nile virus at multiplicity of infection (M.O.I.) of 10. The cells stably transfected with pshCapsid gave the best silencing effect among the three stable cell lines (transfected with pshCapsid, pshNS2B and pshNS4B) at both 12- and 24 h p.i. When compared to the non-transfected WNV-infected cells, pshCapsid stably transfected cells showed more than 4 log(10) unit reduction in viral transcripts and greater than 3 log(10) unit reduction in virus production. Cells stably transfected with pshNS2B did not exhibit as strong an inhibition when compared to the pshCapsid stably transfected cells having only 2 log(10) unit reduction in virus titre. The pshNS4B-stably transfected cells did not suppress WNV replication. Hence, from this study, pshCapsid has the potential to be developed into effective antiviral strategy for WNV infection.

The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry.

Dengue virus (DV) is a flavivirus and its urban transmission is maintained largely by its mosquito vectors and vertebrate host, often human. In this study, investigation was carried out on the involvement of domain III of the envelope (E) glycosylated protein of dengue virus serotypes 1 and 2 (DV-1 and DV-2 DIII) in binding to host cell surfaces, thus mediating virus entry. Domain III protein of flavivirus can also serve as an attractive target in inhibiting virus entry. The respective DV DIII proteins were expressed as soluble recombinant fusion proteins before purification through enzymatic cleavage and affinity purification. The purified recombinant DV-1 and DV-2 DIII proteins both demonstrated the ability to inhibit the entry of DV-1 and DV-2 into HepG2 cells and C6/36 mosquito cells. As such, the DV DIII protein is indeed important for the interaction with cellular receptors in both human and mosquito cells. In addition, this protein induced antibodies that completely neutralized homologous dengue serotypes although not with the same efficiency among the heterologous serotypes. This observation may be of importance when formulating a generic vaccine that is effective against all dengue virus serotypes.

Real-Time Elucidation of Catalytic Pathways in CO Hydrogenation on Ru.

The direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due to the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast time scales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time X-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

Expression of vector-based small interfering RNA against West Nile virus effectively inhibits virus replication.

RNA interference is one of the effective emerging anti-viral strategies to inhibit virus infection in cells. In this study, a small interfering RNA expressing vector (pSilencer-NS5) targeting the NS5 gene of West Nile virus (WNV) was employed to target and destroy WNV transcripts. Real-time PCR revealed drastic reduction in WNV RNA transcripts in pSilencer-NS5-transfected Vero cells. The virus infectious titre was also significantly reduced by 90% as determined by plaque assays. The resulting decrease in virus replication was shown to be specific since both scrambled and nucleotide(s) mismatch siRNA against WNV NS5 gene did not have any effect on WNV productive yields. Furthermore, Western immunoblot analysis on the expression of viral NS5 and envelope (E) proteins showed significant down-regulation on the expression of viral NS5 and envelope (E) proteins in virus-infected cells that were pre-transfected with pSilencer-NS5. These data clearly supported the notion that the expression of vector-based siRNA against WNV NS5 gene is able to exert its silencing effect on WNV-infected cells without inducing cytotoxicity, hence holding promise in therapeutic treatment of this important emerging infectious disease.

Cytostatic effect of antiestrogens in lymphoid cells: relationship to high affinity antiestrogen-binding sites and cholesterol.

The antiproliferative effect of 10(-6) M antiestrogens in an estrogen receptor-negative lymphoid cell line (K36) was enhanced in lipoprotein-poor growth medium. The enhancement was not due to increased bioavailability because cellular uptake of [3H]tamoxifen was not increased and the lipoprotein fraction of serum had negligible [3H]tamoxifen-binding capacity. Cholesterol and lipoproteins, but not mevalonate, reversed the cytostatic effect of antiestrogens. Reversal by cholesterol was dose-related (10(-7) M to 10(-5) M), while that by lipoproteins could also be demonstrated in medium undepleted of lipoproteins. The cytostatic efficacy of a series of ten compounds correlated well with their relative binding affinities for solubilized antiestrogen-binding sites from K36 cells when log IC50 values (concentration required to reduce [3H]thymidine incorporation by 50%) were plotted against log RBA50 values (concentration required to reduce [3H]tamoxifen binding by 50%) (correlation coefficient 0.94). Transmission electron microscopy of antiestrogen-treated cells showed evidence of disordered cytokinesis which was partially reversed by cholesterol. These observations implicate the antiestrogen-binding protein in the antiproliferative effect of antiestrogens in nonestrogen target cells.

Is symptomatology useful in distinguishing between carpal tunnel syndrome and cervical spondylosis?

Hand paraesthesia is a common symptom found in patients either with carpal tunnel syndrome or cervical spondylosis. To differentiate between the two conditions, it is important to identify additional diagnostic symptoms. Ninety-two patients with operated carpal tunnel syndrome and 138 patients with spinal surgery for cervical spondylosis were reviewed. After exclusion of cases co-morbid with both cervical spondylosis and carpal tunnel syndrome or other neurological disorders, 44 patients with carpal tunnel syndrome and 41 patients with cervical spondylosis were compared. There were significant differences in the symptomatology between the two groups. In carpal tunnel syndrome, 84% had nocturnal paraesthesia, 82% hand paraesthesia were aggravated by hand activity, and hand pain occurred in 64%. The incidences were only 10%, 7% and 10%, respectively in cervical spondylosis. Neck pain was present in 76% of cervical spondylosis but only in 14% of carpal tunnel syndrome, and lower limb symptoms were present in 44% of cervical spondylosis and only 9% in carpal tunnel syndrome.

Prevalence of NIDDM and impaired glucose tolerance in aborigines and Malays in Malaysia and their relationship to sociodemographic, health, and nutritional factors.

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake. RESEARCH DESIGN AND METHODS: The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects > or = 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT. RESULTS: The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5-14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, > or = 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes. CONCLUSIONS: Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.

Surface chemistry. Probing the transition state region in catalytic CO oxidation on Ru.

Femtosecond x-ray laser pulses are used to probe the carbon monoxide (CO) oxidation reaction on ruthenium (Ru) initiated by an optical laser pulse. On a time scale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and oxygen (O) on the surface, allowing the reactants to collide, and, with a transient close to a picosecond (ps), new electronic states appear in the O K-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond formation between CO and O with a distribution of OC-O bond lengths close to the transition state (TS). After 1 ps, 10% of the CO populate the TS region, which is consistent with predictions based on a quantum oscillator model.

Structural features of tracheal tube biofilm formed during prolonged mechanical ventilation.

The dissemination of tracheal tube biofilm into the mechanically ventilated lung has been proposed as a contributory factor in the pathogenesis of ventilator-associated pneumonia. In the present study, conventional light microscopy, confocal laser scanning microscopy, and scanning electron microscopy were used to examine luminal tracheal tube biofilm in tubes from ten consecutive medical intensive care patients. Biofilms also were cultured. No tube contained a predominantly microbial aggregate. Microorganisms were either dispersed throughout the biofilm or restricted to the most superficial layer. Neutrophil polymorphonuclear cells were present in all biofilms in a pattern suggesting that a layering or stratification had taken place. The distribution of neutrophils and microorganisms was consistent with a progressive accretion of respiratory secretions, rather than formation of a predominantly microbial biofilm.

Multi-layered microcapsules for cell encapsulation.

Mechanical stability, complete encapsulation, selective permeability, and suitable extra-cellular microenvironment, are the major considerations in designing microcapsules for cell encapsulation. We have developed four types of multi-layered microcapsules that allow selective optimization of these parameters. Primary hepatocytes were used as model cells to test these different microcapsule configurations. Type-1 microcapsules with an average diameter of 400 microm were formed by complexing modified collagen with a ter-polymer shell of 2-hydroxyethyl methylacrylate (HEMA), methacrylic acid (MAA) and methyl methacrylate (MMA), resulting in a capsule thickness of 2-5 microm. Cells in these microcapsules exhibited improved cellular functions over those cultured on collagen monolayers. Type-II microcapsules were formed by encapsulating the Type-I microcapsules in another 2-5 microm ter-polymer shell and a approximately 5 microm collagen layer between the two ter-polymer shells to ensure complete cell encapsulation. Type-II microcapsules comprised of a macro-porous exoskeleton with materials such as alumina sol-gel coated on the Type-I microcapsules. Nano-indendation assay indicated an improved mechanical stability over the Type-I microcapsules. Type-IV microcapsules were created by encapsulating Type-III microcapsules in another 2-5 microm ter-polymer shell, with the aim of imparting a negatively charged smooth surface to minimize plasma protein absorption and ensure complete cell encapsulation. The permeability for nutrient exchange, cellular functions in terms of urea production and mechanical stability of the microcapsules were characterized. The advantages and limitations of these microcapsules for tissue engineering are discussed.

Brefeldin A affects West Nile virus replication in Vero cells but not C6/36 cells.

A fungal metabolite brefeldin A (BFA) was used to study virus-host interaction in glycoprotein processing in West Nile virus-infected Vero and C6/36 cells. The results indicated that as little as 1 microgram/ml of BFA resulted in complete breakdown in the Golgi organelle in infected Vero cells. This led to modifications of the glycoproteins which could not be efficiently used in infectious virion formation. In contrast, as much as 10 micrograms/ml of BFA in culture medium did not affect either glycoprotein formation or production of infectious particles in C6/36 cells. The results showed that in Vero cells, the transport of glycoproteins to the Golgi apparatus is important in West Nile virus infection. It also showed that BFA could be used as a tool to understand further the trafficking of glycoprotein from the ER to Golgi in flavivirus infection in Vero cells.