Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

Dementia is associated with open-angle glaucoma: a population-based study.

PURPOSE: Previous epidemiologic studies that focused on the association between open-angle glaucoma (OAG) and dementia showed inconsistent results. In the present study, we explored the association between OAG and dementia in an ethnic Chinese (i.e., Taiwanese) population using a population-based data set. METHODS: We retrieved data on study subjects for this case-control study from the Longitudinal Health Insurance Database 2000. We identified 7770 patients who had a diagnosis of dementia as cases, and 7770 subjects matched in terms of sex and age, which were randomly extracted as controls. A conditional logistic regression conditioned on age group, sex, and index year was used to assess the association of dementia with previously diagnosed OAG among the sampled patients. RESULTS: Of 15,540 patients, 1.70% had prior OAG, including 2.02% of the dementia group and 1.38% of the controls. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, dementia patients were more likely to have had prior OAG than controls (odds ratio (OR): 1.44; 95% confidence interval (CI): 1.12-1.85; P<0.01). In addition, female dementia patients were more likely to have had prior OAG than controls (OR: 1.93; 95% CI: 1.35-2.77; P<0.001), whereas no statistical difference in prior OAG between male dementia patients and controls was found. CONCLUSIONS: Female dementia patients were associated with a higher proportion of prior OAG than were the controls.

Photoelectrochemical hydrogen generation with linear gradient Al composition dodecagon faceted AlGaN/n-GaN electrode.

We demonstrated photoelectrochemical cells (PECs) with dodecagon faceted AlGaN/n-GaN heterostructure electrode for H(2) generation, where the AlGaN/n-GaN heterostructure has a linear gradient Al composition (LGAC). The separation efficiency of the photo-generated electron-hole pairs in the electrode performs a key function in the H(2) generation efficiency of PEC cells. The linear gradient Al composition, AlGaN, could create more internal field and light absorption because of the linear graded band gap. Therefore, the zero-bias photocurrent density of PEC cells with dodecagon facet LGAC AlGaN/n-GaN heterostructure electrode is around 5.9 times larger than that of dodecagon faceted n-GaN electrode.

LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling.

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.

Adenocarcinoma arising from tubulovillous adenoma in a native bladder following gastrocystoplasty.

Gastrocystoplasty is a surgical form of bladder augmentation which improves bladder capacity and compliance. Patients who undergo bladder augmentation with a gastric remnant are at increased risk for malignancy. The most common types of tumors in this situation were adenocarcinoma and urothelial carcinoma. Most of the adenocarcinomas arise in the gastric remnant or anastomotic site, and adenocarcinomas arising in the residual native bladder are extremely rare. We report on a patient who received gastrocystoplasty 16 years ago. She suffered from recurrent urinary tract infections for a year and cystoscopy showed a tumor in the bladder trigone. Pathologic examination showed tubulovillous adenoma with malignant transformation to adenocarcinoma. The tumor consisted of intact adenomatous architecture from low-grade dysplastic gland to adenocarcinoma, which suggested that the pathogenesis might be related to intestinal metaplasia and dysplasia. The unique location and immunohistologic findings of the tumor suggested that it originated in the bladder mucosa.

Association between multiple sclerosis and chronic periodontitis: a population-based pilot study.

BACKGROUND AND PURPOSE: The pathogenesis of multiple sclerosis (MS) is still not fully understood, but multiple infections are known to be crucial in the development of the disease. Periodontitis caused by periodontopathic polymicrobial infections is among the most common chronic infectious disorders. This case-control study aimed to investigate the association between chronic periodontitis (CP) and MS using a population-based dataset in Taiwan. METHODS: This study included 316 cases who had a diagnosis of MS and 1580 randomly selected controls. We performed conditional logistic regressions to investigate the association between MS and having been previously diagnosed with CP. RESULTS: The results reveal that the prevalence of earlier CP was 25.6% and 15.4% for cases and controls, respectively (P < 0.001). Conditional logistic regression analysis revealed that cases were 1.86 [95% confidence interval (CI) = 1.39-2.48] times as likely as controls to have been previously diagnosed with CP, after adjusting for sociodemographic characteristics as well as hyperlipidemia, hypertension, coronary heart disease, alcohol abuse/alcohol-dependence syndrome, tobacco use disorder and chronic obstructive pulmonary disease. After analyzing by gender, it was realized that while female cases had a higher chance than female controls of having earlier CP (adjusted odds ratio = 2.08; 95% CI = 1.49-2.95), there was no statistical association detected between these two conditions in men. CONCLUSIONS: This study provides evidence for an association between CP and MS in female, but not male, subjects. Further epidemiological studies are needed to confirm the association and gender-specific differences found in the present study.

InGaN working electrodes with assisted bias generated from GaAs solar cells for efficient water splitting.

Hydrogen generation through water splitting by n-InGaN working electrodes with bias generated from GaAs solar cell was studied. Instead of using an external bias provided by power supply, a GaAs-based solar cell was used as the driving force to increase the rate of hydrogen production. The water-splitting system was tuned using different approaches to set the operating points to the maximum power point of the GaAs solar cell. The approaches included changing the electrolytes, varying the light intensity, and introducing the immersed ITO ohmic contacts on the working electrodes. As a result, the hybrid system comprising both InGaN-based working electrodes and GaAs solar cells operating under concentrated illumination could possibly facilitate efficient water splitting.

Association analysis of dopaminergic gene variants (Comt, Drd4 And Dat1) with Alzheimer s disease.

Defects in dopaminergic transmission play important roles in the disturbance of synaptic plasticity and even in advanced cognitive behavior. However, the relationship between genes involved in the regulation of dopamine levels and predisposition for Alzheimer s disease (AD) remains unclear. The potential association of dopamine-modulating gene polymorphisms with AD was evaluated. We performed a case-control study with 120 patients and 86 healthy controls. Two catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms (SNPs) (rs2020917 and rs4646312), two dopamine D4 receptor (DRD4) SNPs (rs3758653 and rs916455), and four dopamine transporter (DAT1) SNPs (rs2937639, rs6347, rs12516948 and rs11133762) were investigated. The T allele at the DRD4 SNP (rs3758653) was found to be significantly associated with AD. Our results also showed that haplotype frequencies, observed from the analyzed SNPs, were distributed significantly differently in AD patients vs control subjects. Moreover, a strong association was observed between the A allele at rs6347 of DAT1 and moderate stage of dementia. These observations suggest that genetic variations in the dopamine-modulating genes, COMT, DRD4 and DAT1, may contribute to AD pathogenesis in the Taiwanese population.

Mn-doped GaN as photoelectrodes for the photoelectrolysis of water under visible light.

Hydrogen generation through direct photoelectrolysis of water was studied using photoelectrochemical (PEC) cells made of Mn-doped GaN photoelectrodes. In addition to its absorption of the ultraviolet spectrum, Mn-doped GaN photoelectrodes could absorb photons in the visible spectrum. The photocurrents measured from PEC cells made of Mn-doped GaN were at least one order higher than those measured from PEC cells made of undoped GaN-working electrodes. Under the visible light illumination and a bias voltage below 1.2 V, the Mn-doped GaN photoelectrodes could drive the water splitting reaction for hydrogen generation. However, hydrogen generation could not be achieved under the same condition wherein undoped GaN photoelectrodes were used. According to the results of the spectral responses and transmission spectra obtained from the experimental photoelectrodes, the enhanced photocurrent in the Mn-doped GaN photoelectrodes, compared with the undoped GaN photoelectrodes, was attributable to the Mn-related intermediate band within the band gap of GaN that resulted in further photon absorption.

Immersed finger-type indium tin oxide ohmic contacts on p-GaN photoelectrodes for photoelectrochemical hydrogen generation.

In this study, we demonstrated photoelectrochemical (PEC) hydrogen generation using p-GaN photoelectrodes associated with immersed finger-type indium tin oxide (IF-ITO) ohmic contacts. The IF-ITO/p-GaN photoelectrode scheme exhibits higher photocurrent and gas generation rate compared with p-GaN photoelectrodes without IF-ITO ohmic contacts. In addition, the critical external bias for detectable hydrogen generation can be effectively reduced by the use of IF-ITO ohmic contacts. This finding can be attributed to the greatly uniform distribution of the IF-ITO/p-GaN photoelectrode applied fields over the whole working area. As a result, the collection efficiency of photo-generated holes by electrode contacts is higher than that of p-GaN photoelectrodes without IF-ITO contacts. Microscopy revealed a tiny change on the p-GaN surfaces before and after hydrogen generation. In contrast, photoelectrodes composed of n-GaN have a short lifetime due to n-GaN corrosion during hydrogen generation. Findings of this study indicate that the ITO finger contacts on p-GaN layer is a potential candidate as photoelectrodes for PEC hydrogen generation.

Clinical characteristics and treatment delay of cerebral infarction in tuberculous meningitis.

BACKGROUND: Cerebral infarction (CI) complicating tuberculous meningitis (TBM) is a major risk factor of permanent disability. The prevention of this complication is an important issue in the quality care of TBM patients. AIM: Our aim was to evaluate the clinical characteristics of TBM patients with CI. METHODS: Ninety-one adult patients with TBM were studied between 1999 and 2007. Clinical, neuroradiological and cerebrospinal fluid data of patients with CI were compared with those without CI. RESULTS: Thirty of the 91 patients had CI, including symptomatic CI occurring before admission in 10 patients, symptomatic CI occurring during hospitalisation in four and silent CI in 16 patients. When compared with non-CI patients, patients with CI were younger and associated with focal weakness on presentation, and had basal meningeal enhancement and hydrocephalus on brain images. Prolonged doctor delays of antituberculosis and steroid therapies, neurosurgical intervention, focal weakness and dementia as sequelae, and poor outcomes were associated with patients with CI than non-CI patients. CONCLUSION: Contrast-enhanced brain imaging is helpful to explore the basal meningeal enhancement in CI patients, and contributes to early diagnosis and treatment of TBM. Early antituberculosis and steroid therapies may help prevent CI in TBM patients.

Hydrogen gas generation using n-GaN photoelectrodes with immersed Indium Tin Oxide ohmic contacts.

An n-GaN photoelectrochemical (PEC) cell with immersed finger-type indium tin oxide (ITO) ohmic contacts was demonstrated in the present study to enhance the hydrogen generation rate. The finger-type ITO ohmic contacts were covered with SiO2 layers to prevent the PEC cell from generating leakage current. Using a 1M NaCl electrolyte and external biases, the typical photocurrent density and gas generation rate of the n-GaN working electrodes with ITO finger contacts were found to be higher than those with Cr/Au finger contacts. The enhancement in photocurrent density or gas generation rate can be attributed to the transparent ITO contacts which allowed the introduction of relatively more photons into the GaN layer. No significant corrosion was observed in the ITO layer after the PEC process compared with the Cr/Au finger contacts which were significantly peeled from the GaN layer. These results indicate that the use of n-GaN working electrodes with finger-type ITO ohmic contacts is a promising approach for PEC cells.

Localized joule heating as a mask-free technique for the local synthesis of ZnO nanowires on silicon nanodevices.

We report a mask-free technique for the local synthesis of ZnO nanowires (NWs) on polysilicon nanobelts and polysilicon NW devices. First, we used localized joule heating to generate a poly(methyl methacrylate) (PMMA) nanotemplate, allowing the rapid and self-aligned ablation of PMMA within a short period of time (ca. 5 µs). Next, we used ion-beam sputtering to prepare an ultrathin Au film and a ZnO seed layer; a subsequent lift-off process left the seed layers selectively within the PMMA nanotemplate. Gold nanoparticles and ZnO NWs were formed selectively in the localized joule heating region.

High-performance GaN metal-insulator-semiconductor ultraviolet photodetectors using gallium oxide as gate layer.

In this study, gallium nitride (GaN)-based metal-insulator-semiconductor (MIS) ultraviolet (UV) photodetectors (PDs) with a gallium oxide (GaO(x)) gate layer formed by alternating current bias-assisted photoelectrochemical oxidation of n-GaN are presented. By introducing the GaO(x) gate layer to the GaN MIS UV PDs, the leakage current is reduced and a much larger UV-to-visible rejection ratio (R(UV/vis)) of spectral responsivity is achieved. In addition, a bias-dependent spectral response results in marked increase of the R(UV/vis) with bias voltage up to ~10(5). The bias-dependent responsivity suggests the possible existence of internal gain in of the GaN MIS PDs.

The CC16 A38G polymorphism is associated with the development of asthma in children with allergic rhinitis.

BACKGROUND: Although asthma and allergic rhinitis (AR) are considered to be one syndrome, many questions remain unanswered. Why do some AR patients develop asthma but others do not, and which factors play a role in the development of asthma that have so far not been clearly elucidated. OBJECTIVE: We hypothesize that children with AR who have the Clara cell secretory protein (CC16, secretoglobin 1A1) 38A/38A genotype (rs3741240) have an increased likelihood of developing asthma. METHODS: The study sample included 117 children, with AR, but no asthma diagnosed within the following 5 years, as the control group. Cases group (n=202) included age- and gender-matched children with AR first, and asthma developed 3-5 years later, as the study group. The CC16 genotype was determined by PCR and Sau96I restriction digestion of PCR products. The serum CC16 levels were measured by ELISA. Total serum IgE, allergen specific IgE, eosinophil count and pulmonary function were also measured. RESULTS: In children with rhinitis who develop asthma, the frequencies of the AA genotype were significantly higher than those who did not develop asthma [odds ratio (OR)=2.527; 95% confidence interval (CI)=1.571-4.065; P<0.01]. Serum CC16 levels in the children with rhinitis who develop asthma and carry the AA genotype were significantly lower than those who carry the non-AA genotype and those who did not develop asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that CC16 38A/38A genotype plays a role in the development of early asthma in children with AR. Early identification of rhinitis children at risk may assist in designing preventative approach to asthma development.

Using silicon nanowire devices to detect adenosine triphosphate liberated from electrically stimulated HeLa cells.

In this study, we used a biosensor chip featuring Abl tyrosine kinase-modified silicon nanowire field-effect transistors (SiNW-FETs) to detect adenosine triphosphate (ATP) liberated from HeLa cells that had been electrically stimulated. Cells that are cultured in high-ionic-strength media or buffer environments usually undermine the sensitivity and selectively of SiNW-FET-based sensors. Therefore, we first examined the performance of the biosensor chip incorporating the SiNW-FETs in both low- and high-ionic-strength buffer solutions. Next, we stimulated, using a sinusoidal wave (1.0 V, 50 Hz, 10 min), HeLa cells that had been cultured on a cell-culture chip featuring interdigitated electrodes. The extracellular ATP concentration increased by ca. 18.4-fold after electrical stimulation. Finally, we detected the presence of extracellular ATP after removing a small amount of buffer solution from the cell-cultured chip and introducing it into the biosensor chip.