Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan

The Cerebellum - Mutations in STUB1 have been identified to cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16), also named as Gordon Holmes syndrome, which is characterized by...     

Using gas chromatography and mass spectrometry to determine 25-hydroxyvitamin D levels for clinical assessment of vitamin D deficiency

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency.     

A quasi-experimental evaluation of advance care planning improves consistency between elderly individuals and their surrogates regarding end-of-life care preferences: Development and application of a decision aid with cartoon pictures

ObjectiveThis study sought to develop a decision aid with cartoon pictures and evaluate its effectiveness in increasing consistency between elderly individuals and their surrogates regarding end-of-life care.MethodsA pre-post quasi-experimental design was adopted using the Life Support Preferences Questionnaire. The intervention had two components: (1) increasing participants’ knowledge of medical treatments related to end-of-life care, and (2) sharing their end-of-life wishes. The experimental group received an intervention, whereas the control group received usual care.ResultsA total of 110 participants in 55 pairs of elderly individuals with average aged 86.4 and their surrogates (27 in the experimental group, 28 in the control group) were recruited from a veterans hospital in northern Taiwan. Nearly 90 % of elderly individuals were male. The multiple linear regression showed that the inconsistent gap between elderly individuals and their surrogates in the experimental group decreased 12 points than the control group after controlling the covariances (B = ?12.116, p = 0.032).ConclusionThe intervention improved the consistency between elderly individuals and their surrogates regarding end-of-life care.Practice implicationsA decision aid with cartoon pictures may support the discussion of end-of-life care in older Asian populations.     

Diverse cellular morphologies during lumen maturation in Anopheles gambiae larval salivary glands

Mosquitoes are the greatest animal threat to human health, causing hundreds of millions of infections and around 1 million deaths each year. All mosquito-borne pathogens must traverse the salivary glands (SGs) to be transmitted to the next host, making this organ an ideal target for interventions. The adult SG develops from precursor cells located in the larval SG duct bud. Characterization of the larval SG has been limited. We sought to better understand larval SG architecture, secretion and gene expression. We developed an optimized method for larval SG staining and surveyed hundreds of larval stage 4 (L4) SGs using fluorescence confocal microscopy. Remarkable variation in SG cell and chromatin organization differed among individuals and across the L4 stage. Lumen formation occurred during L4 stage through secretion likely involving a coincident cellular apical lipid enrichment and extracellular vesicle-like structures. Meta-analysis of microarray data showed that larval SG gene expression is divergent from adult SGs, more similar to larval gastric cecae, but different from other larval gut compartments. This work highlights the variable cell architecture of larval Anopheles gambiae SGs and provides candidate targets for genetic strategies aiming to disrupt SGs and transmission of mosquito-borne pathogens.     

Enhancement of tioconazole ungual delivery: Combining nanocapsule formulation and nail poration approaches

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90–160?μm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.     

Characterization of inter-tissue and inter-strain variability of TCE glutathione conjugation metabolites DCVG,DCVC, and NAcDCVC in the mouse

Trichloroethylene (TCE) is a ubiquitous environmental toxicant that is a liver and kidney carcinogen. Conjugation of TCE with glutathione (GSH) leads to formation of nepthrotoxic and mutagenic metabolites postulated to be critical for kidney cancerdevelopment; however, relatively little is known regarding their tissue levels as previous analytical methods for their detection lacked sensitivity. Here, an LC-MS/MS-based method for simultaneous detection of S-(1,2-dichlorovinyl)-glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC) in multiple mouse tissues was developed. This analytical method is rapid, sensitive (limits of detection (LOD) 3–30 fmol across metabolites and tissues), and robust to quantify all three metabolites in liver, kidneys, and serum. The method was used to characterize inter-tissue and inter-strain variability in formation of conjugative metabolites of TCE. Single oral dose of TCE (24, 240 or 800 mg/kg) was administered to male mice from 20 inbred strains of Collaborative Cross. Inter-strain variability in the levels of DCVG, DCVC, and NAcDCVC (GSD = 1.6–2.9) was observed. Whereas NAcDCVC was distributed equally among analyzed tissues, highest levels of DCVG were detected in liver and DCVC in kidneys. Evidence indicated that inter-strain variability in conjugative metabolite formation of TCE might affect susceptibility to adverse health effects and that this method might aid in filling data gaps in human health assessment of TCE.     

Farming and mortality rates attributed to non–Hodgkin’s lymphoma in Taiwan

Previous studies suggested an elevated risk of non-Hodgkin’s lymphoma (NHL) among farmers. To date, no apparent study examined the association between farming and NHL in Asian countries. The aim of this study was to investigate whether farmers in Taiwan exhibited an increased risk of mortality attributed to NHL. To this end, a mortality odds ratio (MOR) study was conducted to estimate the relative risk of mortality attributed to NHL for farmers in Taiwan. Data on the decedents enrolled in this investigation were derived from the death certificate database for the period 1997–2009. The study group comprised individuals who died from NHL and who were 50 years or older. The control group consisted of subjects who died from all other causes, excluding cancers, in the corresponding age group. Multiple logistic regression analysis was performed to compute the MOR, with adjustments for gender, age at death, year of death, marital status, and urbanizational levels. Among 32,456 deceased farmers, 205 died due to NHL. Farmers were found to have a nonsignificantly higher MOR than nonfarmers. This risk estimate is similar to estimates in previous meta-analyses. The MOR for NHL was higher among farmers who died 65 years or older than among those who died at younger ages. The findings indicate that farming in Taiwan may increase the risk of death attributed to NHL. Exposure to pesticides might be an influential factor contributing to high risk of mortality attributed to NHL among farmers and therefore needs to be further investigated.