Genetic profiles of transcriptomic clusters of childhood asthma determine specific severe subtype.

BACKGROUND: Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable in the clinic, especially for childhood asthma. OBJECTIVE: We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients. METHODS: Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays. We applied the k-means clustering algorithm of 2048 genes to assign asthmatic children into clusters. Genes with differential expression between asthma clusters and healthy controls were used to investigate whether they could identify severe asthma of children and adults. RESULTS: We identified 3 asthma clusters with distinct inflammatory profiles in peripheral blood. Cluster 1 had the highest eosinophil count. Cluster 2 showed lower counts of both eosinophils and neutrophils. Cluster 3 had the highest neutrophil count and the poorest treatment control. Compared with other patients, Cluster 3 exhibited a unique gene expression pattern which was associated with changes in the glucocorticoid signalling and activation of the T helper 1/T helper 17 (TH 1/TH 17) immune pathways. In the validation studies, an 84-gene signature could identify severe asthma in children on leucocytes, as well as severe asthma in adults on CD8+ T cells. CONCLUSIONS AND CLINICAL RELEVANCE: Gene expression profiling of PBMC is useful for the identification of TH 1/TH 17-mediated asthma with poor treatment control. PBMC and CD8+ T cells could be important targets for the investigation and identification of severe asthma.

Childhood asthma clusters reveal neutrophil-predominant phenotype with distinct gene expression.

BACKGROUND: Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments. METHODS: We applied k-means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes. RESULTS: Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil-predominant or neutrophil-predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil-predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil-predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil-predominant asthma may be associated with corticosteroid nonresponsiveness. CONCLUSION: Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil-predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.

Risk of developing pressure sore in amyotrophic lateral sclerosis patients - a nationwide cohort study.

BACKGROUND: Prior investigations with few cases have disclosed lack of pressure sore (PrS) formation was characteristic in amyotrophic lateral sclerosis (ALS) patients. However, studies with larger samples are lacking to ascertain this concept. OBJECTIVE: To investigate whether patients with ALS have higher risk of PrS. METHODS: Utilizing a Taiwan National Insurance claims data set with 23 million participants, we extracted 514 patients with ALS and 2056 controls from 1 January 2000 to 31 December 2008. Both groups were followed up until PrS occurrence during study period (2000-2011). The PrS risk was calculated with Cox proportional regression model. RESULTS: The patients with ALS had a greater PrS risk (adjusted hazard ratio [aHR] = 8.82, 95% confidence interval [CI] = 4.90-15.9, P < 0.001) than the controls did. PrS risk was much higher in ALS women (aHR = 26.6, 95% CI = 9.05-78.2, P < 0.001) than in ALS men (aHR = 4.38, 95% CI = 1.99-9.68, P < 0.001). Besides, in people aged 20-54, ALS was linked with a much greater PrS risk (aHR = 27.7, 95% CI = 5.79-132, P < 0.001) than in those aged ≥55 (aHR = 6.10, 95% CI = 3.10-12.0, P < 0.001). CONCLUSIONS: Amyotrophic lateral sclerosis is discovered to be correlated with an enhanced PrS risk. For PrS prevention, it is needed to pay more attention to the management of the patients with ALS, particularly in women and those with relatively younger age. Further investigations are needed to confirm the findings in this study.

Increased risk of brain tumor in patients with Parkinson's disease: a nationwide cohort study in Taiwan.

OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative disease. A decreased risk of cancer, except for melanoma, has been observed in patients with PD. The aim of this study was to evaluate the association between brain tumor and PD in a Taiwanese population. MATERIALS AND METHODS: We used data from the National Health Insurance program of Taiwan. The PD cohort contained 2998 patients, and each patient was frequency-matched, based on age and sex, with 4 people without PD, who were randomly selected from the general population. Cox's proportional hazard regression analysis was conducted to estimate the effects of PD on the risk of brain tumor. RESULTS: The risk of developing brain tumor was significantly higher in patients with PD than in those without PD (adjusted hazard ratio = 2.11; 95% confidence interval (CI) = 1.24-3.59), and benign brain tumor exhibited a particularly elevated risk of 2.16-fold (95% CI = 1.26-3.68). The hazard ratio (HR) for developing a benign brain tumor was higher in female patients with PD than in female patients without PD, with the risk being 2.65-fold (95% CI = 1.30-5.43). An analysis of the two age groups, 50-64 years and ≥65 years, showed that the HR of only the 50-64-year group was significantly higher between the PD and non-PD groups (HR = 2.77, 95% CI = 1.07-7.14). CONCLUSION: The present study showed that Taiwanese patients with PD are at a higher risk of developing brain tumor than the general population. The exact underlying etiologies require further investigation.

Increased risk of stroke among hip fracture patients: a nationwide cohort study.

SUMMARY: Our study indicates that hip fracture is independently associated with increased risk of developing stroke. In addition, the risk of stroke following the incidence of hip fracture is more prominent in younger patients, men, those with cardiovascular comorbidities, and in patients using specific medication, such as diuretics and ABRs. INTRODUCTION: Hip fractures are associated with increased risk of major morbidity. However, few data are available on the risk of stroke after hip fracture. Therefore, we investigated whether hip fracture increases the risk of stroke in a large nationwide cohort study. METHODS: Using universal insurance claims data, we identified a study cohort comprising of 6013 newly diagnosed with hip fracture patients from 2000 to 2010 and a non-hip fracture cohort of 23,802 participants. Incidence and risk of stroke were estimated for both cohorts until the end of 2011. RESULTS: Stroke incidence was 1.69-fold (95% confidence interval [CI]=1.56-1.83) higher in the hip fracture cohort than in the comparison cohort with an adjusted hazard ratio (HR) of 1.54 (95% CI=1.42-1.67) for the hip fracture cohort. The hip fracture patients were at higher risk of developing ischemic stroke (HR=1.55, 95% CI=1.42-1.69) and hemorrhagic stroke (HR=1.55, 95% CI=1.16-1.89), respectively. At an incidence of 64.6 per 1000 person-years, the adjusted HR of stroke increases to 3.10 (95% CI=2.47-3.90) for patients with coexisting diabetes, hypertension, and heart failure compared with those without these three conditions. At an incidence of 60.4 per 1000 person-years, the adjusted HR of stroke increases to 2.92 (95% CI=2.43-3.51) for hip fracture patients prescribed with diuretics and angiotensin II receptor blockers (ARBs) compared with those without hip fracture or prescriptions for diuretics or ARBs. CONCLUSIONS: Hip fracture is independently associated with a subsequent risk of stroke.

Increased risk of coronary heart disease in patients with hip fracture: a nationwide cohort study.

UNLABELLED: The study indicates that hip fracture is independently associated with increased risk of coronary heart disease. In addition, the highest risk of coronary heart disease following hip fracture appeared within the first year after hip fracture, indicating the need for multidisciplinary care for the patients. INTRODUCTION: Bone and vasculature are modulated through numerous common pathways. However, data on the risk of coronary heart disease (CHD) after hip fracture are scarce. Therefore, we investigated whether hip fracture increased the risk of CHD by conducting a large nationwide cohort study. METHODS: Using universal insurance claims data from 2000 to 2010, we identified a study cohort of 6013 participants newly diagnosed with hip fracture and a control cohort of 23,802 participants. Both cohorts were followed up to the end of 2011 to evaluate the risk of CHD. RESULTS: The overall incidence of CHD was 1.69-fold higher in the hip fracture cohort than it was in the control cohort (29.2 vs. 17.1 per 1000 person-years) with an adjusted hazard ratio of 1.51 (95 % confidence interval [CI] = 1.39-1.65). Sex-, age-, and comorbidity-specific analyses showed a higher relative risk of CHD for both women and men, all age groups, those with and without comorbidities, and patients with hip fracture compared with the control cohort. The highest risk of CHD was within the first year after hip fracture (adjusted HR = 1.72, 95 % CI = 1.45-2.04), and the risk remained high in the following years. CONCLUSION: Hip fracture was independently associated with a subsequent risk of CHD.

Trends in the epidemiology, diagnosed age and mortality rate of haemophiliacs in Taiwan: a population-based study, 1997-2009.

Many studies on epidemiology and mortality in haemophiliacs have been published in Western countries. However, few have been conducted in Asian countries. The purpose of our study was to investigate the nationwide epidemiology and mortality of haemophiliacs in Taiwan. Population-based data from the National Health Insurance Research Database between 1997 and 2009 were analysed using SAS version 9.3. The annual prevalence of haemophilia A (HA) and haemophilia B (HB) increased steadily to 7.30 and 1.34 cases per 100,000 males, respectively, in 2009. The annual crude incidence of HA and HB averaged 8.73 and 1.73 per 100,000 male births respectively. During the study period, the proportion of paediatric haemophiliacs decreased from 41.5% to 28.2% and the proportion of geriatric haemophiliacs increased from 2.5% to 5.7%. Among 493 newly diagnosed cases, the peak diagnostic ages were before 3 and between ages 10 and 40. Of the 76 cases of mortality, most patients died between the ages of 18 and 60. However, an increase in the age of mortality was noted after 2005 (P = 0.033). The overall standardized crude death rate of haemophiliacs was 10.2 per 1000 people, and the standard mortality ratio was 1.98. The annual prevalence of human immunodeficiency virus infection in haemophiliacs grossly declined from 1998 to 2009, with an average of 32.2 per 1000 haemophiliacs. This was a rare population-based study on the epidemiology and mortality of haemophilia in a Chinese population and Asian countries. The 13-year trends showed advances in haemophilia care in Taiwan.

First Report of Maize chlorotic mottle virus on Sweet Corn in Taiwan.

In February 2014, a severe disease on maize (Zea mays L.) broke out in the fields of central and southwestern Taiwan and caused yield losses in sweet corn production. Chlorotic spots first appeared at the base of infected leaves and later developed into systemic mottling. Diffused necrotic patches were also found on leaves or husks of the diseased plants. Moreover, severe rosetting and stunting accompanied by abnormalities in ear production were observed on mature plants. Eighteen leaf samples from symptomatic plants were collected and submitted to our Plant Diagnostic Clinic for virus diagnosis. All of the samples were first tested by reverse transcriptase (RT)-PCR to detect Maize stripe virus (MSpV) and by indirect ELISA to detect Maize dwarf mosaic virus (MDMV) or Sugarcane mosaic virus (SCMV), which were endemic to this area (1). Only 2 out of 18 samples were positive for MDMV, SCMV, or mixed infection of both viruses. Sap inoculation tests conducted on seedlings of sweet corn cv. Honey 236 indicated that the MDMV- and SCMV-negative samples still had an unknown pathogen causing original symptoms in the receptor plants. The isolate from Yunlin county reacted only with the antibody to Maize chlorotic mottle virus (MCMV) (AC Diagnostics, Fayetteville, AR) in ELISA. For further identification, the MCMV-specific primers (forward: MCMVg3514F-GGGAACAACCTGCTCCA; reverse MCMVg4014R-GGACACGGAGTACGAGA) were designed from the nucleotide sequence of MCMV coat protein (CP) gene. In RT-PCR using the AccuPower RT/PCR PreMix kit (Bioneer, Daejeon, Korea), an expected 500-bp DNA fragment was observed. This PCR product was cloned and its nucleotide sequence was determined by Mission Biotech Co., Taipei, Taiwan. BLAST analysis of the CP gene of the MCMV-Yunlin revealed the maximum nucleotide identities (99%) with Chinese Sichuan isolates (GenBank Accession No. JQ984270) and 98% identities to four Chinese Yunnan isolates (GU138674, JQ982468, JQ982469, and KF010583) and one Kenya isolate (JX286709), compared with 97% to Kansas isolate (X14736) and 96% to Nebraska isolate (EU358605). Subsequently, the complete nucleotide sequence of the viral genome (KJ782300) was determined from five overlapping DNA fragments obtained from independent RT-PCR amplification. The virus isolate was infectious to sweet corn cultivars Bai-long-wang, Devotion, SC-34, SC2015, and Zheng-zi-mi, on which similar symptoms were developed after mechanical inoculation. During the spring of 2014, a total of 224 sweet corn samples were collected from the epidemic areas of Taichung, Yunlin, Chiayi, and Kaohsiung counties. Samples (n= 161) reacted positive for MCMV in ELISA and/or RT-PCR. In the field survey, more than 20 adult thrips might be observed on an MCMV-infected plant. Two species of Frankliniella were found on maize plants: F. williamsi Hood and F. intonsa Trybom. Maize thrips (F. williamsi), an occasional pest of maize occurring during winter and spring in Taiwan, was characterized by its abdominal sternite II on which 1 or 2 discal setae of equal length with posteromarginal setae were borne (2). Samples with 1, 5, 10, and 30 F. williamsi collected in the field were tested by RT-PCR; MCMV was detectable not only in the pooled crushed bodies but also in a single maize thrips. This is the first report of MCMV occurrence on maize in Taiwan and of the virus transmitted by maize thrips. References: (1) C. T. Chen et al. Taiwan Sugar 37(4):9, 1990. (2) C.-L. Wang et al. Zool. Stud. 49:824, 2010.

Laparoscopic versus robotic TAPP/TEP inguinal hernia repair: a multicenter, propensity score weighted study.

PURPOSE: The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. METHODS: Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. RESULTS: A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p = 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg, p = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001). CONCLUSIONS: This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.

GSTP1 is a hub gene for gene-air pollution interactions on childhood asthma.

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene-air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two-way gene-air pollution interaction between glutathione S-transferase P (GSTP1) and PM10 on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene-air pollutant combinations. Our study suggests that interaction between GSTP1 and PM10 is the most influential gene-air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti-oxidative pathway that buffers the harmful effects of air pollution.

Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer's disease in a Chinese population.

Previous experiments demonstrated that transgenic mice carrying both amyloid precursor protein and mutant ATP7B transgenes reduce amyloid plaques and diminish plasma Abeta levels. These experiments showed that a structural change of ATP7B may affect Alzheimer’s disease (AD) susceptibility. In this study three missense SNPs in ATP7B gene (rs1801243, rs1801244, and rs1801249) were chosen to test whether they were associated with AD. We tested this hypothesis using a case control design. The experimental data showed that there was a significant deviation from Hardy-Weinberg equilibrium (HWE) for SNP rs1801249 (c.3419 T greater than C, Val1140Ala) in the case group (p = 0.014) but not in the control group and that there was an association between SNP rs1801249 and AD under a recessive model (p = 0.003). The data also showed that the genotype frequency distribution of the ATP7B c.1366 G greater than C polymorphism (rs1801244, Val456Leu) differed significantly between the AD patients and the normal subjects (p = 0.012). In addition, the frequency of the TGC haplotype of SNPs rs1801243, rs1801244, and rs1801249 was significantly higher in the AD patients compared with the normal subjects (p = 8.49×10-7). These observations suggested that genetic variations in the copper transporter gene ATP7B might contribute to AD pathogenesis in the Taiwanese population.

Effects of exercise training on cardiac apoptosis in obese rats.

BACKGROUND AND AIM: The purpose of this study was to evaluate the effects of exercise training on cardiac apoptotic pathways in obesity. METHODS AND RESULTS: Sixteen lean Zucker rats (LZR) and sixteen obese Zucker rats (OZR) of 5-6 months of age as well as the other sixteen obese rats were subjected to treadmill running exercise for 1 h everyday for 3 months (OZR-EX). After exercise training or sedentary status of the rats, the excised hearts from the three groups were measured by heart weight index, H&E staining, TUNEL assays and Western blotting. Cardiac TUNEL-positive apoptotic cells, the protein levels of TNF alpha, Fas ligand, Fas receptors, Fas-associated death domain (FADD), Bad, Bax, activated caspase 8, activated caspase 9, and activated caspase 3 were higher in OZR than those in LZR. The protein levels of TNF alpha, Fas ligand, Fas receptors, FADD, activated caspase 8, and activated caspase 3 (Fas pathway) and the protein levels of Bad, Bax, Bax-to-Bcl2 ratio, activated caspase 9, and activated caspase 3 (mitochondria pathway) were lower in OZR-EX than those in OZR. CONCLUSION: Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways become more activated in obesity. Exercise training can prevent obesity-activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways. Our findings demonstrate a new therapeutic effect of exercise training to prevent delirious cardiac Fas-mediated and mitochondria-mediated apoptosis in obesity.

Charge separation in donor-acceptor spiro compounds at metal and metal oxide surfaces investigated by surface photovoltage.

Molecules with donor (diphenylamine) and acceptor moieties (dicyano or cyanoacrylic acid moieties) were linked by fluorene or spirobisfluorene cores and the chain length has been changed by introducing a thiophene group between fluorene and diphenylamine. Four different kinds of fluorene and spirobisfluorene compounds were adsorbed from highly diluted solutions at ultra-thin nanoporous TiO2 (np-TiO2), Au and ITO surfaces. Charge separation has been investigated by surface photovoltage spectroscopy in the fixed capacitor and Kelvin probe arrangements in vacuum. Striking differences between the interaction of linking (dicyano or cyanoacrylic moieties) and different substrates were observed. Intra-molecular charge separation and electron injection have been distinguished and the directed adsorption of spiro compounds was deduced.

A mouse model for spinal muscular atrophy.

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.

Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Adipocytokine genes encoding adiponectin (ADIPOQ) and the leptin receptor (LEPR) affect glucose and fatty acid metabolism. The purpose of this study was to examine the association between early-onset type 2 diabetes mellitus (T2DM) and variability within these two genes in the Han Chinese population of Taiwan. SUBJECTS: A cross-sectional study of 999 patients from the Han Chinese population of Taiwan with early-onset T2DM (n=264; age at diagnosis, 20 to <45 years) and late-onset T2DM (n=735; age at diagnosis, ~45 years) was performed. Blood samples from T2DM patients were taken for DNA extraction, and levels of serological markers were measured at enrollment. Seven single-nucleotide polymorphisms (SNPs) were selected for genotyping (three SNPs in AIDPOQ and four SNPs in LEPR) by polymerase chain reaction in each patient. RESULTS: Polymorphisms at the position rs10937273 in ADIPOQ and at the positions rs1892534 and rs2211651 in LEPR were statistically associated with early-onset T2DM (P=0.0246, 0.0014 and 0.0012, respectively). C-reactive protein levels were significantly different among the early-onset T2DM patients with different genotypes at the SNPs rs1892534 and rs2211651 in LEPR (P=0.003 and P=0.004, respectively). In addition, fasting glucose levels were also significantly different among different genotypes at the SNP rs1892534 in LEPR (P=0.038). CONCLUSION: We conclude that the polymorphisms in the adipocytokine genes ADIPOQ and LEPR are significantly associated with the age at diagnosis of T2DM in the Han Chinese population of Taiwan.

Medical and non-medical correlates of carpal tunnel syndrome in a Taiwan cohort of one million.

BACKGROUND: Carpal tunnel syndrome (CTS), with unclear etiology, is the most common entrapment neuropathy. Its occurrence is related to lots of medical and non-medical conditions with uncertain causality. With a large population, we characterized selected demographical and clinical factors to add more information on CTS-correlated factors and new insight into future CTS prevention. METHODS: A national insurance claim dataset of one million enrollees in Taiwan was used to identify 15 802 patients with CTS and 31 604 randomly selected controls, during a period of 7 years starting 1 January 2000. Statistical association with CTS was determined for five sociodemographic and nine medical factors. RESULTS: Patients were predominantly women (65.6% vs. 47.7% in the control group) and older (40 and above, 62.6% vs. 36.2%). Rheumatoid arthritis was found to be the most significant comorbidity associated with CTS, followed by gout, hypertension, diabetes, obesity, uremia, and acromegaly. For younger group age ≤39, the association of these comorbidities was stronger, and hypothyroidism and vitamin B(6) deficiency were additional comorbidities. Aging appears to reduce the relative impact of the diseases commonly associated with CTS as the possible risk factors. CONCLUSIONS: Identification of the CTS correlates in younger group would be of greater value in timely detection and treatment for these diseases. Correcting these disorders may aid in removing possible causes of CTS. This is the first report on the effect of aging on probable CTS risk factors. How factors associated with aging contribute to the development of CTS remains to be determined.

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.

Heat shock protein 27 expression in areca quid chewing-associated oral squamous cell carcinomas.

OBJECTIVES: Heat shock protein (HSP) 27 is a low-molecular-weight protein that functions as a molecular chaperone and plays a cytoprotective role through its antioxidant activity during cell stress. Areca quid chewing is associated with the high incidence of oral squamous cell carcinomas (OSCCs) in Taiwan. The aim of this study was to compare heat shock protein 27 (HSP27) expression in OSCCs and the normal oral tissues. METHODS: Forty-eight OSCCs from areca quid chewers and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry for HSP27. The normal human oral keratinocytes (HOKs) were challenged with arecoline, the major alkaloid of areca nut, by Western blot for HSP27. Furthermore, epigallocatechin-3 gallate (EGCG), glutathione precursor N-acetyl-L-cysteine (NAC), cyclooxygenase-2 inhibitor NS-398, HSP inhibitor quercetin, extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, and p38 inhibitor SB203580 were added to find the possible regulatory mechanisms. RESULTS: Heat shock protein 27 exhibited higher expression in OSCCs than normal specimens (P < 0.05). Arecoline was found to elevate HSP27 expression in a dose- and time-dependent manner (P < 0.05). The additions of pharmacological agents were found to inhibit arecoline-induced HSP27 expression (P < 0.05). CONCLUSIONS: Heat shock protein 27 expression is significantly elevated in areca quid chewing-associated OSCCs. Arecoline-induced HSP27 expression was downregulated by EGCG, NS398, NAC, quercetin, PD98059, and SB203580.

Glutathione S-transferase, incense burning and asthma in children.

Incense burning is a popular practice in many family homes and temples. However, little is known about the effects of indoor incense burning and genetic polymorphisms on asthma. This study evaluated the effects of indoor incense burning and glutathione S-transferase (GST) genetic polymorphisms on asthma and wheeze. In 2007, 3,764 seventh-grade schoolchildren (mean±sd age 12.42±0.65 yrs) were evaluated using a standard questionnaire for information about respiratory symptoms and environmental exposures. Multiple logistic regressions were performed to assess the association between GST polymorphisms and incense burning frequency on asthma and wheeze, after adjusting for potential confounders. The frequency of incense burning at home was associated with increased risk of current asthma (p=0.05), medication use (p=0.03) and exercise wheeze (p=0.001). GST1 (GSTT1) null genotypes were associated with current asthma (OR 1.43, 95% CI 1.00-2.04) and medication use (OR 1.46, 95% CI 1.01-2.22). GSTT1 showed a significant interactive effect with incense burning on current asthma, current wheeze and nocturnal wheeze. The frequency of incense burning was associated with increased risk of current asthma, medication use, lifetime wheeze, nocturnal wheeze and exercise wheeze in an exposure-response manner among children with GSTT1 null genotype (p<0.05). Incense burning is a risk factor for asthma and wheezing, especially in GSTT1 genetically susceptible children.

A population-based study on trend in incidence of distal radial fractures in adults in Taiwan in 2000-2007.

UNLABELLED: This population-based study was conducted using claims data obtained from the National Health Insurance to investigate the trend in incidence of distal radial fractures in adults in Taiwan from 2000 to 2007. Our results revealed an increasing trend, particularly among women >50 years of age. INTRODUCTION: This population-based study used insurance claims data from 2000 to 2007 obtained from the National Health Research Institute to investigate the longitudinal trend in distal radial fractures in adults ≥20 years old in Taiwan. METHODS: We estimated the age- and gender-specific annual incidence rates of distal radial fracture and compared the differences in distribution by sociodemographic status between patients with and those without distal radial fracture and the differences in incidence rates between 2000 and 2007. RESULTS: The incidence of fracture was higher in women than in men. The overall female-to-male rate ratios were 1.52 in 2000 (12.3 vs 8.06 per 10,000 persons) and 1.89 in 2007 (18.9 vs 10.0 per 10,000 persons). There was marked increase in age-specific incidence beginning in the 50-54-year age group, particularly among women. CONCLUSION: These results imply the need for more effective intervention for the prevention of subsequent fracture and disability, particularly for perimenopausal women.