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A thyroglossal duct cyst (TGDC) is a common embryological remnant that typically presents as an anterior neck mass; however, this malformation can occur in any adjacent area, including the tongue base (lingual type), along the migration path of the thyroid during embryonic development. Lingual TGDC is often quiescent until infection occurs. Supraglottitis or inflammation of the supraglottis, is a potentially life-threatening disease. Because of the anatomical proximity of lingual TGDC to the supraglottis, lingual TGDC infection might be related to a presentation of supraglottitis. A 49-year-old male initially presented with clinical symptoms of acute supraglottitis. After intensive medical treatment resulting in no improvement, a computed tomography scan was performed. The result raised the suspicion of an infected lingual TGDC. Transoral marsupialization using a rigid laryngoscope was performed to drain the abscess inside the cyst. A diagnosis of lingual TGDC was made based on the characteristic histological pattern of the lesion. After treatment, a follow-up computed tomography scan showed no evidence of recurrence. To the authors' knowledge, only a few reports have pointed out similarities in the clinical and radiological findings between acute supraglottitis and an infected lingual TGDC. Clinicians should consider lingual TGDC during the differential diagnosis of supraglottitis, especially in patients with poor response to medical treatment.

We assessed gene–gene and gene-physical activity interactions of polymorphisms in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and lymphotoxin α (LTA) genes on lower extremity performance in community-dwelling elders in Taiwan. Five SNPs (rs1205, rs1130864, rs1800947, rs2794520, and rs3093059) of CRP gene, three SNPs (rs909253, rs1041981, and rs2239704) of LTA gene, and three SNPs (rs3093662, rs1800629, and rs1799964) of TNF-α gene of 472 unrelated elders were genotyped. Lower extremity performance included timed up-and-go test (TUG), walking speed, weight-adjusted leg press (waLP), and timed chair stand (TCS). We detected significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; LTA rs909253 and rs1041981; and TNF-α rs1799964 for TCS in women after covariate adjustment (all P

Background The integrity of the gut barrier in patients with inflammatory bowel disease is known to be impaired but the exact mechanisms remain mostly unknown. SHANK3 mutations are associated with autism, and patients with autism are known to have higher proportions of inflammatory bowel disease. Here, we explore the role of SHANK3 in inflammatory bowel disease, both in vivo and in vitro. Methods Dextran sulfate sodium colitis was induced in SHANK3 knockout mice. Transepithelial electrical resistance, paracellular permeability, and Salmonella invasion assays were used to evaluate epithelial barrier function, in vitro and in vivo. Expression of tight junction proteins, protein kinases, and MAP kinase phosphorylation changes were analyzed by immunoblotting after overexpression or knockdown of SHANK3 expression. SHANK3 expression in intestinal tissue from patients with Crohn's disease was analyzed by quantitative polymerase chain reaction and immunohistochemistry. Results SHANK3 knockout mice were more susceptible to dextran sulfate sodium. SHANK3 knockout resulted in a leaky epithelial barrier phenotype, as demonstrated by decreased transepithelial electrical resistance, increased paracellular permeability, and increased Salmonella invasion. Overexpression of SHANK3 enhanced ZO-1 expression, and knockdown of SHANK3 resulted in decreased expression of ZO-1. Regulation of ZO-1 expression by SHANK3 seems to be mediated through a PKCe-dependent pathway. SHANK3 expression correlated with ZO-1 and PKCe in colonic tissue of patients with Crohn's disease. Conclusions The expression level of SHANK3 affects ZO-1 expression and the barrier function in intestinal epithelial cells. This may provide novel insights in Crohn's disease pathogenesis and treatment.

Background The incidence of nasopharyngeal carcinoma (NPC) is higher in Chinese than in Caucasian populations. Genetic, viral, and lifestyle factors may explain these ethnic differences in the incidence of NPC. In the present study, we examined the familial aggregation, heritability, and relative risks (RRs) of NPC using a nationwide database in Taiwan. Methods A population-based family study was conducted using the Taiwan National Health Insurance Research Database. Participants included all individuals (N = 23,422,955) registered with that database in 2013; of these, 17,653 had NPC. Among them, 47.45%, 57.45%, 47.29%, and 1.51% had a parent, child, sibling, and twin, respectively, with NPC. Results Among the approximately 23 million Taiwan NHI beneficiaries in 2013, the relative risks (RRs) (95% confidence intervals) for NPC were 34.46 (5.12–231.77) for twins of the patients, 9.23 (6.34–13.43) for siblings, 3.80 (2.97–4.86) for parents, 3.74 (2.60–5.37) for offspring, and 1.78 (1.16–2.74) for spouses without genetic similarity. The mean age of onset in first-degree relative-affected NPC patients was 35.5 years compared to 39.0 years for NPC patients without affected first-degree relatives (p ≤ 0.0001). Using a threshold liability model, the accountability for phenotypic variance of NPC was estimated to be 61.3% for genetic factors (heritability), 13.9% for shared environmental factors, and 24.8% for non-shared environmental factors. The probability of a patient with NPC to be sporadic was 82.8%. Conclusion This population-based analysis suggested a strong familial tendency in the development of NPC. Screening of first-degree relatives of NPC patients is recommended, particularly in endemic regions.

We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10–11.65; OR 4.74, 95 % CI 1.43–15.70; and OR 5.06, 95 % CI 1.08–23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23–23.06 and OR 5.36, 95 % CI 1.11–25.94, respectively). VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ −0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2′-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.

Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61–13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p

This study assesses interactions of tumor necrosis factor α (TNF-α) gene polymorphisms with C-reactive protein (CRP) or lymphotoxin α (LTA) gene on serum CRP and TNF-α levels and handgrip strength. Eleven single nucleotide polymorphisms (SNPs), including rs2794520, rs1205, rs1130864, rs1800947, and rs3093059 in CRP; rs1799964, rs1800629, and rs3093662 in TNF-α; and rs2239704, rs909253, and rs1041981 in LTA, were genotyped in 472 unrelated elders (mean age 73.8 years). Among elders with TNF-α rs1799964 AA genotype, adjusted mean difference for handgrip strength decreased by −2.60 (−4.82, −0.38) and −2.51 kg (−4.75, −0.28) for LTA rs909253 and rs1041981 in women and by −2.39 kg (−3.98, −0.81) for CRP rs3093059 in men. Among elders with TNF-α rs1799964 AA genotype, adjusted mean ratios for hs-CRP levels increased by 2.32 (1.38, 3.90) and 2.27 (1.35, 3.84) for both CRP rs909253 and rs1041981 in women. The A-A-C LTA haplotype was associated with TNF-α levels that were 1.55 times higher than those of the C-G-A haplotype (P = 0.005). The joint effects of SNPs (the rs1800947 or rs3093059 of CRP, rs1799964 or rs1800629 of TNF-α, and rs909253 or rs1041981 of LTA) and physical inactivity appeared to have greater magnitude of decreased handgrip strength than main effects of these SNPs and physical inactivity. Our data showed that significant interactions of TNF-αrs1799964 and LTA rs909253 were observed. Moreover, joint effects of these CRP, TNF-α, and LTA risk alleles with physical inactivity in elders were observed, suggesting that physical activity may modulate effects of genotypes on handgrip strength.

The aim of this study was to evaluate the interacted association between EDNRA and EDN1 polymorphisms and gender, regular exercise, and obesity status on carotid intima media thickness (IMT) in community- dwelling subjects of the Taichung Community Health Study. Five single-nucleotide polymorphisms (SNPs rs1395821, rs1878406, rs5333, rs1800541, and rs5370) of the EDNRA and EDN1 gene were examined in 480 participants from 160 families. The IMT protocol involves scanning the common carotid arteries (CCAs), the carotid bifurcations (bulb), and the origins (first 1 cm) of the internal carotid arteries (ICAs). Generalized linear models with a generalized estimating equation were employed to consider the dependence among family members. After multivariate adjustment, the effects of interactions between EDNRA and EDN1 gene with gender, obesity, and exercise were observed. For gene-gender interaction on CCA IMT, the adjusted mean for men carrying the GA/GG genotype of EDNRASNP rs1878406 was 1.18 times higher than that for men carrying the AA genotype (95% CI: 1.01, 1.37). As for bulb and ICA IMT, the adjusted mean values for women carrying the AC/AA genotype of EDN1 rs5370 was lower than those carrying the CC genotype: 0.89, [0.82, 0.98]; and 0.90 [0.83, 0.99], respectively. We did observe significant effects of EDNRA SNPs rs1395821 and rs5333 in individuals who regularly exercised. A significantly lower adjusted mean in CCA IMT for non-obese individuals carrying EDNRA SNP rs5333 was observed (0.92 [0.86, 0.99]) compared with non-obese individuals carrying the AA genotype. This study first reported significant interactions of EDNRA and EDN1 polymorphisms with gender, regular exercise, and obesity on carotid IMT in Han Chinese participants.

Background Diabetic nephropathy (DN) has become one of the most common causes of end-stage renal disease (ESRD) in many countries, such as 44.5% in Taiwan. Previous studies have shown that there is a genetic component to ESRD. Studies attempting to determine which genetic variants are related to DN in Han Chinese are limited. A case–control study was conducted to identify DN susceptibility variants in Han Chinese patients with type 2 diabetes. Results We included 574 unrelated type 2 diabetes patients (217 DN cases and 357 controls), who were genotyped using Illumina HumanHap550-Duo BeadChip. In single-SNP association tests, the SNPs rs11647932, rs11645214, and rs6499323 located at 16q22.1 under the additive-effect disease model were significantly associated with an approximately 2-fold increased risk of DN. In haplotype association tests, identified haplotypes located in the chromosome 16q22.1 region (containing ST3GAL2, COG4, SF3B3, and IL34 genes) raised DN risk. The strongest association was found with haplotype rs2288491-rs4985534-rs11645214 (C-C-G) (adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.83-2.03, p = 6.25 × 10−7), followed by haplotype rs8052125-rs2288491-rs4985534-rs11645214 (G-C-C-G) (AOR 1.92, 95% CI 1.82-2.02, p = 6.56 × 10−7), and haplotype rs2303792-rs8052125-rs2288491-rs4985534-rs11645214 (A-G-C-C-G) (AOR 1.91, 95% CI 1.81-2.01, p = 1.15 × 10−6). Conclusions Our results demonstrate that the novel SNPs and haplotypes located at the 16q22.1 region may involve in the biological pathways of DN in Han Chinese patients with type 2 diabetes. This study can provide new insights into the etiology of DN. Electronic supplementary material The online version of this article (doi:10.1186/s12863-014-0113-8) contains supplementary material, which is available to authorized users.

With the number of people considered to be obese and having chronic disease rising across the world, the role of IT solution in nutrition management and planning has been receiving increased attention by medical professionals in recent years. A key factor toward a successful personalized nutrition planning is an individual's food preference instead of dogmatic nutrition pattern since it is unlikely that an individual would accept the meal plan merely based on the nutrition supplements. However, personal preferences about foods are obviously relatively harder to acquire comparing to common nutrition requirements that can be easily obtained from guidelines. In this paper, we proposed a personalized nutrition planning method based on random walks theory to maximize the planning satisfaction. The personal guidelines generated by the proposed method are expected to potentially improve the healthy diet compliance and thus reduce the risk of chronic diseases of individuals.

Effective personal dietary guidelines are essential for health management and preventing chronic diseases. The objective of this research is to achieve nutrient-balanced food recommendations for each individual, while considering individual's requirements at the same time. To reach this goal, we developed a location-aware interactive diet consultant named SmartDiet based on the multi-objective optimization. The proposed personalized diet planning approach not only translates nutrient recommendations into realistic dish choices, but also accepts feedbacks from users to fine-tune their meal plans. The results showed that daily nutrition needs can be fulfilled by the designated meals, and the interactive diet planning scheme helps a user adjust the plan in an easier way. The guidelines generated by SmartDiet are expected to potentially improve the overall health and reduce the risk of chronic diseases of individuals.

Background & aimsTo date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.MethodsSNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay.ResultsSLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1.ConclusionsSLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.

Background Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Although cigarette smoking is the primary risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. Since cancer results from progressive accumulation of genetic aberrations, genomic rearrangements may be early events in carcinogenesis. Results In order to identify biomarkers of early-stage adenocarcinoma, the genome-wide DNA aberrations of 60 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined using Affymetrix Genome-Wide Human SNP 6.0 arrays. Common copy number variation (CNV) regions were identified by ≥30% of patients with copy number beyond 2 ± 0.5 of copy numbers for each single nucleotide polymorphism (SNP) and at least 100 continuous SNP variant loci. SNPs associated with lung adenocarcinoma were identified by McNemar’s test. Loss of heterozygosity (LOH) SNPs were identified in ≥18% of patients with LOH in the locus. Aberration of SNP rs10248565 at HDAC9 in chromosome 7p21.1 was identified from concurrent analyses of CNVs, SNPs, and LOH. Conclusion The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 may be a potential biomarker of cancer susceptibility.