Sensory modulation is essential for animal sensations, behaviours and survival. Peripheral modulations of nociceptive sensations and aversive behaviours are poorly understood. Here we identify a ...biased cross-inhibitory neural circuit between ASH and ASI sensory neurons. This inhibition is essential to drive normal adaptive avoidance of a CuSO4 (Cu(2+)) challenge in Caenorhabditis elegans. In the circuit, ASHs respond to Cu(2+) robustly and suppress ASIs via electro-synaptically exciting octopaminergic RIC interneurons, which release octopamine (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In addition, ASIs sense Cu(2+) and permit a rapid onset of Cu(2+)-evoked responses in Cu(2+)-sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation among sensory neurons via reciprocal inhibition fine-tunes the nociception and avoidance behaviour.
Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. ...The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.
Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal orifice and thereby compromise ventilation of the middle ear. The resulting negative pressure in the middle ear may, in turn, lead ...to the formation of an eardrum retraction pocket and subsequent acquired cholesteatoma. This study hypothesizes that CRS may increase the risk of cholesteatoma.
To evaluate the risk of cholesteatoma in patients with CRS.
This study used a nationwide, population-based claims database to test the hypothesis that CRS may increase the risk of cholesteatoma. The Longitudinal Health Insurance Database of Taiwan was used to compile data from (1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was performed from June 1 to October 27, 2015. Each patient was followed up for 8 years to identify those in whom cholesteatoma subsequently developed. The Kaplan-Meier method was used to determine the cholesteatoma-free survival rate, and the log-rank test was used to compare survival curves. Cox proportional hazards regression models were used to compute the 8-year hazard ratios (HRs).
Diagnosis of cholesteatoma.
Among the 76 020 patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was 27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084 person-years) individuals from the CRS cohort and 143 (506 540 person-years) from the comparison cohort were diagnosed with cholesteatoma during the 8-year follow-up period. The incidence of cholesteatoma per 1000 person-years was more than twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per 1000 patient-years. After adjusting for potential confounders, patients with CRS had a 69% increased risk of cholesteatoma within 8 years, compared with those without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a significantly lower 8-year cholesteatoma-free survival rate than did those in the comparison group. The absolute difference in the 8-year cholesteatoma-free survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016-0.0043).
This is the first large-scale study, to date, to demonstrate a prospective link between CRS and the subsequent development of cholesteatoma within a follow-up period of 8 years. The purpose of the study was to draw attention to the possibility of development of cholesteatoma among patients with CRS. Because that possibility exists, clinicians should keep this association in mind as well as the importance of a thorough head and neck examination.
Background
Epidemiological studies have reported an association between urolithiasis and cardiovascular disease. However, studies examining the risks of ischaemic and haemorrhagic stroke in patients ...with urolithiasis are limited.
Aims and methods
By using a nationwide population database, we conducted a matched cohort study to investigate the association between urolithiasis and longitudinal risks of ischaemic and haemorrhagic stroke.
Results
The urolithiasis and non‐urolithiasis cohorts included 12 979 and 64 895 patients respectively. Of these, 728 (5.6%) and 2802 (4.3%) patients in the urolithiasis and non‐urolithiasis cohorts, respectively, had a stroke during the 5‐year follow‐up period. The hazard ratio (HR) for stroke was 1.19 times higher (95% confidence interval CI = 1.10–1.29; P < 0.001) in the urolithiasis cohort than in the non‐urolithiasis cohort after adjustment for potential confounders. The risk of both ischaemic (adjusted HR = 1.16; 95% CI = 1.05–1.29) and haemorrhagic stroke (adjusted HR = 1.30; 95% CI = 1.03–1.64) remained significant in the urolithiasis cohort. Furthermore, the risk of stroke was significant in both men (adjusted HR = 1.16; 95% CI = 1.05–1.28) and women (adjusted HR = 1.26; 95% CI = 1.10–1.45). Middle‐aged (40–59 years; adjusted HR = 1.26; 95% CI = 1.10–1.45) and older (≥60 years; adjusted HR = 1.14; 95% CI = 1.03–1.27) patients had a particularly high risk of stroke.
Conclusions
The present study detected an increased risk of both ischaemic and haemorrhagic stroke in patients with urolithiasis, particularly in those older than 40 years.
Objectives
No large population‐based studies have reported on the risk of cholesteatoma developing after allergic rhinitis (AR). This study used a nationwide population‐based claims database to ...investigate the hypothesis that AR may increase the risk of cholesteatoma.
Study Design
Retrospective cohort study.
Methods
Data from Taiwan's Longitudinal Health Insurance Database were analyzed to compile the following: 1) 15,953 patients newly diagnosed with AR between 1997 and 2000, and 2) a comparison cohort of 63,812 matched non‐AR enrollees (with a ratio of 1 to 4). Each patient was followed for 10 years to identify cases in which cholesteatoma subsequently developed. The Kaplan‐Meier method was used to determine the cholesteatoma‐free survival rate, and the log‐rank test was used to compare survival curves. Cox proportional hazard regressions were performed to compute adjusted hazard ratios (HRs).
Results
Among the 79,765 patients enrolled in this study, 45 (159,364 person‐years) from the AR cohort and 88 (638,130 person‐years) from the comparison cohort were diagnosed with cholesteatoma during the follow‐up period (incidence rates 0.28 and 0.14 of 1,000 person‐years, respectively). Patients with AR were more likely to develop cholesteatoma compared to those without AR (adjusted HR 1.57, 95% confidence interval = 1.05–2.34, P < 0.05). Patients with AR presented a significantly lower 10‐year cholesteatoma‐free survival rate than did those in the comparison group (log‐rank, P < 0.001).
Conclusion
This is the first study to demonstrate a link between AR and the development of cholesteatoma. We suggest that clinicians keep this association in mind and carefully investigate the possibility of development of cholesteatoma among patients with AR.
Level of Evidence
3b. Laryngoscope, 128:547–553, 2018
Highlights • Breast cancer incidence was 1.89-fold higher in women with sleep apnea (SA). • Adjusted hazard ratio was 2.09 during the 5-year follow-up. • Women aged >30 years suffering from SA may be ...more vulnerable to breast cancer development.
The association between chronic obstructive pulmonary disease (COPD) and functional gastrointestinal disorders (FGIDs) remains unclear.
Using Taiwan's National Health Insurance Research Database, we ...conducted a nationwide population-based study to explore the relationship of COPD and future FGIDs development. The COPD cohort consisted of 4107 patients with COPD between 2000 and 2005. For a comparison cohort, 12,321 age- and gender-matched patients without COPD were randomly selected. The two cohorts were tracked for 5 year and observed for occurrence of FGIDs. The operational definition of COPD in the Korean Health Insurance Review and Assessment Service database was used to validate the results. The validation study confirmed the accuracy of definitions of COPD (83.5% sensitivity).
The adjusted hazard ratios (aHR) of FGIDs in patients with COPD was higher (aHR: 1.63; 95% confidence interval (CI): 1.45–1.83; P < .001) than that of the comparison patients. In our secondary analysis in which FGIDs was divided into gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia. Patients with COPD also had higher risk for all three subtypes of FGIDs: irritable bowel syndrome (aHR: 1.55; 95% confidence interval (CI): 1.27–1.90; P < .001), gastroesophageal reflux disease (aHR: 2.10; 95% confidence interval (CI): 1.76–2.49; P < .001), and functional dyspepsia (aHR: 1.34; 95% confidence interval (CI): 1.11–1.62; P = .003). The results in validated COPD group were consistent with those in unvalidated COPD group.
Patients with COPD appeared to be at higher risk for future FGIDs.
•COPD patients had higher risk for all three subtypes of FGIDs: irritable bowel syndrome, gastroesophageal reflux disease, and functional dyspepsia.•The validation study confirmed the accuracy of definitions of COPD.•The results in validated COPD group were consistent with those in unvalidated COPD group.
Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors ...(HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired.
This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition.
Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions.
Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 μM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5′UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression.
Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5’-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis.
Display omitted
Transient liquid phase bonding has been proven to offer exceptional joining strength and dependable high temperature service in chip stacking applications. Nevertheless, conventional Cu/Sn/Cu ...transient liquid phase bumps had shortcomings, such as smooth phase boundaries and coarsening grains. In this study, the variation of microstructure in Cu/Sn-3.0Ag-0.5Cu/Cu, Cu/Sn-3.0Ag-0.5Cu/Ni, and Ni/Sn-3.0Ag-0.5Cu/Cu transient liquid phase bonds with the sizes less than 10 μm before and after long term aging were investigated. Due to the dissolution of Ni atoms from the substrates at the cold or hot end, the structure exhibited randomly-oriented and small-sized grains. After 1000 h aging treatment, the Ni-containing specimen still retained the abundant grain structure and appeared network-like morphology of Cu3Sn near phase boundaries. Additionally, the shear testing was applied in the aged samples, Ni-doped joints demonstrated better mechanical properties than Ni-free joining. The enhancement of shear strength was attributed to Ni addition, retaining the advantageous grain structure. This present work showed that doping Ni to micro-bumps could halt the deterioration of grain structure over extended usage of electronic devices in 3D-IC technology.
•Transient liquid phase bonding micro-bumps with Ni doping under long-term isothermal aging treatment are discussed.•The variation of microstructure in Ni/SAC305/Cu system before and after long-term aging is investigated.•The fine grains and multiple orientations of IMCs after aging treatment are retained to a great extent via Ni addition.•Ni addition can enhance the mechanical characteristics of micro-bumps before and after long-term aging.
Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents ...showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females) from 1 million subjects. The youths of 7–12 years had the highest prevalence of acne (14.39%). Major depression was more common in those with acne (0.77%) than controls (0.56% , P < 0.0001) regardless of gender. Multiple logistic regression showed an increased risk of major depression in women without acne (OR = 1.85, 95% CI 1.75–1.96). The risk is additive in women with acne (OR = 2.78, 95% CI 2.43–3.17). Similar additive risk of suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.
PDF
