PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.
Blotting, Western ; Breast Neoplasms ; Breast ; Cell Movement ; Doxorubicin ; Myosin Light Chains ; Paclitaxel ; Phenotype ; Phosphorylation ; Up-Regulation

BACKGROUND/AIMS: Sleep dysfunction is associated with altered gastrointestinal function and subsequently exacerbations of gastrointestinal problems. We aimed to investigate whether sleep dysfunction would influence anorectal motility as determined by anorectal manometry. The effect of anxiety on anorectal motility was also determined. METHODS: A total of 24 healthy volunteers underwent anorectal manometry. The anorectal parameters included resting and squeeze sphincter pressure, sensory thresholds in response to balloon distension, sphincter length, rectal compliance, and rectoanal inhibitory reflex. Sleep dysfunction was subjectively assessed by using Pittsburgh Sleep Quality Index (PSQI). Anxiety was assessed by the application of the State-Trait Anxiety Inventory questionnaire. RESULTS: There were sixteen subjects without sleep dysfunction (7 women; mean age, 22 years) and eight subjects with sleep dysfunction (2 women; mean age, 22 years). There was no group difference in the volume threshold for rectoanal inhibitory reflux, rectal compliance or sphincter length (P = NS). Anal sphincter pressure did not differ between the groups (P = NS). The rectal sensitivity for different levels of stimulation did not differ between the groups (P = NS). Sleep quality as determined by PSQI correlated with rectal compliance (r = 0.66, P = 0.007). Although there was no differences in any manometric parameters between subjects with and without anxiety, the anxiety score correlated with rectal compliance (r = 0.57, P = 0.003). CONCLUSIONS: Despite a positive association between rectal compliance and the level of subjective sleep or anxiety, sleep dysfunction did not apparently affect most of anorectal function in healthy subjects, nor did anxiety.
Anal Canal ; Anxiety ; Compliance ; Humans ; Manometry ; Reflex ; Sensory Thresholds

PURPOSE: The purpose of this study was to understand the situation of diabetes patients receiving examinations for diabetes complications and to explore the factors influencing their intention to receive examinations for diabetes complications. METHODS: A cross-sectional study was performed that included 251 diabetes patients who visited outpatient clinics in Southern Taiwan. A survey using a self-administered questionnaire was conducted from October 2015 to January 2016. The questionnaire included items on demographic characteristics, perceived susceptibility to diabetes complications, perceived seriousness of diabetes complications, perceived benefits of taking action to receive diabetes complication examinations, perceived barriers to taking action to receive diabetes complication examinations, and the intention to receive diabetes complication examinations. The data were analyzed using regression analysis. RESULTS: The percentage of participants who received fundus, foot, and kidney examinations was 67.7%, 61.4%, and 73.3%, respectively. Every point increase on the perceived barriers to taking action to receive diabetes complication examinations scale increased the intention to receive a foot examination in the following year by 0.91 times (p = .002), and every point increase on the perceived susceptibility to diabetes complications scale increased the intention to receive a kidney examination in the following year by 1.19 times (p = .045). CONCLUSIONS: Nurses should shoulder the responsibility to increase patients' intention to receive examination of diabetes complications. The results of this study can be used to promote nurses' care efficacy in preventing diabetes complications. They can also provide medical institutions with information to establish prevention and control policies for diabetes complications.
Ambulatory Care/utilization ; Cross-Sectional Studies ; Diabetic Angiopathies/nursing/*prevention & control/psychology ; Diabetic Nephropathies/nursing/*prevention & control/psychology ; Disease Susceptibility/psychology ; Early Diagnosis ; Female ; Humans ; Intention ; Kidney Function Tests ; Male ; Middle Aged ; Nurse-Patient Relations ; Ophthalmoscopy ; Patient Acceptance of Health Care/*psychology ; Perception ; Physical Examination/nursing/*psychology/utilization ; Taiwan

Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed.
Absorption ; Antipsychotic Agents* ; Bone Density* ; Clozapine ; Female ; Humans ; Hyperprolactinemia ; Life Style ; Male ; Osteoporosis ; Prognosis ; Prolactin ; Quality of Life ; Risk Factors ; Schizophrenia*

BACKGROUND/AIMS: Atypical symptoms are common in gastroesophageal reflux disease (GERD). Patients with non-erosive reflux disease (NERD) and erosive reflux disease (ERD) exhibit different clinical characteristics and responses to acid suppression treatment. We aimed to compare atypical characteristics in patients with NERD and ERD. We also investigated the presence of histological esophagitis in patients with NERD and ERD. METHODS: Eligible patients completed a questionnaire regarding reflux symptoms and concomitant atypical symptoms. Endoscopic biopsies with histological examination were performed. RESULTS: Of the 210 patients with GERD, 90 patients with ERD and 120 patients with NERD were studied. ERD patients were characterized by higher prevalence of hiatal hernia (P = 0.001) and smoking (P = 0.047). The prevalence of GERD was greater in the age group between 41 and 60 years regardless of endoscopic finding. There was no difference in the prevalence of atypical symptoms or histological esophagitis between NERD and ERD. In all subjects, heartburn was associated with dysphagia (r = 0.16, P = 0.01), dyspepsia (r = 0.22, P = 0.008) and hiccup (r = 0.19, P = 0.003), whereas acid regurgitation was associated with dyspepsia (r = 0.21, P = 0.014), belching (r = 0.15, P = 0.018) and hiccup (r = 0.19, P = 0.002). CONCLUSIONS: Atypical symptoms did not correlate with the presence of histological esophagitis. Atypical symptoms were equally prevalent in patients with NERD and ERD. The existence of atypical symptoms appears to be associated with the presence of typical reflux symptoms irrespective of endoscopic and histological reflux esophagitis.
Biopsy ; Deglutition Disorders ; Dyspepsia ; Eructation ; Esophagitis ; Esophagitis, Peptic ; Gastroesophageal Reflux ; Heartburn ; Hernia, Hiatal ; Hiccup ; Humans ; Prevalence ; Surveys and Questionnaires ; Smoke ; Smoking

BACKGROUND/AIMS: Detailed characterization of the ultrastructural morphology of intercellular space in gastroesophageal reflux disease has not been fully studied. We aimed to investigate whether subtle alteration in intercellular space structure and tight junction proteins might differ among patients with gastroesophageal reflux disease. METHODS: Esophageal biopsies at 5 cm above the gastroesophageal junction were obtained from 6 asymptomatic controls, 10 patients with reflux symptoms but without erosions, and 18 patients with erosions. The biopsies were morphologically evaluated by transmission electron microscopy, and by using immunohistochemistry for tight junction proteins (claudin-1 and claudin-2 proteins). RESULTS: The expressions of tight junction proteins did not differ between asymptomatic controls and gastroesophageal reflux disease patients. In patients with gastroesophageal reflux disease, altered desmosomal junction morphology was only found in upper stratified squamous epithelium. Dilated intercellular space occurred only in upper stratified squamous epithelium and in patients with erosive esophagitis. CONCLUSIONS: This study suggests that dilated intercellular space may not be uniformly present inside the esophageal mucosa and predominantly it is located in upper squamous epithelium. Presence of desmosomal junction alterations is associated with increased severity of gastroesophageal reflux disease. Besides dilated intercellular space, subtle changes in ultrastructural morphology of intercellular space allow better identification of inflamed esophageal mucosa relevant to acid reflux.
Biopsy ; Claudin-2 ; Epithelium ; Esophagogastric Junction ; Esophagus ; Extracellular Space ; Gastroesophageal Reflux ; Humans ; Immunohistochemistry ; Intercellular Junctions ; Microscopy, Electron, Transmission ; Mucous Membrane ; Tight Junction Proteins ; Tight Junctions

Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the "Out of Africa" hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of insular Asia. The results of this analysis will be discussed using a conceptual approach.
Asia, Southeastern ; epidemiology ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Chromosomes, Human, Y ; genetics ; DNA, Mitochondrial ; genetics ; Emigration and Immigration ; Genetics, Population ; Haplotypes ; genetics ; Humans ; Melanesia ; epidemiology ; Microsatellite Repeats ; Nasopharyngeal Neoplasms ; epidemiology ; genetics ; Oceanic Ancestry Group ; genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Taiwan ; epidemiology

Objective: Involuntary admission to psychiatric inpatient care can protect both patients with severe mental illnesses and individuals around them. This study analyzed annual healthcare costs per person for involuntary psychiatric admission and examined categories of mental disorders and other factors associated with mortality. Methods: This retrospective cohort study collected 1 million randomly sampled beneficiaries from the National Health Insurance Database for 2002–2013. It identified and matched 181 patients with involuntary psychiatric admissions (research group) with 724 patients with voluntary psychiatric admissions (control group) through 1:4 propensity-score matching for sex, age, comorbidities, mental disorder category, and index year of diagnosis. Results: Mean life expectancy of patients with involuntary psychiatric admissions was 33.13 years less than the general population. Average annual healthcare costs per person for involuntary psychiatric admissions were 3.94 times higher compared with voluntary admissions. The general linear model demonstrated that average annual medical costs per person per compulsory hospitalization were 5.8 times that of voluntary hospitalization. Survival analysis using the Cox proportional hazards model found no significant association between type of psychiatric admission (involuntary or voluntary) and death. Conclusion This study revealed no significant difference in mortality between involuntary and voluntary psychiatric admissions, indicating involuntary treatment’s effectiveness.

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration ＞ 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or ＜ 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.
Aging ; Awards and Prizes ; Delivery of Health Care ; Education ; Financing, Organized ; Humans ; Mentors ; Osteoporosis ; Practice Guidelines as Topic ; Taiwan