Association Between Endometriosis and Mental Disorders Including Psychiatric Disorders, Suicide, and All-Cause Mortality -A Nationwide Population-Based Cohort Study in Taiwan.

Objective: A multitude of previous studies has substantiated that endometriosis correlated highly with psychiatric health. This study aims to investigate the association between endometriosis and psychiatric health. Methods: Utilizing the National Health Insurance Research Database of Taiwan, 100,770 enrolled participants, including 20,154 patients with endometriosis and 80,616 in the control group (1:4), matched for age, and index date from Taiwan's Longitudinal Health Insurance Database between January 1, 2000, and December 31, 2015. The Cox proportional regression model was used to compare the risk of mental disorders during the 16 years of follow-up after adjusting for confounding factors. Results: Of the study patients, 4083 (20.26%) developed mental disorders; 9225 of the 80,616 controls (11.44%) developed mental disorders. The Cox regression demonstrated that, after adjusting for age, monthly income, urbanization level, etc., people with endometriosis are more likely to suffer from mental disorders compared to those without endometriosis (hazard ratio [HR]=2.131; 95% confidence interval [CI]= 1.531-2.788; p<0.001). The result illustrated that women over 40 years old had a more significant risk. Conclusion: Compared to people without endometriosis, this study provides evidence that patients with endometriosis are at a 2.131-fold higher risk of developing mental disorders, especially in elder women. Regular psychiatric follow-up might be needed for those patients.

A Comprehensive Genetic Study of Microtubule-Associated Gene Clusters for Male Infertility in a Taiwanese Cohort.

Advanced reproductive technologies are utilized to identify the genetic mutations that lead to spermatogenic impairment, and allow informed genetic counseling to patients to prevent the transmission of genetic defects to offspring. The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Genetic variants that may cause infertility are identified by combining the targeted next-generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Our analysis revealed five distinct affected genes covering seven SNPs based on the targeted NGS panel and WES data: SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150), and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. These findings strongly support the hypothesis that the dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2, and DRC7 mutations are associated with male infertility, specifically azoospermia, and a further examination of this genetic function is required.

Xeno-free culture and proliferation of hPSCs on 2D biomaterials.

Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.

Atopic Dermatitis as a Risk Factor for Herpes Zoster Infection Independent of Treatment: A Nationwide Population-Based Cohort Study.

Background: In the wake of the emerging development of biologics in atopic dermatitis (AD), herpes zoster (HZ) infection has been reported as a treatment-related adverse event. Objectives: This study aims at investigating the association between AD and HZ, and the risk factors within. Methods: 28,677 participants with AD from the Taiwan National Health Insurance Research Database 2000-2015 were enrolled. Risk of HZ infection was compared in the study cohort (with AD) and the control cohort (without AD). Further analyses were conducted in gender-, age-, and treatment strategy-stratified subgroups. Results: Significantly higher adjusted hazard ratios (aHRs) of HZ infection were revealed in AD patients (aHR = 2.303, P < 0.001), and remained this trend in gender- and age-stratified models. All AD groups, irrespective of the treatment type, had higher aHRs (AD without systemic treatment: aHR = 2.356, P < 0.001; AD with systemic treatment: aHR = 2.182, P < 0.001) compared with those without AD. However, no differences in HZ risk were shown between each treatment type. Conclusions: Risk of HZ infection in AD is higher irrespective of treatment type. Considering that AD per se increases susceptibility to HZ infection, the administration of biologics requires careful considerations.

Risk of Secondary Malignancies in Hematopoietic Stem Cell Transplantation Recipients: A Nationwide Population-Based Study in Taiwan

Background: The improvement of survival after hematopoietic stem cell transplantation has brought about a need to evaluate long-term complications, for instance, secondary malignancies. The risk of subsequent malignancies after hematopoietic stem cell transplantation must be clarified in a large population. Aims: To estimate the risk of secondary malignancies in hematopoietic stem cell transplantation survivors and compare it with the risk in patients without hematopoietic stem cell transplantation history. Study Design: We conducted a population-based retrospective cohort study of 3,059 hematopoietic stem cell transplantation recipients from the National Health Insurance Research Database of Taiwan, containing 1,378 autologous, 1,641 allogeneic, and 40 cord blood stem cell transplantation recipients between 2000 and 2013. A control group of 12,236 patients without an hematopoietic stem cell transplantation history was identified. Methods: The covariates included age, sex, comorbidities, stem cell source, facility level of care, and history of total body irradiation. Comorbidities were estimated by the revised Charlson comorbidity index, and a higher score suggested more severe comorbidity. Adjusted hazard ratios were determined by adjusting for age, sex, comorbidity, and facility level of care. Results: Overall, hematopoietic stem cell transplantation recipients had a higher risk of secondary malignancies with an adjusted hazard ratios of 1.348 (p = 0.017). Being male and female (adjusted hazard ratios 1.395, p = 0.009 and adjusted hazard ratios 1.291, p = 0.042, respectively) and pre-hematopoietic stem cell transplantation total body irradiation (adjusted hazard ratios 1.591, p < 0.001) were correlated with a high risk of secondary malignancies. Among the subsequent neoplasms, bone cancer showed the highest risk (adjusted hazard ratios 27.899, p < 0.001), followed by laryngeal (adjusted hazard ratios 6.643, p < 0.001), kidney (adjusted hazard ratios 5.580, p < 0.001), esophageal, pancreatic, thyroid (adjusted hazard ratios 1.993, p < 0.001), and skin (adjusted hazard ratios 1.992, p < 0.001) cancers. The median follow-up duration was 2.16 years in the hematopoietic stem cell transplantation group and 2.57 years in the control group, and the overall median follow-up duration was 2.21 years. Conclusion: Medical practitioners should be aware of the high risk of secondary malignancies in hematopoietic stem cell transplantation recipients later in life. These recipients should be informed about the importance of regular follow-up and photoprotective measures. Lifelong surveillance is recommended.

Clinical Characteristics of Hyperandrogenism Include Hirsutism, Polycystic Ovary Syndrome, and Acne: Association with Psychiatric Disease in Women -A Nationwide Population-Based Cohort Study in Taiwan.

Objective: Previous studies have shown an increased in psychiatric disorders in women with disorders associated with hyperandrogenism, but few nationwide cohorts have studied this phenomenon. Therefore, this study is aimed to examine the association between the clinical manifestations of hyperandrogenism and subsequent psychiatric disorders. Methods: Based on the National Health Insurance Research Database, 49,770 enrolled participants were matched for age and index date between January 1, 2000, and December 31, 2015. Hirsutism, polycystic ovary syndrome, and acne are characterized by hyperandrogenism. After adjusting for confounding factors, we used Cox proportional analysis to compare the risk of psychiatric disorders during the 16 years of follow-up. Results: Of all the participants, 1319 (13.25%) had psychiatric disorders in the study group, whereas only 3900(9.80%) had psychiatric disorders in the control group. After adjusting for age, and monthly income, the Cox regression analysis showed that the study patients were more likely to develop psychiatric disorders (hazard ratio [HR]: 2.004, 95% confidence interval [CI] = 1.327-2.724, P < 0.001). The results demonstrated that women aged 20-29 years had a more significant risk. Conclusion: Women with clinical characteristics of hyperandrogenism have a higher risk of developing psychiatric disorders, especially those aged 20-29 years.

Bidirectional Relationship Between Tuberculosis and Hypothyroidism: An 18-Year Nationwide Population-Based Longitudinal Cohort Study.

Some antituberculosis agents may cause hypothyroidism, and thyroid hormones play a vital role in Mycobacterium tuberculosis infection. However, the relationship between tuberculosis (TB) and hypothyroidism has not been clearly established. Therefore, this retrospective, longitudinal cohort study aimed to investigate the association between these two diseases using the 2000-2017 data from the Taiwan's National Health Insurance Research Database. The hypothyroidism and TB cohorts were matched with the control group in a 1:4 ratio. Adjusted hazard ratios (aHRs) were assessed using Cox proportional hazards regression analysis in each cohort. In total, 3,976 individuals with hypothyroidism and 35 120 individuals with TB were included in this study. The risk of developing TB in patients with hypothyroidism was 2.91 times higher than that in those without hypothyroidism (95% confidence interval [CI], 1.50-3.65). The subgroup of thyroxine replacement therapy (TRT) had a 2.40 times higher risk (95% CI, 1.26-3.01), whereas the subgroup of non-TRT had a 3.62 times higher risk of developing TB than those without hypothyroidism (95% CI, 2.19-4.84). On the other hand, the risk of developing hypothyroidism in patients with TB was 2.01 times higher than that in those without TB (95% CI, 1.41-2.38). Our findings provide evidence that TB and hypothyroidism are interrelated. Thus, clinicians and public health authorities should monitor the association between these two diseases to reduce the relevant disease burden.

Effect of extracellular matrix proteins on the differentiation of human pluripotent stem cells into mesenchymal stem cells.

The transplantation of human mesenchymal stem cells (hMSCs), such as bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs), has shown beneficial effects in protecting transplanted tissues and cells against graft-versus-host disease (GVHD). Human pluripotent stem cell (hPSC)-derived mesenchymal stem cells (MSCs) can also be used to generate hMSCs with stable characteristics without limitations. Therefore, we differentiated human induced pluripotent stem cells (hiPSCs, H-M5) and human embryonic stem cells (hESCs, H9) into hMSCs on dishes coated with different extracellular matrix (ECM) proteins to study the effect of cell culture biomaterials on hPSC differentiation into hMSCs. hPSC-derived MSCs cultured on Matrigel (MAT)-coated, collagen (COL)-coated and laminin-521 (LN-521)-coated tissue culture polystyrene (TCP) dishes showed excellent proliferation speed and reduced aging over 10 passages. High MSC surface marker (CD44, CD73, CD90 and CD105) expression was also observed on hPSC-derived MSCs cultured on MAT-coated, COL-coated and LN-521-coated TCP dishes as well as uncoated TCP dishes. Analysis of late osteogenic differentiation by evaluation of mineral deposition revealed that hPSC-derived MSCs cultured on fibronectin (FN)-coated and LN-521-coated TCP dishes showed high osteogenic differentiation. ECM proteins are effective as coating materials on cell culture biomaterials to regulate the proliferation and differentiation fate of hPSC-derived MSCs.

Association of Postpartum Depression with Maternal Suicide: A Nationwide Population-Based Study.

BACKGROUND: To examine the association of postpartum depression (PPD) with maternal suicide in the Taiwanese population. METHODS: We examined the medical records of women aged 18-50 years who experienced childbirth and had PPD (the study cohort, n = 2882), who experienced childbirth but did not have PPD (comparison cohort 1, n = 5764), and who neither experienced childbirth nor had PPD (comparison cohort 2, n = 5764) between 2000 and 2015. The patients were followed up until suicide, withdrawal from the National Health Insurance program, or 31 December 2015. RESULTS: The rates of anxiety and depression symptoms, as well as the cumulative risk of suicide, were significantly higher in the study cohort. PPD was significantly correlated with an increased risk of maternal suicide and was associated with a greater risk of developing comorbidities such as hypertension, diabetes mellitus, hyperlipidemia, and stroke. The comparison cohorts did not differ significantly in terms of suicide risk. CONCLUSION: PPD was associated with a significantly higher rate of suicide and a shorter time to suicide after childbirth. Younger age, winter, and subclinical depression and anxiety positively predicted suicide in the study cohort. To prevent maternal suicide, clinicians should be observant of subclinical depression and anxiety symptoms among patients.

Segregating Suspected Child Maltreatment from Non-Child Maltreatment Injuries: A Population-Based Case-Control Study in Taiwan.

Objective: To identify the differential patient characteristics, injury types, and treatment outcomes between hospitalized child abuse and non-child abuse injuries in Taiwan. Methods: Using the data from the National Health Insurance Research Database, we selected a total of 1525 patients under the age of 18 that were diagnosed with child abuse, as well as an additional 6100 patients as a comparison group. Chi-square test, Fisher exact test, and independent samples t-test were used to compare the differences between the abused children and the non-abuse-related injured children. The multivariate conditional logistic regression was performed to measure the risk factor of child maltreatment in injured children. Results: Intracranial injury was more frequent in the child abuse group than it was in the non-child abuse group (35.0% vs. 8.2%; p < 0.001). Children in the child abuse group tended to stay longer in the hospital and incur higher medical expenses (8.91 days vs. 4.41 days and USD 2564 vs. USD 880, respectively). In multivariate analysis, the Adjusted Odds Ratio (Adjusted OR) of abuse resulting in an injury for children in low-income families is 1.965 times higher than those in non-low-income families (p < 0.001). Children living in high urbanization areas had a significantly higher probability of being abused than those living in low urbanization areas (p < 0.001). Conclusion: Children under the age of 1 who were hospitalized with severe intracranial injuries are highly at risk for child maltreatment. Moreover, numerous high-risk environmental factors were observed in child abuse cases, including living in urban areas, families with low income, and seasonality, as child maltreatment cases occur more frequently in autumn.

Exposure of Child Maltreatment Leads to a Risk of Mental Illness and Poor Prognosis in Taiwan: A Nationwide Cohort Study from 2000 to 2015.

Objective: To investigate whether children with maltreatment exposure were associated with the risk of psychiatric disorders, suicide, and death. Methods: A retrospective cohort study was conducted, with 1592 child maltreatment cases and 6368 comparison cohort (1:4) matched for gender, age, and index year, from the Longitudinal Generation Tracking Database (LGTD2000) sampled from Taiwan National Health Insurance Research Database (NHIRD) in 2000, backtracking between 2000−2015 in Taiwan. The stratified Cox regression model was used to compare the risk of developing a mental illness and poor prognosis during the 15 years of follow-up. Results: There were 473 in the cohort with child maltreatment (675.10 cases per 100,000 person years) and 1289 in the comparison cohort (453.82 cases per 100,000 person years) that developed mental illness and poor prognosis. The stratified Cox regression model revealed that the adjusted hazard ratio (HR) was 1.91 to 11.76 (p < 0.05) after adjusting for monthly income level, occupation, and CCI after violence. Conclusion: Exposure to child maltreatment is associated with the risk of psychiatric disorders, but not suicide or death. This finding could be a reminder for clinicians about the mental health problems in patients with child maltreatment.

Relationship between Injuries and Attention-Deficit Hyperactivity Disorder: A Population-Based Study with Long-Term Follow-Up in Taiwan.

OBJECTIVE: To investigate the association between various injuries and attention-deficit hyperactivity disorder (ADHD) and distinguish ADHD from non-ADHD with regards to risk of various injuries among children in Taiwan. METHOD: Using the data from the National Health Insurance Research Database, we selected a total of 1802 subjects under the age of 18 who were diagnosed with ADHD as well as an additional 7208 subjects as a comparison group. RESULTS: Compared with children who were not diagnosed with ADHD, children diagnosed with ADHD were more likely to intentionally injure themselves. During the school year, ADHD children were injured less frequently than were non-ADHD children on traffic-related incidents. The adjusted hazard ratio of injury for the ADHD children was 2.493 times higher than that of comparison subjects. The ADHD children had a greater length of stay and medical cost when compared to those of the non-ADHD children. Age showed a significant inverse relationship with injury. Among the ADHD children, the injury rate was evidently higher for the low-income group than for the non-low-income group. CONCLUSIONS: Age, cause of injuries, low-income household status, and school season all have a significant connection to the risk of injury for ADHD children.

Chronic Obstructive Pulmonary Disease Effect of Nonapnea Sleep Disorder on the Risk of Obesity: A Nationwide Population-Based Case-Control Study.

Objectives: To investigate whether chronic obstructive pulmonary disease (COPD) affects nonapnea sleep disorder (NASD) on the risk of obesity. Materials and Methods: From 1 January 2000 to 31 December 2015, a total of 24,363 patients with obesity from the 2005 Longitudinal Health Insurance Database were identified; 97,452 patients without obesity were also identified from the same database. Multiple logistic regression was used to analyze the previous exposure risk of patients with obesity and NASD. A p value of <0.05 was considered significant. Results: The risk of developing obesity in patients with COPD is 3.05 times higher than that in patients without COPD. Patients with COPD with NASD had a 1.606-fold higher risk of developing obesity than those without NASD. Patients with obesity were more likely to be exposed to NASD than did those without obesity (adjusted odds ratio, 1.693; 95% confidence interval, 1.575−1.821, p < 0.001). Furthermore, the closeness of the exposure period to the index time was positively associated with the severity of obesity, with a dose−response effect. The exposure duration of NASD in patients with obesity was 1.693 times than that in those without obesity. Longer exposure durations were associated with more severe obesity, also with a dose−response effect. Conclusions: The COPD effect of NASD increases the subsequent risk of obesity, and the risk of obesity was determined to be significantly higher in patients with NASD in this case−control study. Longer exposure to NASD was associated with a higher likelihood of obesity, also with a dose−response effect.

Trends in Homicide Hospitalization and Mortality in Taiwan, 1998-2015.

In Taiwan, the national research on homicide is rare, mostly discussing the issue of child abuse. We sought to better understand the characteristics and risk factors of homicide through a retrospective cohort study from 1998 to 2015. "Child battering and other maltreatment" ranked first for the 0-4 age group and second for the 5-14 age group. The hospital mortality was 511 deaths. We found that the 25-44 age group had the highest risk and accounted for 44.76% of hospitalization. The most common causes were "fight, brawl, and rape" (49.12%), "cutting and piercing instruments," (13.16%) and "child battering and other forms of maltreatment" (4.72%). Additionally, the percentages of "fight, brawl, and rape," "firearms and explosives," and "cutting and piercing instruments" were significantly higher among males than among females. The percentages of "hanging and strangulation," "corrosive or caustic substance," "child battering and other maltreatment," "submersion," and "poisoning" were significantly higher among females than males. Factors associated with homicide in-hospital mortality included gender, age, low income, catastrophic disease, Charlson comorbidity index score, urbanization level, hospital level, classification of hospitalization, and surgery. Overall, the trend of hospitalization rates due to homicide decreased both by gender and age group, except for the 0-4 age group: cause of homicide first, hanging and strangulation second, firearms and explosives third; type of injury, hospitalized patients with "vascular injuries" first, joint and muscle sprain, and intracranial, chest, and abdominal pelvic injuries second, and "burns" third with a higher risk of death. Homicide reduction requires a comprehensive strategy beyond specific victim groups. Interagency collaboration should be strengthened, especially between law enforcement/criminal justice and public health.

Sexual Assault Is the Biggest Risk Factor for Violence against Women in Taiwan-A Nationwide Population Cohort Study from 2000 to 2015.

Objective: To understand the main types of risk of violence against women in Taiwan. Materials and methods: This study used the outpatient, emergency, and hospitalization data of 2 million people in the National Health Insurance sample from 2000 to 2015. The International Classification of Diseases, Ninth Revision diagnostic N-codes 995.5 (child abuse) and 995.8 (adult abuse) or E-codes E960−E969 (homicide and intentional injury by others) were defined as the case study for this study, and the risks of first violent injury for boys and girls (0−17 years old), adults (18−64 years old), and elders (over 65 years old) were analyzed. Logistic regression analysis was used for risk comparison. A p value of <0.05 was considered significant. Results: The proportion of women (12−17.9 years old) who were sexually assaulted was 2.71 times that of women under the age of 12, and the risk of sexual assault for girls and adult women was 100 times that of men. Girls who were insured as labor insurance, farmers, members of water conservancy and fishery associations, low-income households, and community insured population (public insurance as the reference group) were significantly more likely to seek medical treatment from sexual assault than adult women. Among them, the risk was greatest for girls from low-income households (odds ratio = 10.74). Conclusion: Women are at higher risk of sexual assault than men regardless of whether they are children or adults, and the highest risk is for women in senior high schools, especially for girls from low-income households. Therefore, the protection of women's personal autonomy is the direction that the government and people from all walks of life need to continue to strive for. Especially for high school students from low-income households, protection must be strengthened through education, social work, and police administration.

From GWAS to drug screening: repurposing antipsychotics for glioblastoma.

BACKGROUND: Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development. METHODS: We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a 'pathway/gene-set analysis' approach. RESULTS: The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma. CONCLUSION: In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.

Obstructive sleep apnea increases risk of female infertility: A 14-year nationwide population-based study.

OBJECTIVES: To determine the risk of having OSA in a cohort of female subjects who are infertile and the odds of being infertile in women with OSA. PATIENTS AND METHODS: A nationwide, case-control study of female patients 20 years or older diagnosed with female infertility living in Taiwan, from January 1, 2000, through December 31, 2013 (N = 4,078). We identified women who were infertile and created a 2:1 matched control group with women who were not infertile. We used multivariable logistic regression analysis to further estimate the effects of OSA on female infertility. RESULTS: In this 14- year retrospective study, we included 4,078 patients having an initial diagnosis of female infertility. Of those women with infertility, 1.38% had a history of OSA compared with 0.63% of fertile controls (p = 0.002). The mean ages in the study groups were 32.19 ± 6.20 years, whereas the mean ages in the control groups were 32.24 ± 6.37years. Women with OSA had 2.101- times the risk of female infertility compared to women without OSA (p<0.001). CONCLUSION: Our study showed that OSA is more commonly seen in infertile women and increases the odds that a woman will be infertile. More studies need to be done on the whether or not diagnosing and treating OSA can decrease the rate of infertility.

Effect of Obstructive Sleep Apnea on the Risk of Injuries-A Nationwide Population-Based Cohort Study.

Obstructive sleep apnea (OSA) has been reported to increase the risk of motor vehicle accidents. However, only few studies have investigated the effects of OSA on overall risk injury. The aim of study is to investigate whether OSA increases the risk of overall injury. The data were collected during 2000-2015 from Taiwan's National Health Insurance Research Database. A total of 8901 individuals diagnosed with OSA were inpatients, or outpatients at least three times were enrolled. Finally, 6915 participants with OSA were included as the study cohort. We matched the study cohort with a comparison cohort, at a ratio of 1:4. Cox proportional hazards regression was used to analyse the association between OSA and overall injury. Patients with OSA had 83.1% increased risk of overall injury, compared to non-OSA individuals [adjusted hazards ratio (HR) = 1.831, confidence interval (CI) = 1.674-2.020, p < 0.001]. In the stratified age group, patients aged ≧65 years had the highest risk of injury (adjusted HR= 2.014; CI = 1.842-2.222, p < 0.001). Patients with OSA were at a higher risk of falls, traffic injury, poisoning, suffocation, suicide, and abuse or homicide than non-OSA individuals, with falls and traffic injury as the leading causes of injuries. The data demonstrated that patients with OSA have a higher risk of overall injury. The study results can be a reference for developing injury prevention strategies in the future. The general population and clinicians should have more awareness regarding OSA and its negative effects on injury development.

Purification of Colon Carcinoma Cells from Primary Colon Tumor Using a Filtration Method via Porous Polymeric Filters.

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) are key factors for tumor generation and metastasis. We investigated a filtration method to enhance CSCs (CICs) from colon carcinoma HT-29 cells and primary colon carcinoma cells derived from patient colon tumors using poly(lactide-co-glycolic acid)/silk screen (PLGA/SK) filters. The colon carcinoma cell solutions were permeated via porous filters to obtain a permeation solution. Then, the cell cultivation media were permeated via the filters to obtain the recovered solution, where the colon carcinoma cells that adhered to the filters were washed off into the recovered solution. Subsequently, the filters were incubated in the culture media to obtain the migrated cells via the filters. Colon carcinoma HT-29 cells with high tumorigenicity, which might be CSCs (CICs), were enhanced in the cells in the recovered solution and in the migrated cells based on the CSC (CIC) marker expression, colony-forming unit assay, and carcinoembryonic antigen (CEA) production. Although primary colon carcinoma cells isolated from colon tumor tissues contained fibroblast-like cells, the primary colon carcinoma cells were purified from fibroblast-like cells by filtration through PLGA/SK filters, indicating that the filtration method is effective in purifying primary colon carcinoma cells.

Characterization of intracellular buffering power in human induced pluripotent stem cells and the loss of pluripotency is delayed by acidic stimulation and increase of NHE1 activity.

The homeostasis of intracellular pH (pHi ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (ß) and to investigate the effects of extracellular pH and Na+ -H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi was detected by microspectrofluorimetry with pH-sensitive dye-BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (ßtot ), intrinsic (ßi ), and CO2 -dependent ( ßCO2 ) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the ß values of ßtot and ßCO2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive ß during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.