TRIP6 promotes neural stem cell maintenance through YAP-mediated Sonic Hedgehog activation.

In the adult mammalian brain, new neurons are continuously generated from neural stem cells (NSCs) in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. YAP, a transcriptional co-activator of the Hippo pathway, promotes cell proliferation and inhibits differentiation in embryonic neural progenitors. However, the role of YAP in postnatal NSCs remains unclear. Here, we showed that YAP was present in NSCs of the postnatal mouse SVZ. Forced expression of Yap promoted NSC maintenance and inhibited differentiation, whereas depletion of Yap by RNA interference or conditional knockout led to the decline of NSC maintenance, premature neuronal differentiation, and collapse of neurogenesis. For the molecular mechanism, thyroid hormone receptor-interacting protein 6 (TRIP6) recruited protein phosphatase PP1A to dephosphorylate LATS1/2, therefore inducing YAP nuclear localization and activation. Moreover, TRIP6 promoted NSC maintenance, cell proliferation, and inhibited differentiation through YAP. In addition, YAP regulated the expression of the Sonic Hedgehog (SHH) pathway effector Gli2 and Gli1/2 mediated the effect of YAP on NSC maintenance. Together, our findings demonstrate a novel TRIP6-YAP-SHH axis, which is critical for regulating postnatal neurogenesis in the SVZ-OB pathway.

Effectiveness of aftercare program for suicide ideators: Real-world evidence from National Suicide Surveillance System in Taiwan.

Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior.

Knowledge of attention-deficit hyperactivity disorder among the general public, parents, and primary school teachers.

ABSTRACT: We compared the knowledge of attention-deficit hyperactivity disorder (ADHD) among the general public, parents of children with ADHD, and primary school teachers and identified factors associated with ADHD knowledge in each group, separately.Secondary data analysis was made on the pre-lecture data from those (122 from the general public, 64 parents of children with ADHD, and 515 primary school teachers) attending education lectures by the Department of Public Health, New Taipei City Government, Taiwan, 2014.ADHD onset age was least known in these 3 groups. Knowledge of ADHD was significantly better among teachers (test score, 75.3%) than among parents (65.5%) and the general public (59.2%). Among the general public, the test score significantly decreased with age and was worst in those who did not know their friends or relatives with ADHD. Among parents, service workers, and retired/unemployed knew significantly less about ADHD than housewife did. Among teachers, men knew significantly less than women; those who taught children with ADHD knew significantly more than those who did not.Primary school teachers knew more about ADHD than parents and the general public. Factors associated with ADHD knowledge varied among the 3 groups.

Epidemiology of outpatient and inpatient eye injury in Taiwan: 2000, 2005, 2010, and 2015.

PURPOSE: To estimate the incidence rate of eye injuries (EI) requiring inpatient and outpatient treatment in Taiwan and compare the epidemiologic characteristics of EI (age, sex, treatment setting, seasonality, occupation, external cause, diagnosis, and surgery) in the years 2000, 2005, 2010, and 2015. METHODS: We analyzed four random samples of 1,000,000 beneficiaries each from 2000, 2005, 2010, and 2015 of the Taiwan National Health Insurance Program. The direct age-standardized rate, with 95% confidence interval (CI), was used to compare EI rates for the four calendar years. The chi-square test and chi-square test for trend were used to compare data for the four calendar years. RESULTS: Annual EI incidence rates were between 2.57% in 2000 and 3.28% in 2015. The age-standardized rates were 2.73% (95% CI, 2.70%-2.76%) in 2000, 3.37% (95% CI, 3.33%-3.41%) in 2005, 3.31% (95% CI, 3.28%-3.35%) in 2010, and 3.02% (95% CI, 2.99%-3.06%) in 2015. Manual workers had the highest EI incidence rate, followed by non-manual workers and civil servants. The proportion of EI requiring inpatient treatment declined from 1.34% in 2000 to 0.63% in 2015 (P <0.0001). Analysis of seasonality showed a consistent decrease in February in the four sampling years; however, this decrease in EI was only seen in outpatients, not in EI requiring hospitalization. The proportion of outpatients requiring surgery significantly decreased, from 2.53% in 2000 to 1.2% in 2015 (P<0.0001). However, the proportion of inpatients requiring surgery for EI as the principal diagnosis increased from 69.32% in 2000 to 83.02% in 2015 (P = 0.29), and the proportion of inpatients requiring surgery for EI as a secondary diagnosis increased from 54.86% in 2000 to 71.6% in 2015 (P = 0.0019). Among inpatients with EI, the most common cause of EI was a traffic accident (44.79%, especially motorcycles), followed by falls (9.75%) and homicide (6.05%). CONCLUSION: In Taiwan, the annual EI incidence rate slightly increased from 2000 to 2005 and then decreased through 2015. The proportion of EI patients requiring hospitalization decreased from 1.34% in 2000 to 0.63% in 2015, but the percentage of inpatients requiring surgery increased. Traffic accidents (especially those involving motorcyclists) remained the predominant external cause of EI requiring hospitalization during the study period.

Timing and risk of mood disorders requiring psychotropics in long-term survivors of adult cancers: A nationwide cohort study.

BACKGROUND: The increasing number of long-term cancer survivors over the past few decades poses the challenge of mental health care needs. However, little is known about risks of mood disorders in long-term cancer survivors. METHODS: Long-term survivors (≥5 years) of adult cancers (LSAC) (n = 190,748) newly diagnosed between January 1, 2000 and December 31, 2007 were matched with one control. The primary outcome was diagnosis of mood disorders requiring psychotropics. Cumulative incidences and sub-hazard ratios (SHR) were calculated and multivariate analyses were conducted after accounting for mortality. RESULTS: The mood disorder risk was significantly higher in the LSAC cohort than in the control cohort (adjusted SHR = 1.16, 95% confidence interval [CI] = 1.13-1.18, P < 0.001). Patients with certain cancer types were at increased risk, particularly in the first 2 years after diagnosis. However, patients with head and neck cancers or esophageal cancers had a higher risk after the 5-year follow-up period. Multivariate analysis indicated that being female, aged 40-59 years, with more than two primary cancers, receiving two or more treatment modalities, having CCI scores higher than 3, a higher urbanization level, and lower monthly income were independently associated with an increased risk of mood disorders. LIMITATIONS: Some potential confounders such as lifestyle factors were not available in the study. CONCLUSION: These findings call for increased mental health awareness not only in the early years after the cancer diagnosis, but also during long-term follow-up for certain cancer subtypes.

Anterior Chamber Angle and Anterior Segment Structure of Eyes in Children With Early Stages of Retinopathy of Prematurity.

PURPOSE: To compare structural differences in the anterior chamber angle (ACA) and related optic components in children with or without retinopathy of prematurity (ROP). DESIGN: Prospective cross-sectional study. METHODS: Setting: A referred medical center in Taiwan. STUDY POPULATION: The patients included preterm children with a history of ROP who had undergone laser therapy. The controls included age-matched healthy full-term children. OBSERVATION PROCEDURE: The ACA structures were evaluated using gonioscopy. MAIN OUTCOME MEASURES: The angularity of the anterior chamber and associated anatomic changes. RESULTS: We examined 54 eyes of 29 preterm children with ROP and 134 eyes of 67 children born at term. The eyes of the ROP children exhibited a narrower ACA, steeper iris curvature, and more anteriorly inserted iris than those of the full-term children (P < .001, P = .002, and P = .08, respectively). The eyes of the ROP children also exhibited steeper corneas, shallower anterior chamber depths, thicker lenses, and higher degrees of refractive errors (all P < .001) than those of the full-term children. The axial lengths did not differ between the 2 groups (P = .15). CONCLUSIONS: The eyes of the ROP children presented a narrower ACA and a more anteriorly curved and inserted iris than those of the full-term children. A steeper cornea, shallower anterior chamber, and greater lens thickness were the main structural changes in the anterior segment components of these patients. Further research is needed to investigate the association between these structural changes and the development of certain ocular diseases, such as glaucoma, in these patients.

Time trends in cataract surgery and after-cataract laser capsulotomy in Taiwan: A population-based retrospective cohort study.

OBJECTIVES: Determine the incidence rate, risk factors, and time trends from 2000 to 2010 for cataract surgery and after-cataract laser capsulotomy. MATERIALS AND METHODS: Longitudinal Health Insurance Databases (LHID) with approximately 3 million people in Taiwan National Health Insurance Program from 2000, 2005, and 2010 was used. Index year was defined as year 2000 for LHID2000, year 2005 for LHID2005, and year 2010 for LHID2010. RESULTS: The age-standardized rate of first-eye cataract surgery per 100,000 persons was 324 (95% confidence interval [CI] = 288-363) in 2000, 317 (95%CI = 288-353) in 2005, and 342 (95%CI = 308-379) in 2010. Risk factors related to the incidence of cataract surgery included age, sex, diabetes mellitus, geographic region, and income level (all p values < 0.05). The incidence rate of laser posterior capsulotomy within 2 years after cataract surgery was 23.3% in 2000 but decreased to 14.6% in 2005 and to 12.9% in 2010. The incidence of laser capsulotomy for after-cataract was significantly associated with index year, age, sex, in- or out-patient, and edge design of intraocular lenses (all p values < 0.05). CONCLUSION: The incidence rate of cataract surgery over year 2000-2010 remained stable after age standardization. However, the incidence rate of laser capsulotomy for after-cataract significantly decreased during the 10-year study period.

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200µM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1>ALDH2>ADH3≈ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained unchanged. The ADH activity was also significantly reduced in hemorrhoids. ADH4 and ALDH3A1 were uniquely expressed in the squamous epithelium of anus at anorectal junctions. The allele frequencies of ADH1C*1 and ALDH2*2 were significantly higher in colorectal cancer and that of ALDH2*2 also significantly greater in hemorrhoids. In conclusion, ADH and ALDH isozymes are differentially expressed in mucosal cells of rectum and anus. The results suggest that acetaldehyde, an immediate metabolite of ethanol, may play an etiological role in pathogenesis of large bowel diseases.

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human pancreas: implications for pathogenesis of alcohol-induced pancreatic injury.

BACKGROUND: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are major enzymes responsible for metabolism of ethanol. Genetic polymorphisms of ADH1B, ADH1C, and ALDH2 occur among racial populations. The metabolic effect and metabolites contribute to pathogenesis of pancreatic injury. The goal of this study was to determine the functional expressions and cellular localization of ADH and ALDH families in human pancreas. METHODS: Fifty five surgical specimens of normal pancreas as well as 15 samples each for chronic pancreatitis and pancreatic cancer from archival formalin-fixed paraffin-embedded tissue specimens were investigated. Class-specific antibodies were prepared by affinity chromatographies from rabbit antisera raised against recombinant human ADH1C1, ADH4, ADH5, ADH7, ALDH1A1, ALDH2, and ALDH3A1. The isozyme expression patterns of ADH/ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting, and the cellular localizations were detected by immunohistochemistry and histochemistry. RESULTS: At 33 mM ethanol, pH 7.5, the activities were significantly different between allelic phenotypes of ADH1B. The activity of ALDH2-inactive phenotypes was slightly lower than ALDH2-active phenotypes at 200 microM acetaldehyde. The protein contents were in the following decreasing order: ALDH1A1, ALDH2, ADH1, and ADH5. ADH1B was detected in the acinar cells and ADH1C in the ductular, islet, and stellate cells. The expression of ADH1C appeared to be increased in the activated pancreatic stellate cells in chronic pancreatitis and pancreatic cancer. CONCLUSIONS: Alcohol dehydrogenase and ALDH family members are differentially expressed in the various cell types of pancreas. ADH1C may play an important role in modulation of activation of pancreatic stellate cells.