Haloperidol and Other Antipsychotics Exposure before Endometrial Cancer Diagnosis: A Population-based Case-control Study

Wei-Ling Chen,Srinivasan Nithiyanantham,Yan-Chiao Mao,Chih-Hsin Muo,Chih-Pin Chuu,Shih-Ping Liu,Min-Wei Huang,Kuan-Pin Su 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.3

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed. Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed. Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31−2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users. Conclusion: There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden in Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility

Wei-Yi Lei,Shu-Wei Liang,Taher Omari,Wei-Chuan Chang,Ming-Wun Wong,Jui-Sheng Hung,Chih-Hsun Yi,Tso-Tsai Liu,Lin Lin,C Prakash Gyawali,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4

Background/Aims Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry

Wei-Yi Lei,Tso-Tsai Liu,Wei-Chuan Chang,Chih-Hsun Yi,Jui-Sheng Hung,Ming-Wun Wong,Shu-Wei Liang,Lin Lin,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2024 Journal of Neurogastroenterology and Motility (JNM Vol.30 No.1

Background/AimsThis study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). MethodsEighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. ResultsCodeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. ConclusionsIn IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Wei-Chung Hsieh,Pei-Chen Hsu,Ya-Fan Liao,Shu-Ting Young,Zeng-Wei Wang,Chih-Li Lin,Gregory J. Tsay,Huei Lee,Hui-Chih Hung,Guang-Yaw Liu 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.4

Ornithine decarboxylase (ODC), the key enzyme of poly-amine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homolo-gous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC pre-served the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated apoptotic pathway, induced by TG. Finally, overex-pression of ODC maintains the protein and mRNA expres-sion of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Hsieh, Wei-Chung,Hsu, Pei-Chen,Liao, Ya-Fan,Young, Shu-Ting,Wang, Zeng-Wei,Lin, Chih-Li,Tsay, Gregory J.,Lee, Huei,Hung, Hui-Chih,Liu, Guang-Yaw Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.4

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) $Ca^{2+}$ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

3D buckling analysis of FGM sandwich plates under bi-axial compressive loads

Chih-Ping Wu,Wei-Lun Liu 국제구조공학회 2014 Smart Structures and Systems, An International Jou Vol.13 No.1

Based on the Reissner mixed variational theorem (RMVT), finite rectangular layer methods (FRLMs) are developed for the three-dimensional (3D) linear buckling analysis of simply-supported, fiber-reinforced composite material (FRCM) and functionally graded material (FGM) sandwich plates subjected to bi-axial compressive loads. In this work, the material properties of the FGM layers are assumed to obey the power-law distributions of the volume fractions of the constituents through the thickness, and theplate is divided into a number of finite rectangular layers, in which the trigonometric functions and Lagrange polynomials are used to interpolate the in- and out-of-plane variations of the field variables of each individual layer, respectively, and an h-refinement process is adopted to yield the convergent solutions. The accuracy and convergence of the RMVT-based FRLMs with various orders used for expansions of eachfield variables through the thickness are assessed by comparing their solutions with the exact 3D and accurate two-dimensional ones available in the literature.

Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

Wei-Chou Chang,Chang-Hsien Liu,Hsian-He Hsu,Guo-Shu Huang,Ho-Jui Tung,Tsai-Yuan Hsieh,Shih-Hung Tsai,Chung-Bao Hsieh,Chih-Yung Yu 대한영상의학회 2011 Korean Journal of Radiology Vol.12 No.5

Objective: To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods: From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results: Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion: Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage. Objective: To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods: From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results: Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion: Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage.

Clinical Features and Computed Tomography Characteristics of Non-Klebsiella pneumoniae Liver Abscesses in Elderly (>65 Years) and Nonelderly Patients

Chih-Weim Hsiang,Wei-Chou Chang,Chang-Hsien Liu,Hsiu-Lung Fan,Kai-Hsiung Ko,Chih-Yung Yu,Hong-Hau Wang,Wen-I Liao,Hsian-He Hsu 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.2

Purpose: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. Materials and Methods: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and dividedinto two age groups: elderly (age ≥65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. Results: Elderly patients with non-KPLA were associatedwith a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were relatedto the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. Conclusion:In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.

Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus

Liu Wen-Chung,Wu Chih-Wei,Fu Mu-Hui,Tain You-Lin,Liang Chih-Kuang,Chen I-Chun,Hung Chun-Ying,Lee Yu-Chi,Wu Kay L.H. 한국뇌신경과학회 2022 Experimental Neurobiology Vol.31 No.5

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g-1•hour-1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2+-Beclin 1+ and SOX2+-S100β+ cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

FROM BUSINESS STRATEGY AND SOCIAL CAPITAL PERSPECTIVE TO TRAVEL AGENCIES’ COMPETITIVE ADVANTAGE

Chih-Hsing Liu,Jeou-Shyan Horng,Sheng-Fang Chou,Yung-Chuan Huang,Bernard Gan,Wei-Long Lee 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07

Many firms see organizational learning systems as critical to facilitating competitive advantage. However, until now, few tourism studies have empirically investigated and identified how the different characteristics of highly competitive organizations, such as travel agencies, influence competitive advantage in a dynamic environment. This study uses a mediation-moderation analysis for such an empirical examination. A total of 288 travel agencies from Taiwan were analysed. The authors found that travel agencies’ shared goals may influence competitive advantage through characteristics of dynamic capability development, differential strategy implication and social capital accumulation. Greater levels of organizational learning may positively strengthen the relationships between (a) shared goals and dynamic capability, (b) shared goals and social capital, and (c) social capital and competitive advantage. Implications of these findings for managerial and theoretical frameworks are also discussed.