Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan.

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo.

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.

Peri-Neural Invasion Is an Important Prognostic Factor of T2N0 Oral Cancer.

Background and objectives: Among patients with pathologically proven T2N0 oral squamous cell carcinoma (OSCC), a notable amount of patients still die from tumor recurrence although they have radical surgery for early stage cancers. In literature, the prognostic indicators of this specific disease entity were rarely reported. This study aims at analyzing the prognostic factors of T2N0 OSCC patients and discussing possible managements to improve the survival. MATERIALS AND METHODS: From January 2012 to December 2017, the data of 166 pathologically proven T2N0 oral cancer patients proved by radical surgery were retrospectively collected. The clinical and pathologic factors including age, gender, tumor differentiation grade, perineural invasion (PNI), angiolymphatic invasion (ALI), margin status, and adjuvant therapy were analyzed by univariate and multivariate analysis to determine their association with disease-specific survival (DSS), and disease-free survival (DFS), which were calculated by Kaplan-Meier method. RESULTS: After median follow up time of 43.5 months, overall 3-year rates of DSS and DFS were 86.1% and 80.1% respectively for our 166 patients. Univariate analysis showed that the 3-year DSS of 90.8% for PNI negative patients was significantly better than DSS of 57.0% for PNI positive patients (p = 0.0006). The 3-year DFS of 84.2% for PNI negative patients was also significantly better than DFS of 54.6% for PNI positive patients (p = 0.001). Further multivariate analysis revealed PNI was the only independent prognostic factor associated with both DSS (Hazard Ratio (HR) = 5.02; 95% Confidence Interval (CI) = 1.99-12.6; p = 0.001), and DFS (HR = 3.92; 95% CI = 1.65-9.32; p = 0.002). Nearly 10% (16) of the 166 patients had adverse pathologic feature of PNI only. In the 11 patients without adjuvant therapy, 5 patients died from OSCC. No patients had recurrence or mortality after they received adjuvant therapy with chemotherapy ± radiotherapy. CONCLUSION: PNI was an independent prognostic factor for T2N0 oral cancer patients. Adjuvant chemotherapy and radiotherapy may benefit the survival of this specific disease entity, but further investigations are needed to elucidate the optimal regimen.

Transanal Total Mesorectal Excision: Short-term Outcomes of 1283 Cases from a Nationwide Registry in China.

BACKGROUND: Transanal total mesorectal excision is a promising surgical procedure for mid to low rectal cancer. OBJECTIVE: This study aimed to determine the short-term outcomes of Chinese patients treated with transanal total mesorectal excision. DESIGN: This was an observational study using data from an online registry system. SETTING: Study participants were recruited from 40 different centers across 15 provinces in China. PATIENTS: Patients with either benign or malignant rectal disease who underwent transanal total mesorectal excision procedure and were registered in the Chinese Transanal Total Mesorectal Excision Registry Collaborative from May 2010 to November 2019 were included. INTERVENTION: Patients underwent transanal total mesorectal excision. MAIN OUTCOME MEASURES: The primary outcomes measured were the postoperative complications and pathological outcomes. RESULTS: In total, 1283 patients, comprising 888 men (69.2%) and 395 women (39.8%) with a median age of 61 (22-92) years and a median BMI of 23.6 (14.5-46.3) kg/m2, were analyzed. Among 40 participating centers, the average number of registered cases was 32.1±34.7, and 12 centers (30%) registered >40 cases in the registry. Among 849 patients with rectal cancer who underwent laparoscopic-assisted transanal total mesorectal excision, the conversion rate was 0.5% in the abdominal phase and 1.9% in the perineal phase. Three patients reported urethral injury (0.5%). The postoperative complication rate and the anastomotic leakage incidence were 18.4% and 5.8%. The quality of the total mesorectum excision specimens was found to be complete in 81.9% of patients. In addition, the positive circumferential resection margin rate was 2.8%. LIMITATIONS: The primary limitation of this registry study was the high percentage of missing data (10.8% overall), and, for some of the analyzed variables, up to 35% of the data was missing. Postoperative complications were not monitored after discharge, resulting in a lower morbidity rate than the 30-day morbidity rate reported in other studies. CONCLUSIONS: The short-term outcomes of patients who underwent transanal total mesorectal excision procedures in China were acceptable. See Video Abstract at http://links.lww.com/DCR/B414. EXCISIN TOTAL DEL MESORRECTO POR VA TRANSANAL RESULTADOS A CORTO PLAZO DE CASOS DE UN REGISTRO NACIONAL EN CHINA: ANTECEDENTES:La excisión total del mesorrecto por vía transanal es un procedimiento quirúrgico prometedor para el cáncer de recto medio y bajo.OBJETIVO:Determinar los resultados a corto plazo de los pacientes chinos tratados con escisión mesorrectal total transanal.DISEÑO:Estudio observacional con datos de un sistema de registro en línea.AJUSTE:Los participantes del estudio fueron reclutados en 40 centros diferentes en 15 provincias de China.PACIENTES:Se incluyeron pacientes con enfermedad rectal benigna o maligna que se sometieron a una cirugía de excisión total del mesorrecto por vía transanal y que se registraron en el Registro Colaborativo de Excisión Total del Mesorrecto por vía Transanal en China desde mayo de 2010 hasta noviembre de 2019.INTERVENCIÓN:Excisión total delmesorrecto por vía transanal.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias y resultados patológicos.RESULTADOS:Fueron analizados un total de 1.283 pacientes, que comprendían 888 hombres (69,2%) y 395 mujeres (39,8%) con una mediana de edad de 61 (22-92) años y una mediana de índice de masa corporal de 23,6 (14,5-46,3) kg / m2. Entre los 40 centros participantes, el promedio de casos registrados fue de 32,1 ± 34,7, y 12 centros (30%) inscribieron > 40 casos en el registro. Entre 849 pacientes con cáncer de recto que se sometieron a excisión total del mesorrecto pééor vía transanal asistida por laparoscopia, la tasa de conversión fue del 0,5% en la fase abdominal y del 1,9% en la fase perineal. Tres pacientes refirieron una lesión uretral (0,5%). La tasa de complicaciones posoperatorias y la incidencia de fuga anastomótica fueron del 18,4% y el 5,8%, respectivamente. La calidad de las muestras de excisión total del mesorrecto se evaluó como completa en el 81,9% de los pacientes. Además, la tasa de margen de resección circunferencial positiva fue del 2,8%.LIMITACIONES:La principal limitación del presente estudio de registros fue el alto porcentaje de datos faltantes (10,8% en general), y para algunas de las variables analizadas, faltaba hasta el 35% de los datos. Las complicaciones postoperatorias no fueron verificadas después del alta, lo que resultó en una tasa de morbilidad más baja que la tasa de morbilidad a 30 días informada en otros estudios.CONCLUSIONES:Los resultados a corto plazo de los pacientes que se sometieron al procedimiento de excisión total del mesorrecto por vía transanal en China fueron aceptables. Consulte Video Resumen en http://links.lww.com/DCR/B414. (Traducción-Dr. Xavier Delgadillo).

Robotic versus transanal total mesorectal excision in sexual, anorectal, and urinary function: a multicenter, prospective, observational study.

PURPOSE: Improved long-term survival after low anterior resection (LAR) for rectal cancer highlights the importance of functional outcome. Urogenital and anorectal dysfunction is frequently reported after conventional LAR. Advanced minimally invasive techniques such as robotic (RoTME) and transanal total mesorectal excision (TaTME) might improve functional results by precisely dissecting and preserving autonomic nerves. We compared functional outcomes after RoTME or TaTME in a multicenter study. METHODS: One hundred twenty patients (55 RoTME/65 TaTME) were prospectively included in four participating centers. Anorectal (Wexner and low anterior resection syndrome (LARS) Score), urinary (International Consultation on Incontinence-Male/Female Lower Urinary Tract Symptoms Score (ICIQ-MLUTS/ICIQ-FLUTS) and International Prostate Symptom Scale (IPSS)), and sexual (International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI)) outcomes at 12 months after surgery were compared to preoperative scores. The response rate to the 1-year postoperative functional assessment by questionnaire was 79.5%. RESULTS: RoTME enabled better anorectal function compared to TaTME (LARS score 4.3 ± 2.2 vs. 9.8 ± 1.5, p = 0.038, respectively). TaTME proved superior at preserving male urinary function, while female urinary function was comparable in both groups, with only mild postoperative impairment (RoTME vs. TaTME, respectively: ICIQ-MLUTS 13.8 ± 4.9 vs. 1.8 ± 5.8, p = 0.038; ICIQ-FLUTS Incontinence Score - 0.3 ± 1.0 vs. - 0.2 ± 0.9, p = 0.844). Both techniques demonstrated comparable male (RoTME - 13.4 ± 2.7 vs. TaTME - 11.7 ± 3.4, p = 0.615) and female (RoTME 5.2 ± 4.6 vs. TaTME 10.5 ± 6.4, p = 0.254) sexual function. CONCLUSION: After adjustment for risk factors, RoTME provided better anorectal functional results, whereas TaTME was better at preserving male urinary function. Overall, both techniques demonstrated only mild postoperative functional impairment.

Physicians' Risk Tolerance and Head Computed Tomography Use for Pediatric Patients With Minor Head Injury.

OBJECTIVES: Traumatic brain injury is the leading cause of death and disability in children worldwide. The objective of this study was to determine the association between physician risk tolerance and head computed tomography (CT) use in patients with minor head injury (MHI) in the emergency department (ED). METHODS: We retrospectively analyzed pediatric patients (<17 years old) with MHI in the ED and then administered 2 questionnaires (a risk-taking subscale [RTS] of the Jackson Personality Inventory and a malpractice fear scale [MFS]) to attending physicians who had evaluated these patients and made decisions regarding head CT use. The primary outcome was head CT use during ED evaluation; the secondary outcome was ED length of stay and final diagnosis of intracranial injury (ICI). RESULTS: Of 523 patients with MHI, 233 (44.6%) underwent brain CT, and 16 (3.1%) received a final diagnosis of ICI. Among the 16 emergency physicians (EPs), the median scores of the MFS and RTS were 22 (interquartile range, 17-26) and 23 (interquartile range, 19-25), respectively. Emergency physicians who were most risk averse tended to order more head CT scans compared with the more risk-tolerant EPs (56.96% vs 37.37%; odds ratio, 8.463; confidence interval, 2.783-25.736). The ED length of stay (P = 0.442 and P = 0.889) and final diagnosis (P = 0.155 and P = 0.835) of ICI were not significantly associated with the RTS and MFS scores. CONCLUSIONS: Individual EP risk tolerance, as measured by RTS, was predictive of CT use in pediatric patients with MHI.

Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease.

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.

Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway.

Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IκBα, and -p65, as well as κB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-κB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-κB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.

Unveiling Informational Properties of the Chen-Ouillon-Sornette Seismo-Electrical Model.

The seismo-electrical coupling is critical to understand the mechanism of geoelectrical precursors to earthquakes. A novel seismo-electrical model, called Chen-Ouillon-Sornette (COS) model, has been developed by combining the Burridge-Knopoff spring-block system with the mechanisms of stress-activated charge carriers (i.e., electrons and holes) and pressure-stimulated currents. Such a model, thus, can simulate fracture-induced electrical signals at a laboratory scale or earthquake-related geoelectrical signals at a geological scale. In this study, by using information measures of time series analysis, we attempt to understand the influence of diverse electrical conditions on the characteristics of the simulated electrical signals with the COS model. We employ the Fisher-Shannon method to investigate the temporal dynamics of the COS model. The result showed that the electrical parameters of the COS model, particularly for the capacitance and inductance, affect the levels of the order/disorder in the electrical time series. Compared to the field observations, we infer that the underground electrical condition has become larger capacitance or smaller inductance in seismogenic processes. Accordingly, this study may provide a better understanding of the mechanical-electrical coupling of the earth's crust.

Association between the Severity of Nonalcoholic Fatty Liver Disease and the Risk of Coronary Artery Calcification.

Background and Objectives: There are limited data on the association between severity of non-alcoholic fatty liver disease (NAFLD) and coronary artery calcification. This study investigated sonographic diagnosed NAFLD and coronary artery calcium score (CAC) as detected by cardiac multidetector computed tomography in general populations. Materials and Methods: A total of 545 patients were enrolled in this study. NAFLD was diagnosed by ultrasonography examination and CAC score were evaluated by cardiac multidetector computed tomography. The association between NAFLD and artery calcium score stage was determined by logistic regression analysis and Spearman correlation coefficient analysis. Results: Of all the participants, 437 (80.2%) had ultrasonography-diagnosed NAFLD and 242 (44%) had coronary artery calcification (CAC > 0). After adjustment for cardiovascular risk factors, the risk of developing coronary artery calcification was 1.36-fold greater in the patients with different severity of NAFLD compared to those without NAFLD (OR = 1.36, 95% CI = 1.07-1.77, p = 0.016). The highest OR for separate coronary artery calcification was 1.98 (OR = 1.98, 95% CI = 1.37-2.87, p < 0.001) in the left main artery, and the risk was still 1.71-fold greater after adjustments (OR = 1.71, 95% CI = 1.16-2.54, p = 0.007). Conclusions: This cross-sectional study demonstrated that the severity of NAFLD was associated with the presence of significant coronary artery calcification, especially in the left main coronary artery, suggesting increasing the cardiovascular risk.

Ambient air pollution is associated with pediatric pneumonia: a time-stratified case-crossover study in an urban area.

BACKGROUND: Pneumonia, the leading reason underlying childhood deaths, may be triggered or exacerbated by air pollution. To date, only a few studies have examined the association of air pollution with emergency department (ED) visits for pediatric pneumonia, with inconsistent results. Therefore, we aimed to elucidate the impact of short-term exposure to particulate matter (PM) and other air pollutants on the incidence of ED visits for pediatric pneumonia. METHODS: PM2.5, PM10, and other air pollutant levels were measured at 11 air quality-monitoring stations in Kaohsiung City, Taiwan, between 2008 and 2014. Further, we extracted the medical records of non-trauma patients aged ≤17 years and who had visited an ED with the principal diagnosis of pneumonia. A time-stratified case-crossover study design was employed to determine the hazard effect of air pollution in a total of 4024 patients. RESULTS: The single-pollutant model suggested that per interquartile range increment in PM2.5, PM10, nitrogen dioxide (NO2), and sulfur dioxide (SO2) on 3 days before the event increased the odds of pediatric pneumonia by 14.0% [95% confidence interval (CI), 5.1-23.8%], 10.9% (95% CI, 2.4-20.0%), 14.1% (95% CI, 5.0-24.1%), and 4.5% (95% CI, 0.8-8.4%), respectively. In two-pollutant models, PM2.5 and NO2 were significant after adjusting for PM10 and SO2. Subgroup analyses showed that older children (aged ≥4 years) were more susceptible to PM2.5 (interaction p = 0.024) and children were more susceptible to NO2 during warm days (≥26.5 °C, interaction p = 0.011). CONCLUSIONS: Short-term exposure to PM2.5 and NO2 possibly plays an important role in pediatric pneumonia in Kaohsiung, Taiwan. Older children are more susceptible to PM2.5, and all children are more susceptible to NO2 during warm days.

Anti-Inflammatory Effect of Erinacine C on NO Production Through Down-Regulation of NF-κB and Activation of Nrf2-Mediated HO-1 in BV2 Microglial Cells Treated with LPS.

Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action of EC in treating neuroinflammation. Hence, in this study, the inflammatory responses of human BV2 microglial cells induced by LPS were used to establish a model to assess the anti-neuroinflammatory efficacy of EC and to clarify its possible mechanisms of action. The results showed that EC was able to reduce the levels of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) proteins produced by LPS-induced BV2 cells, in addition to inhibiting the expression of NF-κB and phosphorylation of IκBα (p-IκBα) proteins. Moreover, EC was found to inhibit the Kelch-like ECH-associated protein 1 (Keap1) protein, and to enhance the nuclear transcription factor erythroid 2-related factor (Nrf2) and the expression of the heme oxygenase-1 (HO-1) protein. Taken together, these data suggest that the mechanism of action of EC involves the inhibition of IκB, p-IκBα, and iNOS expressions and the activation of the Nrf2/HO-1 pathway.

Role of adjuvant radiotherapy in FIGO stage IIIC endometrial carcinoma: Treatment outcomes and prognostic factors in 52 irradiated patients.

BACKGROUND: To retrospectively review the postoperative radiotherapy treatment outcomes and the prognostic factors for the International Federation of Gynecology and Obstetrics (FIGO) stage IIIC endometrial carcinoma. METHODS: Fifty-two patients who were newly diagnosed and previously untreated FIGO stage IIIC endometrial carcinoma over a 33-year period (September 1983 to April 2015) were retrospectively reviewed. They had received radical surgery followed by adjuvant radiotherapy with or without adjuvant chemotherapy. Those excluded patients had initial distant metastasis disease, palliative intent or incomplete adjuvant radiotherapy. Different subgroups of the stage III patients were compared statistically in terms of their rates of overall survival (OS), loco-regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). RESULTS: The median follow up duration was 51.5 months (range, 5-298). The loco-regional recurrence was found in 4 patients and distant metastasis in 15 patients. Comparing stage IIIC1 vs. IIIC2 patients, their 5-year OS were 69.9% vs. 55% (p = 0.0954), LRRFS 90.3% vs. 94.4% (p = 0.6151), and DMFS 82.5% vs. 53.3% (p = 0.0080). The FIGO stage was a significant factor for DMFS (hazard ratio [HR], 5.440, 95% confidence interval [95% CI] 1.379-21.451, p = 0.0155), but only marginal for OS (HR, 2.137, 95% CI 0.930-4.913, p = 0.0738). The ECOG performance status was marginal significant for DMFS (HR, 4.777, 95% CI 0.976-23.378, p = 0.0536). CONCLUSION: Adjuvant radiotherapy decreased loco-regional recurrence and had good local control in FIGO stage IIIC endometrial carcinoma. The stage IIIC2 patients showed a greater tendency of distant metastases and poorer overall survival rate when compared to patients of stage IIIC1.

The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice.

Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid ß production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid ß and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid ß production and is worth to be further developed for AD therapeutic use.

Anti-inflammatory and Antiosteoporosis Flavonoids from the Rhizomes of Helminthostachys zeylanica.

Chemical investigation of the rhizomes of Helminthostachys zeylanica led to the isolation of eight new flavonoids including six cyclized geranylflavonoids, ugonins V-X (1-3), (10R,11S)-ugonin N (4), (10R,11S)-ugonin S (5), and ugonin Y (6), as well as two quercetin glucosides, quercetin-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (7) and quercetin-3-O-ß-d-glucopyranosyl-4'-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranoside (8). The structures of these compounds were established by spectroscopic analyses and acid hydrolysis of the sugar moiety. Among the isolated compounds, 1, 2, 5, 6, ugonins J-S (9-13), ugonstilbene A (14), and ugonin L (23) were evaluated for their anti-inflammatory activity on lipopolysaccharide-induced nitric oxide (NO) production in microglial cells. Except for 1, 5, and 13, all other compounds inhibited NO production with IC50 values of 6.2-10.1 µM and were more potent than the positive control, pyrrolidine dithiocarbamate. Compounds 1, 2, 5, 6, and 10-13 were tested for antiosteoporotic activities, and ugonin K (10) exhibited the highest inhibitory activity against RANKL-induced osteoclast differentiation in RAW264.7 cells with an IC50 value of 1.8 ± 0.2 µM.

Test-retest reliability of mandibular morphology measurements on cone-beam computed tomography-synthesized cephalograms with random head positioning errors.

BACKGROUND: Cephalometric radiography has been used for orthodontic and surgical treatment planning and assessment, and for quantifying mandibular growth. However, it remains unclear how head positioning errors and the level of examiner experience affect the reliability of such morphometric measurements. The current study aimed to bridge the gap by determining the intra-, inter-rater, and inter-session reliability of measurements of mandibular morphology with random head positioning errors as measured by a junior and a senior dentist. METHODS: Cone-beam computed tomography data of twelve mandibles were obtained with each rotated randomly away from the neutral position within the range of +3 and -3° along each of the anatomical axes to simulate six imaging trials. A synthetic cephalogram for each trial was obtained via a digitally reconstructed radiography (DRR) technique and eleven landmarks for twelve morphological parameters on the cephalogram were identified manually six times by a junior and a senior dentist. The procedure was repeated on another day within 5 days. Test-retest reliability was assessed in terms of an intra-class correlation coefficient (ICC) using a two-way mixed-effects model. RESULTS: Good to very good intra-rater (senior: ICC > 0.92; junior: ICC > 0.78), inter-rater (ICC > 0.70 for most parameters) and inter-session reliability (senior: ICC > 0.84; junior: ICC > 0.62) were found. Bland & Altman plots of inter-rater comparisons show that there were systematical biases between the examiners on most parameters, except for the distance between Gonion and Pogonion. CONCLUSIONS: The current results suggest that good to very good intra-rater, inter-rater and inter-session reliability can be achieved for most parameters with randomized head positioning errors; higher inter-session reliability can be achieved by more experienced examiners; and that long-term monitoring of mandibular growth based on cephalographic measurements should be made by the same more experienced examiner. The current DRR-based approach can be used to evaluate individual factors that affect the morphological measurements.

Real-world cost-effectiveness of laparoscopy versus open colectomy for colon cancer: a nationwide population-based study.

BACKGROUND: Laparoscopic colectomy is increasingly being adopted for the treatment of colon cancer; however, the long-term effectiveness of this approach in a real-world clinical setting has yet to be verified. This study aims to compare the effectiveness and costs associated with laparoscopic and open colectomy from the perspective of the National Health Insurance (NHI) system in Taiwan. METHODS: A nationwide population-based colon cancer cohort was observed by linking the Taiwan Cancer Registry, claims data from NHI system, and the National Death Registry. Adult patients with Stage I to Stage III colon cancer who underwent primary cancer resection using either laparoscopy or open colectomy between 2009 and 2011 were included. A propensity score-matched cohort (1745 pairs) was applied to examine three clinical endpoints: overall survival, recurrence-free survival, and disease-free survival within 2 years after the operation. To comply with the perspective as well as the analytic horizon of the study, we limited the research to NHI claims from the study population for the corresponding time period. The health outcomes and net monetary benefits were verified by multivariate mixed-effect models. RESULTS: This analysis revealed that laparoscopy resulted in longer overall survival (adjusted difference 16.8 days, 95 % CI 7.3-26.2), recurrence-free survival (16.8 days, 5.0-28.6) and disease-free survival (26.4 days, 7.4-45.4), compared to open colectomy at 2 years post-op. Laparoscopy also led to a significantly shorter length of stay (3.2 days, 2.4-3.9) and lower index hospitalization costs (US$ 455, 181-729) than open colectomy; however, no differences in costs were observed over the long term. Overall, laparoscopy was more cost-effective than open colectomy under various willingness-to-pay thresholds in the setting of the Taiwan NHI. CONCLUSIONS: The continued adoption of laparoscopy in primary curable colon cancer resection is expected to reduce health care costs over the short term while providing considerable health benefits over the long term.

The impact of prolonged waiting time for coronary care unit admission on patients with non ST-elevation acute coronary syndrome.

BACKGROUND: The boarding of patients in the emergency department consumes nursing and physician resources, and may delay the evaluation of new patients. It may also contribute to poor cardiovascular outcomes in patients with acute coronary syndrome (ACS). This study analyzed the relationship between the delay in coronary care unit (CCU) admission and the clinical outcomes of patients with ACS with non-ST-segment elevation (NSTE-ACS). METHODS: Patients were divided into 2 groups according to the CCU waiting time (<12h and >12h). Outcome variables including in-hospital mortality, gastrointestinal bleeding and stroke during hospitalization, and duration of hospital stay were compared between the 2 study groups. We used the GRACE risk scores to classify disease severity of the study patients for stratifying analysis. RESULT: A difference was found in the outcome of gastrointestinal bleeding. Among those with GRACE risk scores of <3 (low mortality risk) and 3 (high mortality risk), 5% and 3.1% of patients developed gastrointestinal bleeding, respectively, with CCU waiting time of >12h compared to CCU waiting time of <12h. However, there was no significant statistical difference (P=0.065 and 0.547). In addition, there were no significant differences in the in-hospital mortality rate, incidence of stoke, and duration of hospital stay between the 2 groups. CONCLUSION: There was no significant difference in the clinical outcomes of NSTE-ACS patients without profound shock between those with CCU waiting times of <12 and >12h. If necessary, CCU admission should be prioritized for patients whose hemodynamic instability or respiratory failure.

How Well Can We Extract the Permanent Displacement from Low-Cost MEMS Accelerometers?

Following the recent establishment of a high-density seismic network equipped with low-cost micro-electro-mechanical system (MEMS) P-wave-alert-device (P-Alert) by the earthquake early warning (EEW) research group at the National Taiwan University, a large quantity of strong-motion records from moderate-magnitude earthquakes (ML > 6) around Taiwan has been accumulated. Using a data preprocessing scheme to recover the dynamic average embedded within the P-Alert data, we adopted an automatic baseline correction approach for the P-Alert accelerograms to determine the coseismic deformation (Cd). Comparisons between the Cd values determined using global positioning system (GPS) data, strong-motion records from the P-Alert network, and data from the Taiwan Strong Motion Instrumentation Program (TSMIP) demonstrates that the near-real-time determination of Cd values (>2 cm), which provide crucial information for seismic hazard mitigation, is possible using records from low-cost MEMS accelerometers.

Transanal Total Mesorectal Excision Versus Laparoscopic Surgery for Rectal Cancer Receiving Neoadjuvant Chemoradiation: A Matched Case-Control Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has been indicated for locally advanced rectal cancer. While utilization of laparoscopy in rectal cancer surgery has been popular in recent years, tumors receiving nCRT is still a surgical challenge. Transanal total mesorectal excision (TaTME) has emerged as a focused area of laparoscopic surgery that is becoming an increasingly acceptable approach in the field of rectal surgery. METHODS: Between December 2013 and April 2015, a total of 50 patients (38 males) with post-nCRT middle or lower rectal cancer who then underwent TaTME at two separate institutions were prospectively documented. Overall, 100 matched control cohorts who received conventional laparoscopic rectal surgery (LapTME) were simultaneously retrieved from a prospectively registered database. Four parameters of sex, age, clinical stage, and American Society of Anesthesiologists (ASA) score were matched for surgical outcomes, and short-term oncological results, including complications and pathological outcomes, were analyzed. RESULTS: Both the TaTME and LapTME groups received 5-fluorouracil-based chemotherapy and 5 weeks of long-course radiation therapy. Mean operative time for the TaTME group was 182.1 ± 55.4 min (156.6 ± 37.8 min in two-team-approach cases) and 178.7 ± 34.8 min for the LapTME group. The TaTME group yielded longer distal margin lengths. No significant differences were observed in blood loss, intraoperative complication rate, conversion rate, anastomosis type, and free circumferential margin rate. CONCLUSION: This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.