Search

BACKGROUND CONTEXT Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) with microscopic tubular technique is an established surgical procedure with several potential advantages, including decreased surgical-related morbidity, reduced length of hospital stay, and accelerated early rehabilitation. A recently introduced biportal endoscopic technique for spine surgery presents familiar surgical anatomy and can be conducted using a conventional approach with a minimal footprint; it is also applicable to TLIF. PURPOSE To compare the clinical and radiological outcomes of biportal endoscopic technique transforaminal lumbar interbody fusion (BE-TLIF) and microscopic tubular technique transforaminal lumbar interbody (MT-TLIF) in patients with single- or two-segment lumbar spinal stenosis with or without spondylolisthesis. STUDY DESIGN A retrospective cohort study. PATIENT SAMPLE One hundred two participants with neurogenic intermittent claudication or lumbar radiculopathy with single- or two-level lumbar spinal stenosis with or without spondylolisthesis. OUTCOME MEASURES Clinical outcomes were assessed using the visual analog scale (VAS) score for the back and leg pain, Oswestry Disability Index (ODI), and the Short Form-36 health survey Questionnaire (SF-36). Demographic data, operative data (total operation time, estimated blood loss, amount of surgical drain, postoperative transfusion, and length of hospital stay), and laboratory results (plasma hemoglobin, serum creatine phosphokinase, and C-reactive protein) were also evaluated. The fusion rate was assessed using the Bridwell interbody fusion grading system. Postoperative complications were also noted. METHODS Patients were divided into two groups: group A (BE-TLIF) and group B (MT-TLIF). The clinical outcomes, including VAS-Back and VAS-Leg, ODI, and SF-36 scores, were evaluated at 1 month, 6 months, and 1 year after surgery. Differences in demographics, operative data, and the laboratory and radiological results were assessed between the two groups. The fusion rate was assessed using standard standing lumbar radiographs and computed tomography scans conducted 1 year after surgery. RESULTS Seventy-nine patients were analyzed in this study, 47 from group A and 32 from group B. Demographic and operative data were comparable for both the groups. The VAS-Back and SF-36 scores were more significantly improved in group A than in group B at 1 month after surgery. However, there were no significant differences between groups for the mean VAS-Back, VAS-Leg, ODI, and SF-36 scores at 1year after the surgery. Although the total operation time was significantly longer in group A, the estimated blood loss and the amount of surgical drainage was significantly higher in group B (p CONCLUSION Both BE-TLIF and MT-TLIF provided equivalent and favorable clinical outcomes and fusion rates. Further large-scale, randomized, controlled trials with long-term follow-ups are warranted.

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.

Studies showed that the increase of myeloid‐derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour‐derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)‐secreted exosomes (BCC‐Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour‐bearing mice and BCC‐Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC‐Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs‐related functional proteins Arginase‐1 (Arg‐1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC‐Ex significantly down‐regulated the expressions of chemokine receptor CXCR4 and markedly up‐regulated the levels of inflammatory cytokines IL‐6 and IL‐10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC‐Ex, indicating that BCC‐Ex‐induced MDSCs might be dependent on the down‐regulation of CXCR4. Western blot showed that BCC‐Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

Objective To evaluate the association between intrauterine growth restriction (IUGR) and the incidence of fetuses with patent ductus arteriosus (PDA) and Hemodynamically significant PDA (Hs-PDA) in dichorionic twins (DC) with selective IUGR. Materials and methods This is an observational cohort study and retrospective case assessment, involved twins born at Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan between 2013 and 2018. DC twins with selective IUGR (sIUGR) were defined as the presence of a birth weight discordance of >25% and a smaller twin with a birth weight below the tenth percentile. PDA was diagnosed using echocardiography between postnatal day 3 and 7. Hs-PDA was defined as PDA plus increased pulmonary circulation, poor systemic perfusion, cardiomegaly, pulmonary edema, or hypotension requiring pharmacotherapeutic intervention. Result A total of 1187 twins were delivered during the study period, and 53 DC twins with selective IUGR were included in this study. DC twins with PDA have higher rate of preterm birth, lower gestational age of delivery, and lower mean birth weight of both twins compared with DC twins without PDA. In a comparison of the sIUGR twin with the appropriate for gestational age co-twin, both the incidences of PDA (28.30% vs. 7.55%, respectively; P = 0.003) and Hs-PDA (24.53% vs. 5.66%, respectively; P = 0.002) were higher in sIUGR fetuses than in the appropriate for gestational age co-twins. Small gestational age of delivery was the only variable to predict PDA and Hs-PDA [p = 0.002, Odds ratio = 0.57 (0.39–0.82), p = 0.009, Odds ratio = 0.71 (0.55–0.92), respectively]. Conclusion An analysis of dichorionic twins with sIUGR indicated that IUGR increased the risk of PDA and hemodynamically significant PDA.

Hepatocellular carcinoma (HCC) is the third leading cause of the cancer-related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti-inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour-bearing mice with Hepg2 cells. Cell tracking experiments with GFP-labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC-CM) have the similar antitumour effects in vitro, suggesting that hAMSCs-derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf-3 (DKK-3), dickkopf-1 (DKK-1) and insulin-like growth factor-binding protein 3 (IGFBP-3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK-3, DKK-1 and IGFBP-3 in vitro. Mechanically, hAMSCs-derived DKK-3, DKK-1 and IGFBP-3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β-catenin signalling pathway and IGF-1R-mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.

Aflatoxin is a fungal secondary metabolite with high toxicity that is capable of contaminating various types of food crops. It has been identified as a Group 1 human carcinogen by the International Agency for Research on Cancer. Chronic aflatoxin exposure has caused worldwide concern as a matter of public food safety. Peanuts and peanut products are the major sources of aflatoxin exposure. Therefore, some reduction interventions have been developed to minimize contamination throughout the peanut production chain. The purpose of this study is to estimate the efficacy of interventions in reducing the health impact of hepatocellular carcinoma caused by aflatoxin contamination in peanuts. The estimated total Disability-Adjusted Life Years (DALYs) were calculated using FDA-iRISK software. Six aflatoxin reduction strategies were evaluated, including good agricultural practice (GAP), biocontrol, Purdue Improved Crop Storage packaging, basic processing, ozonolysis, and ultraviolet irradiation. The results indicated that basic processing could prevent huge public health loss of 4,079.7-21,833 total DALYs per year. In addition, GAP and biocontrol were both found to be effective strategies in the farm field. Meanwhile, the other three interventions had limited effectiveness in reducing total DALYs. In conclusion, this study could help farmers, processing plants, and government policy makers to alleviate aflatoxin contamination issues in the peanut production chain.

Background Lower lumbar osteoporotic vertebral compression fracture in extremely elderly patients can often lead to lumbosacral radiculopathy (LSR) due to delayed vertebral collapse (DVC). Surgical intervention requires posterior instrumented lumbar fusion as well as vertebral augmentation or anterior column reconstruction depending on the cleft formation and intravertebral instability. However, it is necessary to decide on surgery in consideration of the patient’s frail status, surgical invasiveness, and rehabilitation. In the lower lumbar DVC without intravertebral instability, biportal endoscopic posterior lumbar decompression and vertebroplasty (BEPLD + VP) can be simultaneously attempted. This study aimed to assess the clinical outcomes of BEPLD + VP for the treatment of DVC-related LSR. Methods This retrospective case series enrolled 18 consecutive extremely elderly (aged ≥ 75-year-old) patients (6 men and 12 women) who had lower lumbar (at or below L3) DVC-related LSR. Patients who require anterior column reconstruction, such as cleft formation accompanied by intravertebral instability and patients who have not been followed for more than 6 months, were excluded from this study. All patients underwent BEPLD + VP under epidural anesthesia. Clinical results were evaluated by the visual analog scale (VAS) score and the modified Japanese Orthopedic Association (mJOA) scores. Results Most of the patients had DVC affecting level L4, with the deformation being a flat type or concave type rather than a wedge type. The VAS score (back and leg) significantly decreased from 7.78 ± 1.17 and 6.89 ± 1.13 preoperatively to 2.94 ± 0.64 and 2.67 ± 1.08 within 2 postoperative days (p < 0.001). The mJOA score significantly improved from 4.72 ± 1.27 preoperatively to 8.17 ± 1.15 in the final follow-up (p < 0.001). The mean recovery rate (RR) in the last follow-up was 56.07% ± 9.98. Incidental durotomy was reported in two patients and epidural hematomas in another two patients; however, all patients improved with conservative treatment, and no re-operation was required. Conclusions BELPD + VP was a type of salvage therapy that reduces surgical morbidity, requires major spine surgery under general anesthesia and provides good clinical outcomes in extremely elderly patients with DVC-related LSR.

Transbronchial lung cryobiopsy (TBLC) has been recently introduced for diagnosing interstitial lung diseases. We aimed to assess the effectiveness and safety of TBLC by identifying the specific patterns of histology in the diagnosis of connective tissue disease–related interstitial lung disease (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF). The clinical-radiological-pathological data from the Affiliated Hospital of Guilin Medical University between July 1, 2017, and October 31, 2020, of patients whose clinical-radiological or clinical-radiological-pathological diagnosis was CTD-ILD or IPAF and who underwent TBLC, transbronchial lung biopsy (TBLB), or surgical lung biopsy were retrospectively analyzed and summarized with review. The size of biopsy samples, complications, and diagnostic yield were compared. Fourteen patients met the inclusion criteria, of whom 12 underwent TBLC, 1 underwent TBLB, and 1 underwent each procedure at different times. Compared to the size of TBLB specimens (5.625 ± 0.479 mm2), the size of TBLC specimens (12.00 (12.00, 15.00) mm2) was much larger (Z = − 3.262, P = 0.001). The diagnostic yields of TBLC and TBLB were 100.00% (13/13) and 0.00% (2/2), respectively (P = 0.0095). The most frequent complication was mild bleeding. The risk of bleeding between TBLB (1/2, 50.00%) and TBLC (10/13, 76.92%) did not differ significantly (P = 0.469). TBLC can add extra diagnostic value by effectively identifying specific types of histology for patients with suspected CTD-ILD or IPAF, with a procedure that is safe from adverse events.

Background This study analyzed the characteristics of hydrogen fluoride-exposed patients (HFEPs) treated in the emergency department (ED) of a local university hospital, and reviewed the hospital’s disaster response according to space, staff, supplies, and systems (4Ss). Methods This retrospective observational chart review and descriptive study included 199 HFEPs among 2588 total ED patients who visited a local university emergency medical center for treatment between September 27, 2012 and October 20, 2012, following a hydrofluoric acid leak at the Hube Globe factory in Gumi City, Republic of Korea. Descriptive results concerning the 4Ss were obtained by interviewing ED specialist staff physicians on duty during the study period. In accordance with American Burn Association criteria, patients requiring burn center referral were assigned to the major burn group (MBG) as severe condition. Results During the acute phase (within 8 h after leak initiation), there were 43 patients in the ED, which was staffed with 3 doctors and 3 nurses, without 4S resources. Of these 43 patients, there were 8 HFEPs (100%) in the MBG and 0 in the non-MBG (NMBG). During the subacute phase (24 h after the acute phase), there were 262 patients in the ED including 167 HFEPs, of whom 45 (26.95%) were in the MBG and 122 (73.05%) were in the NMBG. The ED was then staffed with 6 doctors (3 on day shift and 3 on night shift) and 10 nurses (3 on day shift, 4 on evening shift, and 3 on night shift), and no 4S resources were available. Throughout the study period, no 4Ss were available. First, there was no expansion of ED space or secured disaster reserve beds. Second, there was no increase in manpower with duty time adjustments or duty relocation for ED working personnel. Third, there was no logistics reinforcement (e.g., antidote or personal protective equipment). Fourth, there were no disaster-related measures for the administration department, decontamination zone setup, safety diagnostic testing, or designated disaster triage implementation. Conclusions The hospital’s disaster response was insufficient for all aspects of the 4Ss. Detailed guidance concerning a hospital disaster management plan is required.

Background The sunfleck is an important light environmental factor for plants that live under the shade of trees. Currently, the smartfarm has a system that can artificially create these sunfleks. Therefore, it was intended to find optimal light conditions by measuring and analyzing photosynthetic responses of Eutrema japonica (Miq.) Koidz., a plant living in shade with high economic value under artificial sunflecks. Results For this purpose, we used LED pulsed light as the simulated sunflecks and set the light frequency levels of six chambers to 20 Hz, 60 Hz, 180 Hz, 540 Hz, 1620 Hz, and 4860 Hz of a pulsed LED grow system in a plant factory and the duty ratio of the all chambers was set to 30%, 50%, and 70% every 2 weeks. We measured the photosynthetic rate, transpiration rate, stomatal conductance, and substomatal CO2 partial pressure of E. japonica under each light condition. We also calculated the results of measurement, A/Ci, and water use efficiency. According to our results, the photosynthetic rate was not different among different duty ratios, the transpiration rate was higher at the duty ratio of 70% than 30% and 50%, and stomatal conductance was higher at 50% and 70% than at 30%. In addition, the substomatal CO2 partial pressure was higher at the duty ratio of 50% than 30% and 70%, and A/Ci was higher at 30% than 50% and 70%. Water use efficiency was higher at 30% and 50% than at 70%. While the transpiration rate and stomatal conductance generally tended to become higher as the frequency level decreased, other physiological items did not change with different frequency levels. Conclusions Our results showed that 30% and 50% duty ratios could be better in the cultivation of E. japonica due to suffering from water stress as well as light stress in environments with the 70% duty ratio by decreasing water use efficiency. These results suggest that E. japonica is adapted under the light environment with nature sunflecks around 30–50% duty ratio and low light frequency around 20 Hz.

Aluminum (Al) exposure at human dietary levels raises health concerns, yet little is known about the Al exposure from the Taiwanese diet. The amount of aluminum (Al)-containing food consumption in the Taiwanese total diet is increasing, which contributes to the total diet consumption., which raises the health concerns. In this study, we aim to assess estimated weekly intake (EWI) and the percentage of provisional tolerable weekly intake (%PTWI) of the dietary exposure to Al in different age-sex groups. We also applied probabilistic risk analyses to quantify the parameters&rsquo, uncertainty by focusing on the distribution function for the Al concentration in food, consumption rate, and body weight in specific age groups. Results indicated that the EWIs declined with increasing age after 6-years old (7&ndash, 12 &gt, 13&ndash, 15 &gt, 16&ndash, 18 &gt, 19&ndash, 64 &gt, 65+). Results indicated that the EWIs gradually declined after 6-year of age. The EWIs of Al-rich food in cake + waffle, kelp, snacks, and bread contributed 20%, 17%, 17%, and 11%, respectively, to the total EWIs, corresponding with the much higher consumption rates for these four foods. The 75th percentile of EWIs for the children aged 34&ndash, 6 years had a %PTWI valued at over 100%, indicating a potential risk of Al intake via dietary exposure. Our findings show that there is a concern about the consumption of Al-rich foods for children in Taiwan.

This study explored the cognitive structures that influence mobile information seekers&rsquo, intentions of promoting health behaviors. Using a nationwide self-reported survey (n = 1010) conducted by a national research institute in Korea, the present study conducted multiple regression analyses and moderated mediation tests for its analysis. The results showed that two of the three social cognitive components&mdash, i.e., health information orientation (HIO) and e-health literacy (EHL)&mdash, had a positive effect on users&rsquo, mobile health information seeking behaviors (MHIS), whereas informational social support (ISS) did not. Furthermore, the effects of the social cognition factors varied based on the type of health-promoting behaviors, and the types of health-related behavior predicted by the three factors also differed. Moreover, HIO was a factor that affected only nutritional intake among all of the health promotion behaviors, while ISS was a critical factor that predicted most health-related behaviors, except for the participants&rsquo, regular exercise (REX). The findings also indicated that the respondents&rsquo, levels of health efficacy and the extent of their health-related information seeking on mobile devices partially mediated the associations between the independent variables and their health-related behavioral outcomes. Among the mediated moderation effects of the three factors in social cognition theory (SCT), only the mediated effects of EHL were found to be significant. Based on these findings, the present study highlighted that the predictors of health-promoting behaviors may vary according to the features of the information seekers. The further implications of the study are also discussed.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by immune inflammation.1 Autoimmune haemolytic anaemia (AIHA) is a pathological state in which antibodies attack red blood cells. AIHA and SLE shared genetic and environmental risk factors and pathophysiological mechanisms.2 AIHA is clearly over-represented in patients with SLE and often occurs before a diagnosis of SLE.3 However, at present, studies on the incidence of SLE in patients with AIHA are scarce. Therefore, we explored the correlation between AIHA and SLE risk in a nationwide, population-based, matched cohort study. In the 2003–2013 Taiwanese National Health Insurance Database, we identified patients newly diagnosed with AIHA between 2005 and 2012 (online supplemental figure S1). We selected age-matched and sex-matched (1:20) non-AIHA cohort from one million representative populations. From this cohort, we further selected a comparison group via propensity-score matching (PSM, 1:2) for age, sex, comorbidities and possible confounders using the greedy algorithm (online supplemental methods). Ultimately, we identified 713 patients with AIHA and 1416 PSM-matched individuals …

Background Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history. Case presentation We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes. Conclusions We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.

White spot syndrome virus (WSSV) is the causative agent of white spot syndrome (WSS), a disease that has led to severe mortality rates in cultured shrimp all over the world. The WSSV is a large, ellipsoid, enveloped double-stranded DNA virus with a wide host range among crustaceans. Currently, the main antiviral method is to block the receptor of the host cell membrane using recombinant viral proteins or virus antiserum. In addition to interference with the ligand-receptor binding, disrupting the structure of the virus envelope may also be a means to combat the viral infection. Carbon quantum dots (CQDs) are carbonaceous nanoparticles that have many advantageous characteristics, including small size, low cytotoxicity, cheap, and ease of production and modification. Polyamine-modified CQDs (polyamine CQDs) with strong antibacterial ability have been identified, previously. In this study, polyamine CQDs are shown to attach to the WSSV envelope and inhibit the virus infection, with a dose-dependent effect. The results also show that polyamine CQDs can upregulate several immune genes in shrimp and reduce the mortality upon WSSV infection. This is first study to identify that polyamine CQDs could against the virus. These results, indeed, provide a direction to develop effective antiviral strategies or therapeutic methods using polyamine CQDs in aquaculture.

Study Objective To analyze the surgical outcomes and learning curve of transumbilical single-port laparoscopic subtotal hysterectomy, which requires sutures of the cervical stump. Design A prospective observational study (Canadian Task Force classification II-2). Setting A university-affiliated center. Patients From the first (July 2012) and consecutive patients of benign uterine disease scheduled for subtotal hysterectomy until October 2013. Interventions All single-port laparoscopies were performed using straight instruments by 1 gynecologist. An ancillary port was added whenever technical difficulties could endanger surgical quality. Measurement and Main Results Seventy-five patients were recruited for intention-to-treat analysis with a mean (±SD) age of 44.7 ± 3.8 years and a body mass index of 24.2 ± 3.7 kg/m 2 . No major complication was noted. The mean uterine weight was 432.5 ± 344.0 g with 24 (32%) uteri ≧500 g. The patients' sequential order, or gradually increasing experience, was the determining factor in progressively decreasing operative time. Furthermore, most cases that required an additional ancillary port (67%) were clustered in the first 20 cases, whereas 4 were scattered after the 47th patient because of severe pelvic adhesion. The mean operative time decreased in the power law function of the patients' sequential order with a plateau achieved at the 20th patient. Conclusion The patients' sequential order was identified as an independent factor of achieving purely single-port access, and the trend of decreasing operative time delineated the existence of a learning curve. Approximately 20 patients were needed for an experienced multiport laparoscopist to reach technical competency in the current series.

Yi-Hsien Cheng,1 Yi-Jun Lin,2 Szu-Chieh Chen,3,4 Shu-Han You,5 Wei-Yu Chen,6,7 Nan-Hung Hsieh,8 Ying-Fei Yang,9 Chung-Min Liao9 1Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 2Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Department of Public Health, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 4Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China; 5Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung, Taiwan, Republic of China; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 7Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 8Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA; 9Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, Republic of China Background: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. Objectives: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. Materials and methods: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R0)–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. Results: We showed that R0 and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323(267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. Conclusion: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan. Keywords: dengue, DALYs, modeling, infection, control intervention

We explored the mediation effect of cognitive factors on the relationship between cancer-related online information seeking and cancer-preventative behaviors. Using data obtained from the National Cancer Institute's 2013 Health Information National Trends Survey (N = 2,896), we performed structural equation modeling and demonstrated that online information seeking about cancer did not decrease users' cancer fatalism; however it elevated users' level of self-efficacy. Moreover, the findings show that cancer-related information seeking indirectly influenced cancer-preventative behaviors via self-efficacy, and individuals' level of self-efficacy significantly mediated the association between fatalistic beliefs and cancer-preventative behaviors. The results call for attention to cognitive mediators in explaining the relationship between online information seeking and related behaviors.

Shu-Han You,1 Szu-Chieh Chen,2,3 Chung-Min Liao4 1Institute of Food Safety and Risk Management, National Taiwan Ocean University, Taiwan, Republic of China; 2Department of Public Health, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 3Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China; 4Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, Republic of China Background: It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified.Objectives: The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection.Materials and methods: A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change.Results: The age-specific overlapping percentage was estimated to be 40%–43%, 55%–60%, and 19%–35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%.Conclusion: The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection. Keywords: health-seeking behavior, influenza, infection, network-based information model, probabilistic risk model

The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K–protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K–PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity. In this study, we further examined the molecular pathway linking PKB and Cbl-b in murine models. Our data show that the protein kinase GSK-3, one of the first targets identified for PKB, catalyzes two previously unreported phosphorylation events at Ser476 and Ser480 of Cbl-b. GSK-3 inactivation by PKB abrogates phosphorylation of Cbl-b at these two sites and results in reduced Cbl-b protein levels. We further show that constitutive activation of PKB in vivo results in a loss of tolerance that is mediated through the downregulation of Cbl-b. Altogether, these data indicate that the PI3K–PKB–GSK-3 pathway is a novel regulatory axis that is important for controlling the decision between T cell activation and tolerance via Cbl-b.

Exposure to several specific pesticides has led to an increase of Parkinson’s disease (PD) risk. However, it is difficult to quantify the PD population risk related to certain pesticides in regions where environmental exposure data are scarce. Furthermore, the time trend of the prevalence and incidence of PD embedded in the background relationship between PD risk and pesticide exposures has not been well characterized. It has been convincingly identified that a key pesticide associated significantly with an increased risk trend of PD is paraquat (PQ). Here, we present a novel, probabilistic population-based exposure-response approach to quantify the contribution from PQ exposure to prevalence risk of PD. We found that the largest PQ exposure contributions occurred in its positive trend during 2004–2011, with the PQ contributing nearly 21 and 24%, respectively, to the PD prevalence rates among the age groups of 70–79 and ≥ 80 years in Taiwan. We also employed the present population risk model to predict the PQ-induced PD prevalence based on the projected rates of increase in PQ exposure associated with age-specific population. The predicted outcome can be used as an early warning signal for public health authorities. We suggest that a mechanistic understanding of the contribution of a specific pesticide exposure to PD risk trends is crucial to enhance our insights into the perspective on the impacts of environmental exposure on the neurodegenerative diseases.

Objective Single-nucleotide polymorphism (SNP) microarrays and whole-exome sequencing (WES) are tools to precisely diagnose rare autosomal recessive (AR) diseases. In this study, SNP chip and WES were used to identify a mutated location in WDR34 in a baby born to consanguineous parents. Case report The baby, born at 36 gestational weeks had a small thoracic cage, symmetric short proximal bones, and polydactyly. Radiography showed short ribs with reduced lung volume and pulmonary opacities, compatible with asphyxiating thoracic dystrophy or short rib-polydactyly syndrome (SRPS). At 4 months of age, she died of pulmonary hypoplasia and sepsis. SNP microarray and evaluation tool confirmed WDR34 as the candidate gene. WES detected an AR mutation at c.554C > T [p.Arg182Trp] in WDR34. Conclusion This study was the first to identify c.544C > T [p.Arg182Trp] mutation in WDR34 in a patient with SRPS. According to the database, the homozygous mutation of c.544C > T in WDR34 was deleterious and the prevalence of heterozygous mutation was relatively higher in Asian population. More studies of this mutation in patients with SRPS are required.

Background The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality. This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection. Materials and methods A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose-response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach. Results We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines. We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses. Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads. Conclusion People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation. Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD).

Background Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. Methods We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Results Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50–1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67–77% and 86–95% by adopting the suggested BPb standards of 25 and 15 μg/dL. Conclusions We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4315-7) contains supplementary material, which is available to authorized users.

Human health risks associated with the consumption of metal-contaminated fish over extended periods have become a concern particularly in Taiwan, where fish is consumed on a large scale. This study applied the interaction-based hazard index (HI) to assess the mixture health risks for fishers and non-fishers who consume the arsenic (As), copper (Cu), and zinc (Zn) contaminated milkfish from As-contaminated coastal areas in Taiwan, taking into account joint toxic actions and potential toxic interactions. We showed that the interactions of As–Zn and Cu–Zn were antagonistic, whereas As–Cu interaction was additive. We found that HI estimates without interactions considered were 1.3–1.6 times higher than interactive HIs. Probability distributions of HI estimates for non-fishers were less than 1, whereas all 97.5%-tile HI estimates for fishers were >1. Analytical results revealed that the level of inorganic As in milkfish was the main contributor to HIs, indicating a health risk posed to consumers of fish farmed in As-contaminated areas. However, we found that Zn supplementation could significantly decrease As-induced risk of hematological effect by activating a Zn-dependent enzyme. In order to improve the accuracy of health risk due to exposure to multiple metals, further toxicological data, regular environmental monitoring, dietary survey, and refinement approaches for interactive risk assessment are warranted.

Geminin expression is essential for embryonic development and the maintenance of chromosomal integrity. In spite of this protective role, geminin is also frequently overexpressed in human cancers and the molecular mechanisms underlying its role in tumor progression remain unclear. The histone deacetylase HDAC3 modulates transcription factors to activate or suppress transcription. Little is known about how HDAC3 specifies substrates for modulation among highly homologous transcription factor family members. Here, we have demonstrated that geminin selectively couples the transcription factor forkhead box O3 (FoxO3) to HDAC3, thereby specifically facilitating FoxO3 deacetylation. We determined that geminin-associated HDAC3 deacetylates FoxO3 to block its transcriptional activity, leading to downregulation of the downstream FoxO3 target Dicer, an RNase that suppresses metastasis. Breast cancer cells depleted of geminin or HDAC3 exhibited poor metastatic potential that was attributed to reduced suppression of the FoxO3-Dicer axis. Moreover, elevated levels of geminin, HDAC3, or both together with decreased FoxO3 acetylation and reduced Dicer expression were detected in aggressive human breast cancer specimens. These results underscore a prominent role for geminin in promoting breast cancer metastasis via the enzyme-substrate-coupling mechanism in HDAC3-FoxO3 complex formation.

The pandemic of avian influenza viruses (AIVs) in Asia has caused enormous economic loss in poultry industry and human health threat, especially clade 2.3.4.4 H5 and H7 subtypes in recent years. The endemic chicken H6 virus in Taiwan has also brought about human and dog infections. Since wild waterfowls is the major AIV reservoir, it is important to monitor the diversified subtypes in wildfowl flocks in early stage to prevent viral reassortment and transmission. To develop a more efficient and sensitive approach is a key issue in epidemic control. In this study, we integrate multiplex reverse transcription recombinase polymerase amplification (RT-RPA) and capillary electrophoresis (CE) for high-throughput detection and differentiation of AIVs in wild waterfowls in Taiwan. Four viral genes were detected simultaneously, including nucleoprotein (NP) gene of all AIVs, hemagglutinin (HA) gene of clade 2.3.4.4 H5, H6 and H7 subtypes. The detection limit of the developed detection system could achieve as low as one copy number for each of the four viral gene targets. Sixty wild waterfowl field samples were tested and all of the four gene signals were unambiguously identified within 6 h, including the initial sample processing and the final CE data analysis. The results indicated that multiplex RT-RPA combined with CE was an excellent alternative for instant simultaneous AIV detection and subtype differentiation. The high efficiency and sensitivity of the proposed method could greatly assist in wild bird monitoring and epidemic control of poultry.

BackgroundTo investigate the trends of succession occurring at thePinus thunbergiiforests on the lowlands of Jeju Island, we quantified the species compositions and the importance values by vegetation layers of Braun-Blanquet method on thePinus thunbergiiforests. We used multivariate analysis technique to know the correlations between the vegetation group types and the location environmental factors; we used the location environment factors such as altitudes above sea level, tidal winds (distance from the coast), annual average temperatures, and forest gaps to know the vegetation distribution patterns.ResultsAccording to the results on the lowland of Jeju Island, the understory vegetation of the lowlandPinus thunbergiiforests was dominated by tall evergreen broad-leaved trees such asMachilus thunbergii,Neolitsea sericea, andCinnamomum japonicumshowing a vegetation group structure of the mid-succession, and the distribution patterns of vegetation were determined by the altitudes above sea level, the tidal winds on the distance from the coast, the annual average temperatures, and the forest gaps. We could discriminate the secondary succession characteristics of thePinus thunbergiiforests on the lowland and highland of Jeju Island of South Korea.ConclusionsIn the lowland of Jeju Island, the secondary succession will progress to the form ofPinus thunbergii(early successional species)→Machilus thunbergii,Litsea japonica(mid-successional species)→Machilus thunbergii(late-successional species) sequence in the temperate areas with strong tidal winds. In the highland of Jeju Island, the succession will progress to the form ofPinus thunbergii(early successional species)→Neolitsea sericea,Eurya japonica(mid-successional species)→Castanopsis sieboldii(late-successional species) sequence in the areas where tidal winds are weak and temperatures are relatively low. However, local differences between lowland and highland of Jeju Island will be caused by the micro-environmental factors resulting from the topographic differences and the supply of tree seeds. From the characteristics of succession study, we could properly predict and manage thePinus thunbergiiforest ecosystem on lowland and highland of Jeju Island.

Down syndrome is one of the most common chromosomal disorders and yet our understanding about the dysregulated genes in this disease is limited. Through this case study, we investigated the gene expression profile of primary amniotic fluid mesenchymal stem cells (AFMSCs) isolated from the amniotic sac of monozygotic twins discordant for trisomy 21 with one fetal hydrops at 17 weeks of gestation. AFMSCs were cultured to analyze the gene expression profiles for the human transcriptome array. Gene ontology was used to evaluate dysregulated gene functions. Total 25,799 genes were identified such that 65 were up-regulated (0.25%) and 111 were down-regulated (0.43%) with a log2 fold change trisomy 21/euploidy (log2 [FC]) > 1, p

This research aims to study the effect of climate change on the phenology, growth, and physiological traits of Silene capitata Kom., a Korean endangered species II. This study increased CO2 concentration in a closed glass greenhouse, with the daily mean temperature and CO2 concentration respectively being 4.61 °C and 93.63 ppm higher than the outside temperature (ambient conditions, control). The seeds of S. capitata were sown in control and treatment environments in March 2013 while seedlings were transplanted into individual pots in May 2013. To research phenological changes, the first day of the flowering and ripening of the plants transplanted in 2013 and first day of leafing in 2014 were observed. The growth and physiological responses of mature leaves were also studied in 2013. There was no difference in the first day of flowering, but the first day of ripening was earlier in the treatment group than the control group. There was no difference in the number of rosette leaves between the two groups, but leaf area was wider in the treatment group than the control group. Transpiration rate and stomatal conductance were higher in the treatment group than the control group, chlorophyll content decreased, and photosynthetic rate and water use efficiency were the same for both groups. As a result of simple regression analysis among the transpiration rate, stomatal conductance, photosynthetic rate, and water use efficiency, stomatal conductance increased when transpiration rate increased. Stomatal conductance increased with photosynthetic rate in the control unlike in the treatment group. The photosynthetic rate and water use efficiency increased with transpiration rate in the control group unlike in the treatment group. Furthermore, water use efficiency increased as photosynthetic rate increased in both groups. Due to high CO2 concentration, the photosynthetic rate was no longer controlled by the stomata, which appeared to suppress the excessive production of photosynthetic products by reducing chlorophyll content. It is believed that the phenological responses of S. capitata under climate change conditions will advance and that stable growth will be difficult in regions lacking moisture due to the high transpiration rate.

Background Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. Methods hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway. Results Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway. Conclusion Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury. Electronic supplementary material The online version of this article (10.1186/s13287-019-1366-y) contains supplementary material, which is available to authorized users.

Reactive oxygen species (ROS) production in phagocytes is a major defense mechanism against pathogens. However, the cellular self-protective mechanism against such potential damage from oxidative stress remains unclear. Here we show that the kinases Mst1 and Mst2 (Mst1/2) sense ROS and maintain cellular redox balance by modulating the stability of antioxidant transcription factor Nrf2. Site-specific ROS release recruits Mst1/2 from the cytosol to the phagosomal or mitochondrial membrane, with ROS subsequently activating Mst1/2 to phosphorylate kelch like ECH associated protein 1 (Keap1) and prevent Keap1 polymerization, thereby blocking Nrf2 ubiquitination and degradation to protect cells against oxidative damage. Treatment with the antioxidant N-acetylcysteine disrupts ROS-induced interaction of Mst1/2 with phagosomes or mitochondria, and thereby diminishes the Mst-Nrf2 signal. Consistently, loss of Mst1/2 results in increased oxidative injury, phagocyte ageing and death. Thus, our results identify the Mst-Nrf2 axis as an important ROS-sensing and antioxidant mechanism during an antimicrobial response., Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

STUDY DESIGN A retrospective cohort study. OBJECTIVES The aim of this study was to evaluate radiographic and patient-reported outcomes at minimum 2 years after revision surgery for proximal junctional kyphosis (PJK), correlating these results with PJK etiology. SUMMARY OF BACKGROUND DATA There are no studies detailing the results of revision surgery for PJK following posterior segmental instrumentation. METHODS Thirty-two consecutive patients treated with revision surgery after PJK above posterior fusions (25 women/7 men, average age at surgery 60.6 yrs) were reviewed for radiographic and patient-reported outcomes (mean follow-up, 4.5 yrs; range, 2-10 yrs). Patients were subdivided into fracture (F) and nonfracture (NF) groups on the basis of PJK etiology. RESULTS Radiographic severity of PJK improved significantly with revision surgery and was maintained at ultimate follow-up (P

Smad proteins are central mediators in the canonical transforming growth factor-β (TGF-β) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-β signaling. BRD7 forms a TGF-β inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-β transcriptional, tumor suppressing and epithelial-mesenchymal transition (EMT) responses. Conversely, depletion of BRD7 inhibits TGF-β responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-β physiological responses.

Enterovirus 71 (EV71) is the causative agent of hand, foot and mouth disease and can spread its infections to the central nervous and other systems with severe consequences. The replication of EV71 depends on its 3C proteinase (3Cpro ), a significant drug target. By X-ray crystallography and functional assays, the interactions between inhibitors and EV71 3Cpro were evaluated. It was shown that improved interactions at S4 for the substrate binding could significantly enhance the potency. A new series of potent inhibitors with high ligand efficiency was generated for developing antivirals to treat and control the EV71-associated diseases. Copyright © 2016 John Wiley & Sons, Ltd.

We thank Goulielmos and Zervou1 for their interest on our article entitled ‘Increased risk of systemic lupus erythematosus in patients with autoimmune haemolytic anaemia: a nationwide population-based cohort study.2 Goulielmos and Zervou1 commented that the occurrence of systemic lupus erythematosus (SLE) and autoimmune haemolytic anaemia (AIHA) may be related to genetic and environmental factors, in addition to the abnormal immune system function. In the recently presented data, Goulielmos and Zervou1 showed that various shared genetic polymorphisms were associated with the increased susceptibility of ITP and SLE. According to existing research, it has been reported that AIHA and SLE share common genetic susceptibility as well, including human leucocyte antigen (HLA)-B8 and HLA-DQ6 regions,3 4 and single-nucleotide polymorphisms of the CTLA-4 ,5 NFATC1 ,6 LT-a ,7 FcgRIIa ,8 FOXP3 9 and CARD11 10 genes. We strongly agree with the point put forward by …

214 Background: The ASCO Quality Oncology Practice Initiative identifies ICU admission in the last 30 days and systemic anticancer therapy in the last 14 days of life as indicators of overly aggressive end-of-life care. We sought to delineate clinical factors associated with these indicators. Methods: An IRB approved retrospective chart review was conducted on patients with solid tumors at LCI who died in timepoints ending in January, July and November of 2016 and 2017. Patients were identified through our tumor registry. Patients’ medical records were reviewed for cancer stage, care received, palliative care contact, site of death, ICU admission in last 30 days, and receipt of systemic anticancer therapy (excluding antihormonal therapy) in last 6 months and 2 weeks of life. Results: A total of 250 patients were included in our analysis. 18.8% of LCI patients were admitted to the ICU in the last 30 days of life, 12.8% received systemic anticancer therapy in the last 2 weeks of life, and 19.2% experienced death in the hospital. Significant factors associated with an ICU admission in the last 30 days of life were a diagnosis of lymphoma compared to breast, gynecologic, gastrointestinal, lung, genitourinary, melanoma/carcinoma of unknown primary/head and neck cancer, or other (42.9% vs 20% vs 14.3% vs 9% vs 23.1% vs 25% vs 0% vs 26.3%; P = 0.01), systemic anticancer therapy in last 2 weeks of life (40.6% vs 16.1%; P < 0.005), and age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (50% vs 15.9% vs 18.1%; P < 0.05). A significant factor associated with systemic anticancer therapy in the last 2 weeks of life was age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (35.7% vs 16.9% vs 9.4%; P < 0.05). Lastly, a significant factor associated with death in the hospital was lack of palliative care team contact (28.9% vs 15%; P < 0.05). Conclusions: Understanding factors associated with intensive care at the end of life is critical to the provision of value-based cancer care. In this study, a diagnosis of lymphoma, systemic anticancer treatment in the last 2 weeks of life, and age ≤ 45 years at time of metastatic disease were associated with ICU stays in the last 30 days of life. Age ≤ 45 years at time of metastatic disease was associated with systemic anticancer treatment in the last 2 weeks of life, while lack of palliative care involvement was associated with greater chance of death in the hospital. Further understanding of the complex interplay that governs care and decision making at the end of life is required.

The world&rsquo, s first natural avian-origin H6N1 influenza A virus infection case in dogs was confirmed in Taiwan in 2014. The H6N1 virus in chickens has been endemic in Taiwan since 1972. Whether the dog H6N1 virus has interspecies transmission potential is the key issue we aim to understand. Following one virus passage in embryonated eggs and two further passages in MDCK cells, we obtained two virus derivatives, E01EE (PB1 739E and PB2 627E) and E01GK (PB1 739G and PB2 627K), respectively. The pathogenicity of E01EE and E01GK was investigated using plaque assay, growth dynamic analysis and cell viability quantification in cells from different animal species. The impact of amino acid mutation on PB1 739 and PB2 627 on viral ribonucleoprotein (RNP) activity was also analyzed. Further mouse infection experiments were performed. The results showed that both E01EE and E01GK decreased cell relative viability of canine MDCK cells, human A549 cells and chicken DF1 cells. E01Gk caused greater cellular harm in MDCK and A549 cells and had significantly higher virus titers in all of the cells compared to E01EE. The PB2 627K but not PB1 739G was the critical mutation that influenced the viral RNP activity. Both E01EE and E01GK caused mice pneumonia and considerable virus shedding, especially E01GK. This report verifies PB2 E627K mutation in virulence and spotlights the potential for the dog H6N1 virus to extend interspecies transmission.

Background Understanding the relapse risk among different illicit drugs is vital for developing an adequate relapse prevention policy. Therefore, the current study aims to explore the potential difference in long-term relapse rates between youths who use ketamine and those who use stimulants (3,4-Methylenedioxymethamphetamine [MDMA] or methamphetamine). Methods The study’s participants included 92 youths with ketamine use (ketamine group, mean age: 16.0 years) and 43 youths with MDMA/methamphetamine use (stimulants group, mean age: 16.1 years) that had undergone a family-oriented treatment program in a medical center in Taiwan. All participants were followed up for a maximum of 7 years in order to observe their long-term outcomes with regard to substance use relapse. Results During the follow-up period, compared to the 34.8% relapse rate in ketamine users, their counterparts who used MDMA or methamphetamine had a significantly higher relapse rate (60.5%, Adjusted HR = 1.86, 95%CI: 1.06–3.28, p = 0.032). Of the youths in the ketamine group that relapsed, 65.6% continued to use ketamine in their relapse event, while 34.4% switched to MDMA or methamphetamine. Among the relapsing youths in the stimulants group, 84.6% continued to use MDMA or methamphetamine in their relapse event, while 15.4% switched to ketamine (p = 0.042). Conclusions Compared to adolescents who use ketamine, those using MDMA or methamphetamine had higher relapse rates and were more likely to use the same type of drug upon relapsing. These results can serve as a crucial reference for developing relapse prevention policies of illicit drugs for the youth population. Electronic supplementary material The online version of this article (10.1186/s13011-018-0188-8) contains supplementary material, which is available to authorized users.

In this study, we observed their growth and physiological responses using a variety of duty ratio under the mixed light using red, blue, and white lights. The red+blue mixed light was treated with 95%, 90%, 85%, 80%, and 75% duty ratios and red+blue+white mixed light with 85% and 70% duty ratios. We examined the width and length of leaves, total number of leaves, and number of shoots to examine their growth responses. The physiological responses were studied by measuring their photosynthetic rate, transpiration rate, stomatal conductance, water use efficiency, chlorophyll content, and fluorescence (Fo, Fm, and Fv/Fm). We found that lower duty ratio caused the length and width of the leaves to grow longer under red+blue mixed light but that it did not cause any difference in the red+blue+white mixed light condition. In addition, there was no difference in the number of leaves and shoots among all treatments. In the red+blue mixed light condition, the photosynthetic rate was no difference, but both transpiration rate and stomatal conductance were the highest at 95% duty ratio than in other ratios. Water use efficiency pattern was similar to that of photosynthetic rate; water use efficiency was no difference. Chlorophyll content was the highest at 95% duty ratios, and it was the least at 90%, 85%, and 75% duty ratio. Fo and Fm values were relatively high at 85% and 80% duty ratio and low at 90% duty ratio while Fv/Fm showed no difference. Under the red+blue+white mixed light, all physiological items showed no difference between 70 and 85% treatments. But, photosynthetic rate, water use efficiency, chlorophyll content, and Fv/Fm were relatively greater in the red+blue+white mixed light than in the red+blue mixed light. Therefore, red+blue+white mixed light treated with 70% duty ratio could lessen the environmental stress and save more power when cultivating Silene capitata in a plant factory.

Background Hepatocyte transplantation has been proposed as an effective treatment for patients with acute liver failure (ALF), but its application is limited by a severe shortage of donor livers. Human pluripotent stem cells (hPSCs) have emerged as a potential cell source for regenerative medicine. Human amniotic epithelial stem cells (hAESCs) derived from amniotic membrane have multilineage differentiation potential which makes them suitable for possible application in hepatocyte regeneration and ALF treatment. Methods The pluripotent characteristics, immunogenicity, and tumorigenicity of hAESCs were studied by various methods. hAESCs were differentiated to hepatocyte-like cells (HLCs) using a non-transgenic and three-step induction protocol. ALB secretion, urea production, periodic acid-Schiff staining, and ICG uptake were performed to investigate the function of HLCs. The HLCs were transplanted into ALF NOD-SCID (nonobese diabetic severe combined immunodeficient) mouse, and the therapeutic effects were determined via liver function test, histopathology, and survival rate analysis. The ability of HLCs to engraft the damaged liver was evaluated by detecting the presence of GFP-positive cells. Results hAESCs expressed various markers of embryonic stem cells, epithelial stem cells, and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAESC-derived hepatocytes possess the similar functions of human primary hepatocytes (hPH) such as producing urea, secreting ALB, uptaking ICG, storing glycogen, and expressing CYP enzymes. HLC transplantation via the tail vein could engraft in live parenchymal, improve the liver function, and protect hepatic injury from CCl4-induced ALF in mice. More importantly, HLC transplantation was able to significantly prolong the survival of ALF mouse. Conclusion We have established a rapid and efficient differentiation protocol that is able to successfully generate ample functional HLCs from hAESCs, in which the liver injuries and death rate of CCl4-induced ALF mouse can be significantly rescued by HLC transplantation. Therefore, our results may offer a superior approach for treating ALF.

Background Preeclampsia, a multisystem disorder in pregnancies complicates with maternal and fetal morbidity. Early- and late-onset preeclampsia, defined as preeclampsia developed before and after 34 weeks of gestation, respectively. The early-onset disease was less prevalent but associated with poorer outcomes. Moreover, the risk factors between early -and late- onset preeclampsia could be differed owing to the varied pathophysiology. In the study, we evaluated the incidences, trends, and risk factors of early- and late- onset preeclampsia in Taiwan. Methods This retrospective population-based cohort study included all ≧20 weeks singleton pregnancies resulting in live-born babies or stillbirths in Taiwan between January 1, 2001 and December 31, 2014 (n = 2,884,347). The data was collected electronically in Taiwanese Birth Register and National Health Insurance Research Database. The incidences and trends of early- and late-onset preeclampsia were assessed through Joinpoint analysis. Multivariate logistic regression was used to analyze the risk factors of both diseases. Results The age-adjusted overall preeclampsia rate was slightly increased from 1.1%(95%confidence interval [CI], 1.1–1.2) in 2001 to 1.3% (95%CI, 1.2–1.3) in 2012 with average annual percentage change (AAPC) 0.1%/year (95%CI, 0–0.2%). However, the incidence was remarkably increased from 1.3% (95%CI, 1.3–1.4) in 2012 to 1.7% (95%CI, 1.6–1.8) in 2014 with AAPC 1.3%/year (95%CI,0.3–2.5). Over the study period, the incidence trend in late-onset preeclampsia was steadily increasing from 0.7% (95%CI, 0.6–0.7) in 2001 to 0.9% (95%CI, 0.8–0.9) in 2014 with AAPC 0.2%/year (95%CI, 0.2–0.3) but in early-onset preeclampsia was predominantly increase from 0.5% (95%CI, 0.4–0.5) in 2012 to 0.8% (95%CI, 0.8–0.9) in 2014 with AAPC 2.3%/year (95%CI, 0.8–4.0). Advanced maternal age, primiparity, stroke, diabetes mellitus, chronic hypertension, and hyperthyroidism were risk factors of preeclampsia. Comparing early- and late-onset diseases, chronic hypertension (ratio of relative risk [RRR], 1.71; 95%CI, 1.55–1.88) and older age (RRR, 1.41; 95%CI 1.29–1.54) were more strongly associated with early-onset disease, whereas primiparity (RRR 0.71, 95%CI, 0.68–0.75) had stronger association with late-onset preeclampsia. Conclusions The incidences of overall, and early- and late-onset preeclampsia were increasing in Taiwan from 2001 to 2014, predominantly for early-onset disease. Pregnant women with older age and chronic hypertension had significantly higher risk of early-onset preeclampsia. Electronic supplementary material The online version of this article (10.1186/s12884-018-1845-7) contains supplementary material, which is available to authorized users.

Objective: To study the maternal and fetal outcomes and assess the risk factors in patients with rupture at the lower-segment or non-lower-segment scarred, or unscarred gravid uterus. Materials and Methods: Gravid patients with uterine rupture were retrospectively collected in Chang-Gung Memorial Hospital from November 2004 to July 2017. The rupture timing and location in association with maternal and fetal outcomes were collected as well as the possible risk factors including surgical history and interval prior to conception were analyzed. Results: Thirty patients were included [mean age (±SEM), 34.4 ± 0.7 years; mean body mass index, 25.0 ± 0.6 kg/m2] with mean onset of rupture at 34.2 ± 0.9 weeks, in which, 12 occurred at term and 18 at preterm (range 20–34 weeks). Four fetal demises, 22 transferals to neonatal intensive care unit, and 17 maternal blood transfusions without maternal mortality were noted. Twenty-two patients presented with acute abdominal pain and/or abnormal fetal heart rate tracing were managed with emergent cesarean delivery. Four ruptures were found in postpartum of vaginal delivery, in which 3 were after trials of labor after cesarean delivery and 1 was unscarred uterus, and two of the four eventually underwent hysterectomy. Unscarred uterus (n = 6) without identifiable risk factor ruptured in significantly later gestation associated with higher fetal birthweights than those of the scarred uterus (n = 24) (both p

Activation of phosphatidylinositol 3 kinase (PI3K), Ras, and Her2 signaling plays a critical role in cancer development. Hotspot constitutive activating mutations in oncogenes, such as PIK3CA encoding the p110α catalytic subunit or RAS, as well as overexpression of Her2, are frequently found in human tumors and cancers. It has been well established that activation of these oncogenes profoundly promotes tumor metastasis, whereas decreased expression of ΔNp63α, the major protein isoform of the p53-related p63 expressed in epithelial cells, has been associated with cancer metastasis. In this study, we demonstrate that hotspot oncogenic mutations on PIK3CA and RAS, including p110αH1047R, K-RasG12V, and H-RasG12V, as well as activation of Her2, all led to suppression of ΔNp63α expression via Akt-fork-head transcription factor 3a (Akt-FOXO3a) signaling, resulting in increased cell motility and tumor metastasis. Expression of ΔNp63α effectively reversed p110αH1047R-, K-RasG12V-, H-RasG12V-, or Her2-induced cell motility in vitro and tumor metastasis in mouse models. We show that ΔNp63α was a direct FOXO3a transcriptional target and that expression of FOXO3a and ΔNp63α was correlated in human cancer biopsy samples. Together, these results demonstrate that ΔNp63α is a common inhibitory target of oncogenic PI3K, Ras, and Her2, and that ΔNp63α may function as a critical integrator of oncogenic signaling in cancer metastasis.

Spine surgeons are required to differentiate symptomatic cervical disc herniation with asymptomatic radiographic herniation. Although the dermatomal sensory dysfunction of upper extremity is the most important clue, axial pain including cervicogenic headache and parascapular pain may be helpful to find surgical target level. However, there is no review article about the axial pain originated from cervical spondylotic radiculopathy and relieved by surgical decompression. The purpose is to review the literatures about the axial pain, which can be utilized in determining target level to be decompressed in the patients with cervical radiculopathy at multiple levels. Cervicogenic headaches of suboccipital headaches, retro-orbital pain, retro-auricular pain, or temporal pain may be associated with C2, C3, and C4 radiculopathies. The pain around scapula may be associated with C5, C6, C7, and C8 radiculopathies. However, there is insufficient evidence to make recommendations for the use in clinical practice because they did not evaluate sensitivity and specificity.

Summary The external factors that modulate Hippo signaling remain elusive. Here, we report that FGF15 activates Hippo signaling to suppress bile acid metabolism, liver overgrowth, and tumorigenesis. FGF15 is induced by FXR in ileal enterocytes in response to increased amounts of intestinal bile. We found that circulating enterohepatic FGF15 stimulates hepatic receptor FGFR4 to recruit and phosphorylate NF2, which relieves the inhibitory effect of Raf on the Hippo kinases Mst1/2, thereby switching FGFR4’s role from pro-oncogenic to anti-tumor signaling. The activated Mst1/2 subsequently phosphorylates and stabilizes SHP to downregulate the key bile acid-synthesis enzyme Cyp7a1 expression, thereby limiting bile acid synthesis. In contrast, Mst1/2 deficiency impairs bile acid metabolism and remarkably increases Cyp7a1 expression and bile acid production. Importantly, pharmacological depletion of intestinal bile abrogates Mst1/2-mutant-driven liver overgrowth and oncogenesis. Therefore, FGF15-Hippo signaling along the gut-liver axis acts as a sensor of bile acid availability to restrain liver size and tumorigenesis.