Neuronatin Promotes Neural Lineage in ESCs via Ca2+ Signaling

Neural induction is the first step in the formation of the vertebrate central nervous system. The emerging consensus of the mechanisms underling neural induction is the combined influences from inhibiting bone morphogenetic protein (BMP) signaling and activating fibroblast growth factor (FGF)/Erk signaling, which act extrinsically via either autocrine or paracrine fashions. However, do intrinsic forces (cues) exist and do they play decisive roles in neural induction? These questions remain to be answered. Here, we have identified a novel neural initiator, neuronatin (Nnat), which acts as an intrinsic factor to promote neural fate in mammals and Xenopus. ESCs lacking this intrinsic factor fail to undergo neural induction despite the inhibition of the BMP pathway. We show that Nnat initiates neural induction in ESCs through increasing intracellular Ca2+ ([Ca2+]i) by antagonizing Ca2+-ATPase isoform 2 (sarco/endoplasmic reticulum Ca2+-ATPase isoform 2) in the endoplasmic reticulum, which in turn increases the phosphorylation of Erk1/2 and inhibits the BMP4 pathway and leads to neural induction in conjunction with FGF/Erk pathway. STEM CELLS 2010;28:1950–196

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.Part of the studies were financed by grants from the Swedish Research Council and from the King Gustaf V and Queen Victoria Research Fund and by grants from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucia (Grupo consolidado CTS- 159).Ye

Rest-Mediated Regulation of Extracellular Matrix Is Crucial for Neural Development

Neural development from blastocysts is strictly controlled by intricate transcriptional programmes that initiate the down-regulation of pluripotent genes, Oct4, Nanog and Rex1 in blastocysts followed by up-regulation of lineage-specific genes as neural development proceeds. Here, we demonstrate that the expression pattern of the transcription factor Rest mirrors those of pluripotent genes during neural development from embryonic stem (ES) cells and an early abrogation of Rest in ES cells using a combination of gene targeting and RNAi approaches causes defects in this process. Specifically, Rest ablation does not alter ES cell pluripotency, but impedes the production of Nestin+ neural stem cells, neural progenitor cells and neurons, and results in defective adhesion, decrease in cell proliferation, increase in cell death and neuronal phenotypic defects typified by a reduction in migration and neurite elaboration. We also show that these Rest-null phenotypes are due to the dysregulation of its direct or indirect target genes, Lama1, Lamb1, Lamc1 and Lama2 and that these aberrant phenotypes can be rescued by laminins

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

Impact of hospice care on end-of-life hospitalization of elderly patients with lung cancer in Taiwan

Background: This study investigated the impact of hospice care on end-of-life elderly patients with lung cancer in Taiwan. Methods: Data were collected from deceased inpatients with lung cancer who were at least 65 years old, using the National Health Insurance Research Database of 2004. Results: A total of 1282 patients were enrolled, of whom 277 (21.6%) received hospice care (hospice-care group) and the other 1005 (78.4%) received general acute ward care (control group). The patients' age, gender, and institution of hospitalization did not differ significantly between the two groups, and most of the patients had chosen medical centers and their affiliated hospices for terminal care. The hospice-care group had a significantly shorter hospital stay and lower costs of hospitalization than the control group, with patients cared for primarily by family physicians and radiation oncologists (all p<0.05). The hospice-care group had an elevated incidence of co-morbid diabetes mellitus, higher scores on the Charlson Comorbidity Index, fewer acute lower respiratory conditions, and fewer invasive procedures than the control group (all p<0.05). Natural opium alkaloids were the most commonly prescribed drugs in the hospice-care group, whereas parenteral solutions were most frequently requested in the control group. Conclusion: Hospice care has provided a humane and cost-efficient pathway for end-of-life elderly patients with lung cancer. Parenteral nutrition/hydration should be limited for terminal care patients. Opioids should be promoted for the relief of pain and dyspnea in acute ward care. Family physicians and radiation oncologists play important roles in hospice care. Compared with the prevalence of hospice care in the United Kingdom and other developed countries, hospice care in Taiwan is in the position to be expanded

Trend of urban-rural disparities in hospice utilization in Taiwan.

AIMS: The palliative care has spread rapidly worldwide in the recent two decades. The development of hospice services in rural areas usually lags behind that in urban areas. The aim of our study was to investigate whether the urban-rural disparity widens in a country with a hospital-based hospice system. METHODS: From the nationwide claims database within the National Health Insurance in Taiwan, admissions to hospices from 2000 to 2006 were identified. Hospices and patients in each year were analyzed according to geographic location and residence. RESULTS: A total of 26,292 cancer patients had been admitted to hospices. The proportion of rural patients to all patients increased with time from 17.8% in 2000 to 25.7% in 2006. Although the numbers of beds and the utilizations in both urban and rural hospices expanded rapidly, the increasing trend in rural areas was more marked than that in urban areas. However, still two-thirds (898/1,357) of rural patients were admitted to urban hospices in 2006. CONCLUSIONS: The gap of hospice utilizations between urban and rural areas in Taiwan did not widen with time. There was room for improvement in sufficient supply of rural hospices or efficient referral of rural patients

Interdisciplinary, interinstitutional and international collaboration of family medicine researchers in Taiwan

The family medicine researches flourished worldwide in the past decade. However, the collaborative patterns of family medicine publications had not been reported. Our study analyzed the collaborative activity of family medicine researchers in Taiwan. We focused on the types of collaboration among disciplines, institutions and countries. We searched “family medicine” AND “Taiwan” in address field from Web of Science and documented the disciplines, institutions and countries of all authors. We analyzed the collaborative patterns of family medicine researchers in Taiwan from 2010 to 2014. The journal’s impact factor of each article in the same publication year was also retrieved. Among 1,217 articles from 2010 to 2014, interdisciplinary collaboration existed in 1,185 (97.3%) articles, interinstitutional in 1,012 (83.2%) and international in 142 (11.7%). Public health was the most common collaborative discipline. All international researches were also interdisciplinary and interinstitutional. The United States (75 articles), the United Kingdom (21) and the People’s Republic of China (20) were the top three countries with which family medicine researchers in Taiwan had collaborated. We found a high degree of interdisciplinary and interinstitutional collaboration of family medicine researches in Taiwan. However, the collaboration of family medicine researchers in Taiwan with family medicine colleagues of other domestic or foreign institutions was insufficient. The future direction of family medicine studies could focus on the promotion of communication among family medicine researchers