Systematic Cu-63 NQR studies of the stripe phase in La(1.6-x)Nd(0.4)Sr(x)CuO(4) for 0.07 <= x <= 0.25

We demonstrate that the integrated intensity of Cu-63 nuclear quadrupole resonance (NQR) in La(1.6-x)Nd(0.4)Sr(x)CuO(4) decreases dramatically below the charge-stripe ordering temperature T(charge). Comparison with neutron and X-ray scattering indicates that the wipeout fraction F(T) (i.e. the missing fraction of the integrated intensity of the NQR signal) represents the charge-stripe order parameter. The systematic study reveals bulk charge-stripe order throughout the superconducting region 0.07 <= x <= 0.25. As a function of the reduced temperature t = T/T(charge), the temperature dependence of F(t) is sharpest for the hole concentration x=1/8, indicating that x=1/8 is the optimum concentration for stripe formation.Comment: 10 pages of text and captions, 11 figures in postscript. Final version, with new data in Fig.

Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students

Background: Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. Methods: Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. Results: This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to “their” character initially, but their empathy for the character increased as the SSC progressed. Conclusion: Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation

Characterization of 9-Nitrocamptothecin Liposomes: Anticancer Properties and Mechanisms on Hepatocellular Carcinoma In Vitro and In Vivo

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration

Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis:an international follow-up study

Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points. We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies. Levels of alkaline phosphatase and bilirubin were analyzed in different settings and subpopulations at different time points relative to the clinical end point (liver transplantation or death). Of the 4845 patients, 1118 reached a clinical end point. The median follow-up period was 7.3 years; 77% survived for 10 years after study enrollment. Levels of alkaline phosphatase and bilirubin measured at study enrollment (baseline) and each year for 5 years were strongly associated with clinical outcomes (lower levels were associated with longer transplant-free survival). At 1 year after study enrollment, levels of alkaline phosphatase that were 2.0 times the upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other thresholds. Of patients with alkaline phosphatase levels ≤ 2.0 times the ULN, 84% survived for 10 years compared with 62% of those with levels >2.0 times the ULN (P 1.0 times the ULN (P < .0001). Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times. We confirmed the predictive value of alkaline phosphatase and bilirubin levels in multiple subgroups, such as patients who had not received treatment with ursodeoxycholic acid, and at different time points after study enrollment. Levels of alkaline phosphatase and bilirubin can predict outcomes (liver transplantation or death) of patients with PBC and might be used as surrogate end points in therapy trial

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

Natural history and management of primary biliary cirrhosis

Nadya Al-Harthy,1 Teru Kumagi21Gastroenterology and Hepatology, Royal Hospital, Muscat, Oman; 2Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, JapanAbstract: Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. It is a rare disease with prevalence of less than one in 2000. Its prevalence in developing countries is increasing presumably because of growth in recognition and knowledge of the disease. PBC is thought to result from a combination of multiple genetic factors and superimposed environmental triggers. The contribution of the genetic predisposition is evidenced by familial clustering. Several risk factors, including exposure to infectious agents and chemical xenobiotics, have been suggested. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The prognosis of PBC has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. When administered at adequate doses of 13&amp;ndash;15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches.Keywords: primary biliary cirrhosis, natural history, long-term outcome, ursodeoxycholic acid, biochemical response, target therap