bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of three selective media for isolation of Aggregatibacter actinomycetemcomitans
Authors: Rurenga P. , Raangs E. , Singadji Z. , Wekema‐Mulder G. , Veloo A. C. M. , van Winkelhoff A. J. 
Published: January 2013

Background and ObjectiveAggregatibacter actinomycetemcomitans is a pathogen in oral and nonoral infections. Detection and quantification of this pathogen can be performed using selective culture techniques. The aim of this study was to establish the efficacy of two known selective media in their ability to select and support the growth of A. actinomycetemcomitans.Material and MethodsTrypticase soy bacitracin vancomycin (TSBV) medium and brain–heart infusion agar with vancomycin (Dentaid‐1), as well as a modified Dentaid‐1 medium (in which the brain–heart infusion agar was substituted with brain–heart infusion broth), were compared. Two‐hundred and eighteen clinical samples were used to establish the recovery rate, the number of colony‐forming units (CFUs) of A. actinomycetemcomitans as well as the total number of CFUs on the three different types of medium. In addition, the numbers of gram‐negative aerobic rods and yeasts were determined.ResultsBoth types of Dentaid‐1 medium showed a higher recovery of A. actinomycetemcomitans compared with TSBV. However, these differences did not reach statistical significance. The total number of CFUs of A. actinomycetemcomitans recovered was significantly higher on Dentaid‐1 compared with TSBV (p = 0.029). The mean number of gram‐negative aerobic rods recovered was statistically higher on both types of Dentaid‐1 medium in comparison with TSBV. Low numbers of yeasts were recovered occasionally on all test plates.ConclusionDentaid‐1 is a low‐cost effective alternative to TSBV for the isolation and growth of A. actinomycetemcomitans from clinical samples, such as dental plaque, which contain a complex microflora.
Telbivudine treatment in chronic hepatitis B: experience from China
Authors: You H. , Jia J. 
Published: January 2013

SummaryTelbivudine, one of the oral anti‐hepatitis B virus (HBV) nucleoside analogues, has been used for more than 5 years to treat HBeAg‐positive and ‐negative chronic hepatitis B (CHB) patients. This includes not only global Phase II and III trials, but also Chinese Phase III trials and several real‐world clinical practice studies from China. The present review will first focus on 1‐, 2‐ and 3‐year data of telbivudine therapy on HBV DNA suppression, alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, viral resistance and safety in HBeAg‐positive and ‐negative CHB patients. Second, telbivudine treatment predictors, including HBV DNA undetectability, ALT level and other immune‐related markers at 12 and 24 weeks will be summarized to optimize therapy. Besides several retrospective studies, the Chinese EFFORT prospective study adapted from telbivudine virological response at 24 weeks has shown very promising results. Finally, the Chinese experience of using telbivudine in the second and third trimesters of pregnancy to prevent perinatal transmission of HBV infection will be touched on citing the latest studies.
Telbivudine treatment is associated with high hepatitis B e antigen seroconversion and immune modulatory effects in chronic hepatitis B patients
Authors: Wang G.‐Q. , Ding Y.‐P. , Dong Y.‐H. 
Published: January 2013

SummaryChronic hepatitis B (CHB) is characterized by an impaired immune response to hepatitis B virus. Among the nucleos(t)ides used in CHB treatment, telbivudine is associated with the highest rates of hepatitis B e antigen (HBeAg) seroconversion rates, which are similar to those observed with pegylated interferon (PegIFN). Besides direct antiviral effect, modulation of the immune system may be an additional benefit for telbivudine‐treated patients. Indeed, there is much clinical data indicating an IFN‐like behaviour for telbivudine in contrast to other oral nucleos(t)ides, such as high HBeAg seroconversion, similar hepatitis B surface antigen (HBsAg) decline and biphasic viral kinetics. Clinical studies, animal models and in vitro studies suggest that both the innate and adaptive immune system responses contribute to high HBeAg seroconversion during telbivudine treatment through modulation of the function and/or expression of CD4+/CD8+ T cells, Th1/Th2, Treg, PD‐1/PD‐L1, Th17, IL‐21 and TFH. The results described in this review suggest that the antiviral effect of telbivudine may be attributable not only to direct suppression of hepatitis B virus, but also to immunoregulatory effects. Hypothetically, telbivudine shares some common signal pathways with IFN.
Rapid downregulation of programmed death‐1 and interferon‐γ‐inducible protein‐10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B
Authors: Hou F.‐Q. , Wu X.‐J. , Wang Y. , Chen J. , Liu Y.‐Z. , Ren Y.‐Y. , Song G. , Ding Y.‐P. , Yu M. , Wang G.‐Q. 
Published: January 2013

SummaryThe dynamics of programmed death‐1 (PD‐1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B (CHB) is unclear. This study was conducted in 29 treatment‐naïve patients undergoing telbivudine treatment for 52 weeks. The results showed that PD‐1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus (HBV) DNA levels (r = 0.621, P < 0.0001; r = 0.548, P = 0.002, respectively), and in virological responders, this decrease was directly correlated with a decrease in HBV DNA levels (r = 0.664, P = 0.002; r = 0.572, P = 0.01, respectively). Furthermore, at the end of 52 weeks, in virological responders, the decreased rate in the frequency of PD‐1+ CD8+ T cells was significantly higher than in non‐virological responders (58.3% vs 25.7%, P = 0.001), and at weeks 24 and 52, in virological responders, PD‐1 expression on CD4+ and CD8+ T cells was lower than in non‐virological responders (P = 0.01 and P = 0.035; P < 0.0001 and P < 0.0001, respectively). In 34 cytokines/chemokines detected in serum, IP‐10 expression was positively correlated with viral load, level of ALT and PD‐1 expression on CD8+ and CD4+ T cells at baseline (r = 0.36, P = 0.055, r = 0.635, P < 0.0001, r = 0.414, P = 0.026, and r = 0.402, P = 0.030, respectively). Moreover, the decrease in IP‐10 in serum directly correlated with a decrease in ALT levels (r = 0.751, P < 0.0001). At weeks 24 and 25, IP‐10 expression was significantly lower than baseline in virological responders (both P = 0.005); however, this was not observed in nonresponders. Based on the above findings, PD‐1 and IP‐10 may be used as predictors for virological response, and blockade of their pathway may improve the outcome of patients with CHB.
PD‐1/PDL1 and CD28/CD80 pathways modulate natural killer T cell function to inhibit hepatitis B virus replication
Authors: Wang X. F. , Lei Y. , Chen M. , Chen C. B. , Ren H. , Shi T. D. 
Published: January 2013

Summaryα‐Galactosylceramide (α‐GalCer)‐activated natural killer T (NKT) cells have antiviral properties against hepatitis B virus (HBV). However, α‐GalCer activation of NKT cells can induce anergy. We hypothesized that this effect may be overcome by a treatment strategy that includes manipulation of CD28/CD80 costimulatory and PD‐1/PDL1 coinhibitory signals of NKT cells, thereby enhancing the anti‐HBV effect of α‐GalCer. We established a transgenic mouse model of chronic HBV infection and investigated hepatic NKT cell frequencies, functions and expression of immunomodulatory factors. Our results showed that compared with uninfected control mice, hepatic NKT cells from HBV transgenic mice displayed lower frequencies (7.91% vs 16.74%, P < 0.05), impaired capabilities to produce interferon (IFN)‐γ (5.6% vs 1.4%, P < 0.05) and interleukin (IL)‐4 (6.8% vs 0.3%, P < 0.05), higher expression of PD‐1 (9.64% vs 6.36%, P < 0.05) and lower expression of CD28 (5.05% vs 28.88%, P < 0.05). However, when hepatic mononuclear cells (MNCs) were isolated from HBV transgenic mice, α‐GalCer exposure in culture remarkably upregulated both PD‐1+ NKT cells (P < 0.05) and CD28+ NKT cells (P < 0.05). Furthermore, when HBV transgenic mice were treated with combination therapies consisting of α‐GalCer and anti‐PDL1 monoclonal antibody (mAb) and/or anti‐CD80/anti‐CD28 mAbs, IFN‐γ+ NKT cell frequency was selectively increased (P < 0.05) and HBV replication was suppressed; these effects were accompanied by varying degrees and types of liver damage. Surprisingly, activating CD28/CD80 signal in HBV transgenic mice was more effective but caused less liver injury than blocking PD‐1/PDL1 signal in modulating αGalCer‐activated NKT cell function to inhibit HBV infection. Our findings also show that combined therapy with blocking PD‐1/PDL1 and activating CD28/CD80 signal in the presence of aGalCer cannot superimpose the effect of antivirus. α‐GalCer combination therapy that modulates the CD28/CD80 pathways of NKT cells may represent a promising approach to inhibit HBV replication in chronically infected patients.
Efficacy and safety of telbivudine plus adefovir dipivoxil combination therapy and entecavir monotherapy for HBeAg‐positive chronic hepatitis B patients with resistance to adefovir dipivoxil
Authors: Lu Jia‐Jie , Liu Kai , Ma Yuan‐Ji , Wang Juan , Chen En‐Qiang , Tang Hong 
Published: January 2013

SummaryThe objective of this study was to compare the efficacy and safety of two rescue strategies for hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with resistance to adefovir dipivoxil (ADV). This prospective study included 58 HBeAg‐positive CHB patients with resistance to ADV; 30 patients underwent telbivudine (LdT) plus ADV combination therapy and 28 patients switched to entecavir (ETV) monotherapy. After 48 weeks of treatment, the rates of hepatitis B virus (HBV) DNA <3 log10 copies/mL in the LdT plus ADV group and the ETV group were not significantly different (73.3% vs 57.1%, P = 0.195). Six patients receiving LdT plus ADV had HBeAg seroconversion, while none of the patients receiving ETV alone had HBeAg seroconversion (20% vs 0%, P = 0.039). During the 48‐week treatment period, two patients in the ETV monotherapy group had viral breakthrough and the strains were confirmed to be of a variant associated with ETV resistance (rtM204V+ rtL180M+ rtT184G), while one patient receiving LdT plus ADV had viral breakthrough and an LdT‐associated resistance mutation (rtM204I) was detected. For the majority of the patients, both LdT plus ADV combination treatment or ETV monotherapy were generally well tolerated, and no serious side effects were observed. Both LdT plus ADV combination therapy and ETV monotherapy led to significant decreases in serum HBV DNA in HBeAg‐positive CHB patients with resistance to ADV, and LdT plus ADV combination therapy exhibited a significantly higher rate of HBeAg seroconversion compared with ETV monotherapy.
Efficacy of telbivudine treatment for hepatitis B e antigen‐positive chronic hepatitis B patients with poor response to adefovir dipivoxil
Authors: Li Y. , Zhang Y. , Wang J.‐P. , Lian J.‐Q. , Bai X.‐F. 
Published: January 2013

SummaryTelbivudine (LdT) has demonstrated potent antiviral activity in nucleos(t)ide analogue (NA)‐naïve chronic hepatitis B patients (CHB), but data on its efficacy in NA‐experienced patients are limited. The aim of this study was to investigate the effect of LdT in hepatitis B e antigen‐positive CHB patients with poor response to initial adefovir dipivoxil (ADV). Forty‐two CHB patients with HBV DNA > 4 log10 copies/mL after 12 months of ADV monotherapy were enroled in the study and thereafter treated with LdT 600 mg daily for 18 months. Telbivudine led to a rapid decrease in viral load, and viral replication was persistently suppressed with a reduction of 2.26 log10 copies/mL 18 months after LdT treatment. The rates corresponding to virological and biochemical response at the end of observation were 97.6% (41/42) and 65.8% (25/38), respectively. HBeAg loss was found in 30.8% (12/39) of patients, while HBeAg/anti‐HBe seroconversion was found in 17.9% (7/39). Only one patient was detected to have LdT‐associated mutation, and no severe adverse events were reported. Optimization therapy with LdT monotherapy may be a good choice for CHB patients with poor response to ADV, and switching to LdT may be the most cost‐effective rescue therapeutic strategy for patients with poor response to initial ADV monotherapy.
Efficacy of sequential use of telbivudine in hepatitis B e antigen‐positive chronic hepatitis B patients with partial responses to pegylated interferon: a pilot study
Authors: Huang Z. , Zhao Z. , Zheng Y. , Peng L. , Lin C. , Deng H. , Gao Z. 
Published: January 2013

SummaryThe aim of this study was to investigate the efficacy of sequential use of telbivudine in hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients with partial responses to pegylated interferon. Patients with partial responses to 48 weeks of pegylated interferon treatment were divided into two groups. In group A, patients stopped pegylated interferon directly without sequential treatment. In group B, patients received sequential treatment with telbivudine 600 mg/day. HBeAg, HBeAb, hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) and creatine kinase levels were determined at baseline and at weeks 12, 24, 36 and 48. Responses and safety were assessed after 48 weeks of telbivudine treatment. Thirty‐six patients were recruited. Eighteen of these patients stopped pegylated interferon without sequential treatment (group A). After 48 weeks of follow‐up, five patients (28%) had undergone HBeAg seroconversion, nine patients (50%) had undetectable levels of HBV DNA, and 11 patients (61%) achieved normal alanine aminotransferase (ALT) levels. The other 18 patients received sequential telbivudine treatment (group B). After 48 weeks of treatment, 11 patients (61%) had undergone HBeAg seroconversion, and all patients had undetectable levels of HBV DNA and normal ALT levels. All patients tolerated sequential telbivudine treatment, and only slightly elevated creatine kinase levels were observed. Switching to telbivudine therapy was efficient and safe in HBeAg‐positive chronic hepatitis B patients with partial responses to 48 weeks of pegylated interferon. Sequential treatment with telbivudine resulted in an HBeAg seroconversion rate of 61% and an HBV DNA loss rate of 100% after 48 weeks. This promising strategy warrants further investigation.
Forty‐eight‐week retrospective study of telbivudine and lamivudine treatment in patients with hepatitis B‐related cirrhosis
Authors: Han Z. , Shi Y. , Zhu J. , Chen Y. , Yin F. , Xia L. , Luo G. , Gao Z. , Liu J. , Jia G. , Li C. , Zhou X. , Han Y. 
Published: January 2013

SummaryThe aim of this study was to evaluate the efficacy and safety of telbivudine 600 mg/day compared with lamivudine 100 mg/day for 48 weeks of treatment in patients with hepatitis B‐related cirrhosis. Data were reviewed retrospectively from 165 hepatitis B‐related cirrhotic patients (55 compensated patients and 110 decompensated) who received antiviral therapy with telbivudine or lamivudine. Serum alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA levels, hepatitis B e antigen (HBeAg) loss and seroconversion, histological improvement and various adverse events (AEs) were evaluated. Baseline characteristics were comparable. ALT levels declined but showed no significant difference in treatment with telbivudine or lamivudine (P > 0.05). Reduction in serum HBV DNA levels was evident by week 4 in compensated HBV‐related cirrhosis patients (telbivudine, 2.34 log10 copies/mL; lamivudine, 2.07 log10 copies/mL; P = 0.02) and persisted by week 8. Patients administrated with telbivudine had slightly greater HBeAg loss and seroconversion than patients with lamivudine, but the difference was not statistically significant (P > 0.05). Accumulative HBeAg loss was seen at week 48 (25.0% vs 25.0% and 13.3% vs 10.0% for telbivudine vs lamivudine in compensated and decompensated cirrhotic groups, respectively), as well as HBeAg seroconversion (15.0% vs 8.3% and 8.9% vs 6.7%). Mean Knodell Histologic Activity Index scores decreased in both compensated and decompensated cirrhotic patients (3.92 vs 3.64, 3.85 vs 3.73, for telbivudine vs lamivudine). Telbivudine and lamivudine were both well tolerated with minor AEs. The results of this study support telbivudine as an effective therapy for patients with both compensated and decompensated HBV‐related cirrhosis.
Safety of telbivudine treatment for chronic hepatitis B for the entire pregnancy
Authors: Liu M. , Cai H. , Yi W. 
Published: January 2013

SummaryOrally administered nucleus(t)ide analogues (NA) have brought about a simple, safe and effective therapeutic approach for chronic hepatitis B (CHB). However, treatment duration is long and some female patients become pregnant during treatment. In recent years, there have been gradually increasing reports on the safety of telbivudine (LdT) treatment for chronic hepatitis B virus (HBV) infection in the third trimester of pregnancy to block mother‐to‐infant transmission (MTIT) of HBV; however, the safety of LdT treatment for chronic HBV infection for the entire pregnancy has not been reported. The aim of the present study was to evaluate the safety of LdT treatment for chronic HBV infection for the entire pregnancy and provide a reference for HBV‐infected fertile women on how to block MTIT of HBV. Eighty‐six pregnant women who received LdT treatment either before or in early pregnancy were enrolled in the study. Adverse events were prospectively observed for the entire pregnancy and perinatal period, and short‐term and long‐term follow‐up of infants was conducted, monitoring the abnormalities of infants and blocking rate of MTIT with LdT treatment. Eighty‐six pregnant women treated with LdT had a total of 89 pregnancies: 6 (6.7%) had early embryonic death or spontaneous abortion, 1 (1.1%) had ectopic pregnancy and three had a second pregnancy after initial abortion. Fifty‐one mothers completed pregnancy: one had induction of labour at 24 weeks of pregnancy for cleft lip and palate of the foetus and 50 delivered 52 full‐term live infants. One infant had right ear accessories, and the total occurrence of congenital abnormality was 3.8%. Thirty‐nine infants were followed up for more than 6 months and completed all examinations for MTIT. None of the infants were HBsAg positive, resulting in a 100% success rate of blocking MTIT. All mothers maintained good liver function during the third trimester of pregnancy; 86% maintained complete virological response (HBV DNA <500 copies/mL) prior to delivery, and none developed progression of liver disease. Factors leading to increased adverse effects and drug resistance were not found. LdT treatment is safe and effective in chronic HBV‐infected pregnant mothers for the entire pregnancy.
Effects of Regional Labour Markets on Migration Flows, by Education Level
Authors: Carlsen Fredrik , Johansen Kåre , Stambøl Lasse Sigbjørn 
Published: January 2013

AbstractEuropean economies display large variations in unemployment rates across regions as well as between education groups. Insufficient labour mobility is widely believed to contribute to higher regional disparities and overall unemployment, but few studies have compared mobility responses of different education groups to regional shocks. This paper employs administrative registers covering the entire Norwegian population to compute annual time series from 1994 to 2004 of migration flows and regional labour market conditions by education level for 90 travel‐to‐work areas. We find that regional disparities in unemployment rates are decreasing in education level, whereas the response of migration flows to regional unemployment shocks is increasing in education level. The results suggest that low regional mobility of low‐educated workers may contribute to higher regional disparities and higher overall unemployment among the low educated.
Steal induction in preschool children: is melatonin as good as clonidine? A prospective, randomized study
Authors: Almenrader Nicole , Haiberger Roberta , Passariello Maurizio 
Published: January 2013

SummaryObjectives/AimsTo investigate whether melatonin would be an alternative drug to clonidine for performance of steal induction.BackgroundDistress during induction might have a negative impact on postoperative behavior. A steal induction is a technique for smooth anesthesia induction, and clonidine has been the primary agent for this purpose. There are conflicting results regarding the efficacy of melatonin for premedication, but its sleep inducing properties have been shown in children.MethodsPediatric patients ASA I and II were randomly assigned to receive either melatonin 0.3 mg·kg−1 or clonidine 4 μg·kg−1 orally. Primary outcome was the percentage of successful steal induction, while secondary outcomes were onset of sleep, overall quality of mask induction, and adverse events at emergence from anesthesia.ResultsA total of 87 patients were included for analysis with a median age of 33 months (range, 12–71) and median weight of 14 kg (range, 8–26). A successful steal induction was performed in 88.4% of group C and 75% of group M (P > 0.05). Onset of sleep in these patients occurred after a median time of 45 min (range 10–60) in group C and 35 min (range 15–60) in group M (P > 0.05). Children not falling asleep after melatonin received the premedication at a significantly earlier time point compared to those falling asleep (P = 0.001).ConclusionsMelatonin was effective for steal induction in 75% of children compared to 88% of children who had clonidine. Melatonin resulted less effective when administered early in the morning.
p16INK4a deficiency promotes DNA hyper‐replication and genetic instability in melanocytes
Authors: Fung Carina , Pupo Gulietta M. , Scolyer Richard A. , Kefford Richard F. , Rizos Helen 
Published: January 2013

SummaryActivated oncogenes restrict cell proliferation and transformation by triggering a DNA damage‐dependent senescence checkpoint in response to DNA hyper‐replication. Here, we show that loss of the p16INK4a cyclin‐dependent kinase inhibitor and melanoma tumour suppressor facilitates a DNA damage response after a hyper‐replicative phase in human melanocytes. Unlike cells expressing activated oncogenes, however, melanocytes depleted for p16INK4a display enhanced proliferation and an extended replicative lifespan in the presence of replication‐associated DNA damage. Analysis of human benign naevi confirmed that DNA damage and loss of p16INK4a expression co‐segregate closely. Thus, we propose that loss of p16INK4a facilitates tumourigenesis by promoting the proliferation of genetically unstable cells.
Endothelin‐1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet‐induced melanocyte homeostasis
Authors: Hyter Stephen , Coleman Daniel J. , Ganguli‐Indra Gitali , Merrill Gary F. , Ma Steven , Yanagisawa Masashi , Indra Arup K. 
Published: January 2013

SummaryKeratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here, we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV‐induced melanocyte homeostasis. Selective ablation of endothelin‐1 (EDN1) in murine epidermis (EDN1ep−/−) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN1 in a non‐cell autonomous manner controls melanocyte proliferation, migration, DNA damage, and apoptosis after ultraviolet B (UVB) irradiation. Expression of other keratinocyte‐derived paracrine factors did not compensate for the loss of EDN1. Topical treatment with EDN1 receptor (EDNRB) antagonist BQ788 abrogated UV‐induced melanocyte activation and recapitulated the phenotype seen in EDN1ep−/− mice. Altogether, the present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV‐induced melanocyte homeostasis in vivo.