bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodontitis and atherosclerosis: an observational study
Authors: Pinho M. Morado , Faria‐Almeida R. , Azevedo E. , Conceição Manso M. , Martins L.
Published: January 2013

Background

Poor oral health has been related with cardiovascular diseases. Specifically, periodontitis has been implicated in the pathogenesis of atherosclerosis. Our aim was to evaluate the relationship between the degree of carotid atherosclerosis and severity of periodontitis in a patient cohort.

Methods

Fifty adult patients receiving carotid duplex scans in a cerebral hemodynamics lab were included in the study. Ultrasound protocol included measurement of carotid intima–media thickness (IMT), which is a marker of atherosclerosis, and characterization of any atherosclerotic plaques in the cervical common and internal carotid arteries. Patients were divided into two main groups: the test group had IMT ≥ 1 mm or the presence of any carotid atherosclerotic plaque, and the control group had IMT < 1 mm and absence of atherosclerotic plaques. Periodontal evaluation was performed in all the teeth and characterized according to the clinical attachment level, which between 1 mm and 2 mm was classified as slight, 3 mm and 4 mm as moderate and ≥5 mm as severe.

Results

The control group included 15 (30%), while the test group included 35 (70%) subjects. The most common diagnosis was severe periodontitis (40%); moderate and slight periodontitis were also frequent occurrences (32% and 28%, respectively). In the control group, 53.3% had slight, 33.3% had moderate and 13.3% had severe periodontitis. In the test group, those percentages were respectively 22.2%, 44.4% and 33.3%. Patients with atheroma plaque had the highest percentage of severe periodontitis (70.6%). More severe periodontitis was related to atherosclerosis (P = 0.007).

Conclusion

This study showed an association between periodontitis severity and carotid atherosclerosis, suggesting that periodontal disease might be a risk indicator for atherosclerotic disease.
Gingival crevicular fluid levels of human beta‐defensins 1 and 3 in subjects with periodontitis and/or type 2 diabetes mellitus: a cross‐sectional study
Authors: Ertugrul A. S. , Dikilitas A. , Sahin H. , Alpaslan N. , Bozoglan A. , Tekin Y.
Published: January 2013

Background and Objective

Human β‐defensins (hBDs) have a strong antibacterial action against various microorganisms, especially periodontal pathogens. The aim of this study was to compare the total levels of hBD‐1 and hBD‐3 in the gingival crevicular fluid of healthy patients with gingivitis (HG), healthy patients with chronic periodontitis (HP), patients with type 2 diabetes mellitus (DM) and gingivitis (DM2G) and patients with type 2 DM and chronic periodontitis (DM2P).

Material and Methods

A total of 80 patients were included: 20 HG, 20 HP, 20 DM2G and 20 DM2P. The levels of hBD‐1 and hBD‐3 in gingival crevicular fluid were measured using ELISA.

Results

The DM2P group had significantly higher periodontal clinical parameters at sites from which gingival crevicular fluid was collected compared with the other groups. The HG group had significantly lower periodontal clinical parameters within the gingival crevicular fluid‐collected sites than did the HP, DM2G and DM2P groups. The gingival crevicular fluid of the DM2P group had significantly higher levels of total hBD‐1 and hBD‐3 than did that of the other groups; the hBD‐1 and hBD‐3 levels were significantly higher in the gingival crevicular fluid of the DM2G group than in that of the the non‐DM type 2 groups (HG and HP). The gingival crevicular fluid of the HP group had significantly higher levels of total hBD‐1 and hBD‐3 in comparison with that of the HG group.

Conclusion

As a result of the observed vascular and cell activity changes that occur within patients diagnosed with DM, periodontal diseases become more severe. These changes hinder the migration and the ability of chemotactic factors and leukocytes to protect periodontal tissues from the effects of microorganisms. In order to eliminate microorganisms, the epithelial cells in patients with DM may release more hBD‐1 and hBD‐3 into the gingival crevicular fluid. Determining the amount of hBD‐1 and hBD‐3 in the gingival crevicular fluid of patients with and without DM will help to elucidate the relationship among hBD‐1, hBD‐3, DM and periodontal disease.
Inhibitory effect of Zingiber cassumunar extracts on lipopolysaccharide‐induced cyclooxygenase‐2 and matrix metalloproteinase expression in human gingival fibroblasts
Authors: Koontongkaew S. , Meesuk L. , Aupaphong V. , Ayudhaya T. Dechatiwongse Na , Poachanukoon O.
Published: January 2013

Background and Objective

Lipopolysaccharides (LPS) induce the production of proinflammatory mediators such as prostaglandins and matrix metalloproteinases (MMPs) in human gingival fibroblasts (HGFs). Zingiber cassumunar is a medicinal plant that possesses anti‐inflammatory properties. The aim of this study was to determine the effects of the Z. cassumunar extract on the expression of cyclooxygenase (COX)‐1, COX‐2 and MMP‐2 in HGFs challenged with LPS.

Material and Methods

HGFs were treated with LPS in the presence or absence of Z. cassumunar extracts. The levels of expression of COX‐1, COX‐2 and MMP‐2 mRNAs and of COX‐1, COX‐2 and MMP‐2 proteins were detected by reverse transcription–polymerase chain reaction and western blotting, respectively. MMP‐2 activities in cell‐culture supernatants were determined using gelatin zymography. MAPK activation was evaluated by western blotting.

Results

LPS treatment of HGFs resulted in the activation of ERK1/2, p38 and JNK. Z. cassumunar extracts significantly inhibited the phosphorylation of ERK1/2 and JNK in HGFs stimulated with LPS. A lesser inhibitory effect was observed for the phosphorylation of p38. RT‐PCR and western blot analyses showed that Z. cassumunar extracts inhibited the LPS‐induced expression of COX‐2 mRNA and COX‐2 protein, respectively, but not of COX‐1 mRNA or COX‐1 protein. Pretreatment of HGFs with Z. cassumunar also attenuated the induction of MMP‐2 with LPS.

Conclusion

Our results indicate that Z. cassumunar extracts inhibit COX‐2 and MMP‐2 production by LPS‐activated human gingival fibroblasts through blocking the proinflammatory signaling pathway involving ERK1/2, JNK and p38.
Validation of a quantitative real‐time PCR assay and comparison with fluorescence microscopy and selective agar plate counting for species‐specific quantification of an in vitro subgingival biofilm model
Authors: Ammann T. W. , Bostanci N. , Belibasakis G. N. , Thurnheer T.
Published: January 2013

Background and Objective

Subgingival biofilms are the prime etiological factor of periodontal disease. Owing to their complex polymicrobial nature, quantification of individual bacterial species within the biofilm for research and diagnostic purposes can be methodologically challenging. The aims of this study were to establish a quantitative real‐time PCR (qPCR) assay to quantify the bacteria used in our 10‐species in vitro ‘subgingival’ biofilm model and to compare the quantitative outcome with fluorescence microscopy and colony‐forming unit (CFU) counts on selective agar plates.

Material and Methods

The 10 species included in the in vitro biofilm were Streptococcus oralis, Streptococcus anginosus, Veillonella dispar, Fusobacterium nucleatum, Treponema denticola, Tannerella forsythia, Actinomyces oris, Campylobacter rectus, Porphyromonas gingivalis and Prevotella intermedia. The numbers of each species were quantified at two time points using qPCR, microscopy counting following fluorescence in‐situ hybridization (FISH) or immunofluorescence staining, and counting of CFUs after growth on selective agar plates.

Results

All 10 species were successfully quantified using qPCR and FISH or immunofluorescence, and the eight species culturable on selective agar plates were also quantified by counting the numbers of CFUs after growth on selective agar. In early biofilm cultures, all methods showed a significant correlation, although the absolute numbers differed between methods. In late biofilm cultures, measurements obtained using qPCR and FISH or immunofluorescence, but not by CFU counts, maintained significant correlation. CFU counts yielded lower values than did measurements made using the other two methods.

Conclusion

Quantitative PCR and epifluorescence microscopy can be easily combined with each other to determine species‐specific bacterial numbers within biofilms. However, conventional bacterial cultures cannot be as efficiently combined using these molecular detection methods. This may be crucial in designing and selecting appropriate clinical diagnostic methods for subgingival biofilm samples.
Effects of local simvastatin–alendronate conjugate in preventing periodontitis bone loss
Authors: Price U. , Le H. ‐O. T. , Powell S. E. , Schmid M. J. , Marx D. B. , Zhang Y. , Wang D. , Narayana N. , Reinhardt R. A.
Published: January 2013

Background and Objective

Local host‐modulation therapy is an emerging approach to prevent disease progression in sites with moderate periodontitis. The combination of simvastatin and alendronate would be an intriguing host‐modulatory strategy because of the bone‐anabolic properties of simvastatin and the antiresorptive/bone‐targeting characteristics of alendronate. The objective of this study was to evaluate the effects of local administration of a simvastatin–alendronate–β‐cyclodextrin (SIM–ALN–CD) conjugate for preventing experimental periodontitis bone loss.

Material and Methods

Twenty‐four mature female Sprague–Dawley rats were treated with three, 12 μL injections, administered one week apart, bilaterally into the palatal/interproximal gingiva. The injections contained: (i) a conjugate of 0.5 mg ofSIMand 3.75 mg ofALN–CDin H2O; (ii) H2O alone; or (iii) no treatment. One week later, the same sites were subjected to induction of experimental periodontitis by three injections (i.e. one injection administered every other day for five d) of 0.01 mg ofEscherichia coliendotoxin [lipopolysaccharide (LPS)] in phosphate‐buffered saline (PBS) orPBSalone. After an additional week, the rats were killed, the palates were harvested and interproximal bone volume and adjacent thickness were calculated using microcomputed tomography. Subsequently, specimens were decalcified, and interproximal histologic sections were stained with hematoxylin and eosin for evaluation of alveolar crest osteoclasts and surrounding inflammation. Values were compared among treatment groups using analysis of variance and the Kruskal–Wallis test.

Results

Interproximal bone volume was reduced byLPSinjections (p ≤ 0.04), yet when experimental periodontitis was preceded by treatment withSIM–ALN–CD, more bone was preserved than after treatment with carrier alone (p = 0.007). WhileLPScaused a significant loss in bone thickness over the palatal roots (p ≤ 0.04), the injection protocol (PBS) also caused a significant loss of palatal bone thickness (p ≤ 0.03). However, prophylacticSIM–ALN–CDinjections resulted in no further loss of bone thickness during experimental periodontitis.LPSinjections gave histologic evidence of increased osteoclasts and subsulcular inflammation, both of which were reduced when preceded by treatment withSIM–ALN–CD(p ≤ 0.0002).

Conclusion

The primary conclusion of this study was that locally appliedSIM–ALN–CDhas the potential to prevent episodes of periodontitis bone loss.
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 Objective

Aggregatibacter 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 Methods

Trypticase 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.

Results

Both 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.

Conclusion

Dentaid‐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

Telbivudine, 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

Chronic 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

The 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

α‐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

The 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

Telbivudine (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

The 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

The 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

Orally 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

European 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

Objectives/Aims

To investigate whether melatonin would be an alternative drug to clonidine for performance of steal induction.

Background

Distress 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.

Methods

Pediatric 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.

Results

A 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).

Conclusions

Melatonin 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

Activated 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

Keratinocytes 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.
Therapeutic indicators of acute encephalopathy in patients with complex febrile seizures
Authors: Nagase Hiroaki , Nakagawa Taku , Aoki Kazunori , Fujita Kyoko , Saji Yohsuke , Maruyama Azusa , Uetani Yoshiyuki
Published: January 2013

Background

The aim of this study was to identify predictors of neurologic damage in children with febrile seizures or altered consciousness within 6 h of seizure onset.

Methods

The present study included 86 children (age range, 4–159 months old), who fulfilled the diagnostic criteria for complex febrile seizures on admission between October 2002 and November 2008. Using the Pediatric Cerebral Performance Category Scale (PCPC), the children were classified into two groups: poor outcome (PCPC = 2–6) and good outcome (PCPC = 1). Clinical profiles and laboratory findings were compared between the groups.

Results

Of the 86 children, 17 fell into the poor outcome and 69 into the good outcome group. Using univariate analysis, three early risk factors for poor outcome were identified: (i) consciousness disturbance or hemiplegia at 6 h from onset; (ii) refractory status epilepticus; and (iii) elevation of aspartate aminotransferase to >90 IU/L within 6 h of onset. Using these criteria, children in the poor outcome group were identified with a 94% sensitivity and 67% specificity rate (odds ratio, 36.6; 95% confidence interval: 4.87–1560). During the study period, the inpatients who met the criteria for acute encephalopathy also fell into the poor outcome group.

Conclusions

The development of neurologic damage in children with complex febrile seizures can be predicted within 6 h of onset, using the identified risk factors. The authors propose an assumption of severe febrile seizures (SFS) in children who fulfill these risk factors. Using SFS as an inclusion criterion, an interventional study for acute encephalopathy can be designed.
Relational coping during deployment: Managing communication and connection in relationships
Authors: ROSSETTO KELLY R.
Published: January 2013

Wartime deployment involves prolonged separation and creates uncertainty, fear, and disorganization in families (M. J. Peebles‐Kleiger & J. H. Kleiger, 1994). This study examined how military wives/fiancées reported coping with the demands they associated with spousal deployment. Twenty‐six in‐depth interviews were conducted with wives and fiancées whose partners were currently deployed. Through qualitative analysis, 2 main coping themes emerged: (a) maintaining a mediated interpersonal connection and (b) choosing open versus restricted communication. Further analyses revealed that the former theme promoted 2 relationship functions (e.g., intimacy and positivity, confronting realities and fears) and the latter 4 functions (e.g., closeness, smooth reunion, outlet, and protection). On the basis of these coping strategies and functions, a conceptual framework for understanding relational coping communication patterns is proposed. Themes, practical applications, and theoretical implications are discussed.
Assessing relationship quality across cultures: An examination of measurement equivalence
Authors: GERE JUDITH , MACDONALD GEOFF
Published: January 2013

Researchers are increasingly studying close relationships across cultural contexts. One issue that arises when applying scales originally developed in Western countries to a different cultural context is measurement invariance. Researchers often do not examine whether scales show invariance across cultures and thus can be used with confidence. The goal of this article is to discuss the importance of measurement invariance, to discuss what testing invariance involves, and to test the measurement properties of scales of relationship satisfaction, commitment, intimacy, and trust across 4 samples (United States, Canada, Indonesia, and China). Analyses indicated that weak measurement invariance was met for all 4 scales, and assumptions of strong measurement invariance had to be relaxed for only a few items in each scale. Findings are discussed and recommendations are made regarding using these or other scales that have been shown to meet assumptions of invariance across different cultural groups.
Predicting change in relationship insecurity: The roles of compassionate and self‐image goals
Authors: CANEVELLO AMY , GRANILLO M. TERESA , CROCKER JENNIFER
Published: January 2013

It was hypothesized that self‐image goals to construct, defend, and maintain desired images of the self enhance relationship insecurity, whereas compassionate goals to support others diminish relationship insecurity. Study 1 followed 115 new college roommates for 3 weeks; Study 2 followed 230 new college roommates across a semester. Both studies assessed self‐image and compassionate goals for and anxiety and avoidance in the roommate relationship. Self‐image goals predicted increased relationship anxiety and avoidance across 3 weeks (Study 1) and within weeks, from week to week, and across 3 months (Study 2). Compassionate goals consistently predicted decreased relationship anxiety and avoidance across studies and analyses. These results suggest that through their interpersonal goals, people contribute directly to their own relationship insecurity.
Impact of grass filter strips length on exported dissolved masses of metolachlor, atrazine and deethylatrazine: a four‐season study under natural rain conditions
Authors: Lafrance P. , Caron E. , Bernard C.
Published: January 2013

Herbicides atrazine and metolachlor have been detected in water bodies across the world. The objective of this study was to assess the efficiency of 0‐m, 3‐m, 6‐m and 9‐m grass filter strips to reduce masses of dissolved metolachlor, atrazine and deethylatrazine (a degradation product of atrazine) exported in runoff. For that purpose, 16 uncultivated plots (3‐m wide × 65‐m long) with 0‐m‐, 3‐m‐, 6‐m‐ and 9‐m‐long grass filter strips were setup in a completely randomized block design. During four seasons, masses of dissolved atrazine, metolachlor and deethylatrazine were determined for the first four to five rain events, under natural rain conditions, after atrazine and metolachlor application. Generally, grass filter strips reduced exported herbicide masses by more than 90% and influenced atrazine and metolachlor dissipation kinetics in the field. The 3‐m grass filter strip (area ratio source/strip of 22:1) usually provided a reduction in exported herbicide masses similar to the 6‐ or 9‐m grass filter strips. Therefore, under the present experimental soil and climate conditions, a grass filter strip of 3 m would be a good compromise between environmental protection of surface waters against atrazine and metolachlor contamination and conservation of agricultural land use. Such an approach contributes to the acceptability by producers to implement optimized best management practices such as vegetated filter strips for the preservation of the quality of water resources.
Spatial variability and change in soil organic carbon stocks in response to recovery following land abandonment and erosion in mountainous drylands
Authors: De Baets S. , Meersmans J. , Vanacker V. , Quine T. A. , Van Oost K.
Published: January 2013

This research investigates the impact of human activities on carbon (C) dynamics in a mountainous and semi‐arid environment. Despite the low C status of drylands, soil organic carbon (SOC) is the largest C pool in these systems and therefore may offer significant C sequestration potential in systems recovering from degradation. Nevertheless, quantification of this potential is limited by lack of knowledge concerning the magnitude of and controls on regional SOC stocks. Therefore, this study aimed to (i) investigate the variability of soil organic carbon in relation to recovery period and key soil and topographical variables, and (ii) quantify the effects of recovery period following abandonment on SOC stocks. Soil profiles were sampled in the Sierra de los Filabres (southeast Spain) in different land units along geomorphic and degradation gradients. SOC contents were modelled using recovery period and soil and topographical variables. Sample depth, topographic position, altitude, recovery period and stone content were identified as the main factors for predicting SOC concentrations. SOC stocks in 1 m depth of soil varied between 3.16 and 76.44 t/ha. Recovery period (years since abandonment), topographic position and altitude were used to predict and map SOC stocks in the top 0.2 m. The results show that C accumulates rapidly during the first 10–50 yr following abandonment; thereafter, the stocks evolve towards a steady‐state level. The erosion zones in the study area demonstrate greater potential to increase their SOC stocks when abandoned. Deposition zones have greater SOC values, although their C accumulation rate is lower compared with erosional landscapes in the first 10–50 yr following abandonment. Therefore, full understanding of the C sequestration potential of land use change in areas of complex topography requires knowledge of spatial variability in soil properties and in particular SOC.
Integrating socio‐economic and biophysical assessments using a land use allocation model
Authors: Du Y. , Huffman T. , Toure S. , Feng F. , Gameda S. , Green M. , Liu T. , Shi X.
Published: January 2013

This work is devoted to bridging the gap between large‐area, economically driven macromodels such as the Canadian Regional Agriculture Model (CRAM) and small‐area biophysically based process models used in environmental assessments through the development of a Land Use Allocation Model (LUAM). LUAM is designed to enable environmental assessments of economic scenarios to be conducted by allocating crop area changes predicted for large areas by CRAM to much smaller Soil Landscapes of Canada (SLC) polygons through an optimization method based on land capability, relative crop productivity and current land use. To develop the procedures, we used linear programming to optimize crop production for large areas under current commodity prices and land productivity ratings and then allocated the results to much smaller soil‐landscape polygons based on land capability. To assess the validity of our prototype LUAM, we compared the predicted crop areas with actual crop data from the Census of Agriculture using the method of cumulative residuals (MCR). We concluded that this version of the LUAM model can predict the location of land use to some extent, but requires further refinement. The potential for further development of LUAM using the Land Suitability Rating System (LSRS) is discussed.
The occurrence of inland acid sulphate soils in the floodplain wetlands of the Murray–Darling Basin, Australia, identified using a simplified incubation method
Authors: Creeper N. , Fitzpatrick R. , Shand P.
Published: January 2013

From 2006 to 2010, low water levels resulted in the drying of previously submerged inland acid sulphate soils (IASS) in wetlands of the Murray–Darling Basin (MDB). The potential for widespread severe acidification resulting from the oxidation of pyrite in these wetland soils triggered a basin‐wide study to assess the occurrence and risks posed by IASS material in the floodplain wetlands of the MDB. The results of pH measurements before and following soil incubation from more than 7200 samples (representing ca. 2500 profiles from 1055 georeferenced wetlands) were used to assess the potential occurrence of sulphuric and sulphidic material in IASS across the MDB. Their occurrence was investigated on a regional basis by dividing the MDB into 13 geographical regions whose boundaries roughly follow hydrological catchment boundaries. A total of 238 floodplain wetlands, representing 23% of the total wetlands assessed, were found to contain soils that became ultra‐acidic (pH < 4) when oxidized and therefore present a severe acidification hazard. These soils, the majority of which are likely to be IASS materials, were found in 11 of the 13 geographical regions. Among the 11 geographical regions likely containing IASS materials, the proportion of wetlands that presented an acidification hazard varied between 2 and 52% of those assessed. The geographical regions found to present the greatest acidification hazard were in the southern MDB, downstream of the Murray–Darling confluence, and in catchments on the southern side of the Murray River channel in Victoria. This study provided policy makers with a valuable screening tool, which helped them to identify priority wetlands and regions that required more detailed IASS investigations.
A novel HLA‐B allele, B*13:18, identified by sequence‐based typing
Authors: Liu N. , Zhang Z. , Shan X. , Cui S. , Zhao B.
Published: January 2013

The B*13:18 allele differs from the most closely matching allele B*13:02:01 by one nucleotide substitution in exon 3, at position 539.