Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hep...Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load （HBV-DNA） plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory （interferons） and antiviral suppressants （nucleoside and nucleotide analogues） all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion： chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determi展开更多
In interdigitated back contact(IBC)solar cells,the metal-electrode coverage on a p-type emitter is optimized by a PC2D simulation.The result shows that the variation of the metal coverage ratio(MCR)will affect both th...In interdigitated back contact(IBC)solar cells,the metal-electrode coverage on a p-type emitter is optimized by a PC2D simulation.The result shows that the variation of the metal coverage ratio(MCR)will affect both the surface passivation and the electrode-contact properties for the p-type emitter in IBC solar cells.We find that when R_(c) ranges from 0.08 to 0.16Ω·cm^(2),the MCR is optimized with a value of 25%and 33%,resulting in a highest energy-conversion efficiency.The dependences of both Voc and fill factor on MCR are simulated in order to explore the mechanism of the IBC solar cells.展开更多
Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sust...Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. Methods 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 μg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 μg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 μg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. Findings 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). Interpretation Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.展开更多
1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to ...1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).展开更多
BACKGROUND The use of uncemented cups during total hip arthroplasty(THA)has gained popularity in recent years.The Robert Mathys(RM)pressfit cup,an uncemented monoblock implant is expected to preserve bone density due ...BACKGROUND The use of uncemented cups during total hip arthroplasty(THA)has gained popularity in recent years.The Robert Mathys(RM)pressfit cup,an uncemented monoblock implant is expected to preserve bone density due to its composition and external surface,while reducing backside wear with its monoblock construction.These factors should lead to a high survival rate of the implant.AIM To evaluate the mid-term survival and functional outcome of the RM Pressfit cup in a large study population.METHODS Between 2011 and 2020,we included 1324 patients receiving a primary THA using the RM pressfit cup.Final clinical follow-up was performed at 2 years postoperatively with the Dutch arthroplasty register used to assess implant status thereafter.Revision for acetabular failure and reason for revision were reported to evaluate implant survival,while the hip disability and osteoarthritis outcome score(HOOS)scores were used to assess functional outcome.RESULTS The mean age at surgery was 64.9 years.The mean follow-up was 4.6 years.Of the 1324 THAs performed,13 needed cup revisions within 5 years after index THA:5 due to aseptic loosening,6 due to infection,2 due to dislocation and 2 due to other causes.This resulted in a 5-year cup survival of 98.8%(95%CI:98.1-99.5).Nine of the cup revisions occurred within the first year after index THA.HOOS scores increased significantly in all domains during the first year and levelled out during the second year.CONCLUSION In the present study,the RM pressfit cup demonstrated excellent clinical outcomes at mid-term follow-up;however,future studies are needed to assess the long-term outcomes of this acetabular implant.展开更多
In a recent manuscript in Cell,a first-in-class small molecule inhibitor of the kinase MKK4(mitogen-activated protein kinase kinase 4)was described that greatly enhances liver regeneration after partial hepatectomy in...In a recent manuscript in Cell,a first-in-class small molecule inhibitor of the kinase MKK4(mitogen-activated protein kinase kinase 4)was described that greatly enhances liver regeneration after partial hepatectomy in animal models,with an excellent safety profile in humans.1 The findings of Zwirner et al.hold promise to alter the clinical management of liver failure in critically ill patients.展开更多
BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to...BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year f展开更多
Hepatitis C virus （HCV） infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antivi...Hepatitis C virus （HCV） infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, antisense oligonucleotides （ASO）, or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA （miR-222） in viral replication and discuss its potential for HCV molecular therapy.展开更多
Despite the increase in the number of blockchain-based Decentralized Autonomous Organizations(DAOs),there is no consensus on what constitutes a DAO.This paper provides an in-depth study of DAOs by analyzing their defi...Despite the increase in the number of blockchain-based Decentralized Autonomous Organizations(DAOs),there is no consensus on what constitutes a DAO.This paper provides an in-depth study of DAOs by analyzing their definitions,characteristics,and emerging developments.Existing definitions in the literature hardly recognize common functionalities and intermingle coded DAOs,DAO deployment platforms,and blockchain DAOs.We developed a comprehensive DAO definition by reviewing the literature and empirically analyzing 1,859 DAOs.The findings show that many DAOs were inactive and that a threshold of 20 tokenholders is a tipping point for DAOs to survive over time and maintain sustained levels of activity.Finally,based on an empirical analysis of 9,845 perceived DAOs,we identified the emerging development of off-chain voting.This emerging development challenges the autonomous nature of DAOs.We recommend further research to investigate the effect of governance structures on their long-term sustainability and viability for both on-chain and off-chain DAOs.展开更多
AIM To systematically search literature and determine a preferable surgical procedure in patients with failed conservative treatment of calcifying tendinitis of the shoulder.METHODS The electronic online databases MED...AIM To systematically search literature and determine a preferable surgical procedure in patients with failed conservative treatment of calcifying tendinitis of the shoulder.METHODS The electronic online databases MEDLINE(through PubMed), EMBASE(through OVID), CINAHL(through EBSCO), Web of Science and Cochrane Central Register of Controlled Trials were systematically searched in May 2016. Eligible for inclusion were all available studies with level Ⅱ and level Ⅲ evidence(LoE). Data was assessed and extracted by two independent review authors using a specifically for this study designed data extraction form.RESULTS Six studies(294 surgically treated shoulders) were included in this review. No significant differences between the three available treatment options(acromioplasty with the removal of the calcific deposits, acromioplasty or solely the removal of the calcific deposits) were detected regarding the functional and clinical outcome. The followup ranged from 12 mo to 5 years. Complication rates were low. No reoperations were necessary and the only reported complication was adhesive capsulitis, which in all cases could be treated conservatively with full recovery. CONCLUSION We found that all three available treatment options show good functional and clinical outcomes in the short and midterm. However, a favorable procedure is difficult to determine due to the lack of high-quality comparing studies.展开更多
Forest biodiversity studies conducted across Europe use a multitude of forestry terms,often inconsistently.This hinders the comparability across studies and makes the assessment of the impacts of forest management on ...Forest biodiversity studies conducted across Europe use a multitude of forestry terms,often inconsistently.This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent.Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts.This work aims to establish common standards for silvicultural and vegetation definitions,creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity.We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies.While quantitative data on forest biomass and dominant tree species are frequently included,information on silvicultural activities and vegetation composition is often lacking,shallow,or based on broad and heterogeneous classifications.We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process,and ultimately propose a common framework.This will enhance the comparability of forest biodiversity studies in Europe,and puts the basis for effective implementation and monitoring of sustainable forest management policies.The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.展开更多
Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tre...Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.展开更多
Liposomes effectively transport fatty proteins to targeted tissues. Laboratory experiments use multiple methods to administer liposomes, but comparison of these methods is not available. In this retrospective study, w...Liposomes effectively transport fatty proteins to targeted tissues. Laboratory experiments use multiple methods to administer liposomes, but comparison of these methods is not available. In this retrospective study, we characterized and compared four intravenous administration routes (tail vein, jugular catheter, femoral vein and percutaneous retro-orbital injections) in murine models. ApoE<sup>-/-</sup> mice were used to compare administration routes. Results indicate that the jugular catheter route delivered the highest amount of liposomes to tissues due to longer period of injections compared to other routes;however, this route failed to remain patent for 8/10 animals. Delivery via tail vein, femoral vein and percutaneous retro-orbital injections resulted in similar accumulation in the organs. When including technical difficulty and expense, percutaneous retro-orbital injections of liposomes are the most convenient and efficacious approach.展开更多
An alternative cationic polymerization method is developed to produce high molecular weight polyisobutylene (HM-PIB) with molecular weights above 5×10^5g/mol. The method involves micelle formation via functionali...An alternative cationic polymerization method is developed to produce high molecular weight polyisobutylene (HM-PIB) with molecular weights above 5×10^5g/mol. The method involves micelle formation via functionalized low molecular weight polyisobutylene (LM-PIB) in non-polar solvent. One end of LM-PIB is modified with an imidazolium-containing ionic group, which together with the anion (eg. Al2Cl7) works as Lewis acid. While the monomer isobutylene dissolves readily in non-polar solvent, polymerization can occur only within the micelle, which affords stable HM-PIB particles. HM-PIB with a molecular weight (MW) close to 1 × 10^6 g/mol was produced successfully with the described method.展开更多
Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes.Polymethylmethacrylate(PMMA)cement is the most commonly used bone substitute in...Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes.Polymethylmethacrylate(PMMA)cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability.However,the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors.Here,we introduce porosity into PMMA cement by adding carboxymethylcellulose(CMC)to facilitate such local delivery of chemotherapeutic drugs,while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites.Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content.Upon incorporation of≥3%CMC,the PMMA-based cements released up to 18%of the loaded cisplatin,in contrast to cements containing lower amounts of CMC which only released less than 2%of the cisplatin over 28 days.This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3%at day 7,which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements.Additionally,tibias filled with PMMA-based cements containing up to 3%of CMC exhibit comparable compressive strengths as compared to intact tibias.In conclusion,we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels.As such,these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.展开更多
Background Disturbed circadian rhythm is a potential cause of delirium and is linked to disorganisation of the circadian rhythmicity. Dynamic light （DL） could reset the circadian rhythm by activation of the suprachi...Background Disturbed circadian rhythm is a potential cause of delirium and is linked to disorganisation of the circadian rhythmicity. Dynamic light （DL） could reset the circadian rhythm by activation of the suprachiasmatic nucleus to prevent delirium. Evidence regarding the effects of light therapy is predominantly focused on psychiatric disorders and circadian rhythm sleep disorders. In this study, we investi- gated the effect of DL on the total hospital length of stay （LOS） and occurrence of delirium in patients admitted to the Coronary Care Unit （CCU）. Methods This was a retrospective cohort study. Patients older than 18 years, who were hospitalized longer than 12 h at the CCU and had a total hospital LOS for at least 24 h, were included. Patients were assigned to a room with DL （n = 369） or regular lighting condi- tions （n = 379）. DL was administered at the CCU by two ceiling-mounted light panels delivering light with a colour temperature between 2700 and 6500 degrees Kelvin. Reported outcome data were： total hospital LOS, delirium incidence, consultation of a geriatrician and the amount of prescripted antipsychotics. Results Between May 2015 and May 2016, data from 748 patients were collected. Baseline charac- teristics, including risk factors provoking delirium, were equal in both groups. Median total hospital LOS in the DL group was 100.5 （70.8-186.0） and 101.0 （73.0-176.4） h in the control group （P = 0.935）. The incidence of delirium in the DL and control group was 5.4% （20/369） and 5.0% （19/379）, respectively （P = 0.802）. No significant differences between the DL and control group were observed in secon- dary endpoints. Subgroup analysis based on age and CCU LOS also showed no differences. Conclusion Our study suggests exposure to DL as an early single approach does not result in a reduction of total hospital LOS or reduced incidence of delirium. When delirium was diagnosed, it was associated with poor hospital outcome.展开更多
文摘Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load （HBV-DNA） plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory （interferons） and antiviral suppressants （nucleoside and nucleotide analogues） all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion： chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determi
文摘In interdigitated back contact(IBC)solar cells,the metal-electrode coverage on a p-type emitter is optimized by a PC2D simulation.The result shows that the variation of the metal coverage ratio(MCR)will affect both the surface passivation and the electrode-contact properties for the p-type emitter in IBC solar cells.We find that when R_(c) ranges from 0.08 to 0.16Ω·cm^(2),the MCR is optimized with a value of 25%and 33%,resulting in a highest energy-conversion efficiency.The dependences of both Voc and fill factor on MCR are simulated in order to explore the mechanism of the IBC solar cells.
文摘Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. Methods 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 μg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 μg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 μg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. Findings 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). Interpretation Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
文摘1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).
文摘BACKGROUND The use of uncemented cups during total hip arthroplasty(THA)has gained popularity in recent years.The Robert Mathys(RM)pressfit cup,an uncemented monoblock implant is expected to preserve bone density due to its composition and external surface,while reducing backside wear with its monoblock construction.These factors should lead to a high survival rate of the implant.AIM To evaluate the mid-term survival and functional outcome of the RM Pressfit cup in a large study population.METHODS Between 2011 and 2020,we included 1324 patients receiving a primary THA using the RM pressfit cup.Final clinical follow-up was performed at 2 years postoperatively with the Dutch arthroplasty register used to assess implant status thereafter.Revision for acetabular failure and reason for revision were reported to evaluate implant survival,while the hip disability and osteoarthritis outcome score(HOOS)scores were used to assess functional outcome.RESULTS The mean age at surgery was 64.9 years.The mean follow-up was 4.6 years.Of the 1324 THAs performed,13 needed cup revisions within 5 years after index THA:5 due to aseptic loosening,6 due to infection,2 due to dislocation and 2 due to other causes.This resulted in a 5-year cup survival of 98.8%(95%CI:98.1-99.5).Nine of the cup revisions occurred within the first year after index THA.HOOS scores increased significantly in all domains during the first year and levelled out during the second year.CONCLUSION In the present study,the RM pressfit cup demonstrated excellent clinical outcomes at mid-term follow-up;however,future studies are needed to assess the long-term outcomes of this acetabular implant.
文摘In a recent manuscript in Cell,a first-in-class small molecule inhibitor of the kinase MKK4(mitogen-activated protein kinase kinase 4)was described that greatly enhances liver regeneration after partial hepatectomy in animal models,with an excellent safety profile in humans.1 The findings of Zwirner et al.hold promise to alter the clinical management of liver failure in critically ill patients.
文摘BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year f
文摘Hepatitis C virus （HCV） infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, antisense oligonucleotides （ASO）, or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA （miR-222） in viral replication and discuss its potential for HCV molecular therapy.
文摘Despite the increase in the number of blockchain-based Decentralized Autonomous Organizations(DAOs),there is no consensus on what constitutes a DAO.This paper provides an in-depth study of DAOs by analyzing their definitions,characteristics,and emerging developments.Existing definitions in the literature hardly recognize common functionalities and intermingle coded DAOs,DAO deployment platforms,and blockchain DAOs.We developed a comprehensive DAO definition by reviewing the literature and empirically analyzing 1,859 DAOs.The findings show that many DAOs were inactive and that a threshold of 20 tokenholders is a tipping point for DAOs to survive over time and maintain sustained levels of activity.Finally,based on an empirical analysis of 9,845 perceived DAOs,we identified the emerging development of off-chain voting.This emerging development challenges the autonomous nature of DAOs.We recommend further research to investigate the effect of governance structures on their long-term sustainability and viability for both on-chain and off-chain DAOs.
文摘AIM To systematically search literature and determine a preferable surgical procedure in patients with failed conservative treatment of calcifying tendinitis of the shoulder.METHODS The electronic online databases MEDLINE(through PubMed), EMBASE(through OVID), CINAHL(through EBSCO), Web of Science and Cochrane Central Register of Controlled Trials were systematically searched in May 2016. Eligible for inclusion were all available studies with level Ⅱ and level Ⅲ evidence(LoE). Data was assessed and extracted by two independent review authors using a specifically for this study designed data extraction form.RESULTS Six studies(294 surgically treated shoulders) were included in this review. No significant differences between the three available treatment options(acromioplasty with the removal of the calcific deposits, acromioplasty or solely the removal of the calcific deposits) were detected regarding the functional and clinical outcome. The followup ranged from 12 mo to 5 years. Complication rates were low. No reoperations were necessary and the only reported complication was adhesive capsulitis, which in all cases could be treated conservatively with full recovery. CONCLUSION We found that all three available treatment options show good functional and clinical outcomes in the short and midterm. However, a favorable procedure is difficult to determine due to the lack of high-quality comparing studies.
基金This review was funded by the EU Framework Programme Horizon 2020 through the COST Association(www.cost.eu):COST Action CA18207:BOTTOMS-UP–Biodiversity of Temperate Forest Taxa Orienting Management Sustainability by Unifying Perspectives.TC and TS acknowledge the support of the NBFC to the University of Padova,funded by the Italian Ministry of University and Research,PNRR,Missione 4 Componente 2,“Dalla ricerca all’impresa”,Investimento 1.4,Project CN00000033.
文摘Forest biodiversity studies conducted across Europe use a multitude of forestry terms,often inconsistently.This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent.Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts.This work aims to establish common standards for silvicultural and vegetation definitions,creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity.We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies.While quantitative data on forest biomass and dominant tree species are frequently included,information on silvicultural activities and vegetation composition is often lacking,shallow,or based on broad and heterogeneous classifications.We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process,and ultimately propose a common framework.This will enhance the comparability of forest biodiversity studies in Europe,and puts the basis for effective implementation and monitoring of sustainable forest management policies.The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.
基金Supported by Foundation for Liver and Gastrointestinal Research (SLO)The Netherlands Organisation for Scientific Research (NWO), No. VENI-grant 916-13-032 (to Pan Q)
文摘Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.
文摘Liposomes effectively transport fatty proteins to targeted tissues. Laboratory experiments use multiple methods to administer liposomes, but comparison of these methods is not available. In this retrospective study, we characterized and compared four intravenous administration routes (tail vein, jugular catheter, femoral vein and percutaneous retro-orbital injections) in murine models. ApoE<sup>-/-</sup> mice were used to compare administration routes. Results indicate that the jugular catheter route delivered the highest amount of liposomes to tissues due to longer period of injections compared to other routes;however, this route failed to remain patent for 8/10 animals. Delivery via tail vein, femoral vein and percutaneous retro-orbital injections resulted in similar accumulation in the organs. When including technical difficulty and expense, percutaneous retro-orbital injections of liposomes are the most convenient and efficacious approach.
文摘An alternative cationic polymerization method is developed to produce high molecular weight polyisobutylene (HM-PIB) with molecular weights above 5×10^5g/mol. The method involves micelle formation via functionalized low molecular weight polyisobutylene (LM-PIB) in non-polar solvent. One end of LM-PIB is modified with an imidazolium-containing ionic group, which together with the anion (eg. Al2Cl7) works as Lewis acid. While the monomer isobutylene dissolves readily in non-polar solvent, polymerization can occur only within the micelle, which affords stable HM-PIB particles. HM-PIB with a molecular weight (MW) close to 1 × 10^6 g/mol was produced successfully with the described method.
文摘Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes.Polymethylmethacrylate(PMMA)cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability.However,the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors.Here,we introduce porosity into PMMA cement by adding carboxymethylcellulose(CMC)to facilitate such local delivery of chemotherapeutic drugs,while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites.Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content.Upon incorporation of≥3%CMC,the PMMA-based cements released up to 18%of the loaded cisplatin,in contrast to cements containing lower amounts of CMC which only released less than 2%of the cisplatin over 28 days.This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3%at day 7,which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements.Additionally,tibias filled with PMMA-based cements containing up to 3%of CMC exhibit comparable compressive strengths as compared to intact tibias.In conclusion,we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels.As such,these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.
文摘Background Disturbed circadian rhythm is a potential cause of delirium and is linked to disorganisation of the circadian rhythmicity. Dynamic light （DL） could reset the circadian rhythm by activation of the suprachiasmatic nucleus to prevent delirium. Evidence regarding the effects of light therapy is predominantly focused on psychiatric disorders and circadian rhythm sleep disorders. In this study, we investi- gated the effect of DL on the total hospital length of stay （LOS） and occurrence of delirium in patients admitted to the Coronary Care Unit （CCU）. Methods This was a retrospective cohort study. Patients older than 18 years, who were hospitalized longer than 12 h at the CCU and had a total hospital LOS for at least 24 h, were included. Patients were assigned to a room with DL （n = 369） or regular lighting condi- tions （n = 379）. DL was administered at the CCU by two ceiling-mounted light panels delivering light with a colour temperature between 2700 and 6500 degrees Kelvin. Reported outcome data were： total hospital LOS, delirium incidence, consultation of a geriatrician and the amount of prescripted antipsychotics. Results Between May 2015 and May 2016, data from 748 patients were collected. Baseline charac- teristics, including risk factors provoking delirium, were equal in both groups. Median total hospital LOS in the DL group was 100.5 （70.8-186.0） and 101.0 （73.0-176.4） h in the control group （P = 0.935）. The incidence of delirium in the DL and control group was 5.4% （20/369） and 5.0% （19/379）, respectively （P = 0.802）. No significant differences between the DL and control group were observed in secon- dary endpoints. Subgroup analysis based on age and CCU LOS also showed no differences. Conclusion Our study suggests exposure to DL as an early single approach does not result in a reduction of total hospital LOS or reduced incidence of delirium. When delirium was diagnosed, it was associated with poor hospital outcome.
