Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deterioratin...Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.展开更多
Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neuro...Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neurological function in ASD,as observed in affected children who have regressed,can be explained as neurodegeneration.Although there is research evidence of neurodegeneration or progressive encephalopathy in ASD,the issue of neurodegeneration in ASD is still under debate.Evidence of neurodegeneration in the brain in ASD includes:(1)neuronal cell loss,(2)activated microglia and astrocytes,(3)proinflammatory cytokines,(4)oxidative stress,and(5)elevated 8-oxo-guanosine levels.The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities,and that research into treatments to address the issue of neurodegeneration in ASD are warranted.展开更多
AIM:To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma,who developed serious side effects. METHODS:Serum l...AIM:To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma,who developed serious side effects. METHODS:Serum levels of budesonide,6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging.All values were compared with a matched control patient without side effects. RESULTS:Serum levels of budesonide were 13-fold increased in the index patient.The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH- prednisolone,respectively,and serum levels of budesonide was diminished (1.0 vs.4.0 for 6β-OH-budesonide,4.2 vs. 10.7 for 16α-OH-prednisolone).Both patients had portosystemic SI (5.7 % and 3.1%) within the range of healthy subjects.CONCLUSION:Serum levels of budesonide Vary uP to 13-fold in AIH Patients with Child A eirrhosis in the absenee ofrelevant Portosystemic shunting.Redueed hePatiemetabolism,as indicated by redueed metabolite-to-drugratio,rather than Portosystemie shunting may explainsystemic side effects of this drug in cirrhosis展开更多
The pandemics of coronavirus disease 2019(COVID-19)and non-alcoholic fatty liver disease(NAFLD)coexist.Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD,while preexisting l...The pandemics of coronavirus disease 2019(COVID-19)and non-alcoholic fatty liver disease(NAFLD)coexist.Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD,while preexisting liver damage from NAFLD may influence the course of COVID-19.However,the prognostic relevance of this interaction,though,is unclear.Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19.Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity.Striking molecular similarities of cytokine pathways in both diseases,including postacute sequelae of COVID-19,suggest common pathways for chronic low-activity inflammation.This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.展开更多
Background:Autism spectrum disorder(ASD)is defined by standardized criteria of qualitative impairments in social interaction,qualitative impairments in communication,and restricted and stereotyped patterns of behavior...Background:Autism spectrum disorder(ASD)is defined by standardized criteria of qualitative impairments in social interaction,qualitative impairments in communication,and restricted and stereotyped patterns of behavior,interests,and activities.A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills,which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth.To date,the etiology of ASD remains under debate,however,many studies suggest toxicity,especially from mercury(Hg),in individuals diagnosed with an ASD.The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal(49.55%Hg by weight)in childhood vaccines by conducting a two-phased(hypothesis generating/hypothesis testing)study with documented exposure to varying levels of Thimerosal from vaccinations.Methods:A hypothesis generating cohort study was undertaken to evaluate the relationship between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis(DTaP)vaccine in comparison to a Thimerosal-free DTaP vaccine administered,from 1998 through 2000,for the risk of ASD as reported in the Vaccine Adverse Event Reporting System(VAERS)database(phase I).A hypothesis testing case–control study was undertaken to evaluate the relationship between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines administered at specific intervals in the first six months of life among cases diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine Safety Datalink(VSD)database(phase II).Results:In phase I,it was observed that there was a significantly increased risk ratio for the incidence of ASD reported following the Thimerosal-containing DTaP vaccine in comparison to the Thimerosal-free DTaP vaccine.In phase II,it was observed that cases diagnosed with an ASD were significantly more likely than controls to receive increased organic-Hg from Thimerosal-conta展开更多
Modeling of fluids with complex rheology in the lattice Boltzmann method (LBM) is typically realized through the introduction of an effective viscosity. For fluids with a yield stress behavior, such as so-called Bingh...Modeling of fluids with complex rheology in the lattice Boltzmann method (LBM) is typically realized through the introduction of an effective viscosity. For fluids with a yield stress behavior, such as so-called Bingham fluids, the effective viscosity has a singularity for low shear rates and may become negative. This is typically avoided by regularization such as Papanastasiou’s method. Here we argue that the effective viscosity model can be re-interpreted as a generalized equilibrium in which no violation of the stability constraint is observed. We implement a Bingham fluid model in a three-dimensional cumulant lattice Boltzmann framework and compare the direct analytic effective viscosity/generalized equilibrium method to the iterative approach first introduced by Vikhansky which avoids the singularity in viscosity that can arise in the analytic method. We find that both methods obtain similar results at coarse resolutions. However, at higher resolutions the accuracy of the regularized method levels off while the accuracy of the direct method continuously improves. We find that the accuracy of the proposed direct method is not limited by the singularity in viscosity indicating that a regularization is not strictly necessary.展开更多
Nonalcoholic fatty liver disease(NAFLD)is becoming a frequent liver disease,especially in patients with metabolic syndrome and especially in Western countries.Complications of NAFLD comprise progressive fibrosis,cirrh...Nonalcoholic fatty liver disease(NAFLD)is becoming a frequent liver disease,especially in patients with metabolic syndrome and especially in Western countries.Complications of NAFLD comprise progressive fibrosis,cirrhosis and hepatocellular carcinoma.NAFLD also represents an independent risk factor for cardiovascular disease,extrahepatic neoplasia and other organ damage,such as renal insufficiency.Given the epidemiological importance of the disease,new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis,NAFLD should be subject to screening programs,at least in countries with a high prevalence of the disease.The review discusses prerequisites for screening,cost-effectiveness,current guideline recommendations,suitability of techniques for screening and propositions for the following questions:Who should be screened?Who should perform screening?How should screening be performed?It is time for a screening program in patients at risk for NAFLD.展开更多
Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch,in 2001,the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with...Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch,in 2001,the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components,respectively. After 2 years of patch testing,we present results obtained with these series,based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these,206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens,monoethanolamine ranked 1st with 11.6%positive reactions. Diethanolamine (3.0%)-,triethanolamine (1.1%),and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to paminoazobenzene were frequently observed (6.0%),but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5%for Bioban. CS 1135 to 0.5%for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde,which caused positive reactions in 3.3%,and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate,di-2-ethylhexyl phthalate,tricresyl phosphate,isopropyl myristate or benzotriazole. With the historical MWF test series,positive reactions to methyldibromo glutaronitrile (MDBGN) were observedmost frequently. However,sensitization via allergen sources other than MWF seems likely,as MDBGN,during the study period,has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprisedmorpholinyl mercaptobenzothiazole (3.3%),benzisothiazolinone (BIT; 2.0%) and Bioban. P 1487(1.3%). BIT is currently used in MWF again,so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no lon展开更多
In view of the wide variety of components currently used in metalworking fluids (MWF), relevant contact sensitizations may be overlooked, because commercially available MWF test series cannot cover the full spectrum. ...In view of the wide variety of components currently used in metalworking fluids (MWF), relevant contact sensitizations may be overlooked, because commercially available MWF test series cannot cover the full spectrum. Hence, patch testing with MWF from the patient’s workplace is an important additional diagnostic tool. However, recommendations on how to perform such patch tests vary. We retrospectively analyzed patch test data of the Department of Dermatology in Dortmund, 1992-2003. In 141 metalworkers tested because of suspected occupational contact dermatitis due to MWF, 829 patch tests with 306 samples of MWF were performed. Water-based MWF (wb MWF) were mainly tested in 2 dilution series, i.e. pure (workplace concentration), 10%aq. and 1%aq., and pure, 50%aq. and 10%aq. Positive reactions to wb MWF occurred in 27 patients. Patch testing with wb MWF at workplace concentration resulted in 16.1 %(39/242) positive reactions, with a positivity ratio of 69%and a reaction index of 0. From the analysis of reaction patterns and concomitant reactions,we conclude that most of these positive reactions indicated true contact allergy. With lower concentrations, relevant allergic reactions may be missed. Neat oils were tested as is or diluted from 1 to 50%in olive oil, but no reactions at all were observed. For optimum benefit of patch testing with MWF from the patient’s workplace, breakdown testing is recommended. To overcome the time-consuming difficulties associated with this procedure, we propose a centre for information and documentation of contact allergies due to occupational exposure. Furthermore, full declaration of MWF ingredients is desirable.展开更多
Analyses of the stability of 1 %p-toluene diamine (PTD) in petrolatum used for patch testing showed a rapid decline of the PTD concentration down to 0.1%,possibly due to the generation of dye complexes. To study wheth...Analyses of the stability of 1 %p-toluene diamine (PTD) in petrolatum used for patch testing showed a rapid decline of the PTD concentration down to 0.1%,possibly due to the generation of dye complexes. To study whether the diagnostic quality of this test preparation is compromised by the chemical reactions taken place, a multicentre study was conducted by the German Contact Dermatitis Research Group (DKG), comparing patch test results in 177 patients with simultaneously tested PTD preparations of different ages. During the 10-month course of this study, the age of the batches ranged from 2 to 11 months for batch A, from 7 to 16 months for batch B and from 11 to 20 months for batch C. There were no statistically significant differences between reactions to batches A and B, A and C, and B and C. Agreement of patch test reactions to the 3 batches was very good and comparable to the general reproducibility of patch test with standard allergens. The chemical reactions mentioned above apparently do not affect the diagnostic quality of PTD patch test preparations because the true allergen probably is not PTD itself, but one or more of the reaction products.展开更多
Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he...Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he had started working in aircraft construction. Patch tests showed positive reactions at day 3 to nickel sulfate, epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-aminophenol (TGPAP) applied at 1%and 0.1%induced the strongest (+++positive) reaction. About 4 months after the patch test with TGPAP, the patient presented with 2 circular depigmented spots in the former TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis of contact vitiligo.展开更多
A field study was conducted at two locations in Kansas, USA in 2011 and 2012 to test weed control efficacy and crop response to preemergence-applied pyroxasulfone alone and in combination with sulfentrazone in sunflow...A field study was conducted at two locations in Kansas, USA in 2011 and 2012 to test weed control efficacy and crop response to preemergence-applied pyroxasulfone alone and in combination with sulfentrazone in sunflower. Treatments included three rates of pyroxasulfone (100, 200 and 400 g·ha-1) applied alone and tank-mixed with sulfentrazone at 70, 140 and 280 g·ha-1. Commercial standards sulfentrazone at 140 g·ha-1 + pendimethalin at 1390 g·ha-1 and sulfentrazone at 140 g·ha-1 + S-metolachlor at 1280 g·ha-1 were also included. Pyroxasulfone at 100 g·ha-1 controlled Palmer amaranth 87% at 3 weeks after application (WAA), but control decreased to 76% at 6 WAA. Increasing pyroxasulfone rate to ≥200 g·ha-1 or tank mixing with sulfentazone at 140 g·ha-1 provided ≥90% Palmer amaranth control for at least 6 WAA. Sulfentrazone alone at 70 g·ha-1 controlled Palmer amaranth 77% at 3 WAA, but control dropped to 69% at 6 WAA. Increasing sulfentrazone rate from 70 to 140 or 280 g·ha-1 increased control to >90% at 3 WAA, but did not maintain acceptable control at 6 WAA. Tank mixing sulfentrazone at 140 g·ha-1 with pendimethalin at 1390 g·ha-1 or S-metolachlor at 1280 g·ha-1 controlled Palmer amaranth ≥90 and 84% at 3 WAA and 6 WAA, respectively. The lowest rate of pyroxasulfone (100 g·ha-1) controlled kochia 98% and the control was complete with all other treatments. However, no treatment provided as much as 90% puncturevine control at 3 WAA and the control was commercially unacceptable (<75%) at 6 WAA. No treatment visibly injured sunflower anytime during the season or reduced sunflower plant population.展开更多
Future adaptive applications require lightweight and stiff materials with high active strain but low energy consumption.A suitable combination of these properties is offered by carbon nanotubebased actuators.Papers ma...Future adaptive applications require lightweight and stiff materials with high active strain but low energy consumption.A suitable combination of these properties is offered by carbon nanotubebased actuators.Papers made of carbon nanotubes(CNTs)are charged within an electrolyte,which results in an electrical field forming a double-layer of ions at their surfaces and a deflection of the papers can be detected.Until now,there is no generally accepted theory for the actuation mechanism.This study focuses on the actuation mechanism of CNT papers,which represent architectures of randomly oriented CNTs.The samples are tested electrochemically in an in-plane set-up to detect the free strain.The elastic modulus of the CNT papers is analyzed in a tensile test facility.The influence of various ion sizes of water-based electrolytes is investigated.During the tests,four parameters that have a significant influence on the mechanical performance of CNT papers were identified:the test conditions,the electrical charging,the microstructure and the ion size.All of these influencing factors point to the mechanically weak inter-tube linking at which the actuation seems to take place.Quadratic voltage-strain correlation suggests a combination of electrostatic and volumetric effects as the possible reason for CNT paper actuation.展开更多
Background: Cardiovascular rehabilitation in Germany traditionally is offered as inpatient service often located far from patient’s residence, and ambulatory rehabilitation still represents a minority. The German Reg...Background: Cardiovascular rehabilitation in Germany traditionally is offered as inpatient service often located far from patient’s residence, and ambulatory rehabilitation still represents a minority. The German Registry of Ambulatory Cardiac Rehabilitation (KARREE) was designed to contribute to rehabilitation quality assurance and to evaluate clinical characteristics of patients participating in ambulatory rehabilitation centers. Methods: In four ambulatory rehabilitation centers 2989 patients were consecutively registered from 2008 to 2011 and evaluated with respect to social status, cardiovascular diagnoses and risk factors, psychological status, medication and short term clinical and social outcome. Results: Most patients referred to the ambulatory cardiac rehabilitation had an acute cardiovascular event, with patients after acute coronary syndrome representing the majority (59.9%). Female were strongly underrepresented (16.7%). Patient’s clinical characteristics varied with the age groups evaluated ( 70 years). Whereas the reported physical inactivity, overweight and cigarette smoking was declining with age, diabetes and hypertension significantly increased. Furthermore the reported and evaluated psychosocial stress was declining with age. Regarding the group of patients still employed, 43.5 % were estimated as fit for work directly at the end of the rehabilitation program, whereas a stepwise reintegration into employment was performed in 16.7%. The majority of patients were transferred to ambulatory heart groups or other forms of after care for stabilizing regular physical activity. Conclusions: The large variation of the characteristics of patients participating cardiac rehabilitation underscore the need of an individualized approach for a successful implementation of secondary prevention and reintegration of these patients into their social life.展开更多
AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism up...AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.展开更多
In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25%and 0.5%aq. has been added to routine allergen patc h tests to assess its properties as a convenient diagnostic ...In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25%and 0.5%aq. has been added to routine allergen patc h tests to assess its properties as a convenient diagnostic indicator of individ ual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors o f contact allergy to many allergens, e.g. summarized in the ‘MOAHLFA index’, t he impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. A s a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5%SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an e ven weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almos t halved the odds of an irritant SLS reaction. In conclusion, this type of SLS p atch test can be regarded as robust, indicating individual irritability relative ly independent from the individual factors analysed here.展开更多
文摘Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.
文摘Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neurological function in ASD,as observed in affected children who have regressed,can be explained as neurodegeneration.Although there is research evidence of neurodegeneration or progressive encephalopathy in ASD,the issue of neurodegeneration in ASD is still under debate.Evidence of neurodegeneration in the brain in ASD includes:(1)neuronal cell loss,(2)activated microglia and astrocytes,(3)proinflammatory cytokines,(4)oxidative stress,and(5)elevated 8-oxo-guanosine levels.The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities,and that research into treatments to address the issue of neurodegeneration in ASD are warranted.
文摘AIM:To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma,who developed serious side effects. METHODS:Serum levels of budesonide,6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging.All values were compared with a matched control patient without side effects. RESULTS:Serum levels of budesonide were 13-fold increased in the index patient.The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH- prednisolone,respectively,and serum levels of budesonide was diminished (1.0 vs.4.0 for 6β-OH-budesonide,4.2 vs. 10.7 for 16α-OH-prednisolone).Both patients had portosystemic SI (5.7 % and 3.1%) within the range of healthy subjects.CONCLUSION:Serum levels of budesonide Vary uP to 13-fold in AIH Patients with Child A eirrhosis in the absenee ofrelevant Portosystemic shunting.Redueed hePatiemetabolism,as indicated by redueed metabolite-to-drugratio,rather than Portosystemie shunting may explainsystemic side effects of this drug in cirrhosis
文摘The pandemics of coronavirus disease 2019(COVID-19)and non-alcoholic fatty liver disease(NAFLD)coexist.Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD,while preexisting liver damage from NAFLD may influence the course of COVID-19.However,the prognostic relevance of this interaction,though,is unclear.Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19.Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity.Striking molecular similarities of cytokine pathways in both diseases,including postacute sequelae of COVID-19,suggest common pathways for chronic low-activity inflammation.This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.
基金This study was financially supported by the Dwoskin Family Foundation and the Selz Foundation.
文摘Background:Autism spectrum disorder(ASD)is defined by standardized criteria of qualitative impairments in social interaction,qualitative impairments in communication,and restricted and stereotyped patterns of behavior,interests,and activities.A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills,which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth.To date,the etiology of ASD remains under debate,however,many studies suggest toxicity,especially from mercury(Hg),in individuals diagnosed with an ASD.The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal(49.55%Hg by weight)in childhood vaccines by conducting a two-phased(hypothesis generating/hypothesis testing)study with documented exposure to varying levels of Thimerosal from vaccinations.Methods:A hypothesis generating cohort study was undertaken to evaluate the relationship between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis(DTaP)vaccine in comparison to a Thimerosal-free DTaP vaccine administered,from 1998 through 2000,for the risk of ASD as reported in the Vaccine Adverse Event Reporting System(VAERS)database(phase I).A hypothesis testing case–control study was undertaken to evaluate the relationship between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines administered at specific intervals in the first six months of life among cases diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine Safety Datalink(VSD)database(phase II).Results:In phase I,it was observed that there was a significantly increased risk ratio for the incidence of ASD reported following the Thimerosal-containing DTaP vaccine in comparison to the Thimerosal-free DTaP vaccine.In phase II,it was observed that cases diagnosed with an ASD were significantly more likely than controls to receive increased organic-Hg from Thimerosal-conta
文摘Modeling of fluids with complex rheology in the lattice Boltzmann method (LBM) is typically realized through the introduction of an effective viscosity. For fluids with a yield stress behavior, such as so-called Bingham fluids, the effective viscosity has a singularity for low shear rates and may become negative. This is typically avoided by regularization such as Papanastasiou’s method. Here we argue that the effective viscosity model can be re-interpreted as a generalized equilibrium in which no violation of the stability constraint is observed. We implement a Bingham fluid model in a three-dimensional cumulant lattice Boltzmann framework and compare the direct analytic effective viscosity/generalized equilibrium method to the iterative approach first introduced by Vikhansky which avoids the singularity in viscosity that can arise in the analytic method. We find that both methods obtain similar results at coarse resolutions. However, at higher resolutions the accuracy of the regularized method levels off while the accuracy of the direct method continuously improves. We find that the accuracy of the proposed direct method is not limited by the singularity in viscosity indicating that a regularization is not strictly necessary.
文摘Nonalcoholic fatty liver disease(NAFLD)is becoming a frequent liver disease,especially in patients with metabolic syndrome and especially in Western countries.Complications of NAFLD comprise progressive fibrosis,cirrhosis and hepatocellular carcinoma.NAFLD also represents an independent risk factor for cardiovascular disease,extrahepatic neoplasia and other organ damage,such as renal insufficiency.Given the epidemiological importance of the disease,new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis,NAFLD should be subject to screening programs,at least in countries with a high prevalence of the disease.The review discusses prerequisites for screening,cost-effectiveness,current guideline recommendations,suitability of techniques for screening and propositions for the following questions:Who should be screened?Who should perform screening?How should screening be performed?It is time for a screening program in patients at risk for NAFLD.
文摘Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch,in 2001,the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components,respectively. After 2 years of patch testing,we present results obtained with these series,based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these,206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens,monoethanolamine ranked 1st with 11.6%positive reactions. Diethanolamine (3.0%)-,triethanolamine (1.1%),and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to paminoazobenzene were frequently observed (6.0%),but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5%for Bioban. CS 1135 to 0.5%for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde,which caused positive reactions in 3.3%,and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate,di-2-ethylhexyl phthalate,tricresyl phosphate,isopropyl myristate or benzotriazole. With the historical MWF test series,positive reactions to methyldibromo glutaronitrile (MDBGN) were observedmost frequently. However,sensitization via allergen sources other than MWF seems likely,as MDBGN,during the study period,has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprisedmorpholinyl mercaptobenzothiazole (3.3%),benzisothiazolinone (BIT; 2.0%) and Bioban. P 1487(1.3%). BIT is currently used in MWF again,so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no lon
文摘In view of the wide variety of components currently used in metalworking fluids (MWF), relevant contact sensitizations may be overlooked, because commercially available MWF test series cannot cover the full spectrum. Hence, patch testing with MWF from the patient’s workplace is an important additional diagnostic tool. However, recommendations on how to perform such patch tests vary. We retrospectively analyzed patch test data of the Department of Dermatology in Dortmund, 1992-2003. In 141 metalworkers tested because of suspected occupational contact dermatitis due to MWF, 829 patch tests with 306 samples of MWF were performed. Water-based MWF (wb MWF) were mainly tested in 2 dilution series, i.e. pure (workplace concentration), 10%aq. and 1%aq., and pure, 50%aq. and 10%aq. Positive reactions to wb MWF occurred in 27 patients. Patch testing with wb MWF at workplace concentration resulted in 16.1 %(39/242) positive reactions, with a positivity ratio of 69%and a reaction index of 0. From the analysis of reaction patterns and concomitant reactions,we conclude that most of these positive reactions indicated true contact allergy. With lower concentrations, relevant allergic reactions may be missed. Neat oils were tested as is or diluted from 1 to 50%in olive oil, but no reactions at all were observed. For optimum benefit of patch testing with MWF from the patient’s workplace, breakdown testing is recommended. To overcome the time-consuming difficulties associated with this procedure, we propose a centre for information and documentation of contact allergies due to occupational exposure. Furthermore, full declaration of MWF ingredients is desirable.
文摘Analyses of the stability of 1 %p-toluene diamine (PTD) in petrolatum used for patch testing showed a rapid decline of the PTD concentration down to 0.1%,possibly due to the generation of dye complexes. To study whether the diagnostic quality of this test preparation is compromised by the chemical reactions taken place, a multicentre study was conducted by the German Contact Dermatitis Research Group (DKG), comparing patch test results in 177 patients with simultaneously tested PTD preparations of different ages. During the 10-month course of this study, the age of the batches ranged from 2 to 11 months for batch A, from 7 to 16 months for batch B and from 11 to 20 months for batch C. There were no statistically significant differences between reactions to batches A and B, A and C, and B and C. Agreement of patch test reactions to the 3 batches was very good and comparable to the general reproducibility of patch test with standard allergens. The chemical reactions mentioned above apparently do not affect the diagnostic quality of PTD patch test preparations because the true allergen probably is not PTD itself, but one or more of the reaction products.
文摘Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he had started working in aircraft construction. Patch tests showed positive reactions at day 3 to nickel sulfate, epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-aminophenol (TGPAP) applied at 1%and 0.1%induced the strongest (+++positive) reaction. About 4 months after the patch test with TGPAP, the patient presented with 2 circular depigmented spots in the former TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis of contact vitiligo.
文摘A field study was conducted at two locations in Kansas, USA in 2011 and 2012 to test weed control efficacy and crop response to preemergence-applied pyroxasulfone alone and in combination with sulfentrazone in sunflower. Treatments included three rates of pyroxasulfone (100, 200 and 400 g·ha-1) applied alone and tank-mixed with sulfentrazone at 70, 140 and 280 g·ha-1. Commercial standards sulfentrazone at 140 g·ha-1 + pendimethalin at 1390 g·ha-1 and sulfentrazone at 140 g·ha-1 + S-metolachlor at 1280 g·ha-1 were also included. Pyroxasulfone at 100 g·ha-1 controlled Palmer amaranth 87% at 3 weeks after application (WAA), but control decreased to 76% at 6 WAA. Increasing pyroxasulfone rate to ≥200 g·ha-1 or tank mixing with sulfentazone at 140 g·ha-1 provided ≥90% Palmer amaranth control for at least 6 WAA. Sulfentrazone alone at 70 g·ha-1 controlled Palmer amaranth 77% at 3 WAA, but control dropped to 69% at 6 WAA. Increasing sulfentrazone rate from 70 to 140 or 280 g·ha-1 increased control to >90% at 3 WAA, but did not maintain acceptable control at 6 WAA. Tank mixing sulfentrazone at 140 g·ha-1 with pendimethalin at 1390 g·ha-1 or S-metolachlor at 1280 g·ha-1 controlled Palmer amaranth ≥90 and 84% at 3 WAA and 6 WAA, respectively. The lowest rate of pyroxasulfone (100 g·ha-1) controlled kochia 98% and the control was complete with all other treatments. However, no treatment provided as much as 90% puncturevine control at 3 WAA and the control was commercially unacceptable (<75%) at 6 WAA. No treatment visibly injured sunflower anytime during the season or reduced sunflower plant population.
基金This work was supported by the German Federal Ministry of Education and Research(BMBF)[Aktu_Comp]and the German Research Foundation(DFG)[DFG PAK 355].
文摘Future adaptive applications require lightweight and stiff materials with high active strain but low energy consumption.A suitable combination of these properties is offered by carbon nanotubebased actuators.Papers made of carbon nanotubes(CNTs)are charged within an electrolyte,which results in an electrical field forming a double-layer of ions at their surfaces and a deflection of the papers can be detected.Until now,there is no generally accepted theory for the actuation mechanism.This study focuses on the actuation mechanism of CNT papers,which represent architectures of randomly oriented CNTs.The samples are tested electrochemically in an in-plane set-up to detect the free strain.The elastic modulus of the CNT papers is analyzed in a tensile test facility.The influence of various ion sizes of water-based electrolytes is investigated.During the tests,four parameters that have a significant influence on the mechanical performance of CNT papers were identified:the test conditions,the electrical charging,the microstructure and the ion size.All of these influencing factors point to the mechanically weak inter-tube linking at which the actuation seems to take place.Quadratic voltage-strain correlation suggests a combination of electrostatic and volumetric effects as the possible reason for CNT paper actuation.
文摘Background: Cardiovascular rehabilitation in Germany traditionally is offered as inpatient service often located far from patient’s residence, and ambulatory rehabilitation still represents a minority. The German Registry of Ambulatory Cardiac Rehabilitation (KARREE) was designed to contribute to rehabilitation quality assurance and to evaluate clinical characteristics of patients participating in ambulatory rehabilitation centers. Methods: In four ambulatory rehabilitation centers 2989 patients were consecutively registered from 2008 to 2011 and evaluated with respect to social status, cardiovascular diagnoses and risk factors, psychological status, medication and short term clinical and social outcome. Results: Most patients referred to the ambulatory cardiac rehabilitation had an acute cardiovascular event, with patients after acute coronary syndrome representing the majority (59.9%). Female were strongly underrepresented (16.7%). Patient’s clinical characteristics varied with the age groups evaluated ( 70 years). Whereas the reported physical inactivity, overweight and cigarette smoking was declining with age, diabetes and hypertension significantly increased. Furthermore the reported and evaluated psychosocial stress was declining with age. Regarding the group of patients still employed, 43.5 % were estimated as fit for work directly at the end of the rehabilitation program, whereas a stepwise reintegration into employment was performed in 16.7%. The majority of patients were transferred to ambulatory heart groups or other forms of after care for stabilizing regular physical activity. Conclusions: The large variation of the characteristics of patients participating cardiac rehabilitation underscore the need of an individualized approach for a successful implementation of secondary prevention and reintegration of these patients into their social life.
文摘AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.
文摘In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25%and 0.5%aq. has been added to routine allergen patc h tests to assess its properties as a convenient diagnostic indicator of individ ual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors o f contact allergy to many allergens, e.g. summarized in the ‘MOAHLFA index’, t he impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. A s a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5%SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an e ven weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almos t halved the odds of an irritant SLS reaction. In conclusion, this type of SLS p atch test can be regarded as robust, indicating individual irritability relative ly independent from the individual factors analysed here.
