Objective: To compare 8-month effects ofmedical treatment plusrehabilitation on UPDRS scores ofparkinsonian patientswith that ofmedical treatment withoutrehabilitation.Design: Longtudinal randomized study. Participant...Objective: To compare 8-month effects ofmedical treatment plusrehabilitation on UPDRS scores ofparkinsonian patientswith that ofmedical treatment withoutrehabilitation.Design: Longtudinal randomized study. Participants:27 parkinsonian patients (69.50 ± 10.34 years). We divided our patient into two groups: control group (n = 9, received only medication therapy) and experiment- tal group (n = 18, received physiccal therapy and medication therapy). Intervention:The 8-month exercise interventions were twice-weekly 90-min sessions in group. UPDRS scales were measured before and after the interventions. Results: Two- factor ANOVA analyses revealed a significant main effect fromrehabilitation (p 0.05). Post-hoc analysis shows that UPDRS motor increased in control group (+37%) meanwhile decreased in experimental group (–17%). UPDRS ADL increased significantly more in control group (+26%) than experimental group (+5%).UPDRS total increased in control group (+33%) meanwhile decreased in experimental group(–11%). Conclusions:The results of the study suggest that exercise interventions should be a necessary ongoing adjunct toparkinson’s diseasemedication.展开更多
Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of ...Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients.展开更多
AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze dif...AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.展开更多
The existence of an inflammatory process in the heart muscle,related to a progressive worsening of myocardial function,different etiopathogenetic mechanisms concur and often overlap,thus making the diagnosis and the t...The existence of an inflammatory process in the heart muscle,related to a progressive worsening of myocardial function,different etiopathogenetic mechanisms concur and often overlap,thus making the diagnosis and the therapeutic approach complex.As the COVID-19 pandemic progresses,the effects of the disease on the organ systems and in particular on the cardiovascular system are becoming more and more profound.Cardiac involvement is a well-known event with a high percentage of findings in the heart’s magnetic field,even in asymptomatic areas.There are numerous uncertainties regarding their evolution,in the long and short term,due not only to a difficult to determine the varied clinical expression and the rarely performed intramyocardial biopsy which additionally presents diagnostic problems but also in part to different clinical prognosis.Today,the new SARS-CoV-2 virus that uses the angiotensin converting enzyme 2(ACE2)which is present at high levels in myocardial cells as its entrance it can create even severe heart injury.The pathophysiology in all of these cases can involve multiple immune and non-immune mechanisms within organs and vessels and can be occur in the clinical phases.Possible mechanisms of direct and indirect myocardial infarction in patients with COVID-19 include additional lesion and oxygen-rich and generalized inflammation response with myocardial immune hyperactivity(myocarditis).Therefore,these can occur through the excessive release of cytokines,the presence of thrombocytopenia,endocrine damage,heart failure,arrhythmias and more.Patients can show average signs of myocardial damage,and some develop spontaneous cardiac complications,such as heart failure,arrhythmias and,rarely,rare cardiogenic disorders.Pathophysiology in all of these may involve multiple mechanisms within the cytokine cephalic membrane,endocrine damage and thrombogenicity.The diagnosis of this myocardial injuri is mainly based on the myocardial enzyme troponin.This viewpoint paper explains today’s knowledge on viral myocarditis,in particular that from SARS-CoV-2 infection,if there is a connection with other possible biomolecular pathogenetic factors that can influence its natural course.In fact,it is for this reason that the pathogenetic mechanisms are analyzed and described.At the same time,its possible interaction with other parameters that are documented risk factors for cardiovascular disease was examined.Although these biomolecular findings were mainly related to necrotic parts of the myocardium,it is important to recognize that myocardial damage early for a better approach and prognosis.展开更多
Purpose The aim of this study was to examine the peak locomotor demands of match play and determine if these situations are replicated in training,and analyze their dynamics throughout the competitive microcycle in pr...Purpose The aim of this study was to examine the peak locomotor demands of match play and determine if these situations are replicated in training,and analyze their dynamics throughout the competitive microcycle in professional female soccer players based on their positions.Methods Measurements such as distance covered(DIS),high-speed running distance(HSRD),sprint distance(SPD),accelerating distance(ACCDIS),decelerating distance(DECDIS),and high metabolic load distance(HMLD)were registered during 1,3,5 and 10-min peak locomotor in both competitive matches(MD)and training sessions(ranked based on the number of days remaining until the next match,namely MD-4,MD-3,MD-2,and MD-1)within a competitive mesocycle.Results Central defenders were found to cover significantly less HMLD than full-backs and forwards,regardless of the time frame,as well as less HMLD than center midfielders in the 3,5 and 10-min time frames.Only in MD-3 did players exhibit a similar HMLD to MD,regardless of the analyzed time frame.Players covered significantly less HSRD and SPD in MD-2 and MD-1 compared to MD-3,and less HSRD in MD-4 compared to MD-3.Additionally,HSRD and SPD were significantly higher in MD-4 than in MD-1.There were no significant differences in HSRD or SPD relative to match play workload observed between positions within the same training session.Conclusion The microcycle showed a non-linear training load,with higher external loads in central sessions(e.g.,MD-3)and tapering strategies at the end of the microcycle in peak locomotor demands.展开更多
Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous ...Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,respectively.The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal antibodies.Data sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection criteria.Results We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.Conclusions The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases.Furthermore,for some of them,bone damage began in childhood but only manifested with age.The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out.展开更多
Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis...Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).展开更多
The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interes...The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interest in these fungi,there is a considerable gap of knowledge on their functionality.Their genomic analysis is still in its infancy and the possibility to understand their adaptive strategies and exploit their potentialities in bioremediation is very limited.Here,we supply a genome catalog of 118 black fungi,encompassing different ecologies,phylogenies and lifestyles,as a first example of a comparative genomic study at high level of diversity.Results indicate that,as a rule,Dothideomycetes show more variable genome size and that larger genomes are associated with harshest conditions;low temperature tolerance and DNA repair capacity are overrepresented in their genomes.In Eurotiomycetes high temperature tolerance and capacity to metabolize hydrocarbons are more frequently present and these abilities are positively correlated with the human presence.The genomic features are consistent with the prevalent ecologies in the two classes.Indeed,Dothideomycetes are more common in cold and dry environments with high capacity for DNA repair being consistent with the normally highly UV-impacted conditions in their habitats;in contrast,Eurotiomycetes spread mainly in hot human-impacted sites with industrial pollution.Mean annual temperature and isothermality are positively correlated with tolerance to high temperatures in Dothideomycetes,suggesting that,despite their preference for the cold,they are potentially equipped to survive even when temperatures rise due to the global warming.展开更多
文摘Objective: To compare 8-month effects ofmedical treatment plusrehabilitation on UPDRS scores ofparkinsonian patientswith that ofmedical treatment withoutrehabilitation.Design: Longtudinal randomized study. Participants:27 parkinsonian patients (69.50 ± 10.34 years). We divided our patient into two groups: control group (n = 9, received only medication therapy) and experiment- tal group (n = 18, received physiccal therapy and medication therapy). Intervention:The 8-month exercise interventions were twice-weekly 90-min sessions in group. UPDRS scales were measured before and after the interventions. Results: Two- factor ANOVA analyses revealed a significant main effect fromrehabilitation (p 0.05). Post-hoc analysis shows that UPDRS motor increased in control group (+37%) meanwhile decreased in experimental group (–17%). UPDRS ADL increased significantly more in control group (+26%) than experimental group (+5%).UPDRS total increased in control group (+33%) meanwhile decreased in experimental group(–11%). Conclusions:The results of the study suggest that exercise interventions should be a necessary ongoing adjunct toparkinson’s diseasemedication.
文摘Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients.
基金Supported by Fundación Burgos por la Investigación de la Salud and Gerencia Regional de Salud de Castilla y León,No.BUO/06/15
文摘AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.
文摘The existence of an inflammatory process in the heart muscle,related to a progressive worsening of myocardial function,different etiopathogenetic mechanisms concur and often overlap,thus making the diagnosis and the therapeutic approach complex.As the COVID-19 pandemic progresses,the effects of the disease on the organ systems and in particular on the cardiovascular system are becoming more and more profound.Cardiac involvement is a well-known event with a high percentage of findings in the heart’s magnetic field,even in asymptomatic areas.There are numerous uncertainties regarding their evolution,in the long and short term,due not only to a difficult to determine the varied clinical expression and the rarely performed intramyocardial biopsy which additionally presents diagnostic problems but also in part to different clinical prognosis.Today,the new SARS-CoV-2 virus that uses the angiotensin converting enzyme 2(ACE2)which is present at high levels in myocardial cells as its entrance it can create even severe heart injury.The pathophysiology in all of these cases can involve multiple immune and non-immune mechanisms within organs and vessels and can be occur in the clinical phases.Possible mechanisms of direct and indirect myocardial infarction in patients with COVID-19 include additional lesion and oxygen-rich and generalized inflammation response with myocardial immune hyperactivity(myocarditis).Therefore,these can occur through the excessive release of cytokines,the presence of thrombocytopenia,endocrine damage,heart failure,arrhythmias and more.Patients can show average signs of myocardial damage,and some develop spontaneous cardiac complications,such as heart failure,arrhythmias and,rarely,rare cardiogenic disorders.Pathophysiology in all of these may involve multiple mechanisms within the cytokine cephalic membrane,endocrine damage and thrombogenicity.The diagnosis of this myocardial injuri is mainly based on the myocardial enzyme troponin.This viewpoint paper explains today’s knowledge on viral myocarditis,in particular that from SARS-CoV-2 infection,if there is a connection with other possible biomolecular pathogenetic factors that can influence its natural course.In fact,it is for this reason that the pathogenetic mechanisms are analyzed and described.At the same time,its possible interaction with other parameters that are documented risk factors for cardiovascular disease was examined.Although these biomolecular findings were mainly related to necrotic parts of the myocardium,it is important to recognize that myocardial damage early for a better approach and prognosis.
基金supported by Proyecto:Red en valoración del Fitness femenino.Clave Orgánica:AL 96.
文摘Purpose The aim of this study was to examine the peak locomotor demands of match play and determine if these situations are replicated in training,and analyze their dynamics throughout the competitive microcycle in professional female soccer players based on their positions.Methods Measurements such as distance covered(DIS),high-speed running distance(HSRD),sprint distance(SPD),accelerating distance(ACCDIS),decelerating distance(DECDIS),and high metabolic load distance(HMLD)were registered during 1,3,5 and 10-min peak locomotor in both competitive matches(MD)and training sessions(ranked based on the number of days remaining until the next match,namely MD-4,MD-3,MD-2,and MD-1)within a competitive mesocycle.Results Central defenders were found to cover significantly less HMLD than full-backs and forwards,regardless of the time frame,as well as less HMLD than center midfielders in the 3,5 and 10-min time frames.Only in MD-3 did players exhibit a similar HMLD to MD,regardless of the analyzed time frame.Players covered significantly less HSRD and SPD in MD-2 and MD-1 compared to MD-3,and less HSRD in MD-4 compared to MD-3.Additionally,HSRD and SPD were significantly higher in MD-4 than in MD-1.There were no significant differences in HSRD or SPD relative to match play workload observed between positions within the same training session.Conclusion The microcycle showed a non-linear training load,with higher external loads in central sessions(e.g.,MD-3)and tapering strategies at the end of the microcycle in peak locomotor demands.
文摘Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,respectively.The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal antibodies.Data sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection criteria.Results We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.Conclusions The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases.Furthermore,for some of them,bone damage began in childhood but only manifested with age.The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out.
基金supported by the grants from United Leukodystrophy Foundation(to Alessandro Michienzi)partially supported by the Italian Ministry of Health(No.GR-2019-12368701 to Davide Tonduti and Cristina Cereda).
文摘Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).
基金supported by the European Commission under the Marie Sklodowska-Curie Grant Agreement No.702057(DRYLIFE)M.D-B.is supported by a project from the Spanish Ministry of Science and Innovation(PID2020-115813RA-I00)+4 种基金a project of the Fondo Europeo de Desarrollo Regional(FEDER)the Consejería de Transformación Económica,Industria,Conocimiento y Universidades of the Junta de Andalucía(FEDER Andalucía 2014-2020 Objetivo temático'01-Refuerzo de la investigación,el desarrollo tecnológico y la innovación')associated with the research project P20_00879(ANDABIOMA)N.S.receives funding from the ERC(ERC-STG project MetaPG-716575 and ERC-CoG microTOUCH-101045015)J.E.S.is a CIFAR fellow in the Fungal Kingdom:Threats and Opportunities program.T.K.and J.E.S.were partially supported by NIH NIAID R01-GM108492Data analyses performed at the High-Performance Computing Cluster at the University of California Riverside in the Institute of Integrative Genome Biology were supported by NSF grant DBI-1429826 and NIH grant S10-OD016290.
文摘The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interest in these fungi,there is a considerable gap of knowledge on their functionality.Their genomic analysis is still in its infancy and the possibility to understand their adaptive strategies and exploit their potentialities in bioremediation is very limited.Here,we supply a genome catalog of 118 black fungi,encompassing different ecologies,phylogenies and lifestyles,as a first example of a comparative genomic study at high level of diversity.Results indicate that,as a rule,Dothideomycetes show more variable genome size and that larger genomes are associated with harshest conditions;low temperature tolerance and DNA repair capacity are overrepresented in their genomes.In Eurotiomycetes high temperature tolerance and capacity to metabolize hydrocarbons are more frequently present and these abilities are positively correlated with the human presence.The genomic features are consistent with the prevalent ecologies in the two classes.Indeed,Dothideomycetes are more common in cold and dry environments with high capacity for DNA repair being consistent with the normally highly UV-impacted conditions in their habitats;in contrast,Eurotiomycetes spread mainly in hot human-impacted sites with industrial pollution.Mean annual temperature and isothermality are positively correlated with tolerance to high temperatures in Dothideomycetes,suggesting that,despite their preference for the cold,they are potentially equipped to survive even when temperatures rise due to the global warming.
