Atrial fibrillation （AF） is the most common arrhythmia diagnosed in clinical practice. The consequences of AF have been clearly estab- lished in multiple large observational cohort studies and include increased stro...Atrial fibrillation （AF） is the most common arrhythmia diagnosed in clinical practice. The consequences of AF have been clearly estab- lished in multiple large observational cohort studies and include increased stroke and systemic embolism rates if no oral anticoagulation is prescribed, with increased morbidity and mortality. With the worldwide aging of the population characterized by a large influx of ＂baby boomers＂ with or without risk factors for developing AF, an epidemic is forecasted within the next 10 to 20 years. Although not all studies support this evidence, it is clear that AF is on the rise and a significant amount of health resources are invested in detecting and managing AF This review focuses on the worldwide burden of AF and reviews global health strategies focused on improving detection, prevention and risk stratification of AF, recently recommended by the World Heart Federation.展开更多
Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal t...Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.展开更多
Background:Rapid urbanization and globalization in developing countries have increased health issues like those in developed nations.Non-communicable diseases(NCDs),particularly stroke,have surged to become the leadin...Background:Rapid urbanization and globalization in developing countries have increased health issues like those in developed nations.Non-communicable diseases(NCDs),particularly stroke,have surged to become the leading cause of mortality.This study,conducted in the Ferlo region,Senegal,aims to assess the population’s knowledge,perceptions,and attitudes towards stroke and its preventable aspects.Methods:Conducted from May 2018 to June 2019,this cross-sectional study surveyed 366 participants aged 18 and above in the rural silvopastoral area of Widou Thiengoly.A structured questionnaire covered sociodemographics,medical history,personal habits,stroke awareness,and risk factors.Data analysis utilized Epi-info 2000 and GraphPad 5.Results:Stroke prevalence was 3.3%,with higher rates among those over 65.The term“stroke”was unfamiliar to 99.5% of participants,and only 30.3% recognized its symptoms.Only 11.7% identified stroke risk factors,highlighting the imperative for targeted education.Cultural beliefs,including fatalistic views of stroke,were present in 21% of respondents.Despite these challenges,the study’s robust methodology ensures valuable insights.Conclusion:This research reveals significant gaps in stroke awareness in Senegal,emphasizing the need for targeted educational interventions.The findings underscore the necessity of involving cultural and religious actors to enhance awareness and preventive measures effectively.展开更多
Lysophosphatidic acid(LPA)is an abundant,bioactive phospholipid,with multiple functions both in development and in pathological conditions.Here,we review the literature about the differential signaling of LPA through ...Lysophosphatidic acid(LPA)is an abundant,bioactive phospholipid,with multiple functions both in development and in pathological conditions.Here,we review the literature about the differential signaling of LPA through its specific receptors,which makes this lipid a versatile signaling molecule.This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis;and also,how it can act as a powerful mediator of pathological conditions,such as neuropathic pain,neurodegenerative diseases,and cancer progression.Ultimately,we review the preclinical and clinical uses of Autotaxin,LPA,and its receptors as therapeutic targets,approaching the most recent data of promising molecules modulating both LPA production and signaling.This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.展开更多
COVID-19 global pandemic,caused by severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),1 has swept 185 countries and regions with more than 2,824,728 confirmed cases,and 197,667 death as on April 25,2020 ...COVID-19 global pandemic,caused by severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),1 has swept 185 countries and regions with more than 2,824,728 confirmed cases,and 197,667 death as on April 25,2020 according the Coronavirus Resource Center at Johns Hopkins University.Accumulating data suggest that hypertension,diabetes,and cardiovascular diseases are the most frequent comorbidities in COVID-19 patients,and case mortality rates tended to be high in these individuals.展开更多
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are assoc...Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.展开更多
文摘Atrial fibrillation （AF） is the most common arrhythmia diagnosed in clinical practice. The consequences of AF have been clearly estab- lished in multiple large observational cohort studies and include increased stroke and systemic embolism rates if no oral anticoagulation is prescribed, with increased morbidity and mortality. With the worldwide aging of the population characterized by a large influx of ＂baby boomers＂ with or without risk factors for developing AF, an epidemic is forecasted within the next 10 to 20 years. Although not all studies support this evidence, it is clear that AF is on the rise and a significant amount of health resources are invested in detecting and managing AF This review focuses on the worldwide burden of AF and reviews global health strategies focused on improving detection, prevention and risk stratification of AF, recently recommended by the World Heart Federation.
文摘Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.
文摘Background:Rapid urbanization and globalization in developing countries have increased health issues like those in developed nations.Non-communicable diseases(NCDs),particularly stroke,have surged to become the leading cause of mortality.This study,conducted in the Ferlo region,Senegal,aims to assess the population’s knowledge,perceptions,and attitudes towards stroke and its preventable aspects.Methods:Conducted from May 2018 to June 2019,this cross-sectional study surveyed 366 participants aged 18 and above in the rural silvopastoral area of Widou Thiengoly.A structured questionnaire covered sociodemographics,medical history,personal habits,stroke awareness,and risk factors.Data analysis utilized Epi-info 2000 and GraphPad 5.Results:Stroke prevalence was 3.3%,with higher rates among those over 65.The term“stroke”was unfamiliar to 99.5% of participants,and only 30.3% recognized its symptoms.Only 11.7% identified stroke risk factors,highlighting the imperative for targeted education.Cultural beliefs,including fatalistic views of stroke,were present in 21% of respondents.Despite these challenges,the study’s robust methodology ensures valuable insights.Conclusion:This research reveals significant gaps in stroke awareness in Senegal,emphasizing the need for targeted educational interventions.The findings underscore the necessity of involving cultural and religious actors to enhance awareness and preventive measures effectively.
文摘Lysophosphatidic acid(LPA)is an abundant,bioactive phospholipid,with multiple functions both in development and in pathological conditions.Here,we review the literature about the differential signaling of LPA through its specific receptors,which makes this lipid a versatile signaling molecule.This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis;and also,how it can act as a powerful mediator of pathological conditions,such as neuropathic pain,neurodegenerative diseases,and cancer progression.Ultimately,we review the preclinical and clinical uses of Autotaxin,LPA,and its receptors as therapeutic targets,approaching the most recent data of promising molecules modulating both LPA production and signaling.This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.
文摘COVID-19 global pandemic,caused by severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),1 has swept 185 countries and regions with more than 2,824,728 confirmed cases,and 197,667 death as on April 25,2020 according the Coronavirus Resource Center at Johns Hopkins University.Accumulating data suggest that hypertension,diabetes,and cardiovascular diseases are the most frequent comorbidities in COVID-19 patients,and case mortality rates tended to be high in these individuals.
基金supported by the European Research Council(CoG 2020 grant number 101000948 awarded to GC)the Agence Nationale de la Recherche-Programme d’Investissements d’Avenir(ANR-18-RHUS-005 to GC)+1 种基金the Agence Nationale de la Recherche-Programme de Recherche Collaborative(19-CE14-0030-01 to GC)supported by the CLOVES SYNDROME COMMUNITY(West Kennebunk,USA),Association Syndrome de CLOVES(Nantes,France),Fondation d’entreprise IRCEM(Roubaix,France),Fonds de dotation Emmanuel BOUSSARD(Paris,France),the Fondation DAY SOLVAY(Paris,France),the Fondation TOURRE(Paris,France)to GC,the Fondation BETTENCOURT SCHUELLER(Paris,France)to GC,the Fondation Simone et Cino DEL DUCA(Paris,France),the Fondation Line RENAUD-Loulou GASTE(Paris,France,the Fondation Schlumberger pour l’Education et la Recherche(Paris,France),the Association Robert Debrépour la Recherche.
文摘Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
