Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, c...Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells（h AECs）, which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days poststroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that h AECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.展开更多
Positron emission tomography(PET)is a powerful noninvasive imaging tool for phenotyping patients at risk of or with known coronary artery disease(CAD).One of the key advantages over other imaging modalities is its uni...Positron emission tomography(PET)is a powerful noninvasive imaging tool for phenotyping patients at risk of or with known coronary artery disease(CAD).One of the key advantages over other imaging modalities is its unique ability to quantify physiologic processes,including myocardial blood fl ow(in milliliters per minute per gram of myocardium),metabolism,and cardiac receptors,and its high sensitivity for delineating and quantifying molecular targets in vivo using targeted imaging probes.Cardiac PET/CT offers opportunity for a comprehensive noninvasive evaluation of the consequences of atherosclerosis in the coronary arteries and the myocardium.展开更多
The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the las...The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease（Dinh et al.,2012;]aisser and Farman, 2016）.展开更多
Conventional recommendations for diagnostic testing for the evaluation of stable ischemic heart disease in women have largely paralleled those in men.Although they are designed primarily for the identifi cation of obs...Conventional recommendations for diagnostic testing for the evaluation of stable ischemic heart disease in women have largely paralleled those in men.Although they are designed primarily for the identifi cation of obstructive coronary artery disease(CAD),traditional approaches can lead to overtesting in women without differentiating who is truly at risk.Several unique factors related to the presentation,diagnosis,and underlying pathophysiology of stable ischemic heart disease in women necessitate a more specific approach to the assessment of their risk,complete with separate guidelines when appropriate.This overview highlights how advanced noninvasive imaging tools,including cardiac computed tomography angiography,positron emission tomography,and cardiac magnetic resonance imaging,are enabling very sensitive assessments of anatomic atherosclerotic plaque burden,macrovessel-and microvessel-related ischemia,and myocardial fi brosis,respectively.Moving forward,effective diagnostic testing will need to identify women at high risk of adverse cardiovascular events(not anatomically obstructive CAD per se)without overtesting those at low risk.Judicious application of novel imaging approaches will be critical to broadening the defi nitions of CAD and ischemia to better refl ect the whole spectrum of pathological phenotypes in women,including nonobstructive CAD and coronary microvascular dysfunction,and aid in the development of needed evidence-based strategies for their management.展开更多
Cardiovascular disease remains a leading cause of morbidity and mortality,a fact that is commonly associated with co-morbidities such as clinical depression.While phase II cardiac rehabilitation is an established inte...Cardiovascular disease remains a leading cause of morbidity and mortality,a fact that is commonly associated with co-morbidities such as clinical depression.While phase II cardiac rehabilitation is an established intervention for those with cardiovascular disease,its effect on patients who also suffer from depression are under studied.Aim:To quantify Pre-and Post-cardiac rehabilitation questionnaire scores collected from a large patient data registry.For this investigation,27670 patients completed Patient Health Questionnaire-9 questionnaires both Pre-and Post-rehabilitation(averaging[28.08.7]phase II sessions).Findings reveal that questionnaire scores decreased by 40%–48%across all groups,a finding that was independent of assigned sex,race,and ethnicity.Moreover,when data were stratified for questionnaire scores that may indicate major and minor depressive disorder,phase II cardiac rehabilitation outcomes were lower by 61%and 49%respectively.While all groups exhibited lower questionnaire scores following cardiac rehabilitation participation,numerical differences at Preand Post-rehabilitation time points indicate that males and White patients have more favorable scores.This latter observation,while not confirmed currently,appears to be linked to referral rates to phase II cardiac rehabilitation,which remain poor for females,racial and ethnic minorities.展开更多
Objective: We evaluated the cardiovascular pathologic condition in the recipient twin in twin- to- twin transfusion syndrome and the influence of amnioreduction. Study design: Fetal echocardiograms and medical records...Objective: We evaluated the cardiovascular pathologic condition in the recipient twin in twin- to- twin transfusion syndrome and the influence of amnioreduction. Study design: Fetal echocardiograms and medical records of 54 pregnancies that were complicated by twin-to-twin transfusion syndrome were reviewed. Recipient twin right and left ventricular wall thickness, diameters, systolic and diastolic function, valve regurgitation, and structural cardiac defects were assessed at examination and after amnioreduction. Results: At examination (n = 28 pregnancies), cardiomegaly because of right ventricular and/or left ventricular hypertrophy was observed in 58% of recipient twins, and biventricular hypertrophy was observed in 33% of recipient twins, without ventricular dilation. Biventricular diastolic dysfunction was present in two thirds of recipient twins, and right ventricular systolic dysfunction and significant atrioventricular valve regurgitation was observed in one third of recipient twins. Serial assessment (n = 21 pregnancies) revealed progressive biventricular hypertrophy and right ventricular systolic and biventricular diastolic dysfunction in most recipient twins. Steeper progression of hypertrophy, diastolic dysfunction, and structural or functional right ventricular outflow disease (20% incidence) were associated with an increased perinatal mortality rate. Conclusion: In twin- to- twin transfusion syndrome, the recipient twin has progressive biventricular hypertrophy with predominant right ventricular systolic and biventricular diastolic dysfunction. Despite amnioreduction, the cardiovascular disease persists and even progresses in many recipient twins.展开更多
Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African Amer...Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African American and white men an d women from the Atherosclerosis Risk in Communities Study, categorized by their lifetime history of headaches lasting ≥ 4 hours (migraine with aura, migraine without aura, other headaches with aura, other headaches without aura, no headac hes). Gender-specific associations of headaches with Rose angina and CHD, adju sted for sociodemographic and cardiovascular disease risk factors, were evaluate d using Poisson regression. Results: Participants with a history of migraines an d other headaches were more likely to have a history of Rose angina than those w ithout headaches. The associations were stronger for mi graine and other headaches with aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for men) than for migraine and other head aches without aura (PR = 1.5, 95% CI = 1.2, 1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR = 1.4, 95% CI = 1.0, 1.8 f or men). In contrast, migraine and other headaches were not associated with CHD, regardless of the presence of aura. Conclusions: The lack of association of mig raines with coronary heart disease suggests that the association of migraine wit h Rose angina is not related to coronary artery disease. Future research assessi ng other common underlying pathologic mechanisms is warranted.展开更多
To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficie...To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficiency of healthcare.[1]ACS comprises a wide spectrum of disease subgroups,including ST-segment elevation myocardial infarction(STEMI),unstable angina(UA),and non-ST-segment elevation myocardial infarction(NSTEMI).Previous studies have shown increases in the intensity of testing and treatment while stable in-hospital mortality for STEMI in China between 2001 and 2011.[2]As non-ST-segment elevation acute coronary syndrome(NSTE-ACS)patients,who account for about two-thirds of ACS patients,have a wide spectrum of disease severity,risk-stratified management is recommended to ensure appropriate allocation of resources,especially in limited-resource settings of China.As limited data exist on the use of medical services and clinical outcomes in relation to health reforms,we aimed to determine temporal trends in diagnosis,treatment,and outcome for hospitalized NSTE-ACS patients in three regions of China between 2008 and 2015.展开更多
Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is ...Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is characterised by transient left ventricular(LV)dysfunction independent of obstructive coronary artery disease.TS is a polygenic condition and nowhere is this more evident than the use of positive inotropes,such as isoprenaline(ISO)in pre-clinical models.1 There is no standard therapy for broken-heart syndrome because the mechanisms underlying the condition remain unknown.Furthermore,there is no consensus on predisposition for Takotsubo2 and our goal was to better understand the regulatory mechanism as a first step towards improved treatment plans.Suberanilohydroxamic acid or SAHA,a drug approved for cancer treatment by the US Food and Drug Administration has previously been shown to improve cardiopulmonary function.3 We tested the hypothesis that the cardioprotective benefit of SAHA in a pre-clinical model of Takotsubo is conferred by an epigenetic acetylation/deacetylation(Ac/Dc)axis.展开更多
文摘Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells（h AECs）, which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days poststroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that h AECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.
文摘Positron emission tomography(PET)is a powerful noninvasive imaging tool for phenotyping patients at risk of or with known coronary artery disease(CAD).One of the key advantages over other imaging modalities is its unique ability to quantify physiologic processes,including myocardial blood fl ow(in milliliters per minute per gram of myocardium),metabolism,and cardiac receptors,and its high sensitivity for delineating and quantifying molecular targets in vivo using targeted imaging probes.Cardiac PET/CT offers opportunity for a comprehensive noninvasive evaluation of the consequences of atherosclerosis in the coronary arteries and the myocardium.
基金supported by a postdoctoral fellowship from the National Health and Medical Research Council (NHMRC) of Australiathe Foundation for High Blood Pressure Research Australia (to SC)grants from the NHMRC and the National Heart Foundation of Australia
文摘The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease（Dinh et al.,2012;]aisser and Farman, 2016）.
文摘Conventional recommendations for diagnostic testing for the evaluation of stable ischemic heart disease in women have largely paralleled those in men.Although they are designed primarily for the identifi cation of obstructive coronary artery disease(CAD),traditional approaches can lead to overtesting in women without differentiating who is truly at risk.Several unique factors related to the presentation,diagnosis,and underlying pathophysiology of stable ischemic heart disease in women necessitate a more specific approach to the assessment of their risk,complete with separate guidelines when appropriate.This overview highlights how advanced noninvasive imaging tools,including cardiac computed tomography angiography,positron emission tomography,and cardiac magnetic resonance imaging,are enabling very sensitive assessments of anatomic atherosclerotic plaque burden,macrovessel-and microvessel-related ischemia,and myocardial fi brosis,respectively.Moving forward,effective diagnostic testing will need to identify women at high risk of adverse cardiovascular events(not anatomically obstructive CAD per se)without overtesting those at low risk.Judicious application of novel imaging approaches will be critical to broadening the defi nitions of CAD and ischemia to better refl ect the whole spectrum of pathological phenotypes in women,including nonobstructive CAD and coronary microvascular dysfunction,and aid in the development of needed evidence-based strategies for their management.
文摘Cardiovascular disease remains a leading cause of morbidity and mortality,a fact that is commonly associated with co-morbidities such as clinical depression.While phase II cardiac rehabilitation is an established intervention for those with cardiovascular disease,its effect on patients who also suffer from depression are under studied.Aim:To quantify Pre-and Post-cardiac rehabilitation questionnaire scores collected from a large patient data registry.For this investigation,27670 patients completed Patient Health Questionnaire-9 questionnaires both Pre-and Post-rehabilitation(averaging[28.08.7]phase II sessions).Findings reveal that questionnaire scores decreased by 40%–48%across all groups,a finding that was independent of assigned sex,race,and ethnicity.Moreover,when data were stratified for questionnaire scores that may indicate major and minor depressive disorder,phase II cardiac rehabilitation outcomes were lower by 61%and 49%respectively.While all groups exhibited lower questionnaire scores following cardiac rehabilitation participation,numerical differences at Preand Post-rehabilitation time points indicate that males and White patients have more favorable scores.This latter observation,while not confirmed currently,appears to be linked to referral rates to phase II cardiac rehabilitation,which remain poor for females,racial and ethnic minorities.
文摘Objective: We evaluated the cardiovascular pathologic condition in the recipient twin in twin- to- twin transfusion syndrome and the influence of amnioreduction. Study design: Fetal echocardiograms and medical records of 54 pregnancies that were complicated by twin-to-twin transfusion syndrome were reviewed. Recipient twin right and left ventricular wall thickness, diameters, systolic and diastolic function, valve regurgitation, and structural cardiac defects were assessed at examination and after amnioreduction. Results: At examination (n = 28 pregnancies), cardiomegaly because of right ventricular and/or left ventricular hypertrophy was observed in 58% of recipient twins, and biventricular hypertrophy was observed in 33% of recipient twins, without ventricular dilation. Biventricular diastolic dysfunction was present in two thirds of recipient twins, and right ventricular systolic dysfunction and significant atrioventricular valve regurgitation was observed in one third of recipient twins. Serial assessment (n = 21 pregnancies) revealed progressive biventricular hypertrophy and right ventricular systolic and biventricular diastolic dysfunction in most recipient twins. Steeper progression of hypertrophy, diastolic dysfunction, and structural or functional right ventricular outflow disease (20% incidence) were associated with an increased perinatal mortality rate. Conclusion: In twin- to- twin transfusion syndrome, the recipient twin has progressive biventricular hypertrophy with predominant right ventricular systolic and biventricular diastolic dysfunction. Despite amnioreduction, the cardiovascular disease persists and even progresses in many recipient twins.
文摘Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart di sease (CHD). Methods: Participants were 12,409 African American and white men an d women from the Atherosclerosis Risk in Communities Study, categorized by their lifetime history of headaches lasting ≥ 4 hours (migraine with aura, migraine without aura, other headaches with aura, other headaches without aura, no headac hes). Gender-specific associations of headaches with Rose angina and CHD, adju sted for sociodemographic and cardiovascular disease risk factors, were evaluate d using Poisson regression. Results: Participants with a history of migraines an d other headaches were more likely to have a history of Rose angina than those w ithout headaches. The associations were stronger for mi graine and other headaches with aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for men) than for migraine and other head aches without aura (PR = 1.5, 95% CI = 1.2, 1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR = 1.4, 95% CI = 1.0, 1.8 f or men). In contrast, migraine and other headaches were not associated with CHD, regardless of the presence of aura. Conclusions: The lack of association of mig raines with coronary heart disease suggests that the association of migraine wit h Rose angina is not related to coronary artery disease. Future research assessi ng other common underlying pathologic mechanisms is warranted.
基金the National Key Research and Development Program of the Ministry of Science and Technology of China(2020YFC2004803)the Beijing Municipal Commission of Science and Technology(No.D171100006817001).
文摘To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficiency of healthcare.[1]ACS comprises a wide spectrum of disease subgroups,including ST-segment elevation myocardial infarction(STEMI),unstable angina(UA),and non-ST-segment elevation myocardial infarction(NSTEMI).Previous studies have shown increases in the intensity of testing and treatment while stable in-hospital mortality for STEMI in China between 2001 and 2011.[2]As non-ST-segment elevation acute coronary syndrome(NSTE-ACS)patients,who account for about two-thirds of ACS patients,have a wide spectrum of disease severity,risk-stratified management is recommended to ensure appropriate allocation of resources,especially in limited-resource settings of China.As limited data exist on the use of medical services and clinical outcomes in relation to health reforms,we aimed to determine temporal trends in diagnosis,treatment,and outcome for hospitalized NSTE-ACS patients in three regions of China between 2008 and 2015.
基金A.E-O.dedicates this article to his late grandmother.Professor Sam El-Osta is a National Health and Medical Research Council(NHMRC)Senior Research Fellow(1154650)Funded by NSFC(81561128017)and NHMRC(1113188)International Joint Programme.
文摘Dear Editor,Takotsubo syndrome(TS)is a stress-induced non-ischaemic cardiomyopathy that is more common in women,but is associated with higher morbidity and mortality in males.Also known as broken-heart syndrome,TS is characterised by transient left ventricular(LV)dysfunction independent of obstructive coronary artery disease.TS is a polygenic condition and nowhere is this more evident than the use of positive inotropes,such as isoprenaline(ISO)in pre-clinical models.1 There is no standard therapy for broken-heart syndrome because the mechanisms underlying the condition remain unknown.Furthermore,there is no consensus on predisposition for Takotsubo2 and our goal was to better understand the regulatory mechanism as a first step towards improved treatment plans.Suberanilohydroxamic acid or SAHA,a drug approved for cancer treatment by the US Food and Drug Administration has previously been shown to improve cardiopulmonary function.3 We tested the hypothesis that the cardioprotective benefit of SAHA in a pre-clinical model of Takotsubo is conferred by an epigenetic acetylation/deacetylation(Ac/Dc)axis.
