Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction ...Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.展开更多
In the area of reservoir engineering,the optimization of oil and gas production is a complex task involving a myriad of interconnected decision variables shaping the production system's infrastructure.Traditionall...In the area of reservoir engineering,the optimization of oil and gas production is a complex task involving a myriad of interconnected decision variables shaping the production system's infrastructure.Traditionally,this optimization process was centered on a single objective,such as net present value,return on investment,cumulative oil production,or cumulative water production.However,the inherent complexity of reservoir exploration necessitates a departure from this single-objective approach.Mul-tiple conflicting production and economic indicators must now be considered to enable more precise and robust decision-making.In response to this challenge,researchers have embarked on a journey to explore field development optimization of multiple conflicting criteria,employing the formidable tools of multi-objective optimization algorithms.These algorithms delve into the intricate terrain of production strategy design,seeking to strike a delicate balance between the often-contrasting objectives.Over the years,a plethora of these algorithms have emerged,ranging from a priori methods to a posteriori approach,each offering unique insights and capabilities.This survey endeavors to encapsulate,catego-rize,and scrutinize these invaluable contributions to field development optimization,which grapple with the complexities of multiple conflicting objective functions.Beyond the overview of existing methodologies,we delve into the persisting challenges faced by researchers and practitioners alike.Notably,the application of multi-objective optimization techniques to production optimization is hin-dered by the resource-intensive nature of reservoir simulation,especially when confronted with inherent uncertainties.As a result of this survey,emerging opportunities have been identified that will serve as catalysts for pivotal research endeavors in the future.As intelligent and more efficient algo-rithms continue to evolve,the potential for addressing hitherto insurmountable field development optimization obstacles becomes increasingly viable.This discussion on future prospects aims to inspire critical research,guiding the way toward innovative solutions in the ever-evolving landscape of oil and gas production optimization.展开更多
Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now refe...Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.展开更多
Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC...Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC are best known for their critical role in allergic,but also inflammatory and other neuroimmune conditions.MC are stimulated by allergens,but also by many other environmental,neuroimmune,pathogenic and stress triggers.Stimulation of MC is called“activation”and is associated with the release of numerous neurohormonal,proinflammatory,tissue remodeling and vasoactive mediators via different secretory mechanisms,some of which do not involve the release of histamine and tryptase.However,mast cell activation and the subsequent responses may become excessive either because of persistent stimulation or dysregulation.Clinical and experimental evidence indicates that MC may be regulated by innate molecules,some derived from MC,themselves.However,discovery of such innate,natural,inhibitors has not been a priority even though they would substantially change the treatment of mast cell activation disorders(MCADs)since drugs that are available or under development focus on inducing MC apoptosis.Development of effective inhibitors of MC activation would require access to MC from healthy and MCAD subjects,preferably identical twins,that would allow differential investigation of the respective transcriptome.展开更多
文摘Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.
基金the support of EPIC - Energy Production Innovation Center, hosted by the University of Campinas (UNICAMP) and sponsored by Equinor Brazil and FAPESP - Sao Paulo Research Foundation (2021/04878- 7 and 2017/15736-3)financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior Brasil (CAPES) - Financing Code 001
文摘In the area of reservoir engineering,the optimization of oil and gas production is a complex task involving a myriad of interconnected decision variables shaping the production system's infrastructure.Traditionally,this optimization process was centered on a single objective,such as net present value,return on investment,cumulative oil production,or cumulative water production.However,the inherent complexity of reservoir exploration necessitates a departure from this single-objective approach.Mul-tiple conflicting production and economic indicators must now be considered to enable more precise and robust decision-making.In response to this challenge,researchers have embarked on a journey to explore field development optimization of multiple conflicting criteria,employing the formidable tools of multi-objective optimization algorithms.These algorithms delve into the intricate terrain of production strategy design,seeking to strike a delicate balance between the often-contrasting objectives.Over the years,a plethora of these algorithms have emerged,ranging from a priori methods to a posteriori approach,each offering unique insights and capabilities.This survey endeavors to encapsulate,catego-rize,and scrutinize these invaluable contributions to field development optimization,which grapple with the complexities of multiple conflicting objective functions.Beyond the overview of existing methodologies,we delve into the persisting challenges faced by researchers and practitioners alike.Notably,the application of multi-objective optimization techniques to production optimization is hin-dered by the resource-intensive nature of reservoir simulation,especially when confronted with inherent uncertainties.As a result of this survey,emerging opportunities have been identified that will serve as catalysts for pivotal research endeavors in the future.As intelligent and more efficient algo-rithms continue to evolve,the potential for addressing hitherto insurmountable field development optimization obstacles becomes increasingly viable.This discussion on future prospects aims to inspire critical research,guiding the way toward innovative solutions in the ever-evolving landscape of oil and gas production optimization.
基金suppor ted by the US Depar tment of Defense Congressionally Directed Medical Research Program (CDMRP)awards (http://cdmrp.army.mil/) W81XWH-16-1-0632 (Craddock PI),W81XWH-16-1-0552 (Craddock PI),W81XWH-18-1-0549 (Sullivan PI),W81XWH-13-2-0072 (Sullivan PI),and W81XWH-09-2-0071 (Klimas PI)a Veterans Affairs Merit Award (4987.69) to Dr.Nancy Klimas。
文摘Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
文摘Mast cells(MC)are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis.Yet,MC are best known for their critical role in allergic,but also inflammatory and other neuroimmune conditions.MC are stimulated by allergens,but also by many other environmental,neuroimmune,pathogenic and stress triggers.Stimulation of MC is called“activation”and is associated with the release of numerous neurohormonal,proinflammatory,tissue remodeling and vasoactive mediators via different secretory mechanisms,some of which do not involve the release of histamine and tryptase.However,mast cell activation and the subsequent responses may become excessive either because of persistent stimulation or dysregulation.Clinical and experimental evidence indicates that MC may be regulated by innate molecules,some derived from MC,themselves.However,discovery of such innate,natural,inhibitors has not been a priority even though they would substantially change the treatment of mast cell activation disorders(MCADs)since drugs that are available or under development focus on inducing MC apoptosis.Development of effective inhibitors of MC activation would require access to MC from healthy and MCAD subjects,preferably identical twins,that would allow differential investigation of the respective transcriptome.
