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RETRACTED ARTICLE: Artificial intelligence in disease diagnosis: a systematic literature review, synthesizing framework and future research agenda

Yogesh Kumar, Apeksha Koul, Ruchi Singla +1 more · Journal of Ambient Intelligence and Humanized Computing · 2022 · 975 citations

This systematic review of 219 papers on AI for disease diagnosis was retracted in 2026, meaning its conclusions — that AI achieves 85–99% accuracy across Alzheimer's, cancer, diabetes, heart disease, tuberculosis, stroke, hypertension, skin, and liver disease — cannot be relied upon, and for someone running a self-experiment, the key lesson is to never base personal health decisions on retracted or non-replicable AI research.

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries

Barrak Alahmad, Haitham Khraishah, Dominic Royé +43 more · Circulation · 2022 · 376 citations

Extreme hot and cold days increase your risk of dying from heart disease, stroke, and heart failure, with cold being roughly 4 times more deadly than heat — for every 1,000 cardiovascular deaths, extreme cold causes ~9 excess deaths while extreme heat causes ~2.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document†

A. Pieter Kappetein, Stuart J. Head, Philippe Généreux +19 more · European Heart Journal · 2012 · 1,031 citations

This consensus document standardises how researchers define and measure outcomes in transcatheter aortic valve implantation (TAVI) trials, providing a common language for comparing results across studies—essential for anyone wanting to interpret or replicate findings from heart valve replacement research.

Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline

Margaret E. Wierman, Wiebke Arlt, Rosemary Basson +5 more · The Journal of Clinical Endocrinology & Metabolism · 2014 · 355 citations

This clinical practice guideline, based on a systematic review of existing evidence, concludes that testosterone therapy should not be used routinely in women for any indication except short-term treatment of hypoactive sexual desire disorder in postmenopausal women, and even then only with careful monitoring because long-term safety data are lacking and no physiological testosterone preparations are approved for women in most countries.

Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson's disease: a double-blind, randomised controlled trial

Nicolien M. van der Kolk, Nienke M. de Vries, Roy P. C. Kessels +4 more · The Lancet Neurology · 2019 · 565 citations

Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report

EXPERT PANEL ON INTEGRATED GUIDELINES FOR CARDIOVASCULAR HEALTH AND RISK REDUCTION IN CHILDREN AND ADOLESCENTS · PEDIATRICS · 2011 · 2,570 citations

This expert panel report synthesised evidence from multiple large-scale studies (including the NHLBI-funded RCTs and the PDAY autopsy study) to create the first integrated paediatric cardiovascular health guidelines, finding that atherosclerosis begins in childhood and that specific lipid, blood pressure, and lifestyle targets can meaningfully reduce adult cardiovascular risk — but the evidence base for many recommendations remains surprisingly thin.

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults

John F. Trepanowski, Cynthia M. Kroeger, Adrienne Barnosky +9 more · JAMA Internal Medicine · 2017 · 626 citations

Alternate-day fasting produced the same weight loss as daily calorie restriction after 6 and 12 months (~6–7% of body weight), but had higher dropout rates (38% vs 29%) and worse adherence, with no additional benefits for heart health — and even a concerning rise in LDL cholesterol at 12 months.

A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia

Ronald Goldberg, David M. Kendall, Mark A. Deeg +8 more · Diabetes Care · 2005 · 795 citations

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.

Management of acute myocardial infarction in patients presenting with ST-segment elevation

F VandeWerf · European Heart Journal · 2003 · 1,449 citations

The management of acute myocardial infarction continues to undergo major changes. Good practice should be based on sound evidence derived from well-conducted clinical trials. Because of the great number of trials on new treatments performed in recent years and because of new diagnostic tests, the European Society of Cardiology decided that it was opportune to upgrade the 1996 guidelines and appointed a Task …

Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model

Rabea Hinkel, Daniela Penzkofer, Stefanie Zühlke +8 more · Circulation · 2013 · 315 citations

Blocking a specific microRNA (miR-92a) with a locked nucleic acid (LNA) inhibitor, delivered directly into the heart's blood vessels at the moment of reperfusion, reduced heart attack size by roughly one-third in pigs — but only when delivered locally via catheter, not when given intravenously.

A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes

Bethan E. Phillips, Benjamin M. Kelly, Mats Lilja +9 more · Frontiers in Endocrinology · 2017 · 99 citations

A 6-week program of just 15 minutes of high-intensity interval training (HIT) three times per week—totaling less than 45 minutes of exercise per week—improved aerobic capacity by 10%, reduced blood pressure by ~3%, and improved insulin resistance by ~16% in sedentary adults at risk for type 2 diabetes, with effects comparable to traditional 150-minute-per-week exercise programs.

Breaking Up Prolonged Sitting Reduces Postprandial Glucose and Insulin Responses

David W. Dunstan, Bronwyn A. Kingwell, Robyn N. Larsen +8 more · Diabetes Care · 2012 · 1,178 citations

OBJECTIVE: Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers, but intervention studies are required to investigate causality. We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking. RESEARCH DESIGN AND METHODS: Overweight/obese adults (n = 19), aged 45-65 years, were recruited for a randomized three-period, three-treatment acute crossover trial: 1) uninterrupted sitting; 2) seated with 2-min bouts of light-intensity walking every 20 min; and 3) seated with 2-min bouts of moderate-intensity walking every 20 min. A standardized test drink was provided after an initial 2-h period of uninterrupted sitting. The positive incremental area under curves (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink (75 g glucose, 50 g fat) were calculated for the respective treatments. RESULTS: The glucose iAUC (mmol/L) · h after both activity-break conditions was reduced (light: 5.2 [4.1-6.6]; moderate: 4.9 [3.8-6.1]; both P < 0.01) compared with uninterrupted sitting (6.9 [5.5-8.7]). Insulin iAUC (pmol/L) · h was also reduced with both activity-break conditions (light: 633.6 [552.4-727.1]; moderate: 637.6 [555.5-731.9], P < 0.0001) compared with uninterrupted sitting (828.6 [722.0-950.9]). CONCLUSIONS: Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postprandial glucose and insulin levels in overweight/obese adults. This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk.

High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial

Sophie Cassidy, Christian Thoma, Kate Hallsworth +5 more · Diabetologia · 2015 · 209 citations

Twelve weeks of high intensity intermittent training (HIIT) improved heart structure and pumping function, reduced liver fat by 39%, and lowered HbA1c in people with type 2 diabetes — suggesting that brief, intense exercise intervals can reverse early cardiac damage and metabolic dysfunction without requiring long workout sessions.

Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion

Hajime Kin · Cardiovascular Research · 2004 · 547 citations

OBJECTIVE: We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection. METHODS: In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated. RESULTS: Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*). CONCLUSIONS: (1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.

Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy

Elisa Giannetta, Andrea M. Isidori, Nicola Galea +7 more · Circulation · 2012 · 189 citations

Daily 100 mg sildenafil for 3 months reversed early signs of diabetic heart damage in men with type 2 diabetes, improving cardiac twisting mechanics by ~4 degrees and strain by ~3.3%, independent of blood pressure or blood sugar changes.

Comparison of High-Intensity Interval Training and Moderate-to-Vigorous Continuous Training for Cardiometabolic Health and Exercise Enjoyment in Obese Young Women: A Randomized Controlled Trial

Zhaowei Kong, Xitao Fan, Shengyan Sun +3 more · PLoS ONE · 2016 · 184 citations

Both high-intensity interval training (HIIT) and moderate-to-vigorous continuous training (MVCT) improved cardiorespiratory fitness by about 9–10% over 5 weeks in obese young women, but HIIT was more enjoyable and required half the exercise time (20 minutes vs. 40 minutes per session), making it a time-efficient alternative for people who struggle with exercise adherence.

2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes

Nikolaus Marx, Massimo Federici, Katharina Schütt +97 more · European Heart Journal · 2023 · 1,357 citations

Guidelines evaluate and summarize available evidence, with the aim of assisting health professionals in proposing the best diagnostic or therapeutic approach for an individual patient with a given condition. Guidelines are intended for use by health professionals and the European Society of Cardiology (ESC) makes its Guidelines freely available. ESC Guidelines do not override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient or the patient’s caregiver where appropriate and/or necessary. It is also the health professional’s responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription, and, where appropriate, to respect the ethical rules of their profession. ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. ESC Policies and Procedures for formulating and issuing ESC Guidelines can be found on the ESC website (https://www.escardio.org/Guidelines). The Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. The selection procedure aimed to include members from across the whole of the ESC region and from relevant ESC Subspecialty Communities. Consideration was given to diversity and inclusion, notably with respect to gender and country of origin. The Task Force performed a critical evaluation of diagnostic and therapeutic approaches, including assessment of the risk-benefit ratio. The strength of every recommendation and the level of evidence supporting them were weighed and scored according to pre-defined scales as outlined below. The Task Force followed ESC voting procedures, and all approved recommendations were subject to a vote and achieved at least 75% agreement among voting members. The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. Their declarations of interest were reviewed according to the ESC declaration of interest rules and can be found on the ESC website (http://www.escardio.org/Guidelines), and have been compiled in a report published in a supplementary document with the guidelines. The Task Force received its entire financial support from the ESC without any involvement from the healthcare industry. The ESC Clinical Practice Guidelines (CPG) Committee supervises and co-ordinates the preparation of new guidelines and is responsible for the approval process. ESC Guidelines undergo extensive review by the CPG Committee and external experts, including members from across the whole of the ESC region and from relevant ESC Subspecialty Communities and National Cardiac Societies. After appropriate revisions, the guidelines are signed off by all the experts involved in the Task Force. The finalized document is signed off by the CPG Committee for publication in the European Heart Journal. The guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their writing. Tables of evidence summarizing the findings of studies informing development of the guidelines are included. The ESC warns readers that the technical language may be misinterpreted and declines any responsibility in this respect. Off-label use of medication may be presented in the current Guidelines if a sufficient level of evidence shows that it can be considered medically appropriate for a given condition. However, the final decisions concerning an individual patient must be made by the responsible health professional giving special consideration to: The specific situation of the patient. Unless otherwise provided for by national regulations, off-label use of medication should be limited to situations where it is in the patient’s interest with regard to the quality, safety, and efficacy of care, and only after the patient has been informed and has provided consent. Country-specific health regulations, indications by governmental drug regulatory agencies, and the ethical rules to which health professionals are subject, where applicable.

2021 ESC/EACTS Guidelines for the management of valvular heart disease

Alec Vahanian, Friedhelm Beyersdorf, Fabien Praz +97 more · European Heart Journal · 2021 · 5,362 citations

International audience

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) * Developed with the special contribution of the European Association for Cardiovascular Prevention &amp; Rehabilitation (EACPR)

Authors/Task Force Members:, Joep Perk, Guy De Backer +84 more · European Heart Journal · 2012 · 8,514 citations

This is not a single experiment but a clinical practice guideline that synthesises decades of evidence to recommend specific targets for blood pressure (<140/90 mmHg), LDL cholesterol (<1.8 mmol/L for very high-risk individuals), and lifestyle behaviours (150+ minutes of moderate aerobic activity per week) to reduce cardiovascular disease risk, with the strongest effect sizes coming from smoking cessation (risk reduction of ~50% within one year) and statin therapy (LDL reduction of ~1.8 mmol/L reduces major vascular events by ~22% over five years).

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah A. Terrault, Lolu Ojo +4 more · Liver Transplantation · 2012 · 543 citations

This practice guideline has been approved by the American Association for the Study of Liver Diseases and the American Society of Transplantation. These recommendations provide a data-supported approach to management of adult patients who have successfully undergone liver transplantation. They are based on the following: (1) a formal review and analysis of recently published world literature on the topic (via a MEDLINE search); (2) A Manual for Assessing Health Practices and Designing Practice Guidelines (American College of Physicians)1; (3) guideline policies,2 including the American Association for the Study of Liver Diseases policy on the development and use of practice guidelines and the American Gastroenterological Association policy statement on guidelines3; and (4) the experience of the authors in the specified topic. Intended for use by physicians and health care providers working with adult recipients of liver transplantation (LT), these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the available evidence supporting the recommendations, the American Association for the Study of Liver Diseases Practice Guidelines Committee has adopted the classification used by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1).4 In the GRADE system, the strength of a recommendation is classified as (1) strong or (2) weak. The quality of evidence supporting a strong or weak recommendation is designated by 1 of 3 levels: (A) high, (B) moderate, or (C) low. AIH, autoimmune hepatitis; ALD, alcoholic liver disease; BMD, bone mineral density; CKD, chronic kidney disease; CMV, cytomegalovirus; CNI, calcineurin inhibitor; CUC, chronic ulcerative colitis; DM, diabetes mellitus; EBV, Epstein-Barr virus; ESRD, end-stage renal disease; FDA, Food and Drug Administration; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HAART, highly active antiretroviral therapy; HbA1c, hemoglobin A1c; HBIG, hepatitis B immune globulin; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; LT, liver transplantation; mTOR, mammalian target of rapamycin; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NODM, new-onset diabetes mellitus; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; PTLD, posttransplant lymphoproliferative disorder; TB, tuberculosis. LT is the treatment of choice for patients with decompensated cirrhosis, acute liver failure, small hepatocellular carcinomas (HCCs), or acute liver failure. The success of LT has meant that there is a growing cohort of LT recipients throughout the world. From 1985 through 2011, approximately 100,000 persons in the United States underwent LT. On December 30, 2011, there were 30,000 LT recipients who were alive and had survived at least 5 years, and there were more than 16,000 recipients with 10 or more years' survival. These long-term survivors are at risk of early death and increased morbidity. The purpose of this guideline is to assist in the management of adult recipients of LT, identify the barriers to maintaining their health, and make recommendations on the ways to best prevent or ameliorate these barriers. This guideline focuses on management beyond the first 90 days after transplantation. The greatest proportion of deaths or retransplants after LT occur soon after transplantation. The causes of death and graft loss vary according to the interval from transplantation, with infection and intraoperative and perioperative causes accounting for nearly 60% of deaths and graft losses in the first posttransplant year. After the first year, death due to acute and causes for a proportion of The of the hepatitis C or autoimmune liver is of graft loss the the transplantation for these death a for to acute or chronic is throughout the first 10 after transplantation. The liver of the for after the first 90 LT recipients this is patients throughout the of the The use of increased risk of and which be or as diabetes and and or posttransplant lymphoproliferative The of the of and the of the liver a of for LT analysis of a of LT recipients that the of kidney as a of of or or the development of end-stage renal at 5 and at 10 LT recipients have with a of and new-onset diabetes and and renal are the causes of and after LT (Table The of the as a chronic primary biliary primary sclerosing autoimmune hepatitis or HCC, and of the patients LT have a or of to or which with on health, by with risk of the quality of after LT has that quality in LT patients in in with their transplantation, LT recipients to have in with these are as and a of the of the or of for and the or treatment of liver the and the quality of be In these a to and ameliorate of is to success success for of liver and after LT, and are after the first 3 The is which for is the has The of in a with a liver the development of or a or of the or in a with a infection is a Liver are after LT. liver are for a the of on the and of or liver are in the of graft or in LT The causes of liver in the are in than 1 in the liver are in a LT is to the in 1 to A to be based on the and of the liver a and and of the be that liver and from the of biliary due to or of the or to or biliary to a of to and is with and the use of a including from more from after death with of or The of with liver be by the according to the from LT, the from LT, the of and the on the of liver and be Liver be is as the of liver or the to as or biliary and biliary be in a with in LT and biliary or is by is to the and for the choice of HCV, or autoimmune Drug calcineurin renal of and mammalian target of as are of or experience with the of or risk for of or risk for is for the of the choice of the and be by the and The is by the the target after 3 are 5 to 10 for and to for are The target for is 5 The for for is the used of are in The of LT recipients to graft A small of LT recipients to the and long-term is as that has more than 90 days after transplantation. have been as acute and and as of the and the is through the of liver the be on the of and the have been adopted to the and Liver in patients with with a in and is by the of of the or and a with and in The of be or the is more and as acute from early acute by of or due to autoimmune liver of The and autoimmune and be to from and the In of in of be in or the treatment be a of increased at or at for 3 followed by in the A as a to liver is in approximately of with approximately a of and is in the first occur at suggest that by human leukocyte in with a in the development of as The of is with a in liver with a in and followed by a in In the of and A liver with at least 10 is in to with that to and loss of have In the early of there be a more the the loss of from the and in be and for autoimmune to of a graft to The or and The treatment of is increased and in or to be in early than of the the to graft failure. for LT recipients be and by with and in that The choice of on and be for be at least every and as with the of long-term be on the of liver a be treatment and classified according to the the long-term of be in a small of this be with recipients and the risk of infection with by including and in and be for that and and to of LT recipients to to in as care and be with the to for the of LT recipients the of from and LT recipients and and and and LT recipients which and by LT to be with the a of to for the of LT recipients to prevent These and and LT recipients a review of to with LT recipients be the of and through the use of a with a of at least and They be to their on a and or to their physicians of the strong of and with the of is the LT recipients of a and the and of in the and be after transplantation loss and are with after LT. In the first there is bone loss in liver of the bone mineral that is with the of and After the first with bone and in the there be a in bone the with a in the of In patients with or this bone loss in a to at of bone and in the first after LT, there is a in the of the bone of LT recipients with In the early after LT, be in patients and every to 3 in patients with on risk than or and and risk at is be is or be The of is has been with for 10 for is in In the first 5 after transplantation, by be for patients and every to 3 for patients with on the of and on risk bone is or are patients be for risk for bone in this of and of and a and The LT and and be in LT recipients with or The of LT recipients who the first chronic kidney in this from to The of is due to the used to and the of posttransplant The risk of that or kidney transplantation is to the first 10 after of kidney in the United States are for LT recipients who The of in the LT is (Table and chronic to DM, chronic renal and perioperative acute kidney is with a risk of death more than 1 after LT in with recipients A is a and of in this that has been to have be the of in and the are to and in renal be in the of of the of is best by the of the of to in a and the use of that the are of treatment in the and be to have in LT A in the or a of to after LT is a practice at the of These on or in with to prevent acute use and or is more to be is the is and LT recipients with who a or kidney have a to 60% in long-term in with their of renal in LT recipients for the and management of use to the the of to in a be at least The or of is to the development of in LT recipients transplantation from or is in and be the for LT recipients who The of or in to and The to LT that are in The of after LT and NODM, of which is in the perioperative that is at the of transplantation after LT, and patients on a to early after LT. In LT recipients followed beyond 1 year, of the of vary from to after LT more than and to as are and the is and patients from to to the and in to that LT recipients The of the long-term management of diabetes after LT are from the for patients (Table is the target of hemoglobin and recommendation of a of than the that the more are be is or a be used in LT recipients with renal as and are there is in renal The of in LT recipients is and a small suggest that the of from to in patients with and The treatment of after LT for target of with a of modifications and as are is the and with which to as the interval from LT patients with experience a in and be is or be used in LT recipients with renal as and are there is of renal be to the of from to in LT recipients with in LT recipients the risk of and and there are of in LT is to target a treatment of in LT recipients with the management of LT to as and be the of the including loss in recipients the on and the of are of is and a of the target be as and be more in LT recipients the of The and be used with the of are as as in the treatment of LT and be used as in LT recipients with DM, CKD, of is these are used in with of the increased risk of or be used with The of with of be in LT recipients to the with that in LT The treatment of for a target of with a of modifications and as and be used as in LT recipients with DM, CKD, in to of LT recipients than that and is a risk for and (Table and have and the on the of in LT A and and have (Table The of after a is for LT a for the treatment of after LT. The of after a is for LT with or and are be with be by the of is first with fatty to this is for or be patients be followed for with the use of and is after LT. 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Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Melanie J. Davies, David A. D’Alessio, Judith Fradkin +7 more · Diabetes Care · 2018 · 3,499 citations

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.

2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention

Glenn N. Levine, Eric Bates, James C. Blankenship +15 more · Circulation · 2011 · 3,295 citations

Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology

Marco Ambrosetti, Ana Abreu, Ugo Corrà +25 more · European Journal of Preventive Cardiology · 2020 · 911 citations

This position paper synthesises decades of evidence showing that comprehensive cardiac rehabilitation — combining supervised exercise, risk factor management, psychosocial support, and patient education — reduces cardiovascular mortality by roughly 26% and all-cause hospitalisations by 18% across all major heart conditions, yet fewer than 40% of eligible patients in Europe actually receive it, making implementation the primary barrier to saving lives.

Canadian 24-Hour Movement Guidelines for Adults aged 18–64 years and Adults aged 65 years or older: an integration of physical activity, sedentary behaviour, and sleep

Robert Ross, Jean‐Philippe Chaput, Lora Giangregorio +29 more · Applied Physiology Nutrition and Metabolism · 2020 · 892 citations

This paper synthesises existing evidence to produce the first integrated 24-hour movement guidelines for adults, recommending specific daily targets for physical activity, sedentary behaviour, and sleep — showing that reallocating just 30 minutes of sedentary time to moderate-to-vigorous physical activity is associated with a 4–8% lower risk of all-cause mortality, and that meeting all three movement behaviour targets is associated with better health outcomes than meeting any single target alone.

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness

Raymond R. Townsend, Ian B. Wilkinson, Ernesto L. Schiffrin +11 more · Hypertension · 2015 · 1,408 citations

M uch has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as "cf" is used when speaking of specific segments of the arterial circulation.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy

Jeffrey A. Towbin, William J. McKenna, Dominic J. Abrams +27 more · Heart Rhythm · 2019 · 792 citations

Reduction in Inappropriate Therapy and Mortality through ICD Programming

Arthur J. Moss, Claudio Schuger, Christopher A. Beck +14 more · New England Journal of Medicine · 2012 · 1,357 citations

BACKGROUND: The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects. METHODS: We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay at ≥250 beats per minute) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute). RESULTS: During an average follow-up of 1.4 years, high-rate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (hazard ratio with high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval [CI], 0.13 to 0.34; P<0.001; hazard ratio with delayed therapy vs. conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P<0.001) and reductions in all-cause mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P=0.01; hazard ratio with delayed therapy vs. conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P=0.06). There were no significant differences in procedure-related adverse events among the three treatment groups. CONCLUSIONS: Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up. (Funded by Boston Scientific; MADIT-RIT ClinicalTrials.gov number, NCT00947310.).

2016 European Guidelines on cardiovascular disease prevention in clinical practice

Authors/Task Force Members, Massimo Piepoli, Arno W. Hoes +58 more · European Journal of Preventive Cardiology · 2016 · 1,352 citations

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

David B. Sacks, Mark A. Arnold, George L. Bakris +6 more · Clinical Chemistry · 2011 · 1,357 citations

BACKGROUND: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence Based Laboratory Medicine Committee of the AACC jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. CONTENT: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A(1c) (Hb A(1c)) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of Hb A(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.

The ‘Digital Twin’ to enable the vision of precision cardiology

Jorge Corral Acero, Francesca Margara, M Marciniak +36 more · European Heart Journal · 2020 · 785 citations

Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy

David M. Nathan, John B. Buse, Mayer B. Davidson +4 more · Diabetes Care · 2008 · 3,832 citations

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis

Nathalie Deckx, Inez Wens, Amber H. Nuyts +8 more · Mediators of Inflammation · 2016 · 67 citations

Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L(+) and CD80(+) pDC. Interestingly, the number of CD80(+) pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations

Marco Guazzi, Volker Adams, Viviane M. Conraads +9 more · Circulation · 2012 · 809 citations

American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity

Lawrence H. Kushi, Tim Byers, Colleen Doyle +5 more · CA A Cancer Journal for Clinicians · 2006 · 1,904 citations

The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

Maria Rosa Costanzo, Maria Rosa Costanzo, Anne I. Dipchand +56 more · The Journal of Heart and Lung Transplantation · 2010 · 1,641 citations

End Criteria for Reaching Maximal Oxygen Uptake Must Be Strict and Adjusted to Sex and Age: A Cross-Sectional Study

Elisabeth Edvardsen, Erlend Hem, Sigmund A. Anderssen · PLoS ONE · 2014 · 361 citations

OBJECTIVE: To describe different end criteria for reaching maximal oxygen uptake (VO2max) during a continuous graded exercise test on the treadmill, and to explore the manner by which different end criteria have an impact on the magnitude of the VO2max result. METHODS: A sample of 861 individuals (390 women) aged 20-85 years performed an exercise test on a treadmill until exhaustion. Gas exchange, heart rate, blood lactate concentration and Borg Scale6-20 rating were measured, and the impact of different end criteria on VO2max was studied;VO2 leveling off, maximal heart rate (HRmax), different levels of respiratory exchange ratio (RER), and postexercise blood lactate concentration. RESULTS: Eight hundred and four healthy participants (93%) fulfilled the exercise test until voluntary exhaustion. There were no sex-related differences in HRmax, RER, or Borg Scale rating, whereas blood lactate concentration was 18% lower in women (P<0.001). Forty-two percent of the participants achieved a plateau in VO2; these individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and 5% higher blood lactate concentration (P = 0.047) compared with participants who did not reach a VO2 plateau. When using RER ≥1.15 or blood lactate concentration ≥8.0 mmol•L(-1), VO2max was 4% (P = 0.012) and 10% greater (P<0.001), respectively. A blood lactate concentration ≥8.0 mmol•L(-1) excluded 63% of the participants in the 50-85-year-old cohort. CONCLUSIONS: A range of typical end criteria are presented in a random sample of subjects aged 20-85 years. The choice of end criteria will have an impact on the number of the participants as well as the VO2max outcome. Suggestions for new recommendations are given.

Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain

Matthew T. Buckley, Eric Sun, Benson M. George +9 more · Nature Aging · 2022 · 172 citations

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic regions for two interventions-heterochronic parabiosis and exercise. Aging clocks revealed that heterochronic parabiosis and exercise reverse transcriptomic aging in neurogenic regions, but in different ways. This study represents the first development of high-resolution aging clocks from single-cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.

The Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families

Shibu Yooseph, Granger Sutton, Douglas B. Rusch +30 more · PLoS Biology · 2007 · 928 citations

Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans) from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature.

Effects of age on tissues and regions of the cerebrum and cerebellum

Terry L. Jernigan, Sarah Archibald, Christine Fennema‐Notestine +4 more · Neurobiology of Aging · 2001 · 928 citations

A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue

Tina Rönn, Petr Volkov, Cajsa Davegårdh +10 more · PLoS Genetics · 2013 · 611 citations

Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of physical activity, before and after a six months exercise intervention. We also investigate the differences in adipose tissue DNA methylation between 31 individuals with or without a family history of type 2 diabetes. DNA methylation was analyzed using Infinium HumanMethylation450 BeadChip, an array containing 485,577 probes covering 99% RefSeq genes. Global DNA methylation changed and 17,975 individual CpG sites in 7,663 unique genes showed altered levels of DNA methylation after the exercise intervention (q<0.05). Differential mRNA expression was present in 1/3 of gene regions with altered DNA methylation, including RALBP1, HDAC4 and NCOR2 (q<0.05). Using a luciferase assay, we could show that increased DNA methylation in vitro of the RALBP1 promoter suppressed the transcriptional activity (p = 0.03). Moreover, 18 obesity and 21 type 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (q<0.05), including TCF7L2 (6 CpG sites) and KCNQ1 (10 CpG sites). A simultaneous change in mRNA expression was seen for 6 of those genes. To understand if genes that exhibit differential DNA methylation and mRNA expression in human adipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2 respectively in 3T3-L1 adipocytes, which resulted in increased lipogenesis both in the basal and insulin stimulated state. In conclusion, exercise induces genome-wide changes in DNA methylation in human adipose tissue, potentially affecting adipocyte metabolism.

Television Viewing Time and Mortality

David W. Dunstan, Elizabeth Barr, Geneviève N. Healy +7 more · Circulation · 2010 · 832 citations

BACKGROUND: Television viewing time, the predominant leisure-time sedentary behavior, is associated with biomarkers of cardiometabolic risk, but its relationship with mortality has not been studied. We examined the associations of prolonged television viewing time with all-cause, cardiovascular disease (CVD), cancer, and non-CVD/noncancer mortality in Australian adults. METHODS AND RESULTS: Television viewing time in relation to subsequent all-cause, CVD, and cancer mortality (median follow-up, 6.6 years) was examined among 8800 adults > or =25 years of age in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). During 58 087 person-years of follow-up, there were 284 deaths (87 CVD deaths, 125 cancer deaths). After adjustment for age, sex, waist circumference, and exercise, the hazard ratios for each 1-hour increment in television viewing time per day were 1.11 (95% confidence interval [CI], 1.03 to 1.20) for all-cause mortality, 1.18 (95% CI, 1.03 to 1.35) for CVD mortality, and 1.09 (95% CI, 0.96 to 1.23) for cancer mortality. Compared with a television viewing time of <2 h/d, the fully adjusted hazard ratios for all-cause mortality were 1.13 (95% CI, 0.87 to 1.36) for > or =2 to <4 h/d and 1.46 (95% CI, 1.04 to 2.05) for > or =4 h/d. For CVD mortality, corresponding hazard ratios were 1.19 (95% CI, 0.72 to 1.99) and 1.80 (95% CI, 1.00 to 3.25). The associations with both cancer mortality and non-CVD/noncancer mortality were not significant. CONCLUSIONS: Television viewing time was associated with increased risk of all-cause and CVD mortality. In addition to the promotion of exercise, chronic disease prevention strategies could focus on reducing sitting time, particularly prolonged television viewing.

Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear

JE LeDoux, Jiro Iwata, P Cicchetti +1 more · Journal of Neuroscience · 1988 · 1,596 citations

The purpose of the present study was to determine whether lesions of areas projected to by the central amygdaloid nucleus (ACE) would disrupt the classical conditioning of autonomic and/or behavioral emotional responses. The areas studied included 3 projection targets of the ACE: the lateral hypothalamic area (LH), midbrain central gray (CG) region, and bed nucleus of the stria terminalis (BNST). Lesions were made either electrolytically or by microinjection of ibotenic acid, which destroys local neurons without interrupting fibers of passage. Two weeks later, the animals were classically conditioned by pairing an acoustic stimulus with footshock. The next day, conditioned changes in autonomic activity (increases in arterial pressure) and emotional behavior ("freezing," or the arrest of somatomotor activity) evoked by the acoustic conditioned stimulus (CS) were measured during extinction trials. Electrolytic and ibotenic acid lesions of the LH interfered with the conditioned arterial pressure response, but did not affect conditioned freezing. Electrolytic lesions of the rostral CG disrupted conditioned freezing but not conditioned changes in arterial pressure. Ibotenic acid injected into the rostral CG reduced neither the arterial pressure nor the freezing response. Injection of ibotenic acid in the caudal CG, like electrolytic lesions of the rostral CG, disrupted the freezing, but not the arterial pressure response. Injection of ibotenic acid into the BNST had no effect on either response. These data demonstrate that neurons in the LH are involved in the autonomic, but not the behavioral, conditioned response pathway, whereas neurons in the caudal CG are involved in the behavioral, but not the autonomic, pathway. Different efferent projections of the central amygdala thus appear to mediate the behavioral and autonomic concomitants of conditioned fear.

Aerobic exercise intensity assessment and prescription in cardiac rehabilitation: a joint position statement of the European Association for Cardiovascular Prevention and Rehabilitation, the American Association of Cardiovascular and Pulmonary Rehabilitation and the Canadian Association of Cardiac Rehabilitation

Alessandro Mezzani, Larry F. Hamm, Andrew M. Jones +5 more · European Journal of Preventive Cardiology · 2012 · 545 citations

Aerobic exercise intensity prescription is a key issue in cardiac rehabilitation, being directly linked to both the amount of improvement in exercise capacity and the risk of adverse events during exercise. This joint position statement aims to provide professionals with up-to-date information regarding the identification of different exercise intensity domains, the methods of direct and indirect determination of exercise intensity for both continuous and interval aerobic training, the effects of the use of different exercise protocols on exercise intensity prescription and the indications for recommended exercise training prescription in specific cardiac patients' groups. The importance of functional evaluation through exercise testing prior to starting an aerobic training program is strongly emphasized, and ramp incremental cardiopulmonary exercise test, when available, is proposed as the gold standard for a physiologically comprehensive exercise intensity assessment and prescription. This may allow a shift from a 'range-based' to a 'threshold-based' aerobic exercise intensity prescription, which, combined with thorough clinical evaluation and exercise-related risk assessment, could maximize the benefits obtainable by the use of aerobic exercise training in cardiac rehabilitation.

Race, socioeconomic status, and health: Complexities, ongoing challenges, and research opportunities

David R. Williams, Selina A. Mohammed, Jacinta Leavell +1 more · Annals of the New York Academy of Sciences · 2010 · 1,462 citations

This paper provides an overview of racial variations in health and shows that differences in socioeconomic status (SES) across racial groups are a major contributor to racial disparities in health. However, race reflects multiple dimensions of social inequality and individual and household indicators of SES capture relevant but limited aspects of this phenomenon. Research is needed that will comprehensively characterize the critical pathogenic features of social environments and identify how they combine with each other to affect health over the life course. Migration history and status are also important predictors of health and research is needed that will enhance understanding of the complex ways in which race, SES, and immigrant status combine to affect health. Fully capturing the role of race in health also requires rigorous examination of the conditions under which medical care and genetic factors can contribute to racial and SES differences in health. The paper identifies research priorities in all of these areas.

The effects of saffron (<i><scp>Crocus sativus</scp> L</i>.) in conjunction with concurrent training on body composition, glycaemic status, and inflammatory markers in obese men with type 2 diabetes mellitus: A randomized double‐blind clinical trial

Babak Hooshmand Moghadam, Amir Rashidlamir, Seyyed Reza Attarzadeh Hosseini +2 more · British Journal of Clinical Pharmacology · 2022 · 31 citations

AIMS: Chronic inflammation is one of the major challenges in the management of obesity and type 2 diabetes mellitus (T2DM). Our primary aim was to assess the anti-inflammatory effects of Saffron (Crocus sativus L.) supplementation and concurrent training in obese men with T2DM. METHODS: Sixty obese men with T2DM (age = 39 ± 5 years; body mass = 93.9 ± 6 kg) were randomly assigned to four groups; concurrent training + placebo (CT; n = 15), saffron supplementation (S; n = 15), concurrent training + saffron supplementation (CTS; n = 15), or control (CON; n = 15). The participants in the CT group performed concurrent training (resistance + aerobic) three times per week for 12 weeks and received daily one pill of placebo (maltodextrin); the participants in the S group supplemented with one pill of 100 mg of saffron daily, and the participants in the CTS group participated in both saffron and training intervention while CON group continued regular lifestyle (no training and no supplementation). Inflammatory markers, body composition (evaluated by a multi-frequency bioelectrical impedance device; Jawon X-Contact 356), and metabolic profile were evaluated before and after interventions. RESULTS: All three interventions significantly (P < .05) decreased TNF-α (CT = -4.22, S = -1.91, CTS = -9.69 pg/mL), hs-CRP (CT = -0.13, S = -0.1, CTS = -0.32 ng/mL), IL-6 (CT = -6.84, S = -6.36, CTS = -13.55 pg/mL), IL-1β (CT = -8.85, S = -6.46, CTS = -19.8 pg/mL), FBG (CT = -6.97, S = -2.45, CTS = -13.86 mg/dL), insulin (CT = -0.13, S = -0.03, CTS = -0.21 mU/L), HOMA-IR (CT = -0.12, S = -0.04, CTS = -0.21), HbA1c (CT = -0.17, S = -0.11, CTS = -0.26%), and increased IL-10 (CT = 1.09, S = 0.53, CTS = 2.27 pg/mL) concentrations. There was a positive correlation between changes in BFP with hs-CRP, IL-6, IL-1β and TNF-α, and IL-10 concentrations across the intervention groups. Additionally, significant differences were observed between the changes for all variables in the CTS group compared to CT, S and CON groups (P < .05). CONCLUSION: It seems that an interaction of saffron supplementation and concurrent training has more efficient effects on anti-inflammatory status compared to saffron supplementation or concurrent training alone.

Can exercise affect immune function to increase susceptibility to infection?

Richard J. Simpson, John P. Campbell, Maree Gleeson +5 more · PubMed · 2020 · 378 citations

Multiple studies in humans and animals have demonstrated the profound impact that exercise can have on the immune system. There is a general consensus that regular bouts of short-lasting (i.e. up to 45 minutes) moderate intensity exercise is beneficial for host immune defense, particularly in older adults and people with chronic diseases. In contrast, infection burden is reported to be high among high performance athletes and second only to injury for the number of training days lost during preparation for major sporting events. This has shaped the common view that arduous exercise (i.e. those activities practiced by high performance athletes/ military personnel that greatly exceed recommended physical activity guidelines) can suppress immunity and increase infection risk. However, the idea that exercise per se can suppress immunity and increase infection risk independently of the many other factors (e.g. anxiety, sleep disruption, travel, exposure, nutritional deficits, environmental extremes, etc.) experienced by these populations has recently been challenged. The purpose of this debate article was to solicit opposing arguments centered around this fundamental question in the exercise immunology field: can exercise affect immune function to increase susceptibility to infection. Issues that were contested between the debating groups include: (i) whether or not athletes are more susceptible to infection (mainly of the upper respiratory tract) than the general population; (ii) whether exercise per se is capable of altering immunity to increase infection risk independently of the multiple factors that activate shared immune pathways and are unique to the study populations involved; (iii) the usefulness of certain biomarkers and the interpretation of in vitro and in vivo data to monitor immune health in those who perform arduous exercise; and (iv) the quality of scientific evidence that has been used to substantiate claims for and against the potential negative effects of arduous exercise on immunity and infection risk. A key point of agreement between the groups is that infection susceptibility has a multifactorial underpinning. An issue that remains to be resolved is whether exercise per se is a causative factor of increased infection risk in athletes. This article should provide impetus for more empirical research to unravel the complex questions that surround this contentious issue in the field of exercise immunology.

Effects of Physical Activity and Inactivity on Muscle Fatigue

Gregory C. Bogdanis · Frontiers in Physiology · 2012 · 339 citations

The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural, and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity, and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short-duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fiber composition, neuromuscular characteristics, high energy metabolite stores, buffering capacity, ionic regulation, capillarization, and mitochondrial density. Muscle fiber-type transformation during exercise training is usually toward the intermediate type IIA at the expense of both type I and IIx myosin heavy-chain isoforms. High-intensity training results in increases of both glycolytic and oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis and regulation of K(+), H(+), and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fiber cross-sectional area, decreased oxidative capacity, and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high-intensity exercise training in patients with different health conditions to demonstrate the powerful effect of exercise on health and well being.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol

Katrin A. Dias, Jeff S. Coombes, Daniel J. Green +12 more · BMJ Open · 2016 · 38 citations

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106.

AMON: A Wearable Multiparameter Medical Monitoring and Alert System

U. Anliker, Jamie A. Ward, Paul Lukowicz +13 more · IEEE Transactions on Information Technology in Biomedicine · 2004 · 698 citations

This paper describes an advanced care and alert portable telemedical monitor (AMON), a wearable medical monitoring and alert system targeting high-risk cardiac/respiratory patients. The system includes continuous collection and evaluation of multiple vital signs, intelligent multiparameter medical emergency detection, and a cellular connection to a medical center. By integrating the whole system in an unobtrusive, wrist-worn enclosure and applying aggressive low-power design techniques, continuous long-term monitoring can be performed without interfering with the patients' everyday activities and without restricting their mobility. In the first two and a half years of this EU IST sponsored project, the AMON consortium has designed, implemented, and tested the described wrist-worn device, a communication link, and a comprehensive medical center software package. The performance of the system has been validated by a medical study with a set of 33 subjects. The paper describes the main concepts behind the AMON system and presents details of the individual subsystems and solutions as well as the results of the medical validation.

Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure.

K. T. Weber, Gary T. Kinasewitz, Joseph S. Janicki +1 more · Circulation · 1982 · 918 citations

Muscular work requires the integration of cardiopulmonary mechanisms for gas exchange and O2 delivery. In patients with chronic cardiac failure, the response of these mechanisms may be impaired, and the pattern of O2 utilization (VO2) and gas exchange during exercise would thus provide an objective assessment of the severity of heart failure. Accordingly, rates of air flow, O2 uptake, CO2 elimination and minute ventilation were determined during progressive treadmill exercise in 62 patients with stable heart failure. Exercise cardiac output, systemic O2 extraction and lactate production were measured directly in 40 patients with heart failure of varying severity. As the severity of heart failure increased from class A to D, there was a progressive decrease in exercise capacity (from 1157 +/- 154 to 373 +/- 157 seconds) and maximum VO2 (23 +/- 3.2 to 8.4 +/- 1.5 ml/min/kg). These decreases corresponded with the reduced maximum cardiac output and stroke volume during exercise. The appearance of anaerobic metabolism (580 +/- 17 to 157 +/- 7 seconds of exercise) and the corresponding anaerobic threshold (17 +/- 0.34 to 7.1 +/- 1.5 ml/min/kg), determined noninvasively, were reproducible and correlated with the rise in mixed venous lactate concentration. No apparent untoward effects were experienced during or after the progressive exercise test. We conclude that the measurement of respiratory gas exchange and air flow during exercise is an objective, reproducible and safe noninvasive method for characterizing cardiac reserve and functional status in patients with chronic cardiac failure.