This document summarizes research on quantifying cardiovascular and behavioral correlates of fear in mice, with implications for PTSD and cardiovascular disease risk. The research pairs behavioral and cardiovascular responses to cued fear learning in mice. It demonstrates that fear-based disorders like PTSD can contribute to increased cardiovascular disease risk by causing physiological hyperarousal and impaired fear processing. The researchers developed methods to remotely trigger conditioned stimuli based on a mouse's cardiovascular state, allowing measurement of cardiovascular responses to learned fear in the home cage environment. This integrated approach provides insights into mechanisms linking PTSD and cardiovascular dysfunction.
Postural Orthostatic Tachycardia Syndrome – Overview and Focus on Non-Pharmac...InsideScientific
During this webinar, sponsored by Finapres Medical Systems, Satish Raj, MD MSCI and Kate Bourne, BSc from the University of Calgary will briefly overview POTS, including diagnostic criteria, common symptoms and highlights from a large patient community survey. Following, they will then outline some of the non-pharmacological approaches to the management of the patient with POTS. Throughout this webinar there will be particular emphasis on recent data on the hemodynamic and symptomatic benefits of compression garments in the patients with POTS.
For more information, please visit: https://insidescientific.com/webinar/postural-orthostatic-tachycardia-syndrome-overview-and-focus-on-non-pharmacological-approaches/
Data Collection & Analysis in Human Autonomic Research: How to Guide to Succe...InsideScientific
This document discusses data collection and analysis in human autonomic research. It begins by outlining key learning objectives such as selecting appropriate equipment for research questions and creating a research setting conducive to reliable data collection. Several tests for measuring basal versus reflex autonomic control are described, including measures of sympathetic activity like plasma norepinephrine levels and neural recordings, and parasympathetic activity measured via cardiac vagal recordings and heart rate variability. Guidelines for optimizing heart rate variability analysis and potential issues to consider are also reviewed.
Pulse Wave Velocity: Theory, Applications, Methods, and Future DirectionsInsideScientific
Lee Stoner, PhD and Gabriel Zieff, MA present a complete, in-depth overview of their research involving Pulse Wave Velocity (PWV) in a variety of different applications and a deep dive into the methods they use to record high-quality, repeatable data.
Arguably, the “gold-standard” method for noninvasive assessment of cardiovascular disease risk is pulse wave velocity. The PWV is widely used in both epidemiological and physiological studies to assess arterial stiffness, a construct dependent on the functional and structural characteristics of a vessel. PWV is calculated by measuring the transit time of the arterial waveform between two points of a measured distance. The most widely studied path is between the carotid and femoral arteries, which represents the aorto-illiac pathway. Traditionally, these measurements are made using tonometers, which are highly sensitive pressure transducers. However, alternative approaches to tonometry are available, and pathways other than the aorta can be measured. These alternative approaches may be better suited for use with certain populations or study designs. The focus of the presentation is to assist the audience in identifying the correct research tool for their particular research paradigm. Specifically, these experts outline the theoretical principles underlying PWV, as well as the importance of this measure to both epidemiological and physiological studies. Subsequently, they highlight some of the different approaches for measuring PWV, including technical considerations. This is followed by discussion pertaining to the identification of the appropriate PWV measure for the specific study design and populations of interest. This includes consideration of internal and external validity. They end the session by providing some tips to facilitate high-quality PWV assessments.
Key Topics Include:
- Meaning and clinical importance of pulse wave velocity
- How to measure and interpret pulse wave velocity
- Considerations for internal- and external-validity
- Considerations for the measurement of pulse wave velocity of various study designs and populations
Reducing Perioperative Cardiac Risk: Do Beta blockers Help?Terry Shaneyfelt
Review of the effect of beta blockers on perioperative cardiac events including updated recommendations by the ACC/AHA (August 2014. Watch my YouTube video (http://youtu.be/WPLXDm9Nzoc) describing these slides.
Measuring and Quantifying Sympathetic Control of the Cutaneous MicrovasculatureInsideScientific
Climate change is the biggest global health threat of the 21st century and will continue to result in more intense, more frequent, and longer lasting extreme heat events, all of which have dire implications for nearly every aspect of human life. Older adults are particularly vulnerable to heat exposure, and excessive heat-related mortality in aged adults can be partly attributed to the cardiovascular consequences of age-related impairments in thermoregulatory reflex function. In a series of studies, Dr. Jody Greaney’s laboratory has used microneurography to directly record skin sympathetic nervous system activity in conscious aged humans during environmental provocations as a means to examine the efferent arc of the thermoregulatory reflex axis.
This presentation will provide a brief overview of the development of the technique of microneurography, with a focus on the unique issues related to its analysis, quantification and interpretation. It will also discuss how this approach, coupled with laser Doppler flowmetry-derived estimates of skin blood flow, has helped to advance our understanding of age-related alterations in thermoregulatory reflex function.
Key Topics Include:
- Understand the utility of microneurography as a means to measure and quantify skin sympathetic nervous system activity during thermal perturbations in humans
- Understand the considerations related to the analysis, quantification, and interpretation of microneurographic recordings of skin sympathetic nervous system activity
- Understand the application of these methodological approaches for assessing sympathetic control of microvascular function during whole-body environmental stressors
This document discusses hypoperfusion in acute heart failure. It begins with case examples from Duke Hospital and considerations for diagnosis. It then covers inotropic options and mechanical support devices. Various studies on inotropes, percutaneous support devices, and extracorporeal membrane oxygenation are summarized. The conclusion is that hypoperfusion in acute heart failure presents major challenges for diagnosis and treatment.
This document provides an agenda for the Arrhythmias and Clinical EP session at the ACC.15 conference on March 14, 2015. It includes details on three case presentations that will be given on syncope in an 82-year-old male, a 32-year-old female college student, and an 18-year-old female high school student. It also lists over 200 poster contributions that will be presented on topics related to arrhythmias epidemiology, atrial fibrillation, and more. The document provides times, presenters, locations and other logistical information for the conference sessions.
Postural Orthostatic Tachycardia Syndrome – Overview and Focus on Non-Pharmac...InsideScientific
During this webinar, sponsored by Finapres Medical Systems, Satish Raj, MD MSCI and Kate Bourne, BSc from the University of Calgary will briefly overview POTS, including diagnostic criteria, common symptoms and highlights from a large patient community survey. Following, they will then outline some of the non-pharmacological approaches to the management of the patient with POTS. Throughout this webinar there will be particular emphasis on recent data on the hemodynamic and symptomatic benefits of compression garments in the patients with POTS.
For more information, please visit: https://insidescientific.com/webinar/postural-orthostatic-tachycardia-syndrome-overview-and-focus-on-non-pharmacological-approaches/
Data Collection & Analysis in Human Autonomic Research: How to Guide to Succe...InsideScientific
This document discusses data collection and analysis in human autonomic research. It begins by outlining key learning objectives such as selecting appropriate equipment for research questions and creating a research setting conducive to reliable data collection. Several tests for measuring basal versus reflex autonomic control are described, including measures of sympathetic activity like plasma norepinephrine levels and neural recordings, and parasympathetic activity measured via cardiac vagal recordings and heart rate variability. Guidelines for optimizing heart rate variability analysis and potential issues to consider are also reviewed.
Pulse Wave Velocity: Theory, Applications, Methods, and Future DirectionsInsideScientific
Lee Stoner, PhD and Gabriel Zieff, MA present a complete, in-depth overview of their research involving Pulse Wave Velocity (PWV) in a variety of different applications and a deep dive into the methods they use to record high-quality, repeatable data.
Arguably, the “gold-standard” method for noninvasive assessment of cardiovascular disease risk is pulse wave velocity. The PWV is widely used in both epidemiological and physiological studies to assess arterial stiffness, a construct dependent on the functional and structural characteristics of a vessel. PWV is calculated by measuring the transit time of the arterial waveform between two points of a measured distance. The most widely studied path is between the carotid and femoral arteries, which represents the aorto-illiac pathway. Traditionally, these measurements are made using tonometers, which are highly sensitive pressure transducers. However, alternative approaches to tonometry are available, and pathways other than the aorta can be measured. These alternative approaches may be better suited for use with certain populations or study designs. The focus of the presentation is to assist the audience in identifying the correct research tool for their particular research paradigm. Specifically, these experts outline the theoretical principles underlying PWV, as well as the importance of this measure to both epidemiological and physiological studies. Subsequently, they highlight some of the different approaches for measuring PWV, including technical considerations. This is followed by discussion pertaining to the identification of the appropriate PWV measure for the specific study design and populations of interest. This includes consideration of internal and external validity. They end the session by providing some tips to facilitate high-quality PWV assessments.
Key Topics Include:
- Meaning and clinical importance of pulse wave velocity
- How to measure and interpret pulse wave velocity
- Considerations for internal- and external-validity
- Considerations for the measurement of pulse wave velocity of various study designs and populations
Reducing Perioperative Cardiac Risk: Do Beta blockers Help?Terry Shaneyfelt
Review of the effect of beta blockers on perioperative cardiac events including updated recommendations by the ACC/AHA (August 2014. Watch my YouTube video (http://youtu.be/WPLXDm9Nzoc) describing these slides.
Measuring and Quantifying Sympathetic Control of the Cutaneous MicrovasculatureInsideScientific
Climate change is the biggest global health threat of the 21st century and will continue to result in more intense, more frequent, and longer lasting extreme heat events, all of which have dire implications for nearly every aspect of human life. Older adults are particularly vulnerable to heat exposure, and excessive heat-related mortality in aged adults can be partly attributed to the cardiovascular consequences of age-related impairments in thermoregulatory reflex function. In a series of studies, Dr. Jody Greaney’s laboratory has used microneurography to directly record skin sympathetic nervous system activity in conscious aged humans during environmental provocations as a means to examine the efferent arc of the thermoregulatory reflex axis.
This presentation will provide a brief overview of the development of the technique of microneurography, with a focus on the unique issues related to its analysis, quantification and interpretation. It will also discuss how this approach, coupled with laser Doppler flowmetry-derived estimates of skin blood flow, has helped to advance our understanding of age-related alterations in thermoregulatory reflex function.
Key Topics Include:
- Understand the utility of microneurography as a means to measure and quantify skin sympathetic nervous system activity during thermal perturbations in humans
- Understand the considerations related to the analysis, quantification, and interpretation of microneurographic recordings of skin sympathetic nervous system activity
- Understand the application of these methodological approaches for assessing sympathetic control of microvascular function during whole-body environmental stressors
This document discusses hypoperfusion in acute heart failure. It begins with case examples from Duke Hospital and considerations for diagnosis. It then covers inotropic options and mechanical support devices. Various studies on inotropes, percutaneous support devices, and extracorporeal membrane oxygenation are summarized. The conclusion is that hypoperfusion in acute heart failure presents major challenges for diagnosis and treatment.
This document provides an agenda for the Arrhythmias and Clinical EP session at the ACC.15 conference on March 14, 2015. It includes details on three case presentations that will be given on syncope in an 82-year-old male, a 32-year-old female college student, and an 18-year-old female high school student. It also lists over 200 poster contributions that will be presented on topics related to arrhythmias epidemiology, atrial fibrillation, and more. The document provides times, presenters, locations and other logistical information for the conference sessions.
1. Recurrent myocardial infarction (MI) after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) occurs in about 21% of patients and is associated with worse clinical outcomes.
2. Recurrent MI significantly increases the risks of subsequent cardiac mortality, noncardiac mortality, stroke, and bleeding.
3. Early recurrent MIs within 1 day of the initial PPCI are associated with higher unadjusted cardiac mortality compared to later recurrent MIs, but after adjustment, recurrent MIs occurring more than 1 year after PPCI carry the highest risk of cardiac death.
Prospective, randomized comparison of two biphasicalatawi2
This study compared the effectiveness and safety of two biphasic waveforms - biphasic truncated exponential (BTE) and biphasic rectilinear (BR) - for external cardioversion of atrial fibrillation. 141 patients were randomized to receive transthoracic shocks using either the BTE or BR waveform. The success rate was similar between the two waveforms (93% for BR vs 97% for BTE), though cumulative energy delivered was lower in the BTE group. Only duration of atrial fibrillation was significantly associated with cardioversion success. No significant complications occurred with either waveform. The study found no significant difference in efficacy between the BR and BTE waveforms for transthoracic cardio
A Study of Heart Rate Recovery Following Exercise in Healthy Young Adult MaleIOSR Journals
Abstract: Exercise has positive chronotropic effect on heart rate and on cessation heart rate returns to preexercise
level. A delay in heart rate recovery (HRR) (≤12beats in first minute) is considered abnormal and
reflects autonomic dysfunction.The present study was taken up to find out the presence of abnormal HRR in
normal subjects (Male) and to establish HRR as an independent autonomic marker. For the study 106 healthy
young adults (male) were subjected to exercise by Bicycle ergometer till targeted Heart Rate (85%Maximum
Heart Rate(MHR)) was achieved. HRR at the end of 1 minutefollowingcessation of exercise were tabulated. In
our study 23(21.7%) subjects showed Abnormal HRR indicating HRR could be an independent autonomic
marker. Keyword-HRR, MHR
This document summarizes several recent studies and FDA approvals related to cardiac devices:
1. A study found that a common defibrillation test for ICD patients may be unnecessary, as a no-test group had equivalent safety outcomes.
2. The FDA approved the CardioMEMS pulmonary pressure monitoring system for use in heart failure patients.
3. The FDA approved expanded use of CRT devices for patients with mild heart failure and AV block, based on the BLOCK-HF trial showing benefits of CRT-D and CRT-P in those with LVEF <35% and QRS >130ms.
Cerebral perfusion pressure among acute traumatic brain injury patients at su...Alexander Decker
1. This study assessed the effects of supine and semi-fowler positions on cerebral perfusion pressure (CPP) and other physiological parameters among 39 patients with acute traumatic brain injuries.
2. In the semi-fowler position, patients experienced a significant increase in CPP, oxygen levels, blood pressure, and decrease in carbon dioxide levels compared to supine. The semi-fowler position was found to positively impact blood gas values, blood pressure, respiration, and oxygen saturation.
3. The supine position was associated with a significant decrease in pulse rate but no other significant changes. The study recommends further research on additional positions like side-lying and prone to establish optimal positioning guidelines for traumatic brain injury patients
Therapeutic hypothermia a physiological analysis of a new potential for post...Pedram Rahmanian
Therapeutic hypothermia (TH) involves lowering a patient's body temperature after cardiac arrest to improve outcomes. The document analyzes why TH increases survival rates for out-of-hospital cardiac arrest caused by ventricular fibrillation. It discusses the history of TH, major clinical trials showing improved survival and neurological function with TH, and the physiology of how hypothermia reduces reperfusion injury after cardiac arrest. The author concludes that TH should be implemented as part of standard post-cardiac arrest care due to the compelling evidence that it improves both survival and reduces disability.
This document discusses potential new diagnostic methods for studying sudden cardiac death. It notes that in about 20% of cases, no abnormality is found at autopsy to explain the cause of death. It proposes stressing the heart under normal and abnormal conditions to better understand its metabolic responses. This could help clarify pathological causes and allow for improved drug design strategies. The document advocates translating diagnostic approaches across medical disciplines to gain new insights. Overall, it presents the idea of developing innovative tests to evaluate the heart's local biochemical status under varying conditions in order to help prevent unexpected cardiac events, especially in young people.
This document summarizes several key points about complications related to intensive care, focusing on delirium and ICU-acquired weakness.
The main points are:
1) Delirium and coma in the ICU can lead to acute brain dysfunction and increased mortality. Delirium is also associated with long-term cognitive impairment and brain atrophy.
2) ICU stays can cause rapid muscle weakness starting in the acute phase, and this is related to poorer quality of life and depression after discharge.
3) Delirium is characterized by acute changes in mental state and cognition. It occurs in 40-80% of patients on mechanical ventilation and affects prognosis even after ICU discharge.
This study evaluated how the SGLT2 inhibitor empagliflozin affects cardiac energy production and substrate use in diabetic mice. Untreated diabetic mice developed cardiac failure and had decreased rates of glucose and ketone oxidation but increased fatty acid oxidation, resulting in a 36% lower cardiac ATP production rate compared to nondiabetic mice. Empagliflozin treatment prevented cardiac failure by increasing ATP production rates by 31%, primarily through a 61% increase in glucose oxidation. While ketone oxidation was impaired in diabetic mice, adding ketones did not further increase ATP production, suggesting ketones do not contribute to the cardiac benefits of empagliflozin. The findings indicate empagliflozin enhances cardiac energy status by optimizing
This literature review summarizes the clinical characteristics of myocardial stunning (neurogenic stunned myocardium or NSM) seen in patients after acute ischemic stroke. The review identified 7 case reports/series describing a total of 13 patients with NSM following stroke. Key findings include that NSM after stroke was more common in older females, with involvement of the left ventricle apex. Less than half of cases involved the insular cortex. Troponin levels and left ventricular dysfunction were typically mild. Most patients showed significant left ventricular recovery within 4 weeks, indicating a generally favorable prognosis. However, larger prospective studies are still needed.
Angioplasty outcomes in chronic kidney disease - a literature reviewJunhao Koh
1) Chronic kidney disease (CKD) is associated with more severe and diffuse coronary artery disease (CAD) due to increased inflammation and oxidative stress in CKD patients.
2) Outcomes of percutaneous coronary intervention (PCI) are generally worse in CKD patients compared to those without CKD, with higher mortality rates.
3) For stable CAD, PCI may be considered for CKD patients with significant lesions but is associated with higher risk of major adverse cardiac events compared to patients without CKD.
This document discusses various quality metrics and targets in hemodialysis. It begins by covering dietary compliance metrics like inter-dialytic weight gain and serum levels of potassium, phosphate, and BUN. It then discusses the effects of rapid ultrafiltration and links various metrics like inter-dialytic weight gain and blood pressure to outcomes. The rest of the document outlines targets for hemoglobin, calcium and phosphate levels, lipids, uric acid, ferritin, and other markers based on studies showing associations with mortality rates.
Supervised exercise training involving treadmill or track walking 3-5 times per week for 30-50 minutes per session is recommended as initial treatment for patients with intermittent claudication from PAD. This type of exercise training has been shown to improve maximal walking distance by 100-150% and quality of life. Cilostazol is an effective pharmacological therapy that can improve symptoms and walking distance in patients with claudication, while pentoxifylline may be considered as a second-line alternative.
The document discusses a study analyzing risk factors for cardiac arrhythmias in 402 pediatric patients who underwent cardiac surgery. The study found that arrhythmias occurred in 57 patients (14.2%), with junctional ectopic tachycardia and supraventricular tachycardia being most common. Lower age, lower weight, higher Aristotle Basic Score, longer bypass and clamp times, and use of deep hypothermia were identified as risk factors. Higher score was the only significant independent risk factor based on multivariate analysis.
Death by Neurological Criteria and Organ Donation: Bill KnightSMACC Conference
Bill Knight explains the concept of death by neurological criteria and the complexities surrounding organ donation in such situations.
Bill discusses the process of dying, the definition of death, how to approach the neurologically dead patient and how to consider organ donation.
Death is a complex topic.
Due to advancements in medical technology and processes, the definition of death is a challenging one.
Bill talks at length about the definition of death by the neurological criteria. Dying is an active process, whereas death is an event.
The acceptance of death by the neurological criteria is often challenging as Bill will highlight. Bill talks about the care of the dying or dead patient.
There is a point at which care will transition from supporting the patient to supporting the organs. This is still good care.
There is an alignment of parallel intentions – first and foremost resuscitation of patients and then failing that, proceeding to considering and actioning organ donation. This is important due to the shortage of viable donor organ worldwide.
The donation process itself is complex. Bill provides his thoughts. He insists that an intensivist be involved as this has been shown to increase the number of viable and healthy organs made available.
The timing is also important. Available evidence does not support the need for immediate procurement after brain death. Taking time to optimise perfusion and allow recovery and cardiac function is appropriate and should be done.
Bill also discusses other treatment options at the time of death such as optimising endocrine function.
Finally, Bill will provide some practical considerations when communicating with the dead patient’s family. This involves being clear on your messaging. You are supporting organs, not life.
To reinforce this point, Bill suggests not examining or talking to the patient. He also recommends using all of the available hospital support services.
Similarly, it is best to not introduce the topic of organ donation to the family yourself as the treating clinician. Utilise the Organ Procurement Organisations (or similar services) and get them involved early to speak with the family.
Join Bill Knight in his talk on the North American perspective on Organ Donation, brain death and management of the brain dead donor prior to organ donation.
For more like this, head to our podcast page. #CodaPodcast
The study to measure the level of serum annexin V in patients with renal hype...inventionjournals
ABSTRACT : Renovascular hypertension reflects the causal relation between anatomically evident arterial occlusive disease and elevated blood pressure. The coexistence of renal arterial vascular disease and hypertension roughly defines this type of nonessential hypertension. The aim of this study was to measure the level of serum Anti-Annexin V antibodies in patients with renal hypertension. Methods. This study was conducted on 115 patients, diagnosed with renal hypertension and hypertension. Informed consents were obtained from the patients and the study was approved by the Kharkiv National Medical University ethics committee. Ten healthy age and sex matched volunteers were included as a control group. All patients and controls were subjected to the following full history taking and thorough clinical examination. Routine laboratory testing included a complete blood count, and erythrocyte sedimentation rate (ESR) and kidney function tests (blood urea nitrogen and serum creatinine). Immunological tests for antinuclear antibody (ANA) and anticentromere antibodies (ACA) was performed by the indirect immunofluorescence technique. AntiScl-70 (anti-topoisomerase antibodies) and anticardiolipin antibodies (ACA: IgG and IgM) were tested using the ELISA technique. The anti-annexin V antibodies titre used the ZYMUTEST anti-Annexin IgG ELISA kit. [Hyphen-BioMed, France.]: to measure the IgG isotype of auto-antibodies to annexin V in human serum. Results. Anti-annexin V antibodies were present in 75% of patients (mean 83.46 ± 22.44 AU/mL) vs. 0% in the controls (mean 3.94 ± 4.5 AU/mL). Comparison between patients and controls as regards levels of anti-annexin V showed a highly significant difference (P < 0.001). Furthermore, correlation of anti-annexin V titres with the disease activity score in the patient group showed a statistically significant positive correlation (r = 0.51, P < 0.05).In addition, the anti-annexin V antibody titres in this study showed a highly significant positive correlation with ACL antibodies (r = 0.74, P < 0.001). Patients with antiphospholipid syndrome (APS) have been known to have a higher frequency of anti-annexin V antibodies, and thrombotic events have been reported more frequently in patients with positive anti-annexin V antibodies. Furthermore, inhibition of annexin V binding to negatively charged phospholipids may be an additional pathogenic mechanism of APS.
Organ support during critical illness requires considering many factors: 1) when to start support and how much is needed, 2) safety, costs and technology considerations, 3) appropriate monitoring, and 4) determining when to discontinue support. Essential measures like checklists, early goal-directed therapy, and focusing on basic supportive interventions can help optimize outcomes for critically ill patients.
This document summarizes updates to the 2018 American Heart Association guidelines for advanced cardiovascular life support and pediatric advanced life support. Key points include:
- The International Liaison Committee on Resuscitation began a continuous evidence evaluation process in 2015 to more quickly analyze published resuscitation research and develop treatment recommendations.
- This highlights important updates from the 2018 AHA guideline updates, including changes to treatment of shock-resistant ventricular fibrillation/pulseless ventricular tachycardia and use of antiarrhythmic drugs during cardiac arrest.
- Important quality of CPR factors discussed include compressing at a rate of 100-120/minute to a depth of 5-6 cm for adults and 4-5 cm for
Chronic stress can lead to depression through several pathways in the body and brain. The stress response involves the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which elevate cortisol and catecholamine levels. Over time, prolonged activation of these systems due to stress can result in allostatic load, damaging the body and brain through effects on inflammatory and immune responses. This dysregulation of stress mediators is associated with increased risk of depression as well as medical conditions like heart disease and metabolic syndrome. Meditation may help reduce stress's harmful impacts through effects on the brain's opioid and stress response systems.
The document discusses strategies for managing sedation in neuro-ICU patients, including:
1) Titrating sedative and analgesic medications to keep patients calm, alert, and free of pain while being lightly sedated.
2) Using scales like the SAS and RASS to regularly assess sedation levels.
3) Preventing and identifying delirium using tools like the CAM-ICU, given its high prevalence in ICUs and association with poor outcomes.
4) Considering patient factors and medications when choosing a sedation regimen to balance safety, efficacy and risk of delirium.
1. Recurrent myocardial infarction (MI) after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) occurs in about 21% of patients and is associated with worse clinical outcomes.
2. Recurrent MI significantly increases the risks of subsequent cardiac mortality, noncardiac mortality, stroke, and bleeding.
3. Early recurrent MIs within 1 day of the initial PPCI are associated with higher unadjusted cardiac mortality compared to later recurrent MIs, but after adjustment, recurrent MIs occurring more than 1 year after PPCI carry the highest risk of cardiac death.
Prospective, randomized comparison of two biphasicalatawi2
This study compared the effectiveness and safety of two biphasic waveforms - biphasic truncated exponential (BTE) and biphasic rectilinear (BR) - for external cardioversion of atrial fibrillation. 141 patients were randomized to receive transthoracic shocks using either the BTE or BR waveform. The success rate was similar between the two waveforms (93% for BR vs 97% for BTE), though cumulative energy delivered was lower in the BTE group. Only duration of atrial fibrillation was significantly associated with cardioversion success. No significant complications occurred with either waveform. The study found no significant difference in efficacy between the BR and BTE waveforms for transthoracic cardio
A Study of Heart Rate Recovery Following Exercise in Healthy Young Adult MaleIOSR Journals
Abstract: Exercise has positive chronotropic effect on heart rate and on cessation heart rate returns to preexercise
level. A delay in heart rate recovery (HRR) (≤12beats in first minute) is considered abnormal and
reflects autonomic dysfunction.The present study was taken up to find out the presence of abnormal HRR in
normal subjects (Male) and to establish HRR as an independent autonomic marker. For the study 106 healthy
young adults (male) were subjected to exercise by Bicycle ergometer till targeted Heart Rate (85%Maximum
Heart Rate(MHR)) was achieved. HRR at the end of 1 minutefollowingcessation of exercise were tabulated. In
our study 23(21.7%) subjects showed Abnormal HRR indicating HRR could be an independent autonomic
marker. Keyword-HRR, MHR
This document summarizes several recent studies and FDA approvals related to cardiac devices:
1. A study found that a common defibrillation test for ICD patients may be unnecessary, as a no-test group had equivalent safety outcomes.
2. The FDA approved the CardioMEMS pulmonary pressure monitoring system for use in heart failure patients.
3. The FDA approved expanded use of CRT devices for patients with mild heart failure and AV block, based on the BLOCK-HF trial showing benefits of CRT-D and CRT-P in those with LVEF <35% and QRS >130ms.
Cerebral perfusion pressure among acute traumatic brain injury patients at su...Alexander Decker
1. This study assessed the effects of supine and semi-fowler positions on cerebral perfusion pressure (CPP) and other physiological parameters among 39 patients with acute traumatic brain injuries.
2. In the semi-fowler position, patients experienced a significant increase in CPP, oxygen levels, blood pressure, and decrease in carbon dioxide levels compared to supine. The semi-fowler position was found to positively impact blood gas values, blood pressure, respiration, and oxygen saturation.
3. The supine position was associated with a significant decrease in pulse rate but no other significant changes. The study recommends further research on additional positions like side-lying and prone to establish optimal positioning guidelines for traumatic brain injury patients
Therapeutic hypothermia a physiological analysis of a new potential for post...Pedram Rahmanian
Therapeutic hypothermia (TH) involves lowering a patient's body temperature after cardiac arrest to improve outcomes. The document analyzes why TH increases survival rates for out-of-hospital cardiac arrest caused by ventricular fibrillation. It discusses the history of TH, major clinical trials showing improved survival and neurological function with TH, and the physiology of how hypothermia reduces reperfusion injury after cardiac arrest. The author concludes that TH should be implemented as part of standard post-cardiac arrest care due to the compelling evidence that it improves both survival and reduces disability.
This document discusses potential new diagnostic methods for studying sudden cardiac death. It notes that in about 20% of cases, no abnormality is found at autopsy to explain the cause of death. It proposes stressing the heart under normal and abnormal conditions to better understand its metabolic responses. This could help clarify pathological causes and allow for improved drug design strategies. The document advocates translating diagnostic approaches across medical disciplines to gain new insights. Overall, it presents the idea of developing innovative tests to evaluate the heart's local biochemical status under varying conditions in order to help prevent unexpected cardiac events, especially in young people.
This document summarizes several key points about complications related to intensive care, focusing on delirium and ICU-acquired weakness.
The main points are:
1) Delirium and coma in the ICU can lead to acute brain dysfunction and increased mortality. Delirium is also associated with long-term cognitive impairment and brain atrophy.
2) ICU stays can cause rapid muscle weakness starting in the acute phase, and this is related to poorer quality of life and depression after discharge.
3) Delirium is characterized by acute changes in mental state and cognition. It occurs in 40-80% of patients on mechanical ventilation and affects prognosis even after ICU discharge.
This study evaluated how the SGLT2 inhibitor empagliflozin affects cardiac energy production and substrate use in diabetic mice. Untreated diabetic mice developed cardiac failure and had decreased rates of glucose and ketone oxidation but increased fatty acid oxidation, resulting in a 36% lower cardiac ATP production rate compared to nondiabetic mice. Empagliflozin treatment prevented cardiac failure by increasing ATP production rates by 31%, primarily through a 61% increase in glucose oxidation. While ketone oxidation was impaired in diabetic mice, adding ketones did not further increase ATP production, suggesting ketones do not contribute to the cardiac benefits of empagliflozin. The findings indicate empagliflozin enhances cardiac energy status by optimizing
This literature review summarizes the clinical characteristics of myocardial stunning (neurogenic stunned myocardium or NSM) seen in patients after acute ischemic stroke. The review identified 7 case reports/series describing a total of 13 patients with NSM following stroke. Key findings include that NSM after stroke was more common in older females, with involvement of the left ventricle apex. Less than half of cases involved the insular cortex. Troponin levels and left ventricular dysfunction were typically mild. Most patients showed significant left ventricular recovery within 4 weeks, indicating a generally favorable prognosis. However, larger prospective studies are still needed.
Angioplasty outcomes in chronic kidney disease - a literature reviewJunhao Koh
1) Chronic kidney disease (CKD) is associated with more severe and diffuse coronary artery disease (CAD) due to increased inflammation and oxidative stress in CKD patients.
2) Outcomes of percutaneous coronary intervention (PCI) are generally worse in CKD patients compared to those without CKD, with higher mortality rates.
3) For stable CAD, PCI may be considered for CKD patients with significant lesions but is associated with higher risk of major adverse cardiac events compared to patients without CKD.
This document discusses various quality metrics and targets in hemodialysis. It begins by covering dietary compliance metrics like inter-dialytic weight gain and serum levels of potassium, phosphate, and BUN. It then discusses the effects of rapid ultrafiltration and links various metrics like inter-dialytic weight gain and blood pressure to outcomes. The rest of the document outlines targets for hemoglobin, calcium and phosphate levels, lipids, uric acid, ferritin, and other markers based on studies showing associations with mortality rates.
Supervised exercise training involving treadmill or track walking 3-5 times per week for 30-50 minutes per session is recommended as initial treatment for patients with intermittent claudication from PAD. This type of exercise training has been shown to improve maximal walking distance by 100-150% and quality of life. Cilostazol is an effective pharmacological therapy that can improve symptoms and walking distance in patients with claudication, while pentoxifylline may be considered as a second-line alternative.
The document discusses a study analyzing risk factors for cardiac arrhythmias in 402 pediatric patients who underwent cardiac surgery. The study found that arrhythmias occurred in 57 patients (14.2%), with junctional ectopic tachycardia and supraventricular tachycardia being most common. Lower age, lower weight, higher Aristotle Basic Score, longer bypass and clamp times, and use of deep hypothermia were identified as risk factors. Higher score was the only significant independent risk factor based on multivariate analysis.
Death by Neurological Criteria and Organ Donation: Bill KnightSMACC Conference
Bill Knight explains the concept of death by neurological criteria and the complexities surrounding organ donation in such situations.
Bill discusses the process of dying, the definition of death, how to approach the neurologically dead patient and how to consider organ donation.
Death is a complex topic.
Due to advancements in medical technology and processes, the definition of death is a challenging one.
Bill talks at length about the definition of death by the neurological criteria. Dying is an active process, whereas death is an event.
The acceptance of death by the neurological criteria is often challenging as Bill will highlight. Bill talks about the care of the dying or dead patient.
There is a point at which care will transition from supporting the patient to supporting the organs. This is still good care.
There is an alignment of parallel intentions – first and foremost resuscitation of patients and then failing that, proceeding to considering and actioning organ donation. This is important due to the shortage of viable donor organ worldwide.
The donation process itself is complex. Bill provides his thoughts. He insists that an intensivist be involved as this has been shown to increase the number of viable and healthy organs made available.
The timing is also important. Available evidence does not support the need for immediate procurement after brain death. Taking time to optimise perfusion and allow recovery and cardiac function is appropriate and should be done.
Bill also discusses other treatment options at the time of death such as optimising endocrine function.
Finally, Bill will provide some practical considerations when communicating with the dead patient’s family. This involves being clear on your messaging. You are supporting organs, not life.
To reinforce this point, Bill suggests not examining or talking to the patient. He also recommends using all of the available hospital support services.
Similarly, it is best to not introduce the topic of organ donation to the family yourself as the treating clinician. Utilise the Organ Procurement Organisations (or similar services) and get them involved early to speak with the family.
Join Bill Knight in his talk on the North American perspective on Organ Donation, brain death and management of the brain dead donor prior to organ donation.
For more like this, head to our podcast page. #CodaPodcast
The study to measure the level of serum annexin V in patients with renal hype...inventionjournals
ABSTRACT : Renovascular hypertension reflects the causal relation between anatomically evident arterial occlusive disease and elevated blood pressure. The coexistence of renal arterial vascular disease and hypertension roughly defines this type of nonessential hypertension. The aim of this study was to measure the level of serum Anti-Annexin V antibodies in patients with renal hypertension. Methods. This study was conducted on 115 patients, diagnosed with renal hypertension and hypertension. Informed consents were obtained from the patients and the study was approved by the Kharkiv National Medical University ethics committee. Ten healthy age and sex matched volunteers were included as a control group. All patients and controls were subjected to the following full history taking and thorough clinical examination. Routine laboratory testing included a complete blood count, and erythrocyte sedimentation rate (ESR) and kidney function tests (blood urea nitrogen and serum creatinine). Immunological tests for antinuclear antibody (ANA) and anticentromere antibodies (ACA) was performed by the indirect immunofluorescence technique. AntiScl-70 (anti-topoisomerase antibodies) and anticardiolipin antibodies (ACA: IgG and IgM) were tested using the ELISA technique. The anti-annexin V antibodies titre used the ZYMUTEST anti-Annexin IgG ELISA kit. [Hyphen-BioMed, France.]: to measure the IgG isotype of auto-antibodies to annexin V in human serum. Results. Anti-annexin V antibodies were present in 75% of patients (mean 83.46 ± 22.44 AU/mL) vs. 0% in the controls (mean 3.94 ± 4.5 AU/mL). Comparison between patients and controls as regards levels of anti-annexin V showed a highly significant difference (P < 0.001). Furthermore, correlation of anti-annexin V titres with the disease activity score in the patient group showed a statistically significant positive correlation (r = 0.51, P < 0.05).In addition, the anti-annexin V antibody titres in this study showed a highly significant positive correlation with ACL antibodies (r = 0.74, P < 0.001). Patients with antiphospholipid syndrome (APS) have been known to have a higher frequency of anti-annexin V antibodies, and thrombotic events have been reported more frequently in patients with positive anti-annexin V antibodies. Furthermore, inhibition of annexin V binding to negatively charged phospholipids may be an additional pathogenic mechanism of APS.
Organ support during critical illness requires considering many factors: 1) when to start support and how much is needed, 2) safety, costs and technology considerations, 3) appropriate monitoring, and 4) determining when to discontinue support. Essential measures like checklists, early goal-directed therapy, and focusing on basic supportive interventions can help optimize outcomes for critically ill patients.
This document summarizes updates to the 2018 American Heart Association guidelines for advanced cardiovascular life support and pediatric advanced life support. Key points include:
- The International Liaison Committee on Resuscitation began a continuous evidence evaluation process in 2015 to more quickly analyze published resuscitation research and develop treatment recommendations.
- This highlights important updates from the 2018 AHA guideline updates, including changes to treatment of shock-resistant ventricular fibrillation/pulseless ventricular tachycardia and use of antiarrhythmic drugs during cardiac arrest.
- Important quality of CPR factors discussed include compressing at a rate of 100-120/minute to a depth of 5-6 cm for adults and 4-5 cm for
Chronic stress can lead to depression through several pathways in the body and brain. The stress response involves the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which elevate cortisol and catecholamine levels. Over time, prolonged activation of these systems due to stress can result in allostatic load, damaging the body and brain through effects on inflammatory and immune responses. This dysregulation of stress mediators is associated with increased risk of depression as well as medical conditions like heart disease and metabolic syndrome. Meditation may help reduce stress's harmful impacts through effects on the brain's opioid and stress response systems.
The document discusses strategies for managing sedation in neuro-ICU patients, including:
1) Titrating sedative and analgesic medications to keep patients calm, alert, and free of pain while being lightly sedated.
2) Using scales like the SAS and RASS to regularly assess sedation levels.
3) Preventing and identifying delirium using tools like the CAM-ICU, given its high prevalence in ICUs and association with poor outcomes.
4) Considering patient factors and medications when choosing a sedation regimen to balance safety, efficacy and risk of delirium.
Psychopharmacology and Cardiovascular Disease - psycho cardiologymagdy elmasry
Psychopharmacology andCardiovascular Disease.Your Heart And Mind Are Connected.Psychiatric Disorders and Cardiovascular System .Cardiac response to acute stress .Heart disease and depression are closely linkedCardiovascular Side Effects of Psychotropic Drugs
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lecture 27 from a college level introduction to psychology course taught Fall 2011 by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University, Seyle
The document discusses post-traumatic stress disorder (PTSD) and the role of environmental factors in its onset and treatment. It notes that research has heavily focused on environmental perspectives due to PTSD being triggered by extreme environmental stimuli. However, to fully understand PTSD, future research needs to incorporate other psychological perspectives beyond just external environmental factors. The document also examines specific environmental factors like deployment tempo, occupational roles, and cultural contexts that impact PTSD.
The document proposes a study to examine the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome (CFS). The study would involve testing the HPA axis function of 500 CFS patients and 500 healthy controls using various tests at different times of day. The results would be analyzed to determine if CFS patients have altered HPA axis activity compared to controls. Finding a difference could help understand the pathogenesis and potential treatment of CFS.
This document discusses the effects of stress on the cardiovascular system. It defines stress and explains how chronic stress can increase the risk of cardiovascular diseases like coronary heart disease and hypertension. Specifically, it describes how the fight-or-flight response triggered by stress causes the release of hormones like cortisol and epinephrine that raise blood pressure over time and allow plaque to build up in the arteries. This plaque buildup narrows the arteries and reduces blood flow, potentially leading to heart attacks or other cardiovascular problems if stress is not managed. The document emphasizes the importance of reducing stress through techniques like meditation, yoga, and massage.
Here is a copy of the presentation that I gave to MRC CBU at Cambridge University on the 5th July 2017, essentially a summary of a book chapter of mine to be published later this year. The focus of my presentation was on connections between #self, #other and our #connections with the environment.
Cardiovascular Pathophysiology In the Setting of Spinal Cord InjuryInsideScientific
Dr. Christopher West shares his research that investigates the cardiovascular and autonomic changes that occur following spinal cord injury as well as the efficacy of neuro-therapeutic interventions.
Dr. West’s group uses small and large in vivo animal models to understand how the circuitry that controls the cardiovascular system changes following injury and what the downstream impact of these changes are for heart and blood vessel function. They also use these models to test the efficacy of novel therapies in the both the acute and chronic setting following injury. In the clinical and athletic spinal cord injury population, his group has conducted a number of mechanistic and applied studies to, 1) improve the understanding of how best to hemodynamically manage acutely injured patients, and 2) enhance the capacity of the cardiovascular system to enable an improved exercise response.
This webinar introduces the major cardiovascular changes that have been characterized following spinal cord injury in animal models and the clinical population. Chris shares some exciting results from recent studies in which his group has tested the efficacy of novel therapies to improve cardiovascular function. Finally, he provides his outlook for the future of the field.
This document discusses how the nervous system controls and regulates every system in the body. It explains how problems with the nervous system can lead to issues like neuropathy, heart/blood pressure problems, digestive issues, hormone imbalances, and more. It emphasizes looking at the whole person and nervous system rather than just symptoms. Maintaining a healthy nervous system involves diet, exercise, rest, and chiropractic care to allow the body to function properly.
This document discusses the relationship between personality, stress, and cardiovascular disease. It summarizes several studies that found higher levels of depression, neuroticism, and Type D personality among patients with coronary artery disease compared to healthy controls. Type D personality, characterized by negative affectivity and social inhibition, was found to be more common in patients with coronary artery disease. Stress is identified as a common factor linking depression and cardiovascular disease. The document also discusses the role of context and interpersonal relationships in health, suggesting cardiovascular health and function occurs within social environments and interactions with others.
Incidence and risk factors between TBI/SCI and venous thromboembolismAmit Agrawal
Patients with traumatic brain injury (TBI) or spinal cord injury (SCI) have an increased risk of venous thromboembolism (VTE). The reported incidence of VTE in studies of TBI and SCI patients varies widely from 1-54% depending on factors like injury severity and use of prophylaxis. The true incidence is difficult to determine due to limitations of studies and many cases being asymptomatic. VTE risk is highest in the acute phase after injury.
Post-traumatic stress disorder (PTSD) is a psychological condition that affects many military veterans. It is characterized by flashbacks, nightmares, avoidance of trauma reminders, and hyperarousal. PTSD is linked to combat exposure and is diagnosed in 2-17% of veterans. Common symptoms include anger issues, substance abuse, and relationship problems. Treatment options with positive results include cognitive behavioral therapy and medication. However, many veterans are reluctant to seek help due to stigma. PTSD has significant negative impacts on veterans' lives and mental health.
Brief Report: OSA Evaluations for the Anaesthesiologist, Surgeon, Surgery Centresemualkaira
This short report presents a scope of the medical condition of Obstructive Sleep Apnea (OSA). Current methods for assessment and
diagnosis of OSA are presented. Complications and potential death
from untreated OSA places the anesthesiologist, surgeon and surgical center in a risk situation. Factors related to the risk factors
and points toward resolution are presented.
This document presents a hypothesis that chronic stress can induce bipolar disorder through its effects on astrocytes in the prefrontal cortex. The authors propose that chronic stress leads to high levels of glucocorticoids, which cause astrocyte degeneration in the prefrontal cortex over time. This is supported by evidence that glucocorticoids reduce astrocyte number and function in vitro and in vivo. The authors suggest this astrocyte loss could contribute to bipolar disorder. They propose experiments to test the hypothesis by measuring astrocyte decline after chronic stress exposure and exploring potential treatments like blocking glucocorticoid receptors or promoting astrocyte growth. If validated, this could impact the diagnosis of bipolar disorder by considering
Similar to Quantifying Cardiovascular and Behavioral Correlates of Fear in Mice: Implications for PTSD and Cardiovascular Disease Risk (20)
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...InsideScientific
Join Prof. Victoria Hutter and Dr. Louis Scott as they showcase the application of high-content imaging and advanced cell lines for drug safety assessment.
Safety concerns play a significant role in the unsuccessful progression of candidate compounds in the later stages of drug development. Establishing the connection between in vitro endpoints and human health outcomes is essential.
In this webinar, Prof. Victoria Hutter and Dr. Louis Scott present a novel tool for in vitro safety assessment in drug development. The morph_ONE™ assay provides a human-centric approach to potentially fill specific regulatory gaps concerning safety issues. This tool is capable of profiling both human and rat alveolar macrophages, offering valuable insights for hazard identification and toxicity assessments. By bridging the divide between cellular effects and overall risk, it has the potential to enhance our understanding of safety-related aspects in drug development.
Key Topics Include:
- Explore distinct in vitro screening techniques for evaluating the safety of emerging inhaled products, facilitating early and informed decisions in compound selection and development.
- How high-content image analysis (HCIA) cell painting assays can be used as a forward-looking high-throughput screening tool, distinguishing unique response patterns in alveolar macrophages.
- Understand the use of the ImmuPHAGE™ and ImmuLUNG™ models in conducting customized evaluations focused on inhalation safety.
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...InsideScientific
In this webinar, Aditya Pratapa and Lorcan Sherry present a new workflow for analyzing multiplex immunoflurescence images.
Spatial Signatures are a new class of highly predictive biomarkers that measure the interactions and cellular densities of tumor and immune cells that compose the tumor microenvironment. Based on multiplex immunofluorescence, spatial signatures provide a deeper understanding of complex interactions between tumors and the immune system, enabling improved patient stratification for immunotherapies. A significant hurdle to date has been in developing a data analysis workflow that is straightforward and user-friendly to transform the data rich images into meaningful quantitative spatial signatures.
In this webinar, Aditya and Lorcan review the key features of the new PhenoImager HT 2.0 data analysis workflow. This workflow introduces a simplified framework from scanning to analyzing spectrally unmixed multiplex immunofluorescence images generated on the PhenoImager HT platform. The ready-to-analyze data can be directly imported into image analysis software such as Visiopharm. This presentation covers key aspects of data analysis elements such as image QC, segmentation, phenotyping, and verification – all essential for creating outputs that support the development of a spatial signature.
Key Topics Include:
- Understand Akoya’s new HT 2.0 data analysis workflow
- The challenges in multiplex immunofluorescence analysis and the use of AI and cell
lineage segmentation considerations
- Explore OracleBio’s image analysis workflow incorporating Visiopharm
- Evaluation of analysis data to facilitate spatial profiling and interpretation
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...InsideScientific
In this webinar, Dr. Sabine Kuss will discuss the importance of transmembrane molecule exchange and how to detect and quantify membrane transport of molecules in cells.
Complex biological processes, such as the transport of molecules across cell membranes, are difficult to understand using purely biological methodologies. Investigating cellular transport processes is challenging, because of the highly complex chemical composition of cells and the diffusion of molecules in and around cells at low concentrations. The development and advancement of electroanalytical methods over the last two decades has enabled the monitoring of living cells and their interaction with the environment, including external stimuli, such as pharma-molecules.
This presentation emphasizes electrochemical and electrophysiological methods of detection and quantification but also makes a comparison to other bioanalytical approaches. Join us to discover a substantial diversity in methods used to monitor the transport of cell metabolites, crucial for cell survival, and pharmaceutical compounds, involved in cell characteristics such as drug resistance.
Key Topics Include:
- Understanding transmembrane molecule transport through bioanalytical methods
- Electrochemical approaches to monitor molecule transport across cell membranes
- What bioanalytical and especially electrochemical approaches can reveal
- Challenges associated with instrument limitations
Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in ...InsideScientific
In this webinar, Dr. Victor Arrieta highlights the link between p-ERK activation and improved survival in rGBM patients using anti-PD-1 immunotherapy.
Recurrent glioblastoma (rGBM) has displayed a varied response to anti-PD-1 immunotherapy, necessitating the identification of predictive biomarkers. Through extensive analyses and 3 clinical studies, we have identified that activation of the MAPK/ERK signaling pathway, particularly ERK1/2 phosphorylation (p-ERK), is associated with longer overall survival (OS) in rGBM patients receiving PD-1 blockade. Initially, enrichment of BRAF/PTPN11 mutations was reported in 30% of responsive rGBM patients, prompting the investigation of p-ERK as a potential marker beyond these mutations.
Our research has unraveled an association between p-ERK abundance and better clinical outcomes following PD-1 blockade, with p-ERK mainly localized in tumor cells. Notably, high p-ERK GBMs contained unique microglia and macrophage phenotypes with elevated MHC class II expression, suggesting a novel interplay between MAPK activation and the tumor immune microenvironment.
While these insights establish a pivotal role for p-ERK in predicting PD-1 blockade response in rGBM, the implementation in clinical settings calls for further validation and accuracy. Nonetheless, these findings pave the way for more personalized and effective immunotherapy strategies, emphasizing the significance of the tumor microenvironment and its interaction with therapeutic interventions in GBM.
Key Topics Include:
- The activation of the MAPK signaling pathway, specifically ERK1/2 phosphorylation (p-ERK), is identified as a predictive biomarker for longer overall survival in recurrent glioblastoma (eGBM) patients undergoing PD-1 blockade
- High p-ERK tumors in rGBM present a distinct myeloid cell phenotype with elevated MHC class II expression, signifying a connection between MAPK pathway activation and the immune microenvironment
- The implementation of p-ERK as a predictive biomarker in clinical settings requires further validation and exploration of variables impacting its evaluation
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...InsideScientific
Dr. Reilly Enos and Dr. Eran Levin discuss estrogen's metabolic impact and how isotopic labeling and 13C-labeled nutrients can be used for animal physiology and nutrition research.
Reilly Enos, PhD – Harnessing the power of estrogen to regulate metabolic processes
Dr. Reilly Enos’ research focuses on the role that sex steroids and their receptors play in regulating metabolic processes, particularly in the setting of obesity. In this webinar, Dr. Enos will discuss his research on tissue-specific fluctuations of sex steroids throughout the estrous cycle in mice, provide insights into the importance of the quantity of estrogen necessary to impact physiological processes, as well as an understanding of the central versus peripheral effects of estrogen action.
Eran Levin, PhD – Unlocking Insights: Utilizing 13C Labeled Nutrients for Cutting-Edge Physiology and Nutrition Research
Dr. Eran Levin will discuss the potential of using 13C-labeled nutrients in physiology and nutrition research in animal models. Specifically, he will share practical tips for designing and conducting experiments using isotopic labeling techniques and demonstrate how they can provide unprecedented insights into metabolic pathways, nutrient utilization, and behaviors in both vertebrate and invertebrate models including insects, reptiles, and mammals.
Key Topics Include:
- The role that estrogen plays in regulating metabolic and behavioral processes in males and females
- The tissue-specific fluctuations of sex steroids throughout the estrous cycle
- Insight into the importance of tissue-specificity in developing hormonal therapies
- The importance of estrogen quantity in regulating physiological processes
- Understand the diverse range of 13C labeled nutrients available
- Specific applications of labeled amino acids in studies of protein metabolism, cellular signaling, and typical nutrient utilization
- How to integrate 13C labeling techniques with respirometry for a comprehensive assessment of metabolic processes, energy expenditure, and substrate utilization in animal models
- How to calculate metabolic rates in free-flying animals using 13C bicarbonate
Longitudinal Plasma Samples: Paving the Way for Precision OncologyInsideScientific
Experts present a cell-free plasma biobank and describe the role of longitudinal plasma samples for cancer research, disease monitoring, and biomarker development.
Through liquid biopsies, it is now possible to repeatedly and non-invasively interrogate the molecular landscape of solid tumors via a blood draw over the whole treatment course. Until now, liquid biopsies can be used for screening, disease monitoring and prognosis. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have been the most explored targets in this technology for commercial applications up to the present time.
In collaboration with a continuously expanding oncology network, Indivumed Services has established a unique high-quality cell-free plasma biobank that is exclusively focused on collecting longitudinal whole blood samples from cancer patients. This allows molecular insight by providing quick access to longitudinal plasma from cancer patients that have undergone treatment. ctDNA can then be isolated from longitudinal cell-free plasma to allow for monitoring of disease progression by providing diagnostic and prognostic information, potentially in real time.
Key Topics Include:
- Gain insights into Indivumed Services’ longitudinal plasma collection process
- Understand the advantages and benefits of utilizing longitudinal plasma samples for cancer research
- Explore applications of longitudinal plasma samples for biomarker research and development of companion diagnostics
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...InsideScientific
This document summarizes a webinar presented by Andrew Gaffney and Erin Knock of STEMCELL Technologies. They discussed STEMCELL's development of the healthy control human iPSC line SCTi003-A and single-use iPSCdirect product, which were manufactured to high quality standards. They also discussed STEMCELL's neural progenitor cells derived from SCTi003-A, which can be expanded over multiple passages while maintaining their ability to differentiate into neurons and astrocytes. The neural progenitor cells demonstrate expected marker expression and can be cryopreserved and re-thawed while retaining their differentiation potential.
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...InsideScientific
Ian Foster and Steven Loo-Yong-Kee discuss Artisan Bio's STAR-CRISPR system for optimized gene editing in cell therapy, with a focus on the genetifc modification of T cells for cancer immunotherapy.
Cell therapy is an emerging field with great promise for the treatment of various diseases. One of the most exciting areas of cell therapy is the use of T cells that have been genetically modified to recognize and kill cancer cells. While the use of T cells for cancer immunotherapy has tremendous promise, there is still room for improvement. The efficiency, expansion, and functionality of T cells can be enhanced by genetic modification using the STAR-CRISPR system.
Artisan Bio is a biotechnology company focused on developing a CRISPR-mediated editing platform to improve the efficacy and safety of cell therapy products. In this webinar, we will provide a comprehensive overview of Artisan Bio’s STAR-CRISPR system, which is designed to improve the specificity and efficiency of gene editing for cell therapies. We will explain the system’s key components and how we are using a risk-based approach to optimize and validate the editing platform. The webinar will focus on Artisan Bio’s approach to building T cell OS/APPS through iterative improvements to achieve best-in-class editing capabilities and improved cell health metrics.
Key Topics Include:
- Learn about Artisan Bio’s proprietary high-performance STAR-CRISPR system for improving the specificity and efficiency of gene editing for cell therapies
- Explore Artisan Bio’s risk-based, systems approach to technology development, including how to implement Design of Experiments (DoE) and Quality by Design (QbD) principles to optimize and validate any process
- Case study of the application of QbD to Artisan Bio’s STAR-CRISPR platform to edit T cells for cancer immunotherapy with preliminary data showing improved efficacy, expansion, and functionality
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...InsideScientific
Dr. Bert Bond and Max Weston will present an overview on their study investigating the effects high-intensity interval exercise has on cerebrovascular health.
Physical activity reduces the risk of developing cardiovascular diseases (CVD) and dementia. This benefit cannot be explained by changes in traditional CVD risk factors alone, and direct improvements in vascular health are thought to play a key role. However, our understanding of how exercise can be optimized for improvements in blood-vessel health is limited.
High-intensity interval exercise (HIIE) is known to improve peripheral vascular function, and there is a growing interest in the effects of HIIE on cerebrovascular health. However, it is not clear whether the acute improvements in peripheral vascular function following HIIE are also seen in the major blood-vessels of the brain.
In the Bond lab’s study, 30 minutes of HIIE completed at both 75% and 90% V̇O2max improved peripheral vascular function 1 and 3h following exercise in healthy young adults, compared with work-matched continuous moderate-intensity exercise and a sedentary control condition. By contrast, cerebrovascular function was unchanged following all conditions. This is the first study to identify that acute improvements in peripheral vascular function following high-intensity interval exercise are not mirrored by improvements in cerebrovascular function in healthy young adults.
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...InsideScientific
Dr. Sam Sternberg discusses a novel CRISPR-Cas9 system using programmable, RNA-guided transposase, and highlights its implications for kilobase-scale genome engineering in cell and gene therapies.
The utility of programmable, RNA-guided CRISPR-Cas systems in genome engineering continues to evolve. Nature has afforded scientists novel and diverse gene editing functionality, from nuclease-dependent CRISPR-Cas9 to second-generation base and prime editors that do not produce double-strand breaks.
In this webinar, Dr. Sam Sternberg describes a new CRISPR-Cas9 paradigm relying on nuclease-deficient bacterial transposons that catalyze RNA-guided integration of mobile genetic elements into the genome. The discovery of a fully programmable, RNA-guided transposase lays the foundation for kilobase-scale genome engineering with broad applications for developing cell and gene therapies.
Key Topics Include:
- The basics of first- and second-generation CRISPR-Cas technologies from a scientist at the forefront of their development
- Mechanisms, accommodation, and cell type diversity of CRISPR-Cas programmable transposition
- How transposase factor coordination enables highly specific, genome-wide DNA integration to target sites
- Implications of programmable transposases that obviate the need for DNA double-strand breaks and homologous recombination
Simple Tips to Significantly Improve Rodent Surgical OutcomesInsideScientific
Dr. Marcel Perret-Gentil presents six simple-to-implement techniques to significantly improve surgical outcomes.
You may feel proficient, even confident in performing rodent surgery; however, you may be surprised how simple improvements can have a huge impact to your animal’s recovery and data. The presentation is designed for individuals who have minimal or no rodent surgical skills but is also a great opportunity for those with considerable experience wanting to improve outcomes as well as teach such key principles.
Key Topics Include:
- Improve surgical outcomes that will lessen post-op morbidity and mortality
- Improve data yield after rodent surgery
- Implementation of key principles into a rodent surgical program
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...InsideScientific
This document discusses cardiovascular autonomic dysfunction in post-COVID patients. It begins with a case study of a 41-year-old woman who developed post-COVID symptoms like fatigue, palpitations and orthostatic intolerance. Tests showed she had postural orthostatic tachycardia syndrome (POTS). Between 10-15% of COVID patients develop long COVID, and 30% of highly symptomatic long COVID patients have POTS. Tilt testing, active standing tests and Holter monitoring can help diagnose POTS and other forms of autonomic dysfunction. Treatment focuses on lifestyle changes, compression garments, increasing fluids and salts, and regulating heart rate and blood pressure with medications. Further research is still
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemInsideScientific
Cell lines are the core of biological research. Scientists need cell lines for drug development, basic biology research, safety testing, and biologic therapeutic production. Since the 1980s, genetic manipulation has allowed researchers to tailor cell lines to the experiment or production purpose. Over time, the requirements for these cell lies have risen. In many cases, the cells require multiple genetic edits and must produce data that passes FDA. Moreover, the current funding environment often requires rapid delivery of these cells so scientists can produce data to support further budget and/or investment. This is particularly acute for knock-in cell lines. Current technologies may take months to complete a cell line, allow a limited number of edits, and often have off-target effects that are not suitable for FDA filings. ExpressCells uses its patented FAST-HDR plasmid--along with CRISPR, to address these problems. The FAST-HDR process can precisely knock-in multiple genes (while supporting other types of genetic modifications), ensure precise placement of these edits, and deliver them months faster than competing technologies.
This webinar will discuss the basis of the FAST-HDR technology and illustrate several uses. The first part is a presentation by Oscar Perez-Leal, MD, the inventor of the technology. Oscar will discuss the problems he faced as a researcher and how FAST-HDR was designed to address them. He will outline the details of the technology, the history of its development, and several examples where he used FAST-HDR. The second part is a conversation with Jon Weidanz, PhD. Jon will outline the challenges he faced at AbeXXa and how he selected a FAST-HDR custom cell line for his project. He'll outline the learnings from using this cell line, some of which were unexpected, but valuable to future development.
By attending this program, attendees will:
- Understand the current challenges in creating custom gene-edited cell lines
- Know the technology underlying the FAST-HDR gene-editing system, including its use with CRISPR
- Be able to describe the advantages of the FAST-HDR system
- Learn about several case studies using gene-edited cell lines
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...InsideScientific
Watch Dr. Sarah Greising discuss the current pathophysiologic understanding of the skeletal muscle remaining following traumatic musculoskeletal injuries.
Volumetric muscle loss (VML) injuries result in the abrupt loss of skeletal muscle fibers, causing chronic functional disability in part due to limited muscle regeneration and vast co-morbidities. With a focus on clinically relevant outcome measurements for skeletal muscle function in both small and large animal models of VML injury, this webinar presents various near-term interventions for the restoration of tissue function following complex injuries. Interventions evaluated focus on regenerative rehabilitation approaches using regenerative pharmaceuticals to correct underlying muscle pathophysiology.
Designing Causal Inference Studies Using Real-World DataInsideScientific
In this webinar, experts provide an overview of causal inference, along with step-by-step guidance to designing these studies using real-world healthcare data.
Causal inference is used to answer cause and effect research questions and yield estimates of effect. Causal study design considerations and statistical methods address the effects of confounding variables and other potential biases and allow researchers to answer questions such as, “Does treatment A produce better patient outcomes compared to Treatment B?”
Causal study interpretations have traditionally been restricted to randomized controlled trials; however, causal inference applied to observational healthcare data is growing in importance, driven by the need for generalizable and rapidly delivered real-world evidence to inform regulatory, payer, and patient/provider decision making. The application of causal inference methods leads to stronger and more powerful evidence. When these techniques are applied to observational data, the results generated are both from and for the real world.
Presenters walk through several real-world case studies including the PCORI-funded BESTMED study and a collaborative study with a prominent pharmacy payer.
Social Media Data: Opportunities and Insights for Clinical ResearchInsideScientific
Many new data are emerging in recent years - real time data is collected through digital health technologies, including apps and wearables, monitoring data, social media data, public datasets, and patient organization data, in addition to primary and secondary datasets.
Real life data are highly informative and can be used to address a range of challenges throughout the product life cycle. Data from social media can generate valuable insights as patients often gather in digital communities to get answers and share their experiences. Conversations on social networks merit special consideration as they can have real world influence over treatment management decisions.
Social media data can reveal the motivations that impact patient healthcare decisions and behaviors through each stage of the care pathway. These data provide both the patient and caregiver perspectives at the same time. For this reason, conversations on social networks offer an opportunity to deepen our understanding on:
- The fears and hopes associated with patient treatments
- Daily needs and difficulties patients are facing in managing their disease
- The impact of disease on patient health related quality of life
- Identification in real life of the stages of the care pathway and patient perceptions
- Reactions to health policies
Watch this webinar for insights on how to collect, use, analyze, and interpret social media data in different contexts. Our experts share knowledge from over fifteen years of successfully developing and adapting algorithms to treat this kind of data.
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...InsideScientific
To learn more visit: https://insidescientific.com/webinar/we-are-more-than-what-we-eat-dietary-interventions-depend-on-sex-and-genetic-background/
Despite evidence that sex and genetic background are key factors in the response to diet, most studies of how diet regulates metabolic health and even longevity in mice examine only a single strain and sex.
Using multiple strains and both male and female mice, Dr Lamming's team has found that improvements in metabolic health and in longevity in response to reduced levels of protein or specific amino acids strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, they observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, they identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, gaining new insight into role of the energy balance hormone FG21 in the response to protein restriction.
Antibody Discovery by Single B Cell Screening on Beacon®InsideScientific
Amy Sheng, PhD provides an overview of antibody screening platforms and presents applications and case studies using the Beacon® platform for antibody discovery.
Single B cell screening is a powerful and efficient strategy for generating antigen-specific monoclonal antibodies. Distinguished with fluorescence-activated B cell sorting, the Beacon® platform is based on plasma cell screening, making it easier to obtain antibody genes.
The Beacon® single-cell optofluidic system combines a unique optoelectro positioning (OEP) technology with novel microfluidic technology. It can be used to accurately select single cells on a chip, perform multiple single-cell assays, and export target cells based on specific results. The Beacon® optofluidic platform preserves the diversity of B cells, generating high-quality positive hits at an early stage of discovery and avoiding the loss of “good clones”.
Key Topics Include:
- B cell differentiation and development
- Pros and cons of mainstream antibody screening platforms
- Mechanisms, applications, and case studies using the Beacon® platform for antibody screening
- Sino Biological’s capacity using the Beacon® platform
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...InsideScientific
Phil Griffiths, PhD, presents a summary of chronic cardiovascular telemetry studies and considerations for experimental design.
Ensuring you collect the best and most physiologically accurate data from your chronic telemetry experiments requires careful planning and experimental design. This webinar will give an insight into the practical aspects of designing chronic animal experiments to set you on the best path for success. The benefits of chronic studies, how to select the most appropriate sample size for your study, some basic tips and tricks for data acquisition and handling, and how to ensure high animal welfare are discussed.
Key Topics Include:
- What are the benefits of chronic over acute studies?
- How to decide the best sample sizes and the length of experiments?
- Basic tips for data acquisition and handling
- How to maintain high animal welfare standards
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...InsideScientific
In this webinar, Dr. Dennis Turner delves into dementia syndrome, the metabolic changes that occur, and the importance of proper physiological monitoring of animal models.
Brain metabolism transforms with normal aging, and transient, dynamic metabolic insufficiency may underlie critical progression from aging into dementia syndrome and Alzheimer’s disease (AD). Age-related brain metabolism balances vascular-related substrate supply and transport mechanisms into extracellular space to neurons with cellular metabolic needs and utilization. Dynamic metabolic insufficiency can occur when there is intermittent supply-demand mismatch.
Adequacy of neurovascular coupling to provide sufficient cerebral blood flow (CBF) to meet neuronal demand in vivo in a mouse AD model, compared to aged controls were studied. Dr. Turner’s lab analyzed the response to maximal neuronal metabolic demands, spreading depression and anoxia, using imaging, CBF measurements, and oxygen and glucose levels. These in vivo studies require human-similar anesthesia conditions, through monitoring temperature, blood pressure/pulse oximetry, and respiration, to maintain homeostasis. The lab confirmed abnormal neurovascular coupling in a mouse model of AD in response to these metabolic challenges, showing disruption much earlier in dementia than in equivalently aged individuals. Chronic metabolic treatments could influence dementia syndrome progression.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Equivariant neural networks and representation theory
Quantifying Cardiovascular and Behavioral Correlates of Fear in Mice: Implications for PTSD and Cardiovascular Disease Risk
1. Quantifying Cardiovascular and
Behavioral Correlates of Fear in Mice:
Implications for PTSD and Cardiovascular
Disease Risk
Paul J. Marvar, PhD
Associate Professor
Department of Pharmacology & Physiology
George Washington University
Benjamin Turley
Master's Student
Systems Medicine
Georgetown University
2. Quantifying Cardiovascular and
Behavioral Correlates of Fear in Mice:
Implications for PTSD and Cardiovascular
Disease Risk
Dr. Paul Marvar and Benjamin Turley present
research pairing behavioral and cardiovascular
responses to cued fear learning and demonstrate
how fear-based disorders (such as PTSD) can
contribute to cardiovascular disease risk.
3. Quantifying Cardiovascular and
Behavioral Correlates of Fear in Mice:
Implications for PTSD and Cardiovascular
Disease Risk
Paul J. Marvar, PhD
Associate Professor
Department of Pharmacology & Physiology
George Washington University
Benjamin Turley
Master's Student
Systems Medicine
Georgetown University
V
Copyright 2021 P. Marvar, B. Turley and InsideScientific.
All rights reserved.
4. Key learning objectives:
• To understand the physiological impact
of PTSD on cardiovascular and
autonomic homeostasis, CVD risk
• Demonstrate utility of rodent models
in assessing real-time cardiovascular
and autonomic fear or defensive
emotional states
• Discuss benefits and translational
implications for using integrated
behavioral and cardiovascular multi-
modal methodologies
5. Key learning objectives:
• To understand the physiological impact
of PTSD on cardiovascular and
autonomic homeostasis, CVD risk
• Demonstrate utility of rodent models
in assessing real-time cardiovascular
and autonomic fear or defensive
emotional states
• Discuss benefits and translational
implications for using integrated
behavioral and cardiovascular multi-
modal methodologies
Why study behavioral and cardiovascular
correlates of learned fear in mice?
6. PTSD characterized by a persistent maladaptive reaction to exposure
to severe psychological trauma. (i.e., violent personal assaults, natural
or human made disasters, serious traffic collisions, or military combat)
o Psychological and Behavioral Symptoms:
o Symptoms (>3month) occurring after a traumatic event
• Intrusive recollection, avoidance
• Negative mood alterations
o Physiological Symptoms:
o Hypervigilance / physiological hyperarousual, increased
blood pressure, heart rate, sympathetic outflow,
respiratory distress, shortness of breath, sleep disturbances.
o Limited effective treatment options
o Highly co-morbid with poor overall physical health outcomes
and increased other diseases (ie., CVD, metabolic,
autoimmune)
Post Traumatic Stress Disorder (PTSD)
8. Adopted and modified from
O’Donnell et al., JAMA Cardiol. Published online July 14, 2021. doi:10.1001/jamacardio.2021.2530
9. PTSD as a CVD Risk Factor
Physiological and Behavioral Evidence from Epidemiological Studies
Edmonson et al., 2017 4:320-29
10. High Blood Pressure
1. Elevated blood pressure and
hypertension in trauma-
exposed populations,
including military veteran and
community-based samples.
2. Greater resting blood
pressure (BP) as well as
greater BP response to
trauma-related cues.
(Buckley and Kaloupek, 2001;
Pole, 2007)
PTSD as a CVD Risk Factor
Physiological and Behavioral Evidence from Epidemiological Studies
Edmonson et al., 2017 4:320-29
11. PTSD = impaired ability to process fear and perceived threats
Hippocampus
PTSD = exaggerated behavioral physiological responses
Threat Detection and Fear Circuitry
impacted by PTSD
Blood Pressure
Heart Rate
12. • PTSD = impaired ability to process fear and perceived threats
– Over-generalization of trauma-related stimuli and a reduced ability to suppress emotional
(stress) and physiological (ie., increase in blood pressure, heart rate, sympathetic nervous
system) responses to threat-associated stimuli.
The effects of PTSD are not limited to psychological symptoms.
Meakins and Wilson, 1918
Early observations of abnormal cardiovascular responses associated with trauma describe a
condition called “irritable heart syndrome”, and veterans with this condition exhibited greater
heart rate (HR) and respiratory responses to presentations of bright flames and pistol shots
2. Park, J. et al. Baroreflex dysfunction and augmented
sympathetic nerve responses during mental stress in veterans
with post-traumatic stress disorder. The Journal of Physiology
595, 4893–4908 (2017).
Jeanie Park, MD, MS
Emory University
3. Fonkoue I et al., Sympathoexcitation and impaired arterial
baroreflex sensitivity are linked to vascular inflammation in
individuals with elevated resting blood pressure. Physiol Rep.
2019 Apr;7(7):e14057.
1. Fonkoue, I., et al., Elevated resting blood pressure augments autonomic balance in posttraumatic stress
disorder. Am J Physiol Regul Integr Comp Physiol. 2018 Dec 1;315(6):R1272-R1280
Mechanistic studies using animal
models are required for a more comprehensive understanding, including
neurocircuits, autonomic dysregulation,
neurotransmitter abnormalities, and increased inflammation
Autonomic and Cardiovascular Dysfunction in PTSD
13. Conditioned Stimulus (CS)
(light or tone)
Unconditioned Stimulus (US)
(footshock or airblast)
Threat Stimuli
Conditioned
Stimulus (CS)
Fear Responses
Defensive Behavior
Autonomic Arousal
Reflex potentiation
Stress hormones
Respiratory distress
LeDoux, J. E. (2000) Annual Review of Neuroscience, 23(1), 155-184.
Modeling fear responses in rodents and humans
Pavlovian Fear Conditioning
14. Day 1:
Creating a fearful
association
Day 2:
Weakening the
association via
repeated
presentations
Day 3:
Testing recall of the
weakened association
Modeling fear responses in rodents and humans
Pavlovian Fear Conditioning
18. Heart rate variability (HRV)
is a measure of autonomic
nervous system function
Automatic R-R
detection
Blood Pressure ECG
Systolic Diastolic
Mean Arterial
Pressure
Rejection of R-R not
within ± 2 s.d. of mean
Heart Rate
Variability
Time Domain
Analysis
Frequency Domain
Analysis
Channel 1 Channel 2
Mean Heart Rate
Data Signal Processing and Analysis
19. 24hr baseline
recording
Post-FC
recording
Post-Ext
recording
Swiercz et al., Front Behav Neurosci 2018
We hypothesized that a fear conditioned cardiovascular response could be detected
in a novel context and attenuated by extinction training.
To evaluate the effects of extinction learning on the
conditioned cardio-autonomic response
Experimental Design
2 weeks
Fear Conditioning Extinction Training
Implant transmitter
20. Ext Day 1
recording
Ext Day 2
recording
Behavioral and Cardiovascular Changes During
Extinction Training
Swiercz et al., Front Behav Neurosci 2018
2 weeks
Fear Conditioning Extinction Training
Implant transmitter
21. Effects of Fear Conditioning and Extinction on
Resting Blood Pressure and Heart Rate
Swiercz et al., Front Behav Neurosci 2018
22. Swiercz et al., Front Behav Neurosci 2018
Behavioral and cardiovascular changes during extinction training
23. Novel Context
Swiercz et al., Front Behav Neurosci 2018
Context-Dependent Cardiovascular and Activity Measures
Elevated baseline cardiovascular measures
mask conditioned stimulus (CS) dependent
cardiovascular reactivity to the tone (CS).
Study 2:
To examine the effects of extinction training
on cardiovascular reactivity in a home cage
environment.
24. Novel Context
Swiercz et al., Front Behav Neurosci 2018
Home Cage Context
Context-Dependent Cardiovascular and Activity Measures
25. P
r
e
-
C
S
0
3
0
6
0
9
0
1
2
0
1
5
0
1
8
0
2
1
0
90
100
110
120
130
140
Mean
Arterial
Pressure
(mmHg)
Time (s)
Ext
No Ext
CS1 CS2 CS3 CS4
P
r
e
-
C
S
0
3
0
6
0
9
0
1
2
0
1
5
0
1
8
0
2
1
0
400
450
500
550
600
650
700
Heart
Rate
(BPM)
Time (s)
P
r
e
-
C
S
4
C
S
(
a
v
g
)
P
r
e
-
C
S
4
C
S
(
a
v
g
)
90
100
110
120
130
140
Mean
Arterial
Pressure
(mmHg)
* *
No Ext
Ext
P
r
e
-
C
S
4
C
S
(
a
v
g
)
P
r
e
-
C
S
4
C
S
(
a
v
g
)
400
500
600
700
Heart
Rate
(BPM)
* *
Day 1
Day 2
Day 3
80
100
120
140
Mean
Arterial
Pressure
(mmHg)
*
Pre Post
Sal
Los
(MAP mean)
15 30 45 60 75 90
105
60
80
100
120
140
160
Mean
Arterial
Pressure
(mmHg)
Pre
(30min)
(Minutes)
Post Injection
Sal
Los
15 30 45 60 75 90
105
200
400
600
800
Heart
Rate
(BPM)
Pre
(30min)
(Minutes)
Post Injection
C.
B.
D. E.
200
400
600
800
Heart
Rate
(BPM)
Pre Post
(MAP mean)
80
100
120
140
Mean
Arterial
Pressure
(mmHg)
*
Pre Post
Sal
Los
(MAP mean)
1
5
3
0
4
5
6
0
7
5
9
0
1
0
5
60
80
100
120
140
160
Mean
Arterial
Pressure
(mmHg)
Pre
(30min)
(Minutes)
Post Injection
Sal
Los
1
5
3
0
4
5
6
0
7
5
9
0
1
0
5
200
400
600
800
Heart
Rate
(BPM)
Pre
(30min)
(Minutes)
Post Injection
C.
B.
D. E.
200
400
600
800
Heart
Rate
(BPM)
Pre Post
(MAP mean)
4
Swiercz et al., Front Behav Neurosci 2018
Conditioned Cardiovascular Responses in the Home Cage
26. Conditioned CV Test #3
Fear Conditioning
Test #1
Extinction
x 35
x 4
Extinction
x 35
5 x
Test #2
x 4
Test #3
x 4
Conditioned CV Test #2
Day
1
Day
2
Day
3
Swiercz et al., Front Behav Neurosci 2018
The Effects of Extinction learning on the Conditioned
Cardiovascular (CV) Response
27. Resting blood pressure, heart rate, heart rate variability, or
activity levels were unaltered by fear conditioning and
extinction training.
Recall of consolidated extinction memories modulate the
conditioned cardiovascular response, which is influenced by
context-dependent differences in blood pressure and HR
sensitivity.
*Conditioned blood pressure responses may serve as a novel
index in the evaluation of extinction efficiency and may aid
in further understanding mechanisms driving exaggerated
physiological responses in PTSD
Take Home Points and Conclusion
29. ● Conditioned cardiovascular responses can be confounded by
environmental and physiological factors that affect physiological state
○ Environmental factors (ie., foreign scents, noise)
○ Cage setup and proximity to other animals
○ Physiological – circadian rhythms and routine (e.g. nest building)
● Blood pressure response to acute stress is differentially affected by
circadian rhythms (Bernatova I et al., Hypertension. 2002 Nov;40(5):768-73).
These factors contribute to the variability in recording
cardiovascular measures of learned or conditioned fear as well as
comparing those responses across time.
Challenges with Assessing Integrated Conditioned Cardiovascular,
Autonomic and Behavioral Measures in Mice
30. Triggered audible tone (CS) from customized scheduling program
Turley et al., Physiology & Behavior, 2021-07-01, Volume 236, Article 113414
Software solution for multi-modal cardiovascular and autonomic data
collection of cardiovascular consistent physiological data
o The telemetry system and
data acquisition software
used was Ponemah (version
6.3), which has the ability to
send telemetry information
over Transmission Control
Protocol (TCP)
o The CS delivery program communicates with Ponemah via TCP sockets
o Sent in real-time data packets from Ponemah containing live
physiological information on blood pressure, heart rate, and oxygen
saturation among others.
31. 1) A HDX-11 transmitter was subcutaneously implanted
2) Speakers were wired into home cages
3) Animals were fear conditioned - 5CS/US pairings
4) The software was scheduled to give 6 conditioned stimuli (audible tones) over a
24-hour period only when the mouse’s Mean Arterial Pressure (MAP) was within
85 and 100 mmHg for at least 10 seconds
5) Time MAP must be in parameter range before a CS can be presented.
Methods
32. 1) For multiple speakers, whether
the CS schedule is shared or
randomized.
2) Shifting the parameter range
up for the nighttime to account
for diurnal mouse behavior.
3) Time MAP must be in
parameter range before a CS
can be presented.
4) Enables state-dependent CS
presentation.
Customized software with modifiable physiological, time
and interval dependent parameters
Turley et al., Physiology & Behavior, 2021-07-01, Volume 236, Article 113414
33. Remotely trigger a conditioned stimulus (CS) (i.e., audible tone) based on the
animals instantaneous cardiovascular state while in its home-cage environment
Turley et al., Physiology & Behavior, 2021-07-01, Volume 236, Article 113414
34. Turley et al., Physiology & Behavior, 2021-07-01, Volume 236, Article 113414
Remotely trigger a conditioned stimulus (CS) (i.e., audible tone) based on the
animals instantaneous cardiovascular state while in its home-cage environment
35. 1) CS dependent variation
in MAP response
across day / night.
2) CS presented during
the animal’s active
period (CS 2,3,4), the
response was
immediate.
3) Potential need for a
dynamic baseline
response.
Turley et al., Physiology & Behavior, 2021-07-01, Volume 236, Article 113414
Remotely scheduled (diurnal) conditioned cue delivery
and cardiovascular response
36. o Remote Scheduling and Usage Functionality
Because the schedule is automatic, it removes the need for the experimenter to be
present (day/night) and performed in the animal’s natural (home cage) environment.
Defined set parameter ranges before CS presentation eliminates the possibility
external factors that could confound collected data
o Customizable to multiple behavioral or physiological parameters
The software is open source and can be customized to perform many behavioral and
physiological functions and conditioned triggers beyond the delivery of audible tones.
Ponemah has the capability to send other physiological parameters (e.g. HR, SpO2,
Sys/Dia, EEG)
Defined dynamic baseline can be used for when the animal outside of normal ranges
(ie., day/night)
*Software tool extends the ability to quantify integrated physiological
correlates of learned fear
*May aid in further understanding mechanisms related to enhanced
cardiovascular and autonomic arousal in fear and anxiety based disorders.
Functionality and utility of software TCP application
37. Berntson & Khalsa, (2021) Trends in Neurosciences
Threat dependent
cardiovascular signals and
influence on PTSD risk and
CVD development
Maddox et. al., 2019 Neuron. 2019 Apr 3;102(1):60-74
Interoceptive processes and disease
Cardiovascular
Signals
(ie., baroreceptor
sensitivity,
HR contractility)
Psychopharmacological experimental applications
(Swiercz et al., Transl Psychiatry. 2020 Oct 27;10(1):363.
Animal models of cardiovascular disease
Chemogenetic and Optogenetic integration /
applications
Neuroscience and Cardiovascular Applications
38. Collaborators
Jeanie Park, MD – Emory University
Peter Nemes, PhD – University of Maryland
Robert C. Speth, Phd - Nova Southeastern University
Nikki Posnack, PhD, Childrens National Medical
Antonia Seligowski, PhD Harvard / McLean
Kerry Ressler, MD/Phd – Harvard / McLean Hospital
Murray Stein, MD - UCSD
Anastas Popratiloff MD PhD - Director GWU
Nanofabrication and Imaging Center
University of Florida – Eric Krause / Annete DeKloet labs
Lab Members
Elizabeth Paronett, MS – Research Lab Manager
Zhe Yu, PhD – Post Doctoral Fellow
Laxmi Iyer, PhD – Post Doctoral Fellow
Shara Grant, PhD – Post Doctoral Fellow
Hannah Smith – Grad Stud. IBS 3rd year
Adam P. Swiercz, PhD
(NIMH Postdoc)
Funding
Acknowledgements – Thank You
39. Thanks for participating!
• Want to learn more and watch the webinar on demand?
Visit: www.insidescientific.com
• Want to learn more about DSI’s implantable telemetry
techology? Visit: www.datasci.com
• Want to learn more about Coulbourn Instruments’ behavioral
research instrumentation? Visit: www.coulbourn.com
Editor's Notes
Why Study…
Ans: There is increasing attention to the brain-heart-body relationship to psychological (and physical) health;
In this context, my research is focused on understanding the link between anxiety disorders such as PTSD and CVD risk.
Why Study…
Ans: There is increasing attention to the brain-heart-body relationship to psychological (and physical) health;
In this context, my research is focused on understanding the link between anxiety disorders such as PTSD and CVD risk.
1. Understanding PTSD related physical health (ie., CVD risk) co-morbidities and their underlying mechanisms has become a major public health concern.
This was recently recognized and highlighted by the CDC!
2. As shown here is this schemaitic there is a bi-directional relationship – as population and clinical based studies demonstrate both causal and consequential evidence for the link between PTSD – CVD
Likely contributors stems from both….
Physiological and Behavioral (modifiable) pathways…
The physiological and behavioral mechanisms linking PTSD with CVD risk are yet to be confirmed, and there are many potential confounding
and mediating factors that could contribute to this association.
There is currently a great need for further understanding underlying causal and/or consequential of PTSD / CVD risk
In 2018 the NHLBI assembled a working group of scientists and clinicians (of which I was proud to contribute) who were tasked with identifying the state of this research including, gaps current understanding and opportunities for future research.
PTSD is associated with both an increased prevalence of major CVD risk factors, such as hypertension and diabetes, as
well as an increased risk of CVD events, such as myocardial infarction and stroke, increased progression of CVD to heart failure, and
premature mortality.
In 2018 the NHLBI assembled a working group of scientists and clinicians (of which I was proud to contribute) who were tasked with identifying the state of this research including, gaps current understanding and future opportunities for research.
It was concluded that the research to date has been largely descriptive, with very little known regarding the underlying biological and behavioral mechanisms or insights into the causal nature and reversibility linking PTSD and CVD.
Despite these observations, prospective data from well designed studies that fully account for confounding factors and assess possible pathways in ways that permit causal inference are limited.
Multi-disciplinary approach needed to establish causal inference; Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited.
(Figure) These factors include a wide spectrum of health risk behaviors that characterize PTSD (eg, disturbed sleep physiology, maladaptive dietary changes, tobacco use, substance use, physical inactivity, and noncompliance with medical therapy) and other
associated psychological states (eg, depression or hostility).
Review article by Donald Edmondson – Lancet Psychiatry --- provides a nice illustration that highlights the state of the epidemiological and clinical evidence, (BLUE-strong) vs orange (emerging)…
High blood pressure may be one mechanism by which PTSD contributes to heightened CVD risk.
(Meta101 analytic evidence suggests that…)
PTSD was an independent risk factor for incident coronary heart disease and cardiac-specific mortality8. More recent reports show that the problem is even greater in Veteran populations as those Veterans diagnosed with PTSD are at approximately 45% greater risk of myocardial infarction and roughly 30% greater risk of developing congestive heart failure and peripheral vascular disease later in life compared to veterans without PTSD9,10 .
A comprehensive understanding of ANS / CV dysfunction, including neurocircuits, autonomic dysregulation,
neurotransmitter abnormalities, and increased inflammation, requires mechanistic studies using animal
models…..as much of the experimental work is not feasible in humans (Pitman et al., 2012).
Review article by Donald Edmondson – Lancet Psychiatry --- provides a nice illustration that highlights the state of the epidemiological and clinical evidence, (BLUE-strong) vs orange (emerging)…
High blood pressure may be one mechanism by which PTSD contributes to heightened CVD risk.
(Meta101 analytic evidence suggests that…)
PTSD was an independent risk factor for incident coronary heart disease and cardiac-specific mortality8. More recent reports show that the problem is even greater in Veteran populations as those Veterans diagnosed with PTSD are at approximately 45% greater risk of myocardial infarction and roughly 30% greater risk of developing congestive heart failure and peripheral vascular disease later in life compared to veterans without PTSD9,10 .
A comprehensive understanding of ANS / CV dysfunction, including neurocircuits, autonomic dysregulation,
neurotransmitter abnormalities, and increased inflammation, requires mechanistic studies using animal
models…..as much of the experimental work is not feasible in humans (Pitman et al., 2012).
PTSD can be reflected by altered activity in multiple brain systems, including those that directly modify autonomic functions and behavioral and physiological responses..
Functional neuroimaging studies over the past two decades have implicated PTSD specific changes in regional activation and functional connectivity.
More specifically, hyper-activation of amygdala, insula, dorsal anterior cingulate cortex (dACC), as well as hypo-activation in ventral medial prefrontal cortex (vmPFC) and impaired hippocampal function have been consistently detected (Lebois, Wolff, & Ressler, 2016; Liberzon & Abelson, 2016; Pitman et al., 2012; Stark et al., 2015).
Autonomic neurophysiological states can be influenced by disruption in the hierarchically organized brain systems that comprise the central autonomic network (Williamson, Porges, Lamb, & Porges, 2014)
Circuits of brain impacted by PTSD…….At the level of neural circuits, preclinical and human studies
consistently support the concept of PTSD as a disorder of altered emotional memory formation and/or extinction33 and dysregulation of the response to environmental Threat and stress.34
****The amygdala is part of the limbic system and is involved in processing positive and negative emotions by assigning valence to stimuli, is also involved in innate behaviors such as aggression, mating as well as fear
Sokolowski K and Corbin JG, Frontiers in Molecular Neuroscience, 2012.
(exaggerated physiological responses to threat related cues)
A comprehensive understanding of ANS / CV dysfunction, including neurocircuits, autonomic dysregulation,
neurotransmitter abnormalities, and increased inflammation, requires mechanistic studies using animal
models…..as much of the experimental work is not feasible in humans (Pitman et al., 2012).
A tool for investigating neural substrates of emotion.
A previously neutral stimulus (tone or light) is paired with a noxious stimulus usually a mild electrical footshock so that the neutrail stimulus now becomes predictive of danger.
Freezing is a universal fear response (evolutionarily conserved response across species), observed both in reaction to conditioned (learned) or unconditioned (acutely threatening) stimuli or situations [22].
It is a state of attentive immobility serving to avoid detection by predators and to enhance perception [9,10]
Pavlovian fear conditioning ---The brain mechanisms of fear have been studied extensively using Pavlovian fear conditioning, a procedure that allows exploration of how the brain learns about and later detects and responds to threats. A tool for investigating neural substrates of emotional learning
A typical rodent will show fear in the form of freezing behavior in a fear conditioning test.
Extinction ----- animals can also learn that stimuli previously associated with adverse outcomes no longer represent a threat.
As noted above, the robust and rapidly learned nature of fear memory makes it an ideal model system for investigating memory processes such as learning (memory acquisition), storage (consolidation) and updating and persistence (reconsolidation). Indeed, the traction gained by research into memory recon-solidation, which had originally been described
Pavlovian Fear Conditioning: A Technique and a Process
Fear is the most extensively studied emotion, and the way it has most often been investigated is through Pavlovian fear conditioning. This procedure involves presenting a biologically neutral conditioned stimulus (CS), often a tone, with a noxious or harmful unconditioned stimulus (US), typically a mild electric shock. As a result, the CS comes to elicit species-typical (presumably innate) behavioral responses (e.g., freezing behavior) and supporting physiological adjustments controlled by the autonomic nervous system (e.g., changes in heart rate, blood pressure, respiration) or by endocrine systems (e.g., adrenocorticotropic hormone, cortisol, epinephrine) (7⇓⇓⇓⇓–12). Through fear conditioning, researchers thus have control of the antecedent conditions (the independent variables, namely the CS and US) and can measure the outcomes (dependent variables, such as freezing behavior or autonomic nervous system responses).
The fear-conditioning procedure works because it taps into a process called associative learning that is a feature of circuits in the nervous systems of many if not all animals (4, 13⇓⇓–16) and may also exist in single-cell organisms (17, 18). When associative learning occurs in the circuit engaged by the fear conditioning procedure, the learning process itself is also called fear conditioning. The fear-conditioning process allows the US to alter the effectiveness of the CS in activating circuits that control defense responses in anticipation of harm.
From the blood pressure channel, we can measure systolic, diastolic, and mean arterial pressure.
The ECG channel monitors the electrical activity of the heart, which we analyze to detect R-waves. Ectopic beats and artifiacts are removed by excluding R-R intervals that do not lie within 2 standard deviations of the mean. If the rejected intervals make up more than five percent of the signal, that sample is removed from the study.
We digitize our multilead ECG data, and compute physiologically meaningful parameters on a beat-to beat basis
Heart rate variability is a measure of autonomic nervous system function, and can reflect the ability to adaptively cope with stress.
It describes the variation in intervals between heart beats, and can be measured in both the time and frequency domain. Decreased HRV in humans is an independent predictor of cardiac morbidity and mortality in patients with heart disease.
Heart rate in healthy individuals is not constant. Modulations of autonomic nervous system activity cause the heart rate to oscillate around a mean value. Autonomic control of the heart rate is carried out by the sympathetic and parasympathetic nervous systems.
Time Domain
Freq domain
- High frequency considered to be a marker of vagal activity
-LF power is a marker of both sympathetic, parasympathetic, and vagal activity
The heart accelerates on inspiration and deccelerates on exhalation
Time Domain:
SDNN
RMSSD
pnnX
Frequency Domain:
Frequency Domain Analysis is a complex analysis technique that shows how much of a signal lies within one or more frequency bands (ranges). With regards to Heart Rate Variability, research has identified certain frequency bands that tend to correlate with certain physiological phenomenon, such as Parasympathetic nervous system activity.
(Scroll to the bottom to understand the difference between units of measurement)
Common Frequency Domain HRV metrics include:
High Frequency power (HF): frequency activity in the 0.15 - 0.40Hz range (green in the above chart)
Low Frequency power (LF): frequency activity in the 0.04 - 0.15Hz range (yellow in the above chart)
LF/HF Ratio: A ratio of Low Frequency to High Frequency. Some consider this indicative of Sympathetic to Parasympathetic Autonomic Balance, but that is controversial. Please see this article and this article for more information.
On Day 1 of extinction training, the CS-US group exhibited increased freezing throughout the 30 CS presentations (Figure 1C). Fear acquisition was demonstrated in the CS-US animals compared to the CS by group differences in freezing during the first 4 CS presentations (71% 4 vs. 10% 3, p < 0.05) (Figure 1E). CS-US animals showed a significant reduction in freezing from Day 1–2, with a significant group x
time interaction [F(1,17) = 20.68, p = 0.0003] (Figure 1E).
Integrating wireless telemetry approaches, combined with animal behavioral measures (e.g., Pavlovian fear conditioning), provides a unique way to test the impact of pharmacological, behavioral (e.g., exposure therapy/extinction learning) or other non-invasive interventions (e.g., TMS) on cardiovascular autonomic responses to learned threats and emotional regulation.
Integrating wireless telemetry approaches, combined with animal behavioral measures (e.g., Pavlovian fear conditioning), provides a unique way to test the impact of pharmacological, behavioral (e.g., exposure therapy/extinction learning) or other non-invasive interventions (e.g., TMS) on cardiovascular autonomic responses to learned threats and emotional regulation.
In order to eliminate some of the confounds which may result from cardiovascular changes related to stress or other environmental factors, we developed a program for remote application in Ponemah™ (version 6.3) from Data Sciences International (DSI), St. Paul, MN, United States. The software is built as a standalone CS delivery remote connection scheduling software which can use any connected computer audio outputs in which conditioned stimuli (i.e., audible tones) can be delivered outside of a dedicated testing chamber in a home cage environment.
The software processes and stores this data as well as delivers the conditioned stimuli using native USB audio output channels
PonemahTM software has the capability to send live signals over TCP These signals can be used by local software and processed in real-time for feedback to the animal
This is important because memory cells are very long lived and can sensitize individuals to repeated hypertensive stimuli, thus contributing to end-organ damage.