Platelet and Leukocyte Mitochondrial Function With Cardiac Function and Self-Reported Health Status Among Obese Patients With Heart Failure.

BACKGROUND: Mitochondrial dysfunction plays a key role in the development of heart failure (HF), including HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Impaired mitochondrial function negatively affects cardiac function and, subsequently, the health status of patients. However, measuring mitochondrial function in human myocytes is difficult because of the high risk associated with myocardial biopsy. Platelets and leukocytes have functional mitochondria and can potentially serve as a surrogate for myocardial mitochondria. Roles of platelet and leukocyte mitochondrial function in HF have not yet been fully explored. OBJECTIVE: We aimed to explore the relationships of platelet and leukocyte mitochondrial function with cardiac function and self-reported health status among obese patients with HF and examine if the relationships vary between HFrEF and HFpEF. METHODS: Forty-five obese patients with HF were recruited. Maximal enzymatic activities (Vmax) of platelet cytochrome c oxidase (COX) and citrate synthase (CS) were assessed. Leukocyte mitochondrial mass, membrane potential, superoxide production, and apoptosis were measured in a subset of the sample. Data on cardiac function were retrieved from electronic health records. Self-reported health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Pearson correlations were performed. RESULTS: Platelet COX Vmax was negatively correlated with left ventricular end-systolic diameter. Positive correlations of leukocyte mitochondrial mass and superoxide production with left ventricular mass and mass index were observed, respectively. Leukocyte mitochondrial mass and superoxide production also negatively correlated with KCCQ summary scores. These relationships varied between HFrEF and HFpEF. DISCUSSION: Platelet and leukocyte mitochondrial function was found to significantly correlate with some echocardiographic parameters and KCCQ scores. These findings provided preliminary data to support future research to further explore the potential of using platelets and leukocytes as surrogate biomarkers. Identifying easy-accessible mitochondrial biomarkers will be useful for assessing mitochondrial function to assist with early diagnosis and monitoring the effectiveness of mitochondrial-targeted therapy in HF patients.

Post-COVID-19 Syndrome.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many individuals have reported persistent symptoms and/or complications lasting beyond 4 weeks, which is now called post-COVID-19 syndrome. SARS-CoV-2 is a respiratory coronavirus that causes COVID-19, and injury to the lungs is expected; however, there is often damage to numerous other cells and organs, leading to an array of symptoms. These long-term symptoms occur in patients with mild to severe COVID-19; currently, there is limited literature on the potential pathophysiological mechanisms of this syndrome. OBJECTIVES: The purpose of this integrative review is to summarize and evaluate post-COVID-19 syndrome from a biological perspective. METHODS: An integrative review was conducted using Whittemore and Knafl's methodology for literature published through August 30, 2021. The PubMed, CINAHL, and Web of Science databases were searched for articles published as of August 30, 2021, using combinations of the following key words: post-COVID-19 syndrome, post-SARS-CoV-2, long COVID-19, long COVID-19 syndrome, and pathophysiology of post-COVID-19. Data were analyzed using the constant comparison method. RESULTS: The search generated 27,929 articles. After removing duplicates and screening abstracts and full-text reviews, we retained 68 articles and examined 54 specific articles related to the pathophysiology of post-COVID-19 syndrome. The findings from our review indicated that there were four pathophysiological categories involved: virus-specific pathophysiological variations, oxidative stress, immunologic abnormalities, and inflammatory damage. DISCUSSION: Although studies examining the pathophysiology of post-COVID-19 syndrome are still relatively few, there is growing evidence that this is a complex and multifactorial syndrome involving virus-specific pathophysiological variations that affect many mechanisms but specifically oxidative stress, immune function, and inflammation. Further research is needed to elucidate the pathophysiology, pathogenesis, and longer term consequences involved in post-COVID-19 syndrome.

Obesity-Related High-Output Heart Failure: An Integrative Review.

BACKGROUND: High-output heart failure (HF) is a type of HF characterized by signs and symptoms of HF and a cardiac output of 8 L/min or greater or a cardiac index greater than 3.9 L/min/m 2 . High-output HF occurs secondary to an underlying condition that requires high cardiac output due to an increase in oxygen consumption or decreased systemic vascular resistance. Obesity is a major cause of high-output HF, yet there is limited research on obesity-related high-output HF. Thus, the pathophysiologic mechanisms of this syndrome are not fully understood. OBJECTIVE: The objectives of this integrative review were to describe the current state of the research regarding obesity-related high-output HF and to recommend direction for future research. METHODS: We conducted an integrative review focusing on the peer-reviewed literature on patients with obesity-related high-output HF using Whittemore and Knafl's methodology. MEDLINE, CINAHL, and EMBASE electronic databases were searched for all publications indexed in the databases as of March 9, 2022. A narrative synthesis of definitions and symptoms, obesity as an underlying condition, pathophysiology, and treatments of obesity-related high-output HF was completed. RESULTS: A total of 6 articles were included in the integrative review, with 1 nonexperimental, retrospective study and 5 literature reviews. Understanding of obesity-related high-output HF is very limited because of scant empirical evidence in the existing literature. Possible pathophysiologic mechanisms include increased pressure in the upper airways, adipokine dysregulation, increased metabolic activity, and insulin resistance. CONCLUSION: Additional research is needed on the pathophysiologic mechanisms of obesity-related high-output HF to begin investigations on therapeutic interventions to improve health outcomes.

Implementing a post-traumatic stress disorder screening for first responders in rural area.

OBJECTIVES: Post-traumatic stress disorder (PTSD) is a significant public health problem especially among first responders who are routinely exposed to traumatic events. First responders in rural areas are faced with additional stressors. The purpose of this quality improvement program was to implement PTSD screening for first responders at a primary care concierge clinic. DESIGN: Implementation of PTSD screening program among first responders was conducted from October to December 2020, using the PTSD Checklist for DSM-5 with Life Events Checklist for DSM-5 and Criterion A (PCL-5 with LEC-5 and Criterion A). SAMPLE: First responders who visited the clinic during program implementation period. OUTCOMES: Numbers of PTSD screening, positive screening, positive PTSD symptoms, and referral. RESULTS: Thirty-four first responders completed the PTSD screening. 23.5% (n = 8) of first responders were screened positive. Almost 80% of first responders reported experiencing at least one PSTD symptom (n = 27). Six of the eight screened positive first responders (75%) received a referral. CONCLUSION: The standardized PTSD screening protocol utilizing PCL-5 was effective to identify first responders with PTSD. It can be integrated into the workflow of a primary care concierge clinic and help improving PTSD assessment in first responders and initiated referrals.

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose.

BACKGROUND: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. METHODS: Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). DISCUSSIONS: Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

Kansas nurse leader residency programme: advancing leader knowledge and skills.

AIMS: To evaluate the effectiveness of the Kansas Nurse Leader Residency (KNLR) programme in improving nurses' leadership knowledge and skills and its acceptability, feasibility and fidelity. BACKGROUND: The Future of Nursing Report (Institute of Medicine, 2011) calls for nurses to lead change and advance health. The 6-month KNLR programme was developed by the Kansas Action Coalition to support nurses' leadership development. METHODS: Nurses (n = 36) from four nursing specialties (acute care, long-term care, public health and school health) participated in the programme. The adapted Leader Knowledge and Skill Inventory was used to assess leadership knowledge and skills. Programme acceptability, feasibility and implementation fidelity also were evaluated. RESULTS: The programme completion rate was 67.7% (n = 24). Programme completers had significantly improved self-assessed and mentor-assessed leadership knowledge and skills (p < .05). These post-programme gains were maintained 3 months after programme completion. CONCLUSIONS: The KNLR programme effectively improved leadership knowledge and skills and was positively evaluated by participants. The implementation of the KNLR programme using a hybrid format of in-person sessions and online modules was feasible across four specialty areas in both rural and urban regions. IMPLICATIONS FOR NURSING MANAGEMENT: The next steps include the development of an advanced programme. Residency programmes for new nurse leaders are critical for successful transition into management positions.

The use of antioxidants in the treatment of traumatic brain injury.

AIMS: The aim of this study was to discuss secondary traumatic brain injury, the mitochondria and the use of antioxidants as a treatment. BACKGROUND: One of the leading causes of death globally is traumatic brain injury, affecting individuals in all demographics. Traumatic brain injury is produced by an external blunt force or penetration resulting in alterations in brain function or pathology. Often, with a traumatic brain injury, secondary injury causes additional damage to the brain tissue that can have further impact on recovery and the quality of life. Secondary injury occurs when metabolic and physiologic processes alter after initial injury and includes increased release of toxic free radicals that cause damage to adjacent tissues and can eventually lead to neuronal necrosis. Although antioxidants in the tissues can reduce free radical damage, the magnitude of increased free radicals overwhelms the body's reduced defence mechanisms. Supplementing the body's natural supply of antioxidants, such as coenzyme Q10, can attenuate oxidative damage caused by reactive oxygen species. DESIGN: Discussion paper. DATA SOURCES: Research literature published from 2011-2016 in PubMed, CINAHL and Cochrane. IMPLICATIONS FOR NURSING: Prompt and accurate assessment of patients with traumatic brain injury by nurses is important to ensure optimal recovery and reduced lasting disability. Thus, it is imperative that nurses be knowledgeable about the secondary injury that occurs after a traumatic brain injury and aware of possible antioxidant treatments. CONCLUSION: The use of antioxidants has potential to reduce the magnitude of secondary injury in patients who experience a traumatic brain injury.

A pilot study exploring the effects of ubiquinol on brain genomics after traumatic brain injury.

BACKGROUND: Traumatic brain injury is a major cause of morbidity and mortality that affects military service members and veterans. PURPOSE: Explore the effects of ubiquinol before traumatic brain injury on cerebral gene expression to elucidate molecular mechanisms of ubiquinol neuroprotection. METHOD: In this experimental study, Fisher rats in the untreated (n = 2) and ubiquinol-treated (n = 2) groups received respectively either normal saline or ubiquinol 30 min before traumatic brain injury induced by controlled cortical impact. Ribonucleic acid sequencing and ingenuity pathway analysis were conducted to detect cerebral gene and signaling expression profiles. DISCUSSION: In the ubiquinol-treated group, 67 ingenuity pathway analysis transcripts in the ubiquinol-treated group were statistically different from those in the untreated group (p <.0001). CONCLUSIONS: Administering ubiquinol 30 min before traumatic brain injury significantly affected cerebral gene expression profiles that may be involved in the most fundamental molecular mechanisms of bioenergetics and free radical production.

Systematic Review of Traumatic Brain Injury and the Impact of Antioxidant Therapy on Clinical Outcomes.

BACKGROUND: Traumatic brain injury (TBI) is an acquired brain injury that occurs when there is sudden trauma that leads to brain damage. This acute complex event can happen when the head is violently or suddenly struck or an object pierces the skull or brain. The current principal treatment of TBI includes various pharmaceutical agents, hyperbaric oxygen, and hypothermia. There is evidence that secondary injury from a TBI is specifically related to oxidative stress. However, the clinical management of TBI often does not include antioxidants to reduce oxidative stress and prevent secondary injury. AIMS: The purpose of this article is to examine current literature regarding the use of antioxidant therapies in treating TBI. This review evaluates the evidence of antioxidant therapy as an adjunctive treatment used to reduce the underlying mechanisms involved in secondary TBI injury. METHODS: A systematic review of the literature published between January 2005 and September 2015 was conducted. Five databases were searched including CINAHL, PubMed, the Cochrane Library, PsycINFO, and Web of Science. FINDINGS: Critical evaluation of the six studies that met inclusion criteria suggests that antioxidant therapies such as amino acids, vitamins C and E, progesterone, N-acetylcysteine, and enzogenol may be safe and effective adjunctive therapies in adult patients with TBI. Although certain limitations were found, the overall trend of using antioxidant therapies to improve the clinical outcomes of TBI was positive. LINKING EVIDENCE TO ACTION: By incorporating antioxidant therapies into practice, clinicians can help attenuate the oxidative posttraumatic brain damage and optimize patients' recovery.

Exploring leadership roles, goals, and barriers among Kansas registered nurses: a descriptive cross-sectional study.

OBJECTIVES: The Institute of Medicine's Future of Nursing report advocates for full nurse leader representation across multiple settings to address current challenges in our health care system. The purpose of this study was to examine nursing leadership development needs among Kansas registered nurses (RNs). METHODS: Data were collected through an online survey and analyzed using quantitative and qualitative methods. RESULTS: Nearly 1,000 Kansas RNs participated. Most reported holding one or more leadership positions. Prevalent leadership goals were health care organization volunteer administrative roles. The most frequently identified barrier to developing leadership roles was time constraints. Many wanted to develop skills to serve on a board, 20% were interested in personal leadership development, and 19% in policy development. CONCLUSIONS: Based on the findings, the Kansas Action Coalition leadership team is developing programs to address the leadership needs of Kansas RNs. By building capacity in advanced leadership roles, RNs will be better prepared serve as full partners and lead efforts to promote the health of Kansans.

Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat lungs, diaphragm, heart and kidneys.

Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined the effects of ubiquinol administered with fluid resuscitation following controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected to 60 min of HS by removing 40% of the total blood volume to a mean arterial pressure ∼45-55 mmHg. The animals were resuscitated with blood and lactated Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end of the experiments, the rats were killed and the lungs, diaphragm, heart and kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at baseline, end of shock and 120 min following fluid resuscitation using MitoSOX Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and kidneys was measured using fluorescence microscopy with acridine orange and ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly lower in rats that received ubiquinol than in the control animals. Production of hydrogen peroxide and apoptosis were significantly reduced in the organs of rats treated with ubiquinol. These findings suggest that ubiquinol, administered with fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus, ubiquinol is a potent antioxidant that may be used as a potential treatment to reduce organ injury following haemorrhagic events.

Myocardial energetics and ubiquinol in diastolic heart failure.

Diastolic heart failure, or heart failure with preserved ejection fraction, is a leading cause of morbidity and mortality. There are no current therapies effective in improving outcomes for these patients. The aim of this article is to review the literature and examine the role of coenzyme Q10 in heart failure with preserved ejection fraction related to mitochondrial synthesis of adenosine triphosphate and reactive oxygen species production. The study results reflect that myocardial energetics alters in diastolic heart failure and that there is defective energy metabolism and increased oxidative stress. Studies are emerging to evaluate coenzyme Q10 , particularly ubiquinol, as a supplemental treatment for heart-failure patients. In diastolic heart-failure patients, clinicians are beginning to use supplemental therapies to improve patient outcomes, and one promising complementary treatment to improve left ventricular diastolic function is ubiquinol. Additional studies are needed using large-scale randomized models to confirm if ubiquinol would be beneficial. Since ubiquinol is an antioxidant and is required for adenosine triphosphate production, clinicians and health scientists should be aware of the potential role of this supplement in the treatment of diastolic heart failure.

Growing the Next Generation of Nurse Leaders: A Report of the Process and Outcomes of the Midwest Nursing Research Society Leadership Academy.

BACKGROUND: Leadership development, career advancement, and collaboration among scholars are essential to nurturing nursing research excellence and sustainability. The Midwest Nursing Research Society (MNRS) has incorporated several strategies to advance nursing science and to increase the pool of future nurse leaders. In this article, we describe the process, activities, and outcomes of the Leadership Academy (LA), an innovative initiative from MNRS developed to identify, engage, and nurture future generations of leaders. METHODS: For the LA 2022 to 2023 period, the MNRS leaders selected a cohort of 5 nurse scholars and engaged them in activities to develop, enhance, and advance their leadership skills. By following the LA purposes, the cohort participated in monthly meetings with MNRS leaders, received individual mentoring sessions, assessed strengths and areas for further development, attended seminars, participated in a book club, and implemented a cohort project that focused on the promotion and support of early career scholars. RESULTS: Outcomes showed increased knowledge about organizational governance, direction, and resource development; leadership confidence culminating with leadership positions inside and outside MNRS; career development plans; engagement with board members, and enhanced networking. Moreover, the cohort members planned and executed a well-attended conference special session that engaged a large group of scholars to discuss challenges and opportunities for career development at the MNRS Annual Conference. CONCLUSION: The MNRS LA is a thriving organizational initiative that promotes engagement and leadership skills development thereby increasing the pool of candidates confidently prepared to lead the nursing profession.

Differences in Leukocyte Transcriptomes of Morbidly Obese Patients With High Output Heart Failure: A Pilot Study.

Background and Objectives: Heart failure is characterized by alterations of gene expression that provide insight into the underlying pathophysiologic mechanisms. However, obesity-related high output heart failure (HOHF) is a specific phenotype of heart failure that has not been studied using gene expression. Our aim in this study was to examine the variances in leukocyte transcriptomes of morbidly obese patients with HOHF. Methods: In this cross-sectional study, we applied stranded total RNA-sequencing to six patients with morbid obesity and HOHF and 6 patients with morbid obesity and non-HOHF. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and networks in these patients. Results: We found in patients with HOHF that there were 116 differentially expressed genes with upregulation of 114 genes and downregulation of 2 genes. The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. We identified GATA binding protein 1 as an upstream regulator and nuclear factor kappa-light-chain-enhancer of activated B cells associated network. Conclusions: We are the first to report the differential gene expression in patients with obesity-related HOHF and reveal the various pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Effects of Ubiquinol and/or D-ribose in Patients With Heart Failure With Preserved Ejection Fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) have few pharmacologic therapies, and it is not known if supplementing with ubiquinol and/or d-ribose could improve outcomes. The overall objective of this study was to determine if ubiquinol and/or d-ribose would reduce the symptoms and improve cardiac performance in patients with HFpEF. This was a phase 2 randomized, double-blind, placebo-controlled trial of 216 patients with HFpEF who were ≥ 50 years old with a left ventricular ejection fraction (EF) ≥ 50%. A total of 4 study groups received various supplements over 12 weeks: Group 1 received placebo ubiquinol capsules and d-ribose powder, Group 2 received ubiquinol capsules (600 mg/d) and placebo d-ribose powder, Group 3 received placebo ubiquinol capsules with d-ribose powder (15 g/d), and Group 4 received ubiquinol capsules and d-ribose powder. There were 7 outcome measures for this study: Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score, level of vigor using a subscale from the Profile of Mood States, EF, the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (septal E/e' ratio), B-type natriuretic peptides, lactate/adenosine triphosphate ratio, and the 6-minute walk test. Treatment with ubiquinol and/or d-ribose significantly improved the KCCQ clinical summary score (17.30 to 25.82 points), vigor score (7.65 to 8.15 points), and EF (7.08% to 8.03%) and reduced B-type natriuretic peptides (-72.02 to -47.51) and lactate/adenosine triphosphate ratio (-4.32 to -3.35 × 10-4). There were no significant increases in the septal E/e' or the 6-minute walk test. In conclusion, ubiquinol and d-ribose reduced the symptoms of HFpEF and increased the EF. These findings support the use of these supplements in addition to standard therapeutic treatments for patients with HFpEF.

Clinical Trial Visits in the Age of COVID-19: Implementation of Research Participant Safety Measures.

The COVID-19 pandemic is having a major impact on how current clinical trials are being conducted in the U.S. Researchers have experienced the effects of COVID-19 through the halting and delaying of clinical trials, the lack of personal protection equipment (PPE), the closing of clinical sites, and a decrease in participant recruitment. Many clinical trials will have more missing data because of a participant's inability to attend in-person visits, discontinuation of trial activities, or interruption of time-sensitive study collection data due to COVID-19. All of these events affect the data quality of trials. Government agencies such as the Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and National Institutes of Health (NIH) have issued recommendations for investigators conducting clinical trials to combat the spread of COVID-19 and to maintain data integrity. Institutions sponsoring clinical trials have also provided guidelines to continue, modify, or pause research studies that are essential to ensure participant and research team safety. Key recommendations include implementing telehealth appointments, wearing a protective mask and face shield, quarantining for 14 days if exposed to COVID-19 or having traveled, and, if possible, maintaining a 6-foot distance. It is also recommended that investigators implement COVID-19 screening questionnaires prior to and during on-site visits. This includes participants and research personnel completing a temperature check and questionnaire screen before in-person data collection. This article will discuss the challenges encountered by researchers conducting clinical trials and provide resources and examples to assist investigators during the COVID-19 pandemic.

Understanding Obesity-Related High Output Heart Failure and Its Implications.

Morbid obesity remains most common cause of high output failure. The prevalence of the obesity is growing when two-thirds of American adults already are overweight or obese. Obesity is the risk factor for heart disease and eventually leads to heart failure. High output heart failure is common in obese patients and is characterized by high cardiac output, decreased systemic vascular resistance, and increased oxygen consumption. It often occurs in patients with chronic severe anemia, hyperthyroidism, pregnancy, arterial-venous fistulas, and liver disease. However, the pathogenesis of obesity-related high output heart failure is not fully understood. The clinical management of obesity-related high output heart failure follows conventional heart failure regimens due to lack of specific clinical recommendations. This article reviews the possible pathophysiological mechanisms and causes that contribute to obesity-related high output heart failure. This review also focuses on the implications for clinical practice and future research involved with omics technologies to explore possible molecular pathways associated with obesity-related high output heart failure.

Mitochondrial bioenergetics and D-ribose in HFpEF: a brief narrative review.

OBJECTIVE: In this review article, we briefly describe the status of treatment options for HFpEF and the role of mitochondrial dysfunction in the pathogenesis of HFpEF as an alternative therapeutic target. We also examine the mechanisms of D-ribose in cellular energy production and discuss the potential disadvantages and benefits of supplemental use of D-ribose in patients with HFpEF. BACKGROUND: Heart failure is a major cardiovascular disease that impacts over 6 million Americans and is one of the leading causes for morbidity and mortality. Patients with heart failure often experience shortness of breath and fatigue along with impaired physical capacity, all leading to poor quality of life. As a subtype of heart failure, heart failure with preserved ejection fraction (HFpEF) is characterized with impaired diastolic function. Currently, there are no effective treatments specifically for HFpEF, thus clinicians and researchers are searching for therapies to improve cardiac function. Emerging evidence indicate that mitochondrial dysfunction and impaired cardiac bioenergetics are among the underlying mechanisms for HFpEF. There is increased interest in investigating the use of supplements such as D-ribose to enhance mitochondrial function and improve production of adenosine triphosphate (ATP). METHODS: For this narrative review, more than 100 relevant scientific articles were considered from various databases (e.g., PubMed, Web of Science, CINAHL, and Google Scholar) using the keywords "Heart Failure", "HFpEF", "D-ribose", "ATP", "Mitochondria", Bioenergetics", and "Cellular Respiration". CONCLUSIONS: It is essential to find potential targeted therapeutic treatments for HFpEF. Since there is evidence that the HFpEF is related to impaired myocardial bioenergetics, enhancing mitochondrial function could augment cardiac function. Using a supplement such as D-ribose could improve mitochondrial function by increasing ATP and enhancing cardiac performance for patients with HFpEF. There is a recently completed clinical trial with HFpEF patients that indicates D-ribose increases ATP production and improves cardiac ejection fraction.