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OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) target the reabsorption of sodium and glucose in the kidney proximal tubules to reduce blood sugar levels. However, clinical randomized controlled trials on SGLT2i have yielded inconsistent results, necessitating further research into their efficacy and safety for specific cardiac and renal diseases. METHODS: "Sodium in urine" was selected as a downstream biomarker of SGLT2i. Single nucleotide polymorphisms were extracted from genome-wide association study data as instrumental variables. Mendelian randomization analysis was then conducted for cardiac and renal diseases and potential adverse events. The causal effects of SGLT2i on these diseases were determined based on inverse variance weighted results, followed by sensitivity and pleiotropy tests. RESULTS: SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000-0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000-0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000-0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events. CONCLUSIONS: SGLT2i can act as protective factors against nephrotic syndrome, chronic glomerulonephritis, and hypertensive nephropathy.
Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Nephrotic Syndrome/genetics , Nephrotic Syndrome/drug therapy , Kidney Diseases/genetics , Sodium/urine , Sodium/blood , Glomerulonephritis/genetics , Glomerulonephritis/drug therapy , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/drug therapy , Heart Diseases/geneticsABSTRACT
Cardiovascular disease (CVD) and mental health disorders contribute to significant healthcare expenses. Lifestyle approaches that empower and enable patients to participate in their recovery are needed with the increasing complexity of cardiac patients. Traditional Tamil medical practice of Siddha self-inquiry meditation targets holistic health through intuitive lifestyle transformation. We describe 4 complex cardiac patients who explored Siddha based Hunger Gratitude Experience (HUGE) mindful eating and reported elevated levels of optimism and deeper experience of life as outlined by the 5000-year-old secular Siddha medical tradition. We cannot exclude the role of suggestion and placebo effect in descriptive series. However, the simultaneous improvement in physical health and emotional wellbeing along with demonstrated resilience against unforeseen adversities suggests this is Uvagai, the true essence of Siddha higher consciousness. Uvagai is extreme happiness and may be accessible universally with little formal training and targets positive psychology to improve wellbeing. While flow and bliss states are transient transcendental experiences, Uvagai may be more profound and therapeutic in CVD despite age and comorbidities. Seeking Uvagai can potentially overcome health disparities, including rural, minority, and underprivileged populations for better health. HUGE allows CVD patients to safely engage in Uvagai, experience higher consciousness and intuitively sustain lifestyle transformation.
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BACKGROUND: The presence of bias in artificial intelligence has garnered increased attention, with inequities in algorithmic performance being exposed across the fields of criminal justice, education, and welfare services. In health care, the inequitable performance of algorithms across demographic groups may widen health inequalities. OBJECTIVE: Here, we identify and characterize bias in cardiology algorithms, looking specifically at algorithms used in the management of heart failure. METHODS: Stage 1 involved a literature search of PubMed and Web of Science for key terms relating to cardiac machine learning (ML) algorithms. Papers that built ML models to predict cardiac disease were evaluated for their focus on demographic bias in model performance, and open-source data sets were retained for our investigation. Two open-source data sets were identified: (1) the University of California Irvine Heart Failure data set and (2) the University of California Irvine Coronary Artery Disease data set. We reproduced existing algorithms that have been reported for these data sets, tested them for sex biases in algorithm performance, and assessed a range of remediation techniques for their efficacy in reducing inequities. Particular attention was paid to the false negative rate (FNR), due to the clinical significance of underdiagnosis and missed opportunities for treatment. RESULTS: In stage 1, our literature search returned 127 papers, with 60 meeting the criteria for a full review and only 3 papers highlighting sex differences in algorithm performance. In the papers that reported sex, there was a consistent underrepresentation of female patients in the data sets. No papers investigated racial or ethnic differences. In stage 2, we reproduced algorithms reported in the literature, achieving mean accuracies of 84.24% (SD 3.51%) for data set 1 and 85.72% (SD 1.75%) for data set 2 (random forest models). For data set 1, the FNR was significantly higher for female patients in 13 out of 16 experiments, meeting the threshold of statistical significance (-17.81% to -3.37%; P<.05). A smaller disparity in the false positive rate was significant for male patients in 13 out of 16 experiments (-0.48% to +9.77%; P<.05). We observed an overprediction of disease for male patients (higher false positive rate) and an underprediction of disease for female patients (higher FNR). Sex differences in feature importance suggest that feature selection needs to be demographically tailored. CONCLUSIONS: Our research exposes a significant gap in cardiac ML research, highlighting that the underperformance of algorithms for female patients has been overlooked in the published literature. Our study quantifies sex disparities in algorithmic performance and explores several sources of bias. We found an underrepresentation of female patients in the data sets used to train algorithms, identified sex biases in model error rates, and demonstrated that a series of remediation techniques were unable to address the inequities present.
Subject(s)
Algorithms , Machine Learning , Humans , Female , Male , Heart Diseases , Sex FactorsABSTRACT
[This corrects the article DOI: 10.3389/fvets.2024.1327081.].
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Heart attack is a life-threatening condition which is mostly caused due to coronary disease resulting in death in human beings. Detecting the risk of heart diseases is one of the most important problems in medical science that can be prevented and treated with early detection and appropriate medical management; it can also help to predict a large number of medical needs and reduce expenses for treatment. Predicting the occurrence of heart diseases by machine learning (ML) algorithms has become significant work in healthcare industry. This study aims to create a such system that is used for predicting whether a patient is likely to develop heart attacks, by analysing various data sources including electronic health records and clinical diagnosis reports from hospital clinics. ML is used as a process in which computers learn from data in order to make predictions about new datasets. The algorithms created for predictive data analysis are often used for commercial purposes. This paper presents an overview to forecast the likelihood of a heart attack for which many ML methodologies and techniques are applied. In order to improve medical diagnosis, the paper compares various algorithms such as Random Forest, Regression models, K-nearest neighbour imputation (KNN), Naïve Bayes algorithm etc. It is found that the Random Forest algorithm provides a better accuracy of 88.52% in forecasting heart attack risk, which could herald a revolution in the diagnosis and treatment of cardiovascular illnesses.
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Over the last four decades, cardiac natriuretic peptides have changed our understanding of patients with chronic heart failure. From the discovery of the heart as an endocrine organ with its own hormones and receptors, the biochemistry and physiology of the system have been translated into useful biomarkers and drug targets in cardiovascular disease. The purpose of this review is to provide medical researchers not working in the field with a simple introduction to the system and its molecular components, its quantitative methods, and its physiology and pathophysiology. The hope is that this overview may help to broaden the knowledge of the endocrine heart with the intent that researchers in other areas of medical research will be inspired to seek new facets of the system, both in translational science and in clinical practice.
Subject(s)
Heart Failure , Natriuretic Peptides , Humans , Natriuretic Peptides/metabolism , Heart Failure/metabolism , Heart Failure/physiopathology , Biomarkers , Receptors, Atrial Natriuretic Factor/metabolism , Atrial Natriuretic Factor/metabolism , Animals , Myocardium/metabolismABSTRACT
BACKGROUND: Direct oral anticoagulants (DOACs) have been widely applied in adults for thrombosis prophylaxis. However, the effect of DOACs in pediatric patients with congenital or acquired heart diseases who need anticoagulation therapy remains unclear. METHODS: We systematically searched the databases of PubMed, Embase, and the Cochrane Library, as well as the ClinicalTrials.gov registry and the World Health Organization's International Clinical Trials Registry Platform until June 2024 to identify relevant randomized clinical trials (RCTs). If the number of included studies was less than 5, we performed a narrative review to assess the effect of DOACs in pediatric patients. RESULTS: Four studies were included. In the UNIVERSE study, thrombotic events occurred in 2% of the rivaroxaban group and 9% of the aspirin group, with bleeding events in 36% and 41%, respectively. The ENNOBLE-ATE study showed no thromboembolic events in the edoxaban group and 1.7% in the SOC group (rate difference: -0.07%, 95% CI: -0.22 to 0.07%). Major bleeding rates were similar (rate difference: -0.03%, 95% CI: -0.18 to 0.12%). The SAXOPHONE trial showed no thromboembolic events in either group and similar major bleeding rates (-0.8%, 95% CI: -8.1 to 3.3%). In the DIVERSITY trial, 81% of dabigatran patients achieved the primary outcome versus 59.3% in the SOC group (Odds ratio: 0.342, 95% CI: 0.081-1.229). No major bleeding occurred in either group. CONCLUSION: Existing studies suggest that the use of DOACs hold promise as an effective and safe alternative for preventing and treating thromboembolism in pediatric patients with heart conditions.
Subject(s)
Anticoagulants , Heart Diseases , Randomized Controlled Trials as Topic , Humans , Child , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Administration, Oral , Hemorrhage/chemically inducedABSTRACT
BACKGROUND: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). METHODS: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined. RESULTS: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77), and stroke (OR 1.47, 95%CI 1.04-2.09). CONCLUSIONS: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.
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[This corrects the article DOI: 10.5334/gh.1313.].
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BACKGROUND: Intervention for older patients with cardiac disease and subthreshold depression (StD) may be an effective strategy to prevent the development of major depressive disorder. The subliminal priming with supraliminal reward stimulation (SPSRS) website developed by us is an advanced intervention that can improve depressive symptoms in individuals with StD by presenting positive word stimuli in videos. However, its efficacy for treating depressive symptoms in older patients with cardiac disease and StD has not been investigated. Here, we present a pilot randomized controlled trial protocol to investigate the preliminary efficacy of an intervention for older patients with cardiac disease with StD. METHODS: The study was designed as a single-center, open-label, pilot, randomized, parallel-group trial. The participants will include 30 older patients with cardiac disease and StD who are hospitalized in acute wards. The Experimental group received the SPSRS intervention (video viewing with positive word stimuli; n = 15) and the Control group will receive the YouTube intervention (video viewing without positive word stimuli; n = 15). In both groups, the intervention will be administered for 10 min per day, five times per week for 1 week. The primary outcome will be the change in the scores on the Japanese version of the Beck Depression Inventory-II at 1 week after the baseline assessment. The secondary outcomes will be the changes in the Specific Activity Scale, New York Heart Association functional classification, as well as grip strength at 1 week after the baseline assessment. DISCUSSION: This pilot randomized controlled trial will be the first to evaluate the SPSRS intervention for depressive symptoms in older patients with cardiac disease and StD who are admitted to acute wards. The results will provide tentative indications regarding the impact of the intervention on depressive symptoms among older patients with cardiac disease and StD who are admitted to acute wards, and will contribute to the planning of a full-scale study. TRIAL REGISTRATION: UMIN, UMIN000052155. Registered September 8, 2023, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000059526 . This study was registered with the University Hospital Medical Information Network (UMIN) (UMIN000052155) in Japan.
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Background: Individuals with cardiac disease (CD) who are self-employed may experience ability limitations and especially intensive challenges and uncertainties. These challenges may cause demoralization and impaired well-being. Objectives: To examine: (a) whether work ability limitations are related to demoralization and well-being among self-employed people with CD; (b) rates of demoralization; and (c) how demoralization and intolerance of uncertainty (IU) are associated with well-being. Methods: The study involved 120 self-employed individuals with CD. The PROCESS macro was used to analyze mediation and moderation processes. Results: The prevalence of demoralization syndrome was 37.4%. Work ability-limitations were associated with higher demoralization levels. Demoralization was associated with well-being only among participants with high IU. Further, demoralization mediated the relationship between work ability limitations and well-being only for individuals with high IU. Conclusion: Encountering limitations among self-employed was associated with demoralization and lower levels of well-being, especially among those with high IU. In addition, demoralization syndrome is prevalent among individuals with CD in general. Early recognition and treatment of demoralization as a treatable psychological syndrome are essential for preventing its degeneration into more complex forms. In addition to uncertainty related to health, it is important to pay special attention to other sources of uncertainty.
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Frank's sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient's chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.
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The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases.
Subject(s)
Heart Diseases , Humans , Heart Diseases/therapy , Heart Diseases/physiopathology , Autonomic Nervous System/physiopathology , Autonomic Nervous System/physiology , Heart/physiology , Electric Stimulation Therapy/instrumentation , Electric Stimulation Therapy/methods , Vagus Nerve Stimulation/instrumentationABSTRACT
There are currently no standard methods for diagnosing cardiac diseases in dolphins. These diseases may consequently be overlooked and go undiagnosed. The presence and severity of cardiac diseases in humans can be determined using blood tests. Human atrial natriuretic peptide (hANP) used in human cardiac examinations has low species specificity. There have already been reports of homology between dolphin ANP and hANP; however, its potential for clinical application in dolphins has not been tested. This study was conducted to establish a reference for plasma hANP levels in healthy bottlenose dolphins. Healthy bottlenose dolphins (seven females; estimated to be 7-30 years of age) at an aquarium in Japan were sampled. Each animal was tested for hANP at least three times, and the mean value and standard deviation were calculated to be 43.4 ± 19.2 pg/mL. In humans, patients with high plasma hANP levels have a poor prognosis. In veterinary medicine, cutoff values for the diagnosis of mitral regurgitation and heart failure in dogs have been established and used to predict prognosis. The results of the present study may contribute to the health management of bottlenose dolphins, particularly in the early detection and treatment of cardiac disease.
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Affecting approximately 25% of the global population, steatotic liver disease (SLD) poses a significant health concern. SLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis and fibrosis with a risk of severe liver complications such as cirrhosis and hepatocellular carcinoma. SLD is associated with obesity, atherogenic dyslipidaemia, and insulin resistance, increasing cardiovascular risks. As such, identifying SLD is vital for cardiovascular disease (CVD) prevention and treatment. Bile acids (BAs) have critical roles in lipid digestion and are signalling molecules regulating glucose and lipid metabolism and influencing gut microbiota balance. BAs have been identified as critical mediators in cardiovascular health, influencing vascular tone, cholesterol homeostasis, and inflammatory responses. The cardio-protective or harmful effects of BAs depend on their concentration and composition in circulation. The effects of certain BAs occur through the activation of a group of receptors, which reduce atherosclerosis and modulate cardiac functions. Thus, manipulating BA receptors could offer new avenues for treating not only liver diseases but also CVDs linked to metabolic dysfunctions. In conclusion, this review discusses the intricate interplay between BAs, metabolic pathways, and hepatic and extrahepatic diseases. We also highlight the necessity for further research to improve our understanding of how modifying BA characteristics affects or ameliorates disease.
Subject(s)
Bile Acids and Salts , Cardiovascular Diseases , Humans , Bile Acids and Salts/metabolism , Cardiovascular Diseases/metabolism , Animals , Fatty Liver/metabolism , Lipid Metabolism , Gastrointestinal MicrobiomeABSTRACT
AIMS: Limited data are available that evaluate the efficacy of renin-angiotensin system inhibitor (RASI) dose-reduction in older adults with heart failure with reduced ejection fraction following a heart failure hospitalization. METHODS AND RESULTS: We examined a 5% random sample of Medicare beneficiaries with prescription coverage who were discharged to home following a hospitalization for heart failure with reduced ejection fraction between 1 January 2007 and 30 June 2018 and were treated with RASI prior to hospitalization. We classified patients into three mutually exclusive groups based on RASI dosage before (prescription fills up to 90 days prior to) and after a hospitalization (prescription fills up to 365 days that were most proximate to the discharge date as possible)-same/increased dose, dose-reduction, and discontinuation. We examined associations between RASI prescribing patterns and outcomes (mortality and all-cause readmission at 30 days and 1 year) using Cox proportional hazards models. Among 12 794 unique older adults, 36.8% experienced a RASI reduction following their hospitalization for HFrEF-15.7% had a dose-reduction and 21.1% had a discontinuation. Neither dose-reduction nor discontinuation was associated with 30-day mortality. Discontinuation was associated 1-year mortality, 30-day all-cause readmission, and 1-year all-cause readmission, whereas dose-reduction was not. CONCLUSION: RASI dose-reduction occurs in 1 out of 7 HF hospitalizations. In contrast to RASI discontinuation, RASI dose-reduction was not associated with adverse short or long-term outcomes. These findings indicate that RASI dose-reduction is preferred over RASI discontinuation in selected situations where RASI reduction is needed.
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Calmodulin (CaM) is a ubiquitous, small cytosolic calcium (Ca2+)-binding sensor that plays a vital role in many cellular processes by binding and regulating the activity of over 300 protein targets. In cardiac muscle, CaM modulates directly or indirectly the activity of several proteins that play a key role in excitation-contraction coupling (ECC), such as ryanodine receptor type 2 (RyR2), l-type Ca2+ (Cav1.2), sodium (NaV1.5) and potassium (KV7.1) channels. Many recent clinical and genetic studies have reported a series of CaM mutations in patients with life-threatening arrhythmogenic syndromes, such as long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). We recently showed that four arrhythmogenic CaM mutations (N98I, D132E, D134H, and Q136P) significantly reduce the binding of CaM to RyR2. Herein, we investigate in vivo functional effects of these CaM mutations on the normal zebrafish embryonic heart function by microinjecting complementary RNA corresponding to CaMN98I, CaMD132E, CaMD134H, and CaMQ136P mutants. Expression of CaMD132E and CaMD134H mutants results in significant reduction of the zebrafish heart rate, mimicking a severe form of human bradycardia, whereas expression of CaMQ136P results in an increased heart rate mimicking human ventricular tachycardia. Moreover, analysis of cardiac ventricular rhythm revealed that the CaMD132E and CaMN98I zebrafish groups display an irregular pattern of heart beating and increased amplitude in comparison to the control groups. Furthermore, circular dichroism spectroscopy experiments using recombinant CaM proteins reveals a decreased structural stability of the four mutants compared to the wild-type CaM protein in the presence of Ca2+. Finally, Ca2+-binding studies indicates that all CaM mutations display reduced CaM Ca2+-binding affinities, with CaMD132E exhibiting the most prominent change. Our data suggest that CaM mutations can trigger different arrhythmogenic phenotypes through multiple and complex molecular mechanisms.
Subject(s)
Arrhythmias, Cardiac , Calmodulin , Zebrafish , Animals , Calmodulin/metabolism , Calmodulin/genetics , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/metabolism , Mutation , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Humans , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism , Mutation, Missense , Tachycardia, Ventricular/genetics , Tachycardia, Ventricular/metabolism , Calcium/metabolismABSTRACT
Background: Myxomatous mitral valve disease (MMVD) is prevalent in dogs. Specialized diagnostics (radiography and echocardiography) may be unavailable in some veterinary settings. Cardiac biomarkers offer potential alternatives. Aim: This study evaluated the diagnostic value of N-terminal fragments of pro-brain natriuretic peptides (NT-proBNPs), atrial natriuretic peptides (ANPs), and cardiac troponin I (cTnI) levels in dogs with MMVD. Methods: 69 dogs with MMVD (asymptomatic and symptomatic) and 19 healthy controls were assessed. Biomarker levels were measured using commercial kit rapid tests. Results: Our results showed that the median NT-proBNP level in the symptomatic group was higher than those in the asymptomatic (p < 0.001) and control (p < 0.001) groups. Moreover, the median NT-proBNP level in the asymptomatic group was higher than that in the control group (p < 0.001). The cTnI level in the control group was lower than those in the asymptomatic (p = 0.039) and symptomatic (p = 0.001) groups. No statistically significant difference in the cTnI level was noted between the asymptomatic and symptomatic groups. The best cutoff value of the NT-proBNP level to differentiate the normal controls from dogs with MMVD with or without congestive heart failure was > 505.65 pmol/l [sensitivity, 76.8%; specificity, 89.5%; and area under the curve (AUC), 0.862]. The suggested cutoff value of the NT-proBNP level to differentiate symptomatic MMVD from asymptomatic MMVD was >787.65 pmol/l (sensitivity, 78.38%; specificity, 72.55%; and AUC, 0.792). Conclusion: NT-proBNP and cTnI may serve as point-of-care tests for dyspneic dogs, aiding MMVD assessment where specialized diagnostics are limited.
Subject(s)
Atrial Natriuretic Factor , Biomarkers , Dog Diseases , Natriuretic Peptide, Brain , Peptide Fragments , Troponin I , Dogs , Animals , Dog Diseases/diagnosis , Dog Diseases/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Male , Biomarkers/blood , Female , Troponin I/blood , Atrial Natriuretic Factor/blood , Sensitivity and Specificity , Case-Control Studies , Heart Valve Diseases/veterinary , Heart Valve Diseases/blood , Heart Valve Diseases/diagnosisABSTRACT
The Ketogenic Diet (KD) is a dietary regimen that is low in carbohydrates, high in fats, and contains adequate protein. It is designed to mimic the metabolic state of fasting. This diet triggers the production of ketone bodies through a process known as ketosis. The primary objective of KD is to induce and sustain ketosis, which has been associated with numerous health benefits. Recent research has uncovered promising therapeutic potential for KD in the treatment of various diseases. This includes evidence of its effectiveness as a dietary strategy for managing intractable epilepsy, a form of epilepsy that is resistant to medication. We are currently assessing the efficacy and safety of KD through laboratory and clinical studies. This review focuses on the anti-inflammatory properties of the KD and its potential benefits for neurological disorders and the gut-brain axis. We also explore the existing literature on the potential effects of KD on cardiac health. Our aim is to provide a comprehensive overview of the current knowledge in these areas. Given the encouraging preliminary evidence of its therapeutic effects and the growing understanding of its mechanisms of action, randomized controlled trials are warranted to further explore the rationale behind the clinical use of KD. These trials will ultimately enhance our understanding of how KD functions and its potential benefits for various health conditions. We hope that our research will contribute to the body of knowledge in this field and provide valuable insights for future studies.
Subject(s)
Brain-Gut Axis , Cardiovascular Diseases , Diet, Ketogenic , Nervous System Diseases , Humans , Cardiovascular Diseases/diet therapy , Nervous System Diseases/diet therapy , Nervous System Diseases/metabolism , Animals , Gastrointestinal Microbiome/physiology , Ketone Bodies/metabolismABSTRACT
Implantable cardiac pacemakers are crucial therapeutic tools for managing various cardiac conditions. For effective pacing, electrodes should exhibit flexibility, deformability, biocompatibility, and high conductivity/capacitance. Laser-induced graphene (LIG) shows promise due to its exceptional electrical and electrochemical properties. However, the fragility of LIG and the non-stretchability of polyimide substrates pose challenges when interfacing with the beating heart. Here, we present a simple method for fabricating robust, flexible, and stretchable bioelectronic interfaces by transferring LIG via water-responsive, nonswellable polyvinyl alcohol (PVA) gels. PVA solution penetrates the porous structure of LIG and solidifies into PVA xerogel as the solvent evaporates. The robust PVA xerogel enables the smooth transfer of LIG and prevents stretching of the LIG network during this process, which helps maintain its conductivity. When hydrated, the xerogel becomes a stable, nonswellable hydrogel. This gives the LIG-PVA hydrogel (LIG-PVA-H) composites with excellent conductivity (119.7 ± 4.3Ω sq-1), high stretchability (up to 420%), reliability (cyclic stretch under 15% strain, with â¼ 1-time resistance increase), and good stability in phosphate buffered saline. The LIG-PVA-H composites were used as biointerfaces for electrocardiogram signal recording and electrical pacing on rat hearts ex vivo and in vivo, using commercial setups and a custom-built implantable wireless device. This work expands the application of LIG in bioelectronic interfaces and facilitates the development of electrotherapy for cardiac diseases.