IgG4-Related disease with diffuse myopericardial involvement- value of CMR: a case report and literature review of cardiac involvement.

BACKGROUND: IgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement. CASE PRESENTATION: This paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment. CONCLUSIONS: This case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.

Neonatal Bacillus cereus: an unusual case of congenital pneumonia requiring ECMO.

A term neonate presented with cyanosis from birth, with refractory hypoxaemia despite intubation, administration of 100% oxygen and inhaled nitric oxide. Structural congenital heart disease was excluded. He developed profuse pulmonary haemorrhage at 6 hours of life with worsening hypoxia and was transferred to a paediatric intensive care unit (PICU) for initiation of veno-venous extracorporeal membrane oxygenation (vvECMO). Endotracheal aspirates from both the birth hospital and the PICU were positive for Bacillus cereus, with all other investigations finding no alternative cause for his presentation. Of note, mother was a practising veterinarian raising another potential source of exposure to this pathogen. A full recovery occurred after a total of 5 days of vvECMO, 13 days of ventilation and 20 days of PICU stay.

Severe DRESS with myocarditis secondary to naproxen/esomeprazole.

A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood tests showed hypereosinophilia (0.73×109/L) and moderate acute kidney injury. Histology revealed parakeratosis, mild spongiosis with eosinophils. He developed acute coronary syndrome with rapid atrial fibrillation. Coronary angiogram was non-obstructive. Cardiac MRI (CMR) revealed acute myocarditis secondary to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Naproxen/esomeprazole was discontinued, and he was supported with oral corticosteroids. A repeat CMR 3 months later showed resolution of myocarditis. Naproxen/esomeprazole is not a common offending drug. DRESS is a rare drug-induced hypersensitivity reaction with a mortality rate of 10%. The objective of this case report is to highlight the significant but rare cardiac complications that can ensue from DRESS, which warrant prompt recognition and withdrawal of the causative drug.

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Serotonin Receptors in Myocardial Infarction: Friend or Foe?

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide and treatment costs pose a major burden on the global health care system. Despite the variety of treatment options, individual recovery can be still poor and the mortality rate, especially in the first few years after the event, remains high. Therefore, intense research is currently focused on identifying novel target molecules to improve the outcome following AMI. One of the potentially interesting targets is the serotonergic system (5-HT system), not at least because of its connection to mental disorders. It is known that patients suffering from AMI have an increased risk of developing depression and vice versa. This implicates that the 5-HT system can be affected in response to AMI and might thus represent a target structure for patients' treatment. This review aims to highlight the importance of the 5-HT system after AMI by describing the role of individual serotonin receptors (5-HTR) in the regulation of physiological and pathophysiological responses. It particularly focuses on the signaling pathways of the serotonin receptors 1, 2, 4, and 7, which are expressed in the cardiovascular system, during disease onset, and the following remodeling process. This overview also emphasizes the importance of the 5-HT system in AMI etiology and highlights 5-HTRs as potential treatment targets.

Anatomy after Hippocrates.

This brief chapter has a single purpose which is not directly related to cranial surgery. However, between Hippocrates and Celsus and Galen a number of improvements in the understanding of anatomy had been discovered and this chapter briefly outlines the nature and importance of these advances.

The circadian rhythm: A new target of natural products that can protect against diseases of the metabolic system, cardiovascular system, and nervous system.

BACKGROUND: The treatment of metabolic system, cardiovascular system, and nervous system diseases remains to be explored. In the internal environment of organisms, the metabolism of substances such as carbohydrates, lipids and proteins (including biohormones and enzymes) exhibit a certain circadian rhythm to maintain the energy supply and material cycle needed for the normal activities of organisms. As a key factor for the health of organisms, the circadian rhythm can be disrupted by pathological conditions, and this disruption accelerates the progression of diseases and results in a vicious cycle. The current treatments targeting the circadian rhythm for the treatment of metabolic system, cardiovascular system, and nervous system diseases have certain limitations, and the identification of safer and more effective circadian rhythm regulators is needed. AIM OF THE REVIEW: To systematically assess the possibility of using the biological clock as a natural product target for disease intervention, this work reviews a range of evidence on the potential effectiveness of natural products targeting the circadian rhythm to protect against diseases of the metabolic system, cardiovascular system, and nervous system. This manuscript focuses on how natural products restore normal function by affecting the amplitude of the expression of circadian factors, sleep/wake cycles and the structure of the gut microbiota. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: This work proposes that the circadian rhythm, which is regulated by the amplitude of the expression of circadian rhythm-related factors and the sleep/wake cycle, is crucial for diseases of the metabolic system, cardiovascular system and nervous system and is a new target for slowing the progression of diseases through the use of natural products. This manuscript provides a reference for the molecular modeling of natural products that target the circadian rhythm and provides a new perspective for the time-targeted action of drugs.

Neural Circuits Underlying Reciprocal Cardiometabolic Crosstalk: 2023 Arthur C. Corcoran Memorial Lecture.

The interplay of various body systems, encompassing those that govern cardiovascular and metabolic functions, has evolved alongside the development of multicellular organisms. This evolutionary process is essential for the coordination and maintenance of homeostasis and overall health by facilitating the adaptation of the organism to internal and external cues. Disruption of these complex interactions contributes to the development and progression of pathologies that involve multiple organs. Obesity-associated cardiovascular risks, such as hypertension, highlight the significant influence that metabolic processes exert on the cardiovascular system. This cardiometabolic communication is reciprocal, as indicated by substantial evidence pointing to the ability of the cardiovascular system to affect metabolic processes, with pathophysiological implications in disease conditions. In this review, I outline the bidirectional nature of the cardiometabolic interaction, with special emphasis on the impact that metabolic organs have on the cardiovascular system. I also discuss the contribution of the neural circuits and autonomic nervous system in mediating the crosstalk between cardiovascular and metabolic functions in health and disease, along with the molecular mechanisms involved.

Case Report: A case of Kounis syndrome induced by iodine contrast agent during coronary angiography.

Kounis Syndrome (KS), a seldom-seen adverse reaction to iodine contrast agents, has an incidence that remains unclear. At present, there are no unified guidelines for managing KS either nationally or internationally. Ioversol, a new triiodinated hypotonic nonionic contrast agent, is commonly used in cardiovascular Computed Tomography (CT) and vascular imaging for diagnostic purposes. Its principal adverse reactions encompass fever, dermatological responses, convulsions, respiratory distress, hypersensitivity reactions including KS, and acute renal injury. This paper documents a case of KS induced by an iodine contrast agent during coronary angiography and, at the same time, searches for related literature and carries out a summary analysis in an attempt to provide a dependable reference for clinicians to make accurate diagnoses and treatments.

Beyond the Finish Line: Examining the Role of Children in Marathon Races-A Narrative Review.

Compared with other sports, running is popular sport for children throughout the world. Over the last few decades, marathon running has become increasingly popular even in the age group below 18 years. While the majority of youth athletes fall within the 16-18 age range, it is noteworthy that there are also participants younger than 12 years engaging in marathon races. Advice on the safety of youth athletes participating in these events is frequently sought by parents, coaches, sport scientists, and medical professionals, particularly concerning potential short- and long-term health consequences. The act of marathon running has the potential to impact key organ systems during the crucial phases of growth and development. To ensure the safety of marathon running in youth runners, it is essential to address multiple physiological and psychological aspects of health. These recommendations are directed towards ensuring the safe participation of youth athletes in marathon races through proper and individualized assessments.

Tributyltin-induced oxidative stress causes developmental damage in the cardiovascular system of zebrafish (Danio rerio).

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.

A hybrid neural ordinary differential equation model of the cardiovascular system.

In the human cardiovascular system (CVS), the interaction between the left and right ventricles of the heart is influenced by the septum and the pericardium. Computational models of the CVS can capture this interaction, but this often involves approximating solutions to complex nonlinear equations numerically. As a result, numerous models have been proposed, where these nonlinear equations are either simplified, or ventricular interaction is ignored. In this work, we propose an alternative approach to modelling ventricular interaction, using a hybrid neural ordinary differential equation (ODE) structure. First, a lumped parameter ODE model of the CVS (including a Newton-Raphson procedure as the numerical solver) is simulated to generate synthetic time-series data. Next, a hybrid neural ODE based on the same model is constructed, where ventricular interaction is instead set to be governed by a neural network. We use a short range of the synthetic data (with various amounts of added measurement noise) to train the hybrid neural ODE model. Symbolic regression is used to convert the neural network into analytic expressions, resulting in a partially learned mechanistic model. This approach was able to recover parsimonious functions with good predictive capabilities and was robust to measurement noise.

Flecainide causing elevated capture thresholds on pacemaker implantation.

Flecainide is a Vaughan Williams class 1c antiarrhythmic used to treat supraventricular and ventricular arrhythmias. It has been described as a rare cause for increased pacemaker capture thresholds. We describe a report of a patient, in her early 80s, presenting with tachy-brady syndrome on a background of permanent atrial fibrillation. She was treated with metoprolol and flecainide by her private cardiologist. Permanent right ventricular chamber pacing was recommended for her slow heart rate. At insertion of her single chamber pacemaker, she was noted to have elevated capture thresholds despite appropriate lead positioning. A flecainide level was elevated at 1.1 µg/mL, and it was subsequently ceased. This was associated with a rapid improvement in her capture threshold. Flecainide should be considered as a cause for elevated pacing thresholds at the time of implant. Particular care should be taken for at-risk groups such as the elderly and patients with renal impairment.

Colchicine's Role in Cardiovascular Disease Management.

Colchicine-an anti-inflammatory alkaloid-has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration-approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine's safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

Differential effects of physiological agonists on the proteome of platelet-derived extracellular vesicles.

Arterial thrombosis manifesting as heart attack and stroke is the leading cause of death worldwide. Platelets are central mediators of thrombosis that can be activated through multiple activation pathways. Platelet-derived extracellular vesicles (pEVs), also known as platelet-derived microparticles, are granular mixtures of membrane structures produced by platelets in response to various activating stimuli. Initial studies have attracted interest on how platelet agonists influence the composition of the pEV proteome. In the current study, we used physiological platelet agonists of varying potencies which reflect the microenvironments that platelets experience during thrombus formation: adenosine diphosphate, collagen, thrombin as well as a combination of thrombin/collagen to induce platelet activation and pEV generation. Proteomic profiling revealed that pEVs have an agonist-dependent altered proteome in comparison to their cells of origin, activated platelets. Furthermore, we found that various protein classes including those related to coagulation and complement (prothrombin, antithrombin, and plasminogen) and platelet activation (fibrinogen) are attributed to platelet EVs following agonist stimulation. This agonist-dependent altered proteome suggests that protein packaging is an active process that appears to occur without de novo protein synthesis. This study provides new information on the influence of physiological agonist stimuli on the biogenesis and proteome landscape of pEVs.

In Silico Evaluation of NO-Sartans against SARS-CoV-2.

INTRODUCTION: Numerous clinical trials are currently investigating the potential of nitric oxide (NO) as an antiviral agent against coronaviruses, including SARS-CoV-2. Additionally, some researchers have reported positive effects of certain Sartans against SARS-CoV-2. METHOD: Considering the impact of NO-Sartans on the cardiovascular system, we have compiled information on the general structure, synthesis methods, and biological studies of synthesized NOSartans. In silico evaluation of all NO-Sartans and approved sartans against three key SARS-CoV- -2 targets, namely Mpro (PDB ID: 6LU7), NSP16 (PDB ID: 6WKQ), and ACE-2 (PDB ID: 1R4L), was performed using MOE. RESULTS: Almost all NO-Sartans and approved sartans demonstrated promising results in inhibiting these SARS-CoV-2 targets. Compound 36 (CLC-1280) showed the best docking scores against the three evaluated targets and was further evaluated using molecular dynamics (MD) simulations. CONCLUSION: Based on our in silico studies, CLC-1280 (a Valsartan dinitrate) has the potential to be considered as an inhibitor of the SARS-CoV-2 virus. However, further in vitro and in vivo evaluations are necessary for the drug development process.

Role of hydrogen sulfide in the regulation of lipid metabolism: Implications on cardiovascular health.

The World Health Organization (WHO) defines obesity as an urgency for health and a social emergency. Today around 39 % of people is overweight, of these over 13 % is obese. It is well-consolidated that the adipose cells are deputy to lipid storage under caloric excess; however, despite the classical idea that adipose tissue has exclusively a passive function, now it is known to be deeply involved in the regulation of systemic metabolism in physiological as well as under obesogenic conditions, with consequences on cardiovascular health. Beside two traditional types of adipose cells (white and brown), recently the beige one has been highlighted as the consequence of the healthy remodeling of white adipocytes, confirming their metabolic adaptability. In this direction, pharmacological, nutraceutical and nutrient-based approaches are addressed to positively influence inflammation and metabolism, thus contributing to reduce the obese-associated cardiovascular risk. In this scenario, hydrogen sulfide emerges as a new mediator that may regulate crucial targets involved in the regulation of metabolism. The current evidence demonstrates that hydrogen sulfide may induce peroxisome proliferator activated receptor γ (PPARγ), a crucial mediator of adipogenesis, inhibit the phosphorylation of perlipin-1 (plin-1), a protein implicated in the lipolysis, and finally promote browning process, through the release of irisin from skeletal muscle. The results summarized in this review suggest an important role of hydrogen sulfide in the regulation of metabolism and in the prevention/treatment of obese-associated cardiovascular diseases and propose new insight on the putative mechanisms underlying the release of hydrogen sulfide or its biosynthesis, delineating a further exciting field of application.

Obstructive Sleep Apnea-Associated Intermittent Hypoxia-Induced Immune Responses in Males, Pregnancies, and Offspring.

Obstructive sleep apnea (OSA), a respiratory sleep disorder associated with cardiovascular diseases, is more prevalent in men. However, OSA occurrence in pregnant women rises to a level comparable to men during late gestation, creating persistent effects on both maternal and offspring health. The exact mechanisms behind OSA-induced cardiovascular diseases remain unclear, but inflammation and oxidative stress play a key role. Animal models using intermittent hypoxia (IH), a hallmark of OSA, reveal several pro-inflammatory signaling pathways at play in males, such as TLR4/MyD88/NF-κB/MAPK, miRNA/NLRP3, and COX signaling, along with shifts in immune cell populations and function. Limited evidence suggests similarities in pregnancies and offspring. In addition, suppressing these inflammatory molecules ameliorates IH-induced inflammation and tissue injury, providing new potential targets to treat OSA-associated cardiovascular diseases. This review will focus on the inflammatory mechanisms linking IH to cardiovascular dysfunction in males, pregnancies, and their offspring. The goal is to inspire further investigations into the understudied populations of pregnant females and their offspring, which ultimately uncover underlying mechanisms and therapeutic interventions for OSA-associated diseases.