Arrhythmogenic atrial remodeling during pregnancy in mice.

Background: Pregnancy is associated with greater vulnerability to supraventricular tachyarrhythmias.

Objective: As the underlying mechanisms remain to be elucidated, we investigated whether pregnancy induces atrial remodeling that might contribute to this.

Methods: Atrial electrophysiological and contractile properties were examined in nonpregnant and pregnant (P) mice.

Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.

Aims: Pregnant (P) women have a significantly elevated resting heart rate (HR), which makes cardiac arrhythmias more likely to occur. Although electrical remodelling of the sinoatrial node (SAN) has been documented, the underlying mechanism is not fully understood. The acetylcholine-activated potassium current (IKACh), one of the major repolarizing currents in the SAN, plays a critical role in HR control by hyperpolarizing the maximal diastolic potential (MDP) of the SAN action potential (AP), thereby reducing SAN automaticity and HR.

Early life seizures and olfactory communication in rats.

Objective: Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats.

Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes.

Males and females exhibit intrinsic differences in the structure and function of the heart, while the prevalence and severity of cardiovascular disease vary in the two sexes. However, the mechanisms of this sex-based dimorphism are yet to be elucidated. Sex chromosomes and sex hormones are the main contributors to sex-based differences in cardiac physiology and pathophysiology.

US-guided EM tracked system for HDR brachytherapy: A first in-men randomized study for whole prostate treatment.

Purpose: An electromagnetic tracking device (EMT) has been integrated in an HDR 3D ultrasound guidance system for prostate HDR. The aim of this study was to compare the efficiency of HDR workflows with and without EM tracking.

Methods And Materials: A total of 58 patients with a 15 Gy HDR prostate boost were randomized in two arms and two operation room (OR) procedures using: (1) the EMT investigational device, and (2) the Oncentra prostate system (OCP).

Infection after prostatic transrectal fiducial marker implantation for image guided radiation therapy.

Purpose: The aim of this retrospective study is to assess the risk of infection after transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy of prostate cancer.

Material And Methods: Between January 2016 and December 2020, 829 patients scheduled for intensity-modulated radiotherapy for prostate cancer had an intraprostatic fiducial marker transrectal implantation under ultrasound guidance by radiation-oncologists specialized in brachytherapy. Patients received standard oral prophylactic antibiotic with quinolone.

Rapamycin treatment unmasks a sex-specific pattern of scar expansion of the infarcted rat heart: The relationship between mTOR and K channel.

Inhibition of the mammalian target of rapamycin (mTOR) with the macrolide rapamycin or pharmacological suppression of K channel opening translated to scar expansion of the myocardial infarcted (MI) adult female rodent heart. The present study tested the hypotheses that rapamycin-mediated scar expansion was sex-specific and that mTOR signaling directly influenced K channel subunit expression/activity. Scar size was significantly larger in post-MI male rats as compared to the previous data reported in post-MI female rats.

Programmable self-regulated molecular buffers for precise sustained drug delivery.

Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier's principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine.

Higher Na-Ca Exchanger Function and Triggered Activity Contribute to Male Predisposition to Atrial Fibrillation.

Male sex is one of the most important risk factors of atrial fibrillation (AF), with the incidence in men being almost double that in women. However, the reasons for this sex difference are unknown. Accordingly, in this study, we sought to determine whether there are sex differences in intracellular Ca homeostasis in mouse atrial myocytes that might help explain male predisposition to AF.

Connexin Lateralization Contributes to Male Susceptibility to Atrial Fibrillation.

Men have a higher risk of developing atrial fibrillation (AF) than women, though the reason for this is unknown. Here, we compared atrial electrical and structural properties in male and female mice and explored the contribution of sex hormones. Cellular electrophysiological studies revealed that action potential configuration, Na and K currents were similar in atrial myocytes from male and female mice (4-5 months).

Atrial Electrical Remodeling in Mice With Cardiac-Specific Overexpression of Angiotensin II Type 1 Receptor.

Background Elevated angiotensin II levels are thought to play an important role in atrial electrical and structural remodeling associated with atrial fibrillation. However, the mechanisms by which this remodeling occurs are still unclear. Accordingly, we explored the effects of angiotensin II on atrial remodeling using transgenic mice overexpressing angiotensin II type 1 receptor (AT1R) specifically in cardiomyocytes.

Early-life seizures modify behavioral response to ultrasonic vocalization playback in adult rats.

Early-life seizures (ELS) are associated with autism spectrum disorder (ASD); however, due to a lack of effective treatments for ELS, it is not clear whether ELS plays a causal role, potentiates the ASD phenotype, or is the result of a common pathophysiology. Deficits in communications are a core feature of ASD. To isolate the impact of ELS on communication, we probed the behavioral consequences of a single episode of kainic acid-induced early-life seizures (KA-ELS) in male and female Sprague-Dawley (CD) rats.

Pregnancy-induced increased heart rate is independent of thyroid hormones.

Background: The heart rate increases by 10-20 beats per minute (bpm) throughout pregnancy in women, reaching maximum heart rate in the third trimester. During pregnancy, important changes in thyroid hormones also occur, with increases of up to 50% in the levels of triiodothyronine (T), the biological active thyroid hormone. In addition, T has been shown to regulate cardiac electrophysiology.

GATA6 is a regulator of sinus node development and heart rhythm.

The sinus node (SAN) is the primary pacemaker of the human heart, and abnormalities in its structure or function cause sick sinus syndrome, the most common reason for electronic pacemaker implantation. Here we report that transcription factor GATA6, whose mutations in humans are linked to arrhythmia, is highly expressed in the SAN and its haploinsufficiency in mice results in hypoplastic SANs and rhythm abnormalities. Cell-specific deletion reveals a requirement for GATA6 in various SAN lineages.

Contribution of estrogen to the pregnancy-induced increase in cardiac automaticity.

Background: The heart rate progressively increases throughout pregnancy, reaching a maximum in the third trimester. This elevated heart rate is also present in pregnant mice and is associated with accelerated automaticity, higher density of the pacemaker current I and changes in Ca homeostasis in sinoatrial node (SAN) cells. Strong evidence has also been provided showing that 17β-estradiol (E) and estrogen receptor α (ERα) regulate heart rate.

The macromolecular composition of noncalcified marine macroalgae.

The macromolecular composition of macroalgae influences nutrient flow and food quality in aquatic ecosystems and the value of macroalgae species for human consumption, aquaculture, biofuels, and other applications. We used literature data (125 publications, 1,117 observations) and a hierarchal Bayesian statistical model to estimate the average macromolecular composition, protein, lipid, and carbohydrate of macroalgae as a whole and at the phylum level. Our focus was on marine, noncalcified macroalgae sampled from wild-grown populations in the field.

Mechanisms of Arrhythmia and Sudden Cardiac Death in Patients With HIV Infection.

Long-term survival of HIV-infected patients has significantly improved with the use of antiretroviral therapy (ART). As a consequence, cardiovascular diseases are now emerging as an important clinical problem in this population. Sudden cardiac death is the third leading cause of mortality in HIV patients.

Pregnancy and oestrogen regulate sinoatrial node calcium homeostasis and accelerate pacemaking.

Aims: During pregnancy, there is a significant increase in heart rate (HR) potentially associated with an increased risk of arrhythmias or exacerbation of pre-existing cardiac conditions endangering both mother and foetus. Calcium homeostasis plays an important role in regulating automaticity of the sinoatrial node (SAN); however, its contribution to the accelerated HR during pregnancy remains unknown.

Methods And Results: Using murine SAN cells, we showed that pregnancy increased L-type Ca2+ current (ICaL) and CaV1.

Angiotensin II Overstimulation Leads to an Increased Susceptibility to Dilated Cardiomyopathy and Higher Mortality in Female Mice.

Heart failure (HF) is associated with high mortality and affects men and women differently. The underlying mechanisms for these sex-related differences remain largely unexplored. Accordingly, using mice with cardiac-specific overexpression of the angiotensin II (ANGII) type 1 receptor (AT1R), we explored male-female differences in the manifestations of hypertrophy and HF.

Characterization of a Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for the Study of Variant Pathogenicity: Validation of a Mutation.

Background: Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality.

Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus.

Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The phase 3 studies SOLO I and SOLO II demonstrated comparable efficacy and safety of a single dose of oritavancin compared with 7-10 days of twice-daily vancomycin in adults with acute bacterial skin and skin-structure infections (ABSSSIs). The present analysis assessed clinical responses by pathogen at 48-72 h and at study days 14-24 in SOLO patients within the pooled data set.

Reduction in Na(+) current by angiotensin II is mediated by PKCα in mouse and human-induced pluripotent stem cell-derived cardiomyocytes.

Background: Ventricular arrhythmias and sudden cardiac deaths are among the leading causes of mortality in patients with heart failure, and the underlying mechanisms remain incompletely understood. Chronic elevation of angiotensin II (ANGII) is known to be one of the main contributors to heart failure.

Objective: We tested whether ANGII can alter ventricular conduction and Na(+) current using transgenic mice with cardiomyocyte-restricted overexpression of ANGII type 1 receptor (AT1R).

Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity.

Alteration in the L-type current density is one aspect of the electrical remodeling observed in patients suffering from cardiac arrhythmias. Changes in channel function could result from variations in the protein biogenesis, stability, post-translational modification, and/or trafficking in any of the regulatory subunits forming cardiac L-type Ca(2+) channel complexes. CaVα2δ1 is potentially the most heavily N-glycosylated subunit in the cardiac L-type CaV1.

Estrogen regulation of the transient outward K(+) current involves estrogen receptor α in mouse heart.

Background And Objective: We have previously shown that androgens upregulate cardiac K(+) channels and shorten repolarization. However, the effects that estrogens (E2) and estrogen receptors (ER) might have on the various repolarizing K(+) currents and underlying ion channels remain incompletely understood. Accordingly, our objective was to verify whether and how E2 and its ERs subtypes influence these K(+) currents.