Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

Sex differences in glutamate transmission and plasticity in reward related regions.

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.

Management of Rapid Atrial Fibrillation Using Stellate Ganglion Blockade.

Background: Stellate ganglion blockade has been demonstrated as an efficacious treatment for refractory ventricular tachyarrhythmias. There are no published reports of the use of this technique in management of rapid atrial arrhythmia. Case Summary: A 73-year-old woman presented to our institution in rapid atrial fibrillation and cardiogenic shock. She was intubated for airway protection and underwent successful electrical cardioversion. However, atrial fibrillation returned multiple times with weaning of sedation for extubation. Stellate ganglion infusion catheter was placed with infusion of ropivacaine and subsequent maintenance of sinus rhythm, with successful extubation, ablation of atrial fibrillation, improvement of left ventricular ejection fraction, and discharge. Take-Home Message: For selected patients, stellate ganglion blockade can be used as a technique to aid in the management of rapid atrial fibrillation.

When Is Mitral Regurgitation Not Just Systolic?: A Case of Near-Continuous Mitral Regurgitation.

A 30-year-old man presented with symptomatic severe chronic aortic regurgitation, first-degree atrioventricular block, and near-continuous mitral regurgitation. Surgical intervention, including aortic root replacement and mitral valve repair, was successful, highlighting the close relationship between valvular diseases and emphasizing the importance of comprehensive assessment for optimal management.

Prevalence and Predictors of Carpal Tunnel Syndrome Symptoms Among Teachers in Jazan: A Cross-Sectional Study.

Background  Carpal tunnel syndrome (CTS) is a common musculoskeletal condition of the hand and wrist frequently associated with repetitive hand motion and environmental considerations. Teachers are more likely to acquire CTS because of their lengthy writing and computer use. This study aimed to determine the prevalence of CTS symptoms and related variables among schoolteachers in Jazan, Saudi Arabia. Methods This study was conducted as a cross-sectional survey of teachers in Jazan, utilizing an online platform for data collection. The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) was the primary tool used to determine symptom intensity and functional status. The data were rigorously analyzed using a range of statistical methods, including descriptive statistics, the Mann-Whitney U test, the Kruskal-Wallis test, Spearman's correlation, the chi-square test, Fisher's exact test, and binary logistic regression, ensuring the robustness of the findings. Results The study comprised 336 schoolteachers with a mean age of 43.3 ± 6.5 years, of whom 58.0% were female and 42.0% were male. About 8.0% of instructors reported CTS symptoms. Female gender (median Symptom Severity Scale (SSS): 15.0 vs. 12.0, p < 0.001; median Functional Status Scale (FSS): 8.0 vs. 8.0, p < 0.001), increased time spent writing (r = 0.237, p < 0.001 for SSS; r = 0.217, p < 0.001 for FSS), and presence of comorbidities such as diabetes (median SSS: 16.0, p = 0.002; median FSS: 8.0, p = 0.001) had a negative correlation with symptom severity (r = -0.174, p = 0.002) and functional impairment (r = -0.141, p = 0.011). Surgical therapy (median SSS: 32.0; median FSS: 24.0; p<0.001) and post-treatment symptom recurrence (median SSS: 28.0; median FSS: 22.0; p<0.001) were associated with increased severity and disability. According to binary logistic regression, increased writing time significantly predicted CTS diagnosis (OR = 1.151, 95% CI: 1.024-1.295, p = 0.018). Conclusion CTS symptoms are common among Jazan teachers, and various sociodemographic, vocational, and clinical variables influence their intensity and functional status. Ergonomic treatment, early identification, and suitable management measures are critical for preventing and mitigating the effects of CTS among teachers. Additional research is required to develop focused therapies and enhance the results of this occupational group.

Rapid and local neuroestrogen synthesis supports long-term potentiation of hippocampal Schaffer collaterals-cornu ammonis 1 synapse in ovariectomized mice.

In aging women, cognitive decline and increased risk of dementia have been associated with the cessation of ovarian hormones production at menopause. In the brain, presence of the key enzyme aromatase required for the synthesis of 17-ß-estradiol (E2) allows for local production of E2 in absence of functional ovaries. Understanding how aromatase activity is regulated could help alleviate the cognitive symptoms. In female rodents, genetic or pharmacological reduction of aromatase activity over extended periods of time impair memory formation, decreases spine density, and hinders long-term potentiation (LTP) in the hippocampus. Conversely, increased excitatory neurotransmission resulting in rapid N-methyl-d-aspartic acid (NMDA) receptor activation rapidly promotes neuroestrogen synthesis. This rapid modulation of aromatase activity led us to address the hypothesis that acute neuroestrogens synthesis is necessary for LTP at the Schaffer collateral-cornu ammonis 1 (CA1) synapse in absence of circulating ovarian estrogens. To test this hypothesis, we did electrophysiological recordings of field excitatory postsynaptic potential (fEPSPs) in hippocampal slices obtained from ovariectomized mice. To assess the impact of neuroestrogens synthesis on LTP, we applied the specific aromatase inhibitor, letrozole, before the induction of LTP with a theta burst stimulation protocol. We found that blocking aromatase activity prevented LTP. Interestingly, exogenous E2 application, while blocking aromatase activity, was not sufficient to recover LTP in our model. Our results indicate the critical importance of rapid, activity-dependent local neuroestrogens synthesis, independent of circulating hormones for hippocampal synaptic plasticity in female rodents.

Common SYNE2 Genetic Variant Associated With Atrial Fibrillation Lowers Expression of Nesprin-2α1 With Downstream Effects on Nuclear and Electrophysiological Traits.

BACKGROUND: Atrial fibrillation GWAS (genome-wide association studies) identified significant associations for rs1152591 and linked variants in the SYNE2 gene encoding Nesprin-2, which connects the nuclear membrane with the cytoskeleton. METHODS: Reporter gene vector transfection and CRISPR-Cas9 editing were used to identify the causal variant regulating the expression of SYNE2α1. After SYNE2 knockdown or SYNE2α1 overexpression in human stem cell-derived cardiomyocytes, nuclear phenotypes were assessed by imaging and atomic force microscopy. Gene expression was assessed by RNAseq and gene set enrichment analysis. Fura-2 AM staining assessed calcium transients. Optical mapping assessed action potential duration and conduction velocity. RESULTS: The risk allele of rs1152591 had lower promoter and enhancer activity and was significantly associated with lower expression of the short SYNE2α1 isoform in human stem cell-derived cardiomyocytes, without an effect on the expression of the full-length SYNE2 mRNA. SYNE2α1 overexpression had dominant negative effects on the nucleus with its overexpression or SYNE2 knockdown leading to increased nuclear area and decreased nuclear stiffness. Gene expression results from SYNE2α1 overexpression demonstrated both concordant and nonconcordant effects with SYNE2 knockdown. SYNE2α1 overexpression had a gain of function on electrophysiology, leading to significantly faster calcium reuptake and decreased assessed action potential duration, while SYNE2 knockdown showed both shortened assessed action potential duration and decreased conduction velocity. CONCLUSIONS: rs1152591 was identified as a causal atrial fibrillation variant, with the risk allele decreasing SYNE2α1 expression. Downstream effects of SYNE2α1 overexpression include changes in nuclear stiffness and electrophysiology, which may contribute to the mechanism for the risk allele's association with AF.

Children's Heartbeat: A Web-Based Program to Spread Knowledge on Arrhythmias in Children.

Expertise in pediatric arrhythmia management is lacking in most low- and middle- income countries (LMIC). Strategies to disseminate education in pediatric electrophysiology are essential to meet this need. Children's Heartbeat was created to meet the growing demand for pediatric electrophysiologic consultation in LMIC. Children's Heartbeat is a virtual video-conferencing program that uses the Extension for Community Healthcare Outcomes model to disseminate knowledge about pediatric arrhythmia management from pediatric electrophysiologists to clinicians in medically under-resourced regions worldwide. Monthly virtual case-based sessions are held with pediatric electrophysiologists and clinicians in medically under-resourced settings to discuss pediatric electrophysiology management. Since its inception, Children's Heartbeat viewership has grown exponentially to include 181 total registrants, 64 average monthly participants, and an additional 121 average viewers of recorded sessions. Attendees have expressed increased confidence in pediatric arrhythmia management. Children's Heartbeat has successfully provided pediatric electrophysiology consultation to medically under-resourced regions globally and have increased clinicians' confidence in caring for children with arrhythmias. Future directions include spreading the program to general pediatric and pediatric cardiology trainees and practicing pediatricians in rural parts of high-income countries and evaluating the direct impact of Children's Heartbeat on the management of arrhythmias in pediatric patients in LMIC.

The α3ß4 nAChR tissue distribution identified by fluorescent α-conotoxin [D11A]LvIA.

α3ß4, a vital subtype of neuronal nicotinic acetylcholine receptors (nAChRs), is widely distributed in the brain, ganglia, and adrenal glands, associated with addiction and neurological diseases. However, the lack of specific imaging tools for α3ß4 nAChRs has hindered the investigation of their tissue distribution and functions. [D11A]LvIA, a peptide derived from marine cone snails, demonstrates high affinity and potency for α3ß4 nAChRs, making it a valuable pharmacological tool for studying this receptor subtype. In this study, three fluorescent conjugates of [D11A]LvIA were synthesized using 6-TAMRA-SE (R), Cy3-NHS-ester (Cy3), and BODIPY-FL NHS ester (BDP) dyes. The electrophysiological activities were assessed in Xenopus laevis oocytes by two-electrodes voltage clamp (TEVC). [D11A]LvIA-Cy3 and [D11A]LvIA-BDP show improved selectivity and affinity, with IC50 values of 512.70 nM and 343.50 nM, respectively, and [D11A]LvIA-Cy3 exhibits better stability in cerebrospinal fluid (CSF). Utilizing [D11A]LvIA-Cy3, we successfully visualized the distribution of α3ß4 nAChRs in rat trigeminal ganglia, retina, adrenal glands, and various brain regions. This novel fluorescent peptide provides a significant pharmacological tool for the exploration and visualization in-situ distribution of α3ß4 nAChRs in different tissues and also assists in clarifying the function.

Hybrid versus catheter ablation for Hypertrophic CardioMyopathy with Atrial Fibrillation (HCM-AF): study protocol for a randomised controlled trial.

INTRODUCTION: Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF. METHODS/ANALYSIS: This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments. ETHICS AND DISSEMINATIONAPPROVAL: The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05610215.

Mnemonically modulated perceptual processing to represent allocentric space in macaque inferotemporal cortex.

To encode allocentric space information of a viewing object, it is important to relate perceptual information in the first-person perspective to the representation of an entire scene which would be constructed before. A substantial number of studies investigated the constructed scene information (e.g., cognitive map). However, only few studies have focused on its influence on perceptual processing. Therefore, we designed a visually guided saccade task requiring monkeys to gaze at objects in different locations on different backgrounds clipped from large self-designed mosaic pictures (parental pictures). In each trial, we presented moving backgrounds prior to object presentations, indicating a frame position of the background image on a parental picture. We recorded single-unit activities from 377 neurons in the posterior inferotemporal (PIT) cortex of two macaques. Equivalent numbers of neurons showed space-related (119 of 377) and object-related (125 of 377) information. The space-related neurons coded the gaze locations and background images jointly rather than separately. These results suggest that PIT neurons represent a particular location within a particular background image. Interestingly, frame positions of background images on parental pictures modulated the space-related responses dependently on parental pictures. As the frame positions could be acquired by only preceding visual experiences, the present results may provide neuronal evidence of a mnemonic effect on current perception, which might represent allocentric object location in a scene beyond the current view.

Zebrafish as a Model System for Brugada Syndrome.

Brugada syndrome (BrS) is an inheritable cardiac arrhythmogenic disease, associated with an increased risk of sudden cardiac death. It is most common in males around the age of 40 and the prevalence is higher in Asia than in Europe and the United States. The pathophysiology underlying BrS is not completely understood, but several hypotheses have been proposed. So far, the best effective treatment is the implantation of an implantable cardioverter-defibrillator (ICD), but device-related complications are not uncommon. Therefore, there is an urgent need to improve diagnosis and risk stratification and to find new treatment options. To this end, research should further elucidate the genetic basis and pathophysiological mechanisms of BrS. Several experimental models are being used to gain insight into these aspects. The zebrafish (Danio rerio) is a widely used animal model for the study of cardiac arrhythmias, as its cardiac electrophysiology shows interesting similarities to humans. However, zebrafish have only been used in a limited number of studies on BrS, and the potential role of zebrafish in studying the mechanisms of BrS has not been reviewed. Therefore, the present review aims to evaluate zebrafish as an animal model for BrS. We conclude that zebrafish can be considered as a valuable experimental model for BrS research, not only for gene editing technologies, but also for screening potential BrS drugs.

Membrane Physiology Symposium April 22nd-23rd, 2024, Napa California, USA.

The Membrane Physiology Symposium was created with the goal of joining basic research with technology companies, where questions and conversations are open and welcomed in a universal language. For many years, academic physiology research areas have been naturally siloed into their own niche communities, which can surely be beneficial. Linking different technological application areas with varied research sectors is an integral formula for successful scientific breakthroughs. The meeting covers a wide variety of topics related to channelopathies, neurological and cardiac disease, drug development, and therapeutic applications, with research programs represented by core academic facilities, medical science institutions, small and large pharmaceutical enterprises, as well as novel cell-based and reagent providers. For this reason, gathering the brightest minds of all relevant fields in one integrative forum is essential for new avenues of discovery, development, and process optimization to occur.

Adolescent alcohol consumption predicted by differences in electrophysiological functional connectivity and neuroanatomy.

Alcohol consumption during adolescence has been associated with neuroanatomical abnormalities and the appearance of future disorders. However, the latest advances in this field point to the existence of risk profiles which may lead to some individuals into an early consumption. To date, some studies have established predictive models of consumption based on sociodemographic, behavioral, and anatomical-functional variables using MRI. However, the neuroimaging variables employed are usually restricted to local and hemodynamic phenomena. Given the potential of connectome approaches, and the high temporal dynamics of electrophysiology, we decided to explore the relationship between future alcohol consumption and electrophysiological connectivity measured by MEG in a cohort of 83 individuals aged 14 to 16. As a result, we found a positive correlation between alcohol consumption and the functional connectivity in frontal, parietal, and frontoparietal connections. Once this relationship was described, multivariate linear regression analyses were used to evaluate the predictive capacity of functional connectivity in conjunction with other neuroanatomical and behavioral variables described in the literature. Finally, the multivariate linear regression analysis determined the importance of anatomical and functional variables in the prediction of alcohol consumption but failed to find associations with impulsivity, sensation seeking, and executive function scales. In conclusion, the predictive traits obtained in these models were closely associated with changes occurring during adolescence, suggesting the existence of different paths in neurodevelopment that have the potential to influence adolescents' relationship with alcohol consumption.

Unveiling the mystery of the female heart's rhythm: a look into gender inequalities in electrophysiology.

This review explores gender disparities in cardiac electrophysiology, highlighting differences in the electrical activity of the heart between men and women. It emphasizes the importance of understanding these variances for correct diagnosis and effective treatment of cardiac arrhythmias. Women show distinct cardiac characteristics influenced by sex hormones, affecting their susceptibility to various arrhythmias. The manuscript covers the classification, mechanisms, and management of arrhythmias in women, considering factors such as pregnancy and menopause. By addressing these gender-specific nuances, it aims to improve healthcare practices and outcomes for female patients with cardiac rhythm disorders.

Esta revisión explora las disparidades de género en la electrofisiología cardiaca, destacando las diferencias en la actividad eléctrica del corazón entre hombres y mujeres. Se enfatiza la importancia de comprender estas variaciones para un diagnóstico correcto y un tratamiento efectivo de las arritmias cardiacas. Las mujeres muestran características cardiacas distintas influenciadas por las hormonas sexuales, lo que afecta su susceptibilidad a diversas arritmias. La revisión abarca la clasificación, los mecanismos y el manejo de las arritmias en las mujeres, considerando factores como el embarazo y la menopausia. Al abordar estos matices específicos de género, el objetivo es mejorar las prácticas de atención médica y los resultados para las pacientes de sexo femenino con trastornos del ritmo cardiaco.

Simple biomarkers to distinguish Parkinson's disease from its mimics in clinical practice: a comprehensive review and future directions.

In the last few years, a plethora of biomarkers have been proposed for the differentiation of Parkinson's disease (PD) from its mimics. Most of them consist of complex measures, often based on expensive technology, not easily employed outside research centers. MRI measures have been widely used to differentiate between PD and other parkinsonism. However, these measurements were often performed manually on small brain areas in small patient cohorts with intra- and inter-rater variability. The aim of the current review is to provide a comprehensive and updated overview of the literature on biomarkers commonly used to differentiate PD from its mimics (including parkinsonism and tremor syndromes), focusing on parameters derived by simple qualitative or quantitative measurements that can be used in routine practice. Several electrophysiological, sonographic and MRI biomarkers have shown promising results, including the blink-reflex recovery cycle, tremor analysis, sonographic or MRI assessment of substantia nigra, and several qualitative MRI signs or simple linear measures to be directly performed on MR images. The most significant issue is that most studies have been conducted on small patient cohorts from a single center, with limited reproducibility of the findings. Future studies should be carried out on larger international cohorts of patients to ensure generalizability. Moreover, research on simple biomarkers should seek measurements to differentiate patients with different diseases but similar clinical phenotypes, distinguish subtypes of the same disease, assess disease progression, and correlate biomarkers with pathological data. An even more important goal would be to predict the disease in the preclinical phase.