Parasympathetic Research Articles

9271 Cholinergic Signaling in the Mouse Embryonic Pancreas Targets Early Endocrine Cells

Abstract Disclosure: C. Duarte: None. J.K. Panzer: None. N. Borowsky: None. A. Caicedo: None. The parasympathetic vagus nerve affects pancreas function by activating local intrapancreatic neurons that release acetylcholine (ACh). These neurons are derived from progenitors of the vagal neural crest and colonize the pancreas during embryonic development. The specific mechanisms by which ACh is released from these neurons influence embryonic development of the islet and, specifically, beta cells remain largely unknown. The purpose of this study was to identify cholinergic signaling components and assess early physiological responses to ACh during murine development of endocrine lineage cells. We extracted pancreatic rudiments from mice at embryonic stages E15 to E18 and stained them for neuronal and endocrine markers, along with components associated with cholinergic signaling. We further performed Ca2+ imaging of the pancreatic rudiments from NGN3CRE-GCaMP3 mice to record responses to ACh in cells of the endocrine lineage. At E15, we observed a significantly higher concentration of glucagon+ cells compared to insulin+ cells, consistent with the earlier differentiation of alpha cells in the developing pancreas. Neuronal body clusters were identified in close proximity to endocrine lineage cells from E15 to E18, with the neuronal network becoming more dispersed and interconnected. At E15, wide distribution of the presynaptic vesicular acetylcholine transporter (VAChT) was observed later becoming localized around insulin+ and glucagon+ cells at E18. Postsynaptic acetylcholinesterase (AChE) colocalized with glucagon+ cells from E15 to E18 and with insulin+ cells by E18. ACh elicited Ca2+ responses in individual endocrine cells as early as E15. Our results show that cholinergic nerve terminals target early endocrine cells and elicit responses to ACh, indicating that local cholinergic neurons innervate and activate endocrine progenitors in the embryonic pancreas. Our current studies are aimed at determining how cholinergic signaling contributes to beta cell differentiation and function. We expect this knowledge to guide future protocols for deriving beta cells from stem cells. Presentation: 6/2/2024

8715 Cholinergic Signaling in the Mouse Embryonic Pancreas Targets Early Endocrine Cells

Abstract Disclosure: C. Duarte: None. J.K. Panzer: None. N. Borowsky: None. A. Caicedo: None. The parasympathetic vagus nerve affects pancreas function by activating local intrapancreatic neurons that release acetylcholine (ACh). These neurons are derived from progenitors of the vagal neural crest and colonize the pancreas during embryonic development. The specific mechanisms by which ACh is released from these neurons influence embryonic development of the islet and, specifically, beta cells remain largely unknown. The purpose of this study was to identify cholinergic signaling components and assess early physiological responses to ACh during murine development of endocrine lineage cells. We extracted pancreatic rudiments from mice at embryonic stages E15 to E18 and stained them for neuronal and endocrine markers, along with components associated with cholinergic signaling. We further performed Ca2+ imaging of the pancreatic rudiments from NGN3CRE-GCaMP3 mice to record responses to ACh in cells of the endocrine lineage. At E15, we observed a significantly higher concentration of glucagon+ cells compared to insulin+ cells, consistent with the earlier differentiation of alpha cells in the developing pancreas. Neuronal body clusters were identified in close proximity to endocrine lineage cells from E15 to E18, with the neuronal network becoming more dispersed and interconnected. At E15, wide distribution of the presynaptic vesicular acetylcholine transporter (VAChT) was observed later becoming localized around insulin+ and glucagon+ cells at E18. Postsynaptic acetylcholinesterase (AChE) colocalized with glucagon+ cells from E15 to E18 and with insulin+ cells by E18. ACh elicited Ca2+ responses in individual endocrine cells as early as E15. Our results show that cholinergic nerve terminals target early endocrine cells and elicit responses to ACh, indicating that local cholinergic neurons innervate and activate endocrine progenitors in the embryonic pancreas. Our current studies are aimed at determining how cholinergic signaling contributes to beta cell differentiation and function. We expect this knowledge to guide future protocols for deriving beta cells from stem cells. Presentation: 6/2/2024

7068 Paraganglioma in Cyanotic Congenital Heart Disease

Abstract Disclosure: R. Lis: None. V. Hamidi: None. Paragangliomas arise from the non-chromaffin cells of the parasympathetic nervous system, which are composed of glomus cells. These function as chemoreceptors in response to hypoxia. Carotid body paragangliomas have been linked to conditions with chronic hypoxia. This was first seen in residents of high altitude locations in a case report presented by Saldana et. al and regression of a paraganglioma with resolution of hypoxia was reported by Gruber et. al. There have been few additional case reports of Paraganglioma in other hypoxic states. We present a rare case of a functional Paraganglioma in a patient with Cyanotic Congenital Heart Disease (CCHD).This is a 19 year old female with a history of CCHD due to double inlet left ventricle and transposition of the great arteries. Soon after birth, she had a fontan procedure. She subsequently developed fontan associated liver disease as well as chronic kidney disease, hypertension, sinus node dysfunction, and complete heart block. Her baseline oxygen saturation was 78-85%. Her heart rate was 40-49 beats per minute with upcoming plans for pacemaker placement. Her blood pressure ranged 90/50 to 150/80 mmHg on Amlodipine 5 mg and Lisinopril 2.5 mg. She routinely received abdominal imaging to monitor her liver disease. A liver MRI incidentally revealed a retroperitoneal mass concerning for a paraganglioma. Serum Normetanephrines were found to be 26.60 nmol/L (reference range less than 0.89). 24 hr Urine Norepinephrine was 1,187 ug/d (reference range 14-20). Further imaging was negative for additional sites of disease. Given her complete heart block, she was started on alpha blockade only prior to pacemaker placement. After the pacemaker was placed, she was started on beta blockade and underwent surgical resection of her paraganglioma. The pathology confirmed paraganglioma and mutation testing was negative for germline mutations including SDH, VHL, RET, NF1 mutations. Paragangliomas in patients with CCHD have been scarcely described in the literature given the rarity of both of these conditions. However, there is a relatively increased incidence of paragangliomas in the CCHD population due to chronic hypoxia triggering the hypoxia pathway. EPAS1 mutated HIF2alpha is often found to be the culprit in these patients. In addition, case reports have often described these patients to either be asymptomatic or have potential symptoms masked by their cardiac disease. Therefore, CCHD patients are at increased risk for paragangliomas and warrant additional awareness and regular screening. Screening has been proposed to start after 10 years of hypoxia in a case review by Agarwal et. al. as paraganglioma incidence in CCHD populations has not been seen before age 11. Incidence of recurrence is not yet widely studied, but significant concern for recurrence is warranted if the etiology of hypoxia is not reversed. Presentation: 6/3/2024

To the issue of vagosympathetic balance assessment in patients with facial phlegmon

Objective. To assess the influence of the autonomic nervous system tone on the activity of the inflammatory process in facial phlegmon. Materials and methods. A group of patients with facial phlegmon (n = 74) was divided into two parts according to the predominant type of ANS. To identify the dominant type of ANS the method of A.M. Vayne was used. The content of leukocytes and their types was assessed in peripheral blood samples. The concentration of glucose, total protein, C-reactive protein was determined in the patients` blood serum. Statistical data processing was carried out using Student's t-test. Results. Significant differences in laboratory parameters of patients with facial phlegmons with different types of the autonomic nervous system are demonstrated. In patients with prevailing sympathetic division, leukocytosis with a shift of the formula to the left was more pronounced. When the parasympathetic division dominated, a higher concentration of C-reactive protein was observed. Conclusion. Assessment of the autonomic nervous system tone in case of facial phlegmons indicates its significant impact on the activity of the inflammatory process, which affects the duration of inpatient treatment.

The infant parasympathetic nervous system is socially embedded and dynamic at multiple timescales, within and between people.

Human interpersonal capacities emerge from coordinated neural, biological, and behavioral activity unfolding within and between people. However, developmental research to date has allocated comparatively little focus to the dynamic processes of how social interactions emerge across these levels of analysis. Second-person neuroscience and dynamic systems approach together to offer an integrative framework for addressing these questions. This study quantified respiratory sinus arrhythmia and social behavior (∼360 observations per system) from 44 mothers and typically developing 9-month-old infants during a novel modified "still-face" (text message perturbation) task. Stochastic autoregression models indicate that the infant parasympathetic nervous system is coupled within and between people second by second and is sensitive to social context. Intraindividual, we found positive coupling between infants' parasympathetic nervous system activity and their social behavior in the subsequent second, but only during the moments and periods of active caregiver engagement. Between people, we found a bidirectional coregulatory feedback loop: Mothers' parasympathetic activity positively predicted that of their infant in the subsequent second, a form of synchrony that decreased during the text message perturbation and did not fully recover. Conversely, infant parasympathetic activity negatively predicted that of their mother at the subsequent second, a form of synchrony that was invariant over social context. Findings reveal unidirectional parasympathetic coupling within infants and a complementary allostatic feedback loop between mother and infant parasympathetic systems. They offer novel evidence of a dynamic, socially embedded parasympathetic system at previously undocumented timescales, contributing to both basic science and potential clinical targets to better support adaptive, multisystem social development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Measuring the Pupillary Light Reflex Using Portable Instruments in Applied Settings.

The early components of the pupillary light reflex (PLR) are governed by the parasympathetic nervous system. The use of cheap, portable pupillometry devices may allow for the testing of parasympathetic-system health in field settings. We examined the reliability of two portable instruments for measuring the PLR and their sensitivity to individual differences known to modulate the PLR. Parameters of the PLR were measured in a community sample (N = 108) in a variety of field settings. Measurements were taken using a commercial pupillometer (NeuroLight, IDMED) and an iPhone using the Reflex Pro PLR analyser (Brightlamp). The parameters of baseline pupil diameter, constriction latency, amplitude and relative amplitude of constriction, and constriction velocity were measured. Individual differences related to age, levels of anxiety, and post-traumatic stress disorder (PTSD) symptomology were assessed. Some measures could not be attained using the iPhone under these field conditions. The reliability of the measures was high, save for the measurement of contraction latency which was particularly unreliable for the iPhone system. The parameters of the PLR showed the same internal relationships as those established in laboratory-based measurements. Age was negatively correlated with all the reliable PLR parameters for both systems. Effects of anxiety and PTSD symptomology were also apparent. The study demonstrated that a hand-held portable infrared pupillometer can be used successfully to measure the PLR parameters under field settings and can be used to examine individual differences. This may allow these devices to be used in workplaces, sports fields, roadsides, etc., to examine parasympathetic activity where needed.

Impact of Multi versus Single Arterial Coronary Bypass Graft Surgery on Postoperative Atrial Fibrillation

The effect of multi-arterial (MA) versus single arterial (SA) coronary bypass graft surgery on postoperative atrial fibrillation (POAF) was not investigated. From May 2017 to May 2024, the patients with CYP2C19*2 or *3 allele receiving coronary artery grafting and post-operational aspirin 100 mg/day and clopidogrel 75mg/day were retrospectively reviewed and assigned into MA or SA group. The primary endpoint was the incidence rate of POAF in first week. The secondary endpoints were POAF burden, platelet aggregation, systemic immune-inflammation (SII) index and heart rate variability (HRV). The study included 58 cases in MA group and 174 cases in SA group. The incidence of POAF was 17% in MA group contrasting with 42% in SA group (hazard ratio: 0.353; 95% confidence interval: 0.218 to 0.569, P=0.0012). A lower POAF burden was observed in MA group than that in SA group (2 h [1, 5] versus 10 h [6, 20], P=0.02). Platelet aggregation (arachidonic acid, 46%±10% vs. 56%±8%, P<0.01; adenosine diphosphate, 58%±17% vs. 75%±13%, P<0.01) and inflammation response index (neutrophil-lymphocyte ratio, 26±4 vs. 28±5, P=0.006; SII index, 5019±771 vs. 5382±1204, P=0.032) was notably lower in MA group than those in SA group at one day after CABG. Holter electrocardiogram showed a higher HRV value in standard deviation of normal-to-normal RR intervals, and decreased low-frequency/high-frequency ratio in MA group. In conclusion, MA was associated with a lower incidence rate of POAF, and paralleled with a lower AF burden, platelet aggregation, inflammation reaction and a higher parasympathetic nerve tone compared with SA regimen.

Examining the Anti-inflammatory and Renoprotective Effects Resulting from Parasympathetic Nerve Stimulation after Inflammation

Examining the Anti-inflammatory and Renoprotective Effects Resulting from Parasympathetic Nerve Stimulation after Inflammation

What can the psychoneuroimmunology of yoga teach us about depression's psychopathology?

Depression, the most prevailing mental health condition, remains untreated in over 30% of patients. This cluster presents with sub-clinical inflammation. Investigations trialling anti-inflammatory medications had mixed results. The lack of results may result from inflammation's complexity and targeting only a few of depression's abnormal pathways. Mind-body therapies' biological and neuro-imaging studies offer valuable insights into depression psychopathology. Interestingly, mind-body therapies, like yoga, reverse the aberrant pathways in depression. These aberrant pathways include decreased cognitive function, interoception, neuroplasticity, salience and default mode networks connectivity, parasympathetic tone, increased hypothalamic-pituitary-adrenal (HPA) axis activity, and metabolic hyper/hypofunction. Abundant evidence found yogic techniques improving self-reported depressive symptoms across various populations. Yoga may be more effective in treating depression in conjunction with pharmacological and cognitive therapies. Yoga's psychoneuroimmunology teaches us that reducing allostatic load is crucial in improving depressive symptoms. Mind-body therapies promote parasympathetic tone, downregulate the HPA axis, reduce inflammation and boost immunity. The reduced inflammation promotes neuroplasticity and, subsequently, neurogenesis. Improving interoception resolves the metabolic needs prediction error and restores homeostasis. Additionally, by improving functional connectivity within the salience network, they restore the dynamic switching between the default mode and central executive networks, reducing rumination and mind-wandering. Future investigations should engineer therapies targeting the mechanisms mentioned above. The creation of multi-disciplinary health teams offering a combination of pharmacological, gene, neurofeedback, behavioural, mind-body and psychological therapies may treat treatment-resistant depression.

Autonomic Dysfunction in Psychiatric Disorders

The autonomic nervous system and its dysfunction are associated with many diseases. For a healthy individual, it is essential that the sympathetic and parasympathetic systems are balanced and functioning at a high capacity. Psychiatric disorders often exhibit disruptions in the activity of the vagus nerve, which can lead to autonomic dysfunction. People with psychiatric disorders, including panic disorder, depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety disorders, and substance addiction, often show reduced heart rate variability. Heart rate variability is a reliable marker for assessing autonomic functions, and decreased heart rate variability in individuals with psychiatric disorders can lead to an increased risk of sudden cardiac death. Autonomic dysfunction is observed in psychiatric disorders, and it occurs during the course of the illness, not necessarily at its onset. Autonomic dysfunction accelerates the progression of the disease. Therefore, controlling autonomic functions is crucial. This can help reduce disease symptoms and decrease the morbidity and mortality caused by autonomic dysfunction."

AFTER-CA: Autonomic Function Transformation and Evaluation Following Catheter Ablation in Atrial Fibrillation.

Background: Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). However, its effects on autonomic function and underlying mechanisms remain poorly understood. This study investigated autonomic and haemodynamic changes following CA and explored their potential implications for patient outcomes. Methods: Seventy-eight patients with AF underwent CA and were followed up at one, three, and six months. Autonomic function was assessed using a combination of head-up tilt (HUT), handgrip (HG), and deep breathing (DB) manoeuvres along with baroreflex sensitivity (BRS) and baroreflex effectiveness index (BEI) evaluation. Heart rate (HR), blood pressure (BP), and their variability were measured at each time point. Results: Significant autonomic alterations were observed after ablation, particularly at one month, with reductions in parasympathetic tone and baroreflex function. These changes gradually normalised by six months. Both pulmonary vein isolation (PVI) and cryoablation (CryO) had similar effects on autonomic regulation. Improvements in quality of life, measured by the AFEQT scores, were consistent with these physiological changes. Conclusions: CA for AF induces significant time-dependent autonomic and haemodynamic changes with recovery over six months. These findings underscore the need for ongoing monitoring and personalised post-ablation management. Further research is required to explore the mechanisms driving these alterations and their long-term impacts on patient outcomes.

The impact of regular physical training on the function of the autonomic nervous system in patients with inappropriate sinus tachycardia

Introduction: Sympathetic overactivity plays a crucial role in the pathogenesis of inappropriate sinus tachycardia (IST). It has been shown that regular physical activity positively affects the balance between the sympathetic and parasympathetic nervous systems, which may benefit patients with IST.Objective: This study aimed to assess the impact of regular physical training on the autonomic nervous system (ANS) function in patients with IST, focusing on heart rate variability (HRV) as an indicator of autonomic balance.Methods:The study included 32 female patients diagnosed with IST, with 16 in the study group (Group A) and 16 in the control group (Group B). The women in Group A participated in a structured physical training program lasting 12 weeks. HRV was analyzed based on 24-hour Holter monitoring recordings before and after the intervention. The statistical data obtained were presented as graphs illustrating changes in selected HRV parameters in response to physical training.Results:The study results indicate a significant improvement in heart rate variability (HRV) after 12 weeks of regular physical training in the study group. Notably, there was an increase in parameters associated with parasympathetic activity, such as the HF (High Frequency) index. Additionally, the SDNN index, which measures overall heart rate variability, also improved. These observations suggest that physical training contributed to an improvement in autonomic balance. The graphs in the study clearly depict changes in individual HRV parameters, confirming the positive impact of physical activity on the function of the autonomic nervous system in patients with IST.

Mechanistic insights into Suanzaoren Decoction's improvement of cardiac contractile function in anxiety-induced cardiac insufficiency

Ethnopharmacological relevanceAccording to traditional Chinese medicine, Anxiety-induced cardiac blood insufficiency leads to palpitations and restlessness. Suanzaoren Decoction (SD) is effective in replenishing blood and promoting blood circulation. Clinical practice has shown that it has a better therapeutic effect on cardiac insufficiency. However, its mechanism of action is still unclear. Aim of the studyThe study aims to determine the mechanism by which SD treats chronic restraint stress (CRS)-induced anxiety-induced cardiac insufficiency (ACI). Materials and methodsSD was orally administered to mice with CRS-induced ACI. Firstly, we constructed an anxiety model in mice by CRS. Subsequently, SD was investigated to assess cardiac function and pathological changes through echocardiography, H&E staining, and Masson staining. Thirdly, the function of sympathetic and parasympathetic nerves was evaluated using enzyme-linked immunosorbent assay (ELISA) and enzyme activity assays. Network pharmacology and molecular docking were employed to predict potential targets for SD treatment of cardiac insufficiency. CaMKII expression was scrutinized utilizing publicly accessible databases. CaMKII was identified as a target through immunohistochemistry and Western Blot analysis in mouse hearts. Finally, the therapeutic mechanism of SD was confirmed in injured cardiomyocytes via Western Blot and quantitative PCR. ResultsSD exerted anxiolytic effects by increasing the frequency of entries into and the duration spent in open arms while reducing the time spent in the light chamber and increasing the number of transitions between light and dark chambers. Additionally, it mitigated cardiac insufficiency, as evidenced by the enhancement of left ventricular ejection fraction (LVEF) and attenuation of cardiomyocyte damage and inflammatory infiltration.However, SD did not alleviate the elevated norepinephrine (NE) and decreased Acetylcholine (Ach) in anxiety states. To investigate the mechanism of action of SD, we constructed a Drug-Component-Target-Disease network, identifying 13 potential active compounds. Additionally, leveraging bioinformatics analysis and molecular docking targeting heart diseases characterized by clinical left ventricular ejection fraction (LVEF), we focused on the CaMKII target. The ability of SD to modulate CaMKII expression and phosphorylation in the mouse heart was investigated using immunohistochemistry and Western blotting. SD was found to alleviate NE-injured cardiomyocytes by modulating the Ca2+/CaMKII/MEF2 and GATA4 pathways. ConclusionSD is a potential formula for the treatment of chronic restraint stress (CRS)-induced ACI that ameliorates cardiomyocyte injury and improves cardiac function. Its efficacy is associated with the inhibition of the Ca2+/CaMKII/MEF2 and GATA4 signaling pathways.

The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

Associations between Sleep Duration and Autonomic Nervous System Regulation in Patients with Probable Alzheimer's Disease: A Cross-Sectional Pilot Study.

In this study, we aimed to investigate the relationships between sleep duration and autonomic nervous system (ANS) regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer's disease who were hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity via the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, hypertension status, and medication use (antipsychotics) as covariates. A sleep duration of 6-9 h per night compared to shorter than 6 h was associated with a greater increase in parasympathetic nervous system activity (p = 0.03), and a sleep duration longer than 9 h was associated with a decrease sympathovagal balance (p = 0.02). In addition, we observed an inverted U-shaped association between sleep duration and ANS regulation. In this pilot study, we demonstrated that a sleep duration of 6-9 h per night may be beneficial for ANS regulation; however, the present study involved only a few participants and had some limitations. Additional research with a larger cohort is needed to confirm these findings.

Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being.

Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called "peak experiences," characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extent changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT). We derived measures of SNS and PNS activity from the electrocardiograms of 17 participants (11 males, mean age = 33.8 years, SD = 8.3) while they received either DMT or placebo. Results show that the joint influence of SNS and PNS ("sympathovagal coactivation") over cardiac activity was positively related to participants' ratings of "Spiritual Experience" and "Insightfulness" during the DMT experience, while also being related to improved well-being scores 2 weeks after the session. In addition, we found that the state of balance between the two ANS branches ("sympathovagal balance") before DMT injection predicted scores of "Insightfulness" during the DMT experience, as well as subsequent sympathovagal coactivation. These findings demonstrate the involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic therapy.

Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review).

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of β-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.

Elevated correlations in cardiac–neural dynamics: An impact of mantra meditation on stress alleviation

Mantra meditation is a widely practiced technique with a demonstrated ability to promote relaxation and alleviate stress. This study aims to evaluate the impact of regular mantra meditation practice on electroencephalogram (EEG) patterns and heart rate variability (HRV) in young adults grappling with increased stress levels. Furthermore, the study explored possible correlations between these two physiological markers. Thirty-eight participants practiced mantra meditation for eight weeks, and their EEG and HRV were recorded before and after. The pre-post analysis evaluated brain activity and autonomic nervous system regulation alterations by examining EEG and HRV in the time, frequency, and nonlinear domains. Data analysis revealed significant correlations between EEG patterns and HRV indices following mantra meditation, suggesting a potential interconnection between neural and cardiovascular regulation. A notable increase in Root Mean Square of Successive Differences (RMSSD) and Standard Deviation of NN intervals (SDNN) within HRV, along with a decrease in Heart Rate (HR) and Stress Index (SI) and an increase in EEG alpha and theta power, accompanied by a reduction in their ratio, was observed. Three pivotal correlations consistently increased during eight weeks: Alpha/Theta Ratio (ATR) with Low-Frequency/High-Frequency Ratio (LHR), ATR with SD2/SD1 Ratio (SDR), and Relaxation Index (RI) with Stress Index (SI). After eight weeks, these correlations attained statistical significance, optimizing the balance between calmness and vigilance, boosting parasympathetic activity, and reducing chaos between the parasympathetic and sympathetic systems. The study elucidates the scientific mechanisms of mantra meditation, enriching research on its stress-reducing effects and emphasizing mental and physical well-being.

Rita Levi-Montalcini: From Persecution to the Nobel Prize and an Honorary Degree From a Canadian University.

Rita Levi-Montalcini (RLM) is recognized as a prestigious and renowned researcher of her time. She was the fourth woman to earn the Nobel Prize in Physiology and Medicine in 1986 for the discovery of nerve growth factor (NGF). We review her biography and scientific discovery, and provide an example of why her discovery is still important. She had a special relationship with McGill University, Canada, which we describe. We searched for articles and books about her for biographical and scientific material and met with Dr. Claudio Cuello, Former Chair of McGill's Faculty of Medicine. RLM was born in 1909 in Turin, Italy, where she had studied medicine. She started her career in research. Because of the anti-Jewish racial laws in Italy in 1938, she went underground and continued her projects in her bedroom. After the war, she visited St. Louis, USA, and conducted research there. Her experiments confirmed that tumors release a factor that causes nerve growth and cancer proliferation. Initially, scientists responded to this discovery with skepticism, but after its purification in 1959 and determination of its protein structure in 1971, NGF became widely accepted.Currently, crosstalk between cancers and nerves is poorly understood. The example of prostate cancer shows that surgical or chemical denervation of sympathetic nerves prevents the initiation of prostate tumors, whereas inhibition of parasympathetic nerve signaling reduces the spread of prostate cancer. McGill University awarded RLMa doctoral degree in 2011. It was the first time in itshistory that the University awarded an honorary doctorate outside of Canada, and the second one outside of Quebec.Through her discovery of NGF, RLM exemplified the power of passion and determination despite the obstacles she faced. Her relentless dedication has led to remarkable achievements.

Clinical Characteristics and Outcomes of Tympanomastoid Paragangliomas: A Report from Slovenia.

(1) Background: Head and neck paragangliomas are neuroendocrine tumors that typically originate from the parasympathetic nervous system and are predominantly non-secretory. Their clinical manifestations result from their mass effect on the surrounding tissues. The approach to treating these tumors depends on factors such as their location, size, impact on adjacent structures, and the patient's overall health and preferences. (2) Methods: A retrospective analysis of the management of temporal bone paraganglioma classes A and B (according to the modified Fisch classification) was performed at the University Medical Centre, Ljubljana, between 2011 and 2023. (3) Results: We analyzed 23 cases, 19 of which underwent surgery; complete tumor removal was achieved in 18 of them. Four patients were irradiated due to tumor progression to class C. Three of these four patients initially refused surgery and were treated with radiotherapy (RT) 7, 13, and 18 years after diagnosis. In the fourth patient, complete surgical resection was not achieved and she was treated with RT four years after surgery, due to the growth of the tumor to class C. The average follow-up time from diagnosis was 8.9 years (median 6 years; range 1-26 years). (4) Conclusions: The surgical treatment of patients with class A and B paragangliomas is effective and safe. In cases where surgery is refused but the tumor continues to grow to class C, RT is an alternative and efficient method of controlling tumor growth.