Parasympathetic Research Articles

Intracellular calcium dysregulation in heart and brain diseases: Insights from induced pluripotent stem cell studies.

The central nervous system (CNS) plays a role in regulating heart rate and myocardial contractility through sympathetic and parasympathetic nerves, and the heart can impact the functional equilibrium of the CNS through feedback signals. Although heart and brain diseases often coexist and mutually influence each other, the potential links between heart and brain diseases remain unclear due to a lack of reliable models of these relationships. Induced pluripotent stem cells (iPSCs), which can differentiate into multiple functional cell types, stem cell biology and regenerative medicine may offer tools to clarify the mechanisms of these relationships and facilitate screening of effective therapeutic agents. Because calcium ions play essential roles in regulating both the cardiovascular and nervous systems, this review addresses how recent iPSC disease models reveal how dysregulation of intracellular calcium might be a common pathological factor underlying the relationships between heart and brain diseases.

Pain-induced effects on the pupillary light response under high and low illumination conditions.

The present study investigated the impact of two different light intensities on the pain-modulated pupillary light response (PLR). Additionally, it aimed to demonstrate parasympathetic and sympathetic influences on PLR parameters in response to pain, as predicted by functional models. A total of 24 participants were included in a randomized, repeated-measures design. The PLR was measured in response to both dark and bright light stimuli within two test cycles. Pain was induced using the cold pressor test (CPT), which involved immersing participants' feet in ice water. PLR measurements were taken during baseline and ice-water immersion within each test cycle. The assessed PLR parameters included initial diameter (INIT), latency (LAT), amplitude (AMP), and re-dilation time (ReDIL25). Along with these parameters, heart rate (HR) and pain ratings were also computed and analyzed. The CPT caused moderate pain in participants, and the resulting PLR parameters were found to be congruent with the expected parasympathetic and sympathetic nervous system activities. Although the luminance of the stimulus did influence PLR parameters, no interaction with pain exposure was found. The results showed that different aspects of pain experienced by an individual, as modulated through the sympathetic and parasympathetic nervous systems, are visible in their pupillary reactions to light. Notably, within the range used in the current study, light intensity did not significantly affect the pain-related PLR effects.

Phenotypes of COVID-19-associated dysautonomia in patients requiring veno-venous extracorporeal membrane oxygenation

Background. Patients with novel coronavirus infection (COVID-19) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) are typically prone to hemodynamic disorders of various severity. Tachycardia, increased cardiac output, or arterial hypotension affect the effectiveness of VV-ECMO. One of the possible causes of hemodynamic disorders leading to ineffective VV-ECMO may be dysautonomia (DA), which refers to an imbalance of sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). The development of DA in various critical conditions was described previously. Dysautonomia also develops in COVID-19 (COVID-19-associated DA), but it was studied only in stable non-ICU patients. The presented study focuses on COVID-19-associated DA in critical COVID-19 patients requiring VV-ECMO support. The study was aimed at determining COVID-19-associated DA phenotypes, their impact on VV-ECMO effectiveness and disease outcomes. Materials and methods. The study included 20 patients: 12 (60%) females, 8 (40%) males. The patients had an average age of 55 years. All the patients underwent 24-hour Holter monitoring with spectral analysis of heart rate variability (HRV) assessing low-frequency component of the spectrum (LF), the high-frequency component of the spectrum (HF), the LF/HF ratio on days 1, 3, and 5 of VV-ECMO. Diagnostic criteria for COVID-19-associated DA was a decrease in LF/HF 2.28 or an increase in LF/HF 6.94. The diagnostic criteria of predominant tone of sympathetic nervous system (sympathetic tone) was an increase in LF/HF 6.94, while a decrease in LF/HF 2.28 indicated predominant parasympathetic tone. Low sympathetic tone was determined by a decrease in LF 15%, and an increase in LF 40%. Low parasympathetic tone was determined by a decrease in HF 15%, and an increase in HF 25%. The criteria used were based on the results of previous studies. The following parameters were registered in the study population: VV-ECMO weaning, duration of respiratory and VV-ECMO support, length of stay in the intensive care unit (ICU) and in hospital, and disease outcomes. Results. COVID-19-associated DA was diagnosed in all the patients. LF/HF median value was 0.1. HRV spectrum parameters changed significantly over time: on day 5 of VV-ECMO support LF and HF values significantly decreased. The patients were divided into three groups according to the DA phenotype: group 1 (n = 4 [20%]) with normal sympathetic tone and high parasympathetic tone (nShP phenotype); group 2 (n = 14 [70%]) with low sympathetic tone and high parasympathetic tone (lShP phenotype); group 3 (n = 2 [10%]) with low sympathetic tone and normal parasympathetic tone (lSnP phenotype). The latter group was excluded from further statistical analysis due to the small sample size. In group 2, the mean HR was significantly higher compared with group 1. In group 1, VV-ECMO weaning was successful in 50% of cases, whereas in group 2 it was successful in 7.2% (p = 0.04). Conclusions. To determine a dysautonomia phenotype, it is necessary to continuously monitor DA status in COVID-19 patients during VV-ECMO. Tachycardia in COVID-19 patients during VV-ECMO does not exclude the ANS imbalance with a significant predominance of parasympathetic tone over the sympathetic tone. It is this COVID-19-associated DA phenotype that is significantly associated with the unfavorable outcomes.

Personalized interpretable prediction of perceived sleep quality: Models with meaningful cardiovascular and behavioral features.

Understanding a person's perceived quality of sleep is an important problem, but hard due to its poor definition and high intra- as well as inter-individual variation. In the short term, sleep quality has an established impact on cognitive function during the following day as well as on fatigue. In the long term, good quality sleep is essential for mental and physical health and contributes to quality of life. Despite the need to better understand sleep quality as an early indicator for sleep disorders, perceived sleep quality has been rarely modeled for multiple consecutive days using biosignals. In this paper, we present novel insights on the association of cardiac activity and perceived sleep quality using an interpretable modeling approach utilizing the publicly available intensive-longitudinal study M2Sleep. Our method takes as input signals from commodity wearable devices, including motion and blood volume pulses. Despite processing only simple and clearly interpretable features, we achieve an accuracy of up to 70% with an AUC of 0.76 and reduce the error by up to 36% compared to related work. We further argue that collected biosignals and sleep quality labels should be normalized per-participant to enable a medically insightful analysis. Coupled with explainable models, this allows for the interpretations of effects on perceived sleep quality. Analysis revealed that besides higher skin temperature and sufficient sleep duration, especially higher average heart rate while awake and lower minimal activity of the parasympathetic and sympathetic nervous system while asleep increased the chances of higher sleep quality.

INFLUENCE OF LISTENING TO AL-FATIHA ON BLOOD PARAMETERS AND COGNITIVE FUNCTIONS IN PATIENTS WITH CEREBRAL PALSY

Background of the Study: Cerebral Palsy also referred as CP is a neurodevelopmental disorder that disturbs balance, blood parameters, cognition, movement, muscle coordination, oral health, and various other functions. Many studies have demonstrated that Quranic verses have therapeutic effects on several diseases. This study explored the influence of listening to Al-Fatiha on blood parameters and cognitive functions in patients with CP. Methodology: This first phase clinical trial was conducted from February 1st to March 30th, 2021 after obtaining ethical permission from the Institutional Bioethics Committee (IBC-2017) and the rehabilitation centre. Inducted pparticipants were assigned randomly into control (11 males and 1 female; age in years 14±5) and Al-Fatiha groups (11 males and 5 females; age in years 14±4.5). The Al-Fatiha group participants received thirty-one structured sessions of listening to Al-Fatiha. Blood analyses encompassed a spectrum of parameters, including blood urea nitrogen, calcium, creatinine, electrolytes, liver function tests, protein levels, and random blood sugar. Cognitive functions were evaluated using 5 Lumosity software games. Paired t-tests and descriptive statistics were performed using SPSS v28. Results: The findings indicated a significant improvement in cognition however, blood parameters remained within normal levels. Alpha brain waves, various hormones, the parasympathetic nervous system, the prefrontal cortex, and the neurotransmitter serotonin have been suggested as potential contributors to improving patients. Conclusion: The findings imply that Al Fatiha can be a therapeutic, non-pharmacological, cost-effective, and miracle approach for the overall improvement of CP patients.

EFFECTS OF SHORT-TERM PRACTICE OF FAST DEEP BREATHING EXERCISE ON PARASYMPATHETIC FUNCTIONS IN TRANS-FEMORAL AND TRANS-TIBIAL-AMPUTATION PATIENTS

Background of the Study: After lower limb amputation, the functioning parasympathetic system is compromised so the regular practice of breathing techniques improves cardiorespiratory functions. To determine the effects of short-term fast-breathing exercises on parasympathetic functions in amputees. Methodology: The study was conducted at the Armed Forces Institute of Rehabilitation Medicine Rawalpindi, on 61 stable transfemoral and transtibial amputation patients within the duration of six months (January to June 2017), performed fast deep breathing exercises Parasympathetic functions were observed through different variables. Data was analyzed using IBM® SPSS® v 21. Results: Breathing exercises showed significant effects on HR with a p-value of (0.000), the Valsalva ratio had a p-value of (0.000), and oxygen saturation was improved in both control and experimental groups with p-values of (0.000) and (0.000). Valsalva’s BP systolic and diastolic p values were (0.001) (0.012), breathing exercise BP systolic and diastolic values were (0.16) and (0.000), and orthostatic testing BP systolic and diastolic p values were (0.134) and (0.389). Post Borg scale readings showed a significant decrease in exertion level Conclusion: The study concludes that short-term fast deep breathing exercise improves cardiovagal functioning.

Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.

Midazolam versus Ondansetron versus Dexamethasone in Preventing Post-Operative Nausea and Vomiting after Elective Laparoscopic Abdominal Surgeries

Abstract Background Laparoscopic surgery is associated with a remarkably high risk of post-operative nausea and vomiting. The reasons for this high rate of PONV include mechanical factors (such as pressure on the stomach and gut caused by the pneumoperitoneum), neural factors (such as vagal reflexes elicited by irritation of parasympathetic nerve endings in the abdomen), and chemical factors (which include speculative considerations regarding a possible influence of CO2 on PONV). Objective To compare the effect of midazolam, ondansetron or dexamethasone on prophylaxis against PONV in patients undergoing laparoscopic abdominal surgeries. Patients and Methods After approval of anesthesiology department, scientific and ethical committees in Ain Shams University Hospitals, patients were included in the study, and were divided into three groups (n = 40; each); group M (midazolam group) and Group O (ondansetron group) and group D (dexamethasone group). Results The three groups were adequately monitored and assessed post-operatively and they were compared regarding post-operative nausea and vomiting outcome by recording the incidence of nausea and vomiting and recording the call for rescue antiemetic. Demographic data, intra-operative hemodynamics and post-operative pain score, occurrence of side effects, sedation score and patient satisfaction scores were also assessed, we found about 95% of (M) group achieve the complete response, that mean midazolam provided PONV prophylaxis comparable to dexamethasone and ondansetron in patients who underwent laparoscopic abdominal surgeries. Conclusion From this study, we can conclude that the midazolam is as effective as ondansetron and dexamethasone in reducing the incidence of nausea and vomiting in post-operative period of laparoscopic abdominal surgeries.

Computational modeling for the quantitative assessment of cardiac autonomic response to orthostatic stress

Objective. The autonomic nervous system (ANS) plays a critical role in regulating not only cardiac functions but also various other physiological processes, such as respiratory rate, digestion, and metabolic activities. The ANS is divided into the sympathetic and parasympathetic nervous systems, each of which has distinct but complementary roles in maintaining homeostasis across multiple organ systems in response to internal and external stimuli. Early detection of ANS dysfunctions, such as imbalances between the sympathetic and parasympathetic branches or impairments in the autonomic regulation of bodily functions, is crucial for preventing or slowing the progression of cardiovascular diseases. These dysfunctions can manifest as irregularities in heart rate, blood pressure regulation, and other autonomic responses essential for maintaining cardiovascular health. Traditional methods for analyzing ANS activity, such as heart rate variability (HRV) analysis and muscle sympathetic nerve activity recording, have been in use for several decades. Despite their long history, these techniques face challenges such as poor temporal resolution, invasiveness, and insufficient sensitivity to individual physiological variations, which limit their effectiveness in personalized health assessments. Approach. This study aims to introduce the open-loop Mathematical Model of Autonomic Regulation of the Cardiac System under Supine-to-stand Maneuver (MMARCS) to overcome the limitations of existing ANS analysis methods. The MMARCS model is designed to offer a balance between physiological fidelity and simplicity, focusing on the ANS cardiac control subsystems’ input–output curve. The MMARCS model simplifies the complex internal dynamics of ANS cardiac control by emphasizing input–output relationships and utilizing sensitivity analysis and parameter subset selection to increase model specificity and eliminate redundant parameters. This approach aims to enhance the model’s capacity for personalized health assessments. Main results. The application of the MMARCS model revealed significant differences in ANS regulation between healthy (14 females and 19 males, age: 42 ± 18) and diabetic subjects (8 females and 6 males, age: 47 ± 14). Parameters indicated heightened sympathetic activity and diminished parasympathetic response in diabetic subjects compared to healthy subjects (p < 0.05). Additionally, the data suggested a more sensitive and potentially more reactive sympathetic response among diabetic subjects (p < 0.05), characterized by increased responsiveness and intensity of the sympathetic nervous system to stimuli, i.e. fluctuations in blood pressure, leading to more pronounced changes in heart rate, these phenomena can be directly reflected by gain parameters and time response parameters of the model. Significance. The MMARCS model represents an innovative computational approach for quantifying ANS functionality. This model guarantees the accuracy of physiological modeling while reducing mathematical complexity, offering an easy-to-implement and widely applicable tool for clinical measurements of cardiovascular health, disease progression monitoring, and home health monitoring through wearable technology.

Rhinorrhea and watery eyes in infancy and risk of attention-deficit hyperactivity disorder in school-age children.

Increased parasympathetic nervous system (PNS) activity is associated with attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms, but not hyperactive-impulsive symptoms, and may contribute to inattentive subtype etiology. Guided by prior work linking infant rhinorrhea and watery eyes without a cold (RWWC) to PNS dysregulation, we examined associations between infant RWWC and childhood ADHD symptoms in a longitudinal cohort of Black and Latinx children living in the context of economic disadvantage (N=301 youth: 158 females, 143 males). Infant RWWC predicted higher inattentive (relative risk [RR] 2.16, p<.001) but not hyperactive-impulsive (RR 1.53, p=.065) ADHD symptoms (DuPaul scale), administered to caregivers at child age 8-14 years. Stratified analyses revealed that these associations were present in females but not males, who were three times more likely to have higher ADHD current total symptoms if they had infant RWWC than if they did not. Additionally, associations between RWWC and inattention symptoms were observed only in females. RWWC may thus serve as a novel risk marker of ADHD inattentive-type symptoms, especially for females.

The Neurophysiological Effects of Craniosacral Treatment on Heart Rate Variability: A Systematic Review of Literature and Meta-Analysis.

Craniosacral treatment (CST) is an osteopathic technique grounded in the assumption that there is an intrinsic, fine movement of the cerebrospinal fluid. This rhythmic movement can be utilized for diagnostic and therapeutic purposes by palpation and manipulation of the skull, spine, and associated connective tissues. Therapeutic benefit is likely due to action on the autonomic nervous system (ANS), specifically through the vagus nerve. Current literature on the neurophysiological effects of CSTis limited, which has contributed to controversy regarding its effectiveness. Heart rate variability (HRV) as a measure of cardiovascular stress and autonomic system activity is thus proposed as a tool to evaluate the neurophysiologic effects of CST. HRV can be analyzed in two different bands, high-frequency (HF) and low-frequency (LF) power associated with a parasympathetic and sympathetic response. In this meta-analysis, we provide a brief introduction to CST, analyze three primary studies, and summarize the therapeutic benefits and pitfalls of this alternative treatment on the ANS. A significant negative HF standardized mean difference after CST was observed; standardized mean difference = -0.46; 95% CI (-0.79,-0.14). No significant effect on LF power was observed. We conclude that CST does provide a moderate short-term increase in parasympathetic activity. These findings suggest that CST may be used to treat patients with an overactive sympathetic state. Further studies should be conducted for comparison against a control group to eliminate the possibility of a placebo effect and to elucidate long-term effects.

Right vagotomy alters heart rate variability temporarily and increases total choline levels in rats

Abstract Objectives The variability in the time intervals between heartbeats, known as heart rate variability (HRV), serves as a reflection of the intricate interplay between the sympathetic and parasympathetic neural systems. While the potential asymmetric effects of the left and right branches of the vagus nerve remain uncertain, this study aims to investigate the impact of unilateral, bilateral, and atropine interventions on HRV parameters and choline levels within cardiac tissue. Methods 40 male adult Wistar albino rats were randomly assigned to the five groups (each n=8): sham-operated, atropine, right vagotomy, left vagotomy, and bilateral vagotomy. Heart rate variability (HRV) analyses were conducted, and the levels of total choline/acetylcholine in heart tissues were quantified. Statistical analyses were performed to assess the results. Results The bilateral vagotomy and atropine groups exhibited higher heart rates and high frequency power (HF), along with reduced low frequency power (LF). Total power (TP) remained relatively unchanged. In the bilateral vagotomy group, DFAα1 was significantly elevated while DFAα2 was reduced significantly. SD1 and SampEn were significantly lower in both the bilateral vagotomy and atropine groups. Notably, the right vagotomy group displayed significant changes primarily in the 15th minute, particularly in time-domain parameters, HF, TP, and SD1, with a significant increase observed in total choline levels. Conclusions Our results revealed that asymmetrical vagal innervation induces distinct effects on heart rate variability parameters and total choline/acetylcholine levels in heart tissues. Our findings suggest that compensatory hemodynamic recovery, possibly driven by contralateral vagal overactivity, may contribute to these observed results.

What is the Vagal-Adrenal Axis?

Some recent publications have used the term "vagal-adrenal axis" to account for mechanisms involved in the regulation of inflammation by electroacupuncture. This concept proposes that efferent parasympathetic nerve fibers in the vagus directly innervate the adrenal glands to influence catecholamine secretion. Here, we discuss evidence for anatomical and functional links between the vagi and adrenal glands that may be relevant in the context of inflammation and its neural control by factors, including acupuncture. First, we find that evidence for any direct vagal parasympathetic efferent innervation of the adrenal glands is weak and likely artifactual. Second, we find good evidence that vagal afferent fibers directly innervate the adrenal gland, although their function is uncertain. Third, we highlight a wealth of evidence for indirect pathways, whereby vagal afferent signals act via the central nervous system to modify adrenal-dependent anti-inflammatory responses. Vagal afferents, not efferents, are thus the likely key to these phenomena.

Holmes-Adie syndrome associated with BNT162b2 mRNA COVID-19 vaccine

Adie’s tonic pupil is a neuro-ophthalmologic disorder with dilation and poor light response. When deep tendon reflex loss accompanies the tonic pupil, it is called Adie syndrome or Holmes-Adie syndrome. The pupillary symptoms result from damage to the ciliary ganglion and the post-ganglionic parasympathetic nerves. Corona virus 2, which causes severe acute respiratory syndrome, has been named corona virus 19 (COVID-19) by the World Health Organization. It has been reported that the coronavirus infection has neurological manifestations including pupillary involvement.[1,2] The cases of two patients with Adie’s tonic pupil 10–15 days after they had BNT16b2b mRNA (Pfizer, BioNTech, Germany) vaccine were reported. One of them had Holmes-Adie syndrome.[3,4] In this case report, we aim to describe two patients who are a married couple with possible coronavirus BNT16b2b mRNA vaccine (Pfizer, BioNTech, Germany)-related Holmes-Adie syndrome.

The Impacts of The Earthquake on The Cardiovascular System

Introduction: Various physiological and psychological effects of earthquakes can be seen on the human body, even without a direct physical impact from the earthquake. Both the experience of the earthquake process and the earthquake-related subsequent life changes cause stress through the activation of the sympathetic and parasympathetic systems in the body. This stress can affect various physiological processes, including the cardiovascular system. In this review, the effect of earthquakes on the cardiovascular system was aimed to be discussed in line with the available evidence. Discussion: There are studies showing that natural events such as earthquakes increase the incidence of adverse cardiac events, such as myocardial infarction, heart failure, hypertension, and sudden cardiac death, or cause existing cardiac diseases to worsen during these periods. However, there are also some evidences with conflicting results. Therefore, the effect of earthquakes on cardiovascular diseases has not been clearly demonstrated yet. Conclusion: Even survivors of earthquakes without physical injury are exposed to stress secondary to both internal and external factors. Studies indicate that individuals who are involved in the earthquake process may have adverse effects on cardiovascular health in the short and long term. Therefore, it is important to take necessary precautions and create appropriate conditions, especially in people with cardiovascular disease.

High-rise window views: Evaluating the physiological and psychological impacts of green, blue, and built environments

A growing body of research indicates that visual exposure to nature can enhance mental well-being. However, the impact of such contact through high-rise building windows remains unclear. To address this significant knowledge gap, we utilized aerial drone-captured videos taken from a height of 90 m to present comprehensive visual panoramas encompassing various scenes observed through high-rise building windows. These scenes included three key elements: built structures, greenery, and water bodies. Forty-five participants were randomly assigned to view six conditions in a laboratory setting. Physio-psychological responses to each condition were measured using a portable electroencephalogram device, which continuously recorded brainwaves, and ErgoLAB, which monitored heart rate variability. Additionally, participants completed anxiety level assessments and subjective feelings questionnaires. Our findings revealed that visual contact with all window views produced significantly greater positive effects compared to viewing control or built environments. Among the window views, those featuring green space with water or green space alone elicited the most beneficial outcomes, including increased alpha brainwave activity, enhanced parasympathetic nervous system activation, heightened levels of relaxation and comfort, and lower anxiety levels. The study's findings indicate that high-rise building residents can benefit from 4-min exposure to greenery, either with water or alone, through window views, in promoting mental health. The study emphasizes the importance of considering window views in urban high-rise planning and design to enhance the mental health and well-being of city dwellers.

Effect of acetylcholinesterase inhibition on immune cells in the murine intestinal mucosa

The gastrointestinal tract (GI) is the largest immune organ whose function is controlled by a complex network of neurons from the enteric nervous system (ENS) as well as the sympathetic and parasympathetic system. Evolving evidence indicates that cross-communication between gut-innervating neurons and immune cells regulates many essential physiological functions including protection against mucosal infections. We previously demonstrated that following paraoxon treatment, 70 % of the mice were able to survive an oral infection with S. typhimurium, a virulent strain of Salmonella enterica serovar Typhimurium. The present study aims to investigate the effect that rivastigmine, a reversible AChE inhibitor used for the treatment of neurodegenerative diseases, has on the murine immune defenses of the intestinal mucosa. Our findings show that, similar to what is observed with paraoxon, administration of rivastigmine promoted the release of secretory granules from goblet and Paneth cells, resulting in increased mucin layer. Surprisingly, however, and unlike paraoxon, rivastigmine treatment did not affect overall mortality of infected mice. In order to investigate the mechanistic basis for the differential effects observed between paraoxon and rivastigmine, we used multi-color flowcytometric analysis to characterize the immune cell landscape in the intraepithelial (IE) and lamina propria (LP) compartments of intestinal mucosa. Our data indicate that treatment with paraoxon, but not rivastigmine, led to an increase of resident CD3+CD8+ T lymphocytes in the ileal mucosa (epithelium and lamina propria) and CD11b− CD11c+ dendritic cells in the LP. Our findings indicate the requirement for persistent cholinergic pathway engagement to effect a change in the cellular landscape of the mucosal tissue that is necessary for protection against lethal bacterial infections. Moreover, optimal protection requires a collaboration between innate and adaptive mucosal immune responses in the intestine.

Importance of neuro-urological care in patients with spinal cord injuries/diseases

Integrity, control and regulation of the urinary tract are subject to a complex neuronal regulation, in which portions of the sympathetic, parasympathetic and somatic nervous system are involved. The spinal cord plays a central role in regulation and serves as a transmitter for the motor and sensory pathways. Bladder dysfunction followed by renal dysfunction was the most frequent cause of death in patients with spinal cord injuries/diseases (paraplegia) as recently as half a decade ago. Thanks mainly to diagnostic and therapeutic advances made in neuro-urology, urological problems are no longer life-limiting. A vital role is played not only by the actual function of the urinary tract but also by the complex interactions in patients living with paraplegia. Issues such undertreated hyperactivity of the detrusor muscle with autonomous dysregulation, incontinence with secondary skin changes, or insufficient hand function to perform intermittent catheterisation must be evaluated in an interdisciplinary approach. Spinal cord injury/disease implies numerous functional disorders and secondary impairments of the organism. In addition to bladder function, sexual dysfunction also plays a crucial role. Especially in younger patients who sustain paraplegia before or during the family planning phase, this disruption and limitation is an essential reason for reduced quality of life. Neurogenic intestinal function plays an additional crucial role with regard to quality of life and management of everyday life. In recent years, the range of neuro-urological topics has expanded significantly. The focus of our work shifted from being merely on the urinary tract and urodynamics. In particular, the diagnostic investigation and treatment of neurogenic intestinal dysfunction is increasingly in the hands of neuro-urologists. The complex presentation of paraplegia involves an interaction of bladder, intestinal and sexual dysfunction in a way that these influence one another. Therefore, the sustained care and re-integration of these patients essentially includes lifelong and regular neuro-urological care in a paraplegia centre. Last but not least, it is exactly these neuro-urological topics such as urinary tract infections, urinary and intestinal incontinence and faecal impaction, which most commonly lead to re-hospitalisation.

Test-retest reliability and validity of vagally-mediated heart rate variability to monitor internal training load in older adults: a within-subjects (repeated-measures) randomized study

BackgroundVagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL.MethodsA within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., “easy”, “challenging”, and “excessive”) in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC3,1), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA.ResultsFourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m−2) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity.ConclusionOnly mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.

Upregulation of Amy1 in the salivary glands of mice exposed to a lunar gravity environment using the multiple artificial gravity research system.

Introduction: Space is a unique environment characterized by isolation from community life and exposure to circadian misalignment, microgravity, and space radiation. These multiple differences from those experienced on the earth may cause systemic and local tissue stress. Autonomic nerves, including sympathetic and parasympathetic nerves, regulate functions in multiple organs. Saliva is secreted from the salivary gland, which is regulated by autonomic nerves, and plays several important roles in the oral cavity and digestive processes. The balance of the autonomic nervous system in the seromucous glands, such as the submandibular glands, precisely controls serous and mucous saliva. Psychological stress, radiation damage, and other triggers can cause an imbalance in salivary secretion systems. A previous study reported that amylase is a stress marker in behavioral medicine and space flight crews; however, the detailed mechanisms underlying amylase regulation in the space environment are still unknown. Methods: In this study, we aimed to elucidate how lunar gravity (1/6g) changes mRNA expression patterns in the salivary gland. Using a multiple artificial gravity research system during space flight in the International Space Station, we studied the effects of two different gravitational levels, lunar and Earth gravity, on the submandibular glands of mice. All mice survived, returned to Earth from space, and their submandibular glands were collected 2days after landing. Results: We found that lunar gravity induced the expression of the salivary amylase gene Amy1; however, no increase in Aqp5 and Ano1, which regulate water secretion, was observed. In addition, genes involved in the exocrine system, such as vesicle-associated membrane protein 8 (Vamp8) and small G proteins, including Rap1 and Rab families, were upregulated under lunar gravity. Conclusion: These results imply that lunar gravity upregulates salivary amylase secretion via Rap/Rab signaling and exocytosis via Vamp8. Our study highlights Amy1 as a potential candidate marker for stress regulation in salivary glands in the lunar gravity environment.