Autonomic Function Research Articles

Improved heart rate variability in postmenopausal women following short-term combined exercise training

Imbalances in cardiac autonomic nervous systems are associated with cardiovascular risk factors and poor cardiac outcomes. Heart rate variability (HRV) is a practical and reproducible measure of cardiac autonomic nervous system function. Exercise training promotes positive adjustments in HRV. However, previous studies have reported mixed results. Therefore, this study aimed to investigate the effects of short-term combined exercise training on heart rate variability in post-menopausal women. Thirty-four women aged 50-80 years, at least 12 months post-menopause, were divided into a control (CON) group and an exercise (EX) training group. The participants in the exercise group underwent a 2-week of combined exercise program consisting of aerobic, strength, flexibility, and balance exercises. HRV was recorded using an Actiheart device, before and after the final exercise intervention in a sitting position. The significant main effects of time and group were found in the parameter of SDNN (p time = 0.039; p group = 0.026). Post-hoc analysis showed a borderline increase in SDNN in the EX group (POST: 48.79 ± 17.88 VS 44.54 ± 17.39, p = 0.055). No significant change was observed in the CON group (POST: 35.55 ± 13.51 VS 33.17 ± 8.74, p = 0.288). Statistical analysis of other HRV components revealed no significant results (all P > 0.05). In conclusion, a 2-week of combined exercise training program, including aerobic, resistance, balance, and flexibility exercises improves global cardiac autonomic function in post-menopausal women. Keywords: combined exercise training, heart rate variability, blood pressure, menopause, and women

Multi-Objective Optimization of Orchestra Scheduler for Traffic-Aware Networks

The Internet of Things (IoT) presents immense opportunities for driving Industry 4.0 forward. However, in scenarios involving networked control automation, ensuring high reliability and predictable latency is vital for timely responses. To meet these demands, the contemporary wireless protocol time-slotted channel hopping (TSCH), also referred to as IEEE 802.15.4-2015, relies on precise transmission schedules to prevent collisions and achieve consistent end-to-end traffic flow. In the realm of diverse IoT applications, this study introduces a new traffic-aware autonomous multi-objective scheduling function called OPTIMAOrchestra. This function integrates slotframe and channel management, adapts to varying network sizes, supports mobility, and reduces collision risks. The effectiveness of two versions of OPTIMAOrchestra is extensively evaluated through multi-run experiments, each spanning up to 3600 s. It involves networks ranging from small-scale setups to large-scale deployments with 111 nodes. Homogeneous and heterogeneous network topologies are considered in static and mobile environments, where the nodes within a network send packets to the server with the same and different application packet intervals. The results demonstrate that OPTIMAOrchestra_ch4 achieves a current consumption of 0.72 mA while maintaining 100% reliability and 0.86 mA with a 100% packet delivery ratio in static networks. Both proposed Orchestra variants in mobile networks achieve 100% reliability, with current consumption recorded at 6.36 mA. Minimum latencies of 0.073 and 0.02 s are observed in static and mobile environments, respectively. On average, a collision rate of 5% is recorded for TSCH and RPL communication, with a minimum of 0% collision rate observed in the TSCH broadcast in mobile networks. Overall, the proposed OPTIMAOrchestra scheduler outperforms existing schedulers regarding network efficiency, time, and usability, significantly improving reliability while maintaining a balanced latency–energy trade-off.

Heart Rate Variability in Elite Team Sports: A Systematic Review

Background: Heart rate variability (HRV) is recognized as a crucial indicator of autonomic nervous system function and is valuable in sports science for monitoring athlete health and performance. This systematic review investigates the use of HRV in elite team sports to monitor training adaptations, athlete status, and overall health. The purpose is to consolidate recent findings and provide a comprehensive understanding of HRV's application in elite team sports. Methods: The review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42023431208). A comprehensive search was performed across PubMed, Science Direct, Web of Science, and Google Scholar, covering studies from January 2013 to November 2023. Studies included involved elite team-sport athletes, with HRV measured immediately after waking. Exclusion criteria were underage athletes, injured athletes, and studies using HRV for different purposes. The review process involved screening titles, abstracts, and full texts, with a final inclusion of 12 studies. Results: Out of 277 identified articles, 12 studies met the inclusion criteria, involving sports such as water polo, rugby, football, basketball, volleyball, handball, futsal, hockey, and rowing. The studies highlighted HRV as a valuable tool for tracking training load adaptations, monitoring athlete readiness, recovery, and mental stress. Daily HRV measurements were commonly used, showing effectiveness in detecting overtraining and ensuring adequate recovery. Various HRV parameters and recording methods were discussed, emphasizing the need for individualized assessment. RMSSD and LnRMSSD were the most commonly used parameters, with variations in recording times and positions. Conclusions: HRV is an effective non-invasive marker for optimizing training regimens and improving athlete health, making it a significant tool in sports medicine. This review provides actionable insights for integrating HRV monitoring into daily training practices, ultimately enhancing athletic performance and preventing overtraining. Standardized protocols for HRV measurement are recommended to ensure consistency and reliability in data collection and interpretation. The findings highlight the need for further research to refine HRV applications and establish best practices in elite team sports

Pupil to limbus diameter ratio as an emerging autonomic function test and its correlation with anthropometric parameters in different phases of menstrual cycle

The menstrual cycle is a physiological change in normal females, indicating the proper functioning of both endocrine and reproductive health. The pupil to limbus diameter (PLD) ratio is defined as the ratio of pupil diameter measured at an axial plane to the limbus diameter measured at the same or a parallel axial plane. Alterations in estrogen and progesterone levels may influence cardiac autonomic functions. This study aimed to correlate the PLD ratio with anthropometric parameters, such as body mass index (BMI) and waist circumference (WC), during different phases of the menstrual cycle among medical students.Methods: A cross-sectional study was conducted among first- and second-year female MBBS students aged 17 to 22 years. Anthropometric parameters, including height, weight, BMI, and WC, were measured for all participants. Eye photographs were taken during the follicular and luteal phases of the menstrual cycle, and the diameters were measured manually using the two-box method. The PLD ratios for both eyes showed a significant positive correlation with BMI (right eye: r = 0.682, p < 0.000; left eye: r = 0.430, p < 0.000) and waist circumference (right eye: r = 0.456, p < 0.000; left eye: r = 0.315, p < 0.001). The PLD ratio can serve as a simple, non-invasive, and cost-effective autonomic function test.

High‐Performance Dynamic Photo‐Responsive Polymers With Superior Closed‐Loop Recyclability

AbstractChemical recycling to monomer (CRM) provides an ideal solution for reducing plastic waste and achieving a circular polymer economy. Cyclopentene (CP) and its derivatives are representative molecules that exemplify an efficient CRM process under mild conditions. However, most CP‐based polymers possess limited thermal and mechanical properties, constraining their potential applications. Herein, new CP‐based polymers with superior thermo‐mechanical properties and autonomous functions are proposed by integrating anthracene as a dynamic functional motif. Anthracenes not only serve as supramolecular cross‐linkages through strong π–π interactions but also form stronger chemical ones under UVA light irradiation, enhancing thermo‐mechanical properties. Furthermore, damage‐reporting, self‐healing, and local shape reprogramming capabilities are accomplished by utilizing the reversible nature of photodimerized anthracene. A mild and orthogonal depolymerization condition for the CP‐based polymers facilitates efficient monomer recovery even from mixed plastic wastes. This work presents a simple yet effective strategy to expand the usability of chemically recyclable polymers and contribute to a closed‐loop polymer economy.

Impact of yoga-based interventions on cognitive and autonomic functions in major depressive disorder population.

Cognitive and autonomic dysfunction is increasingly being recognized as an important clinical dimension in major depressive disorder. The aim of this study is to evaluate the effect of a combined approach of yoga and diet intervention on cognitive and autonomic functions in individuals with major depressive disorders. This experimental observational study was conducted at RUHS College of Medical Sciences and Associated Hospitals, Jaipur, on the major depressive disorder population of either sex cognitive function (mini-mental score, Montreal cognitive protocol A and B, P300 latency and amplitude) and autonomic function parameters (frequency and time domain) were recorded at baseline and after three months of a combined approach of yoga and diet intervention. This study compared cognitive and autonomic function parameters at baseline and after three months of yoga and diet intervention in a major depressive disorder population. Analysis revealed a significant decrease in body mass index (<0.05), systolic blood pressure (<0.001), Hamilton rating scale for depression (<0.001), P300 latency (<0.001), standard deviation of NN interval (SDNN) (<0.001), and mean heart rate (<0.001), whereas there was a significant increase in mini-mental score (<0.001), Montreal cognitive protocol A and B (<0.001), high frequency (HF) (<0.001), root mean square standard deviation (RMSSD) (<0.001), and PNN50 (<0.001) after a combined approach of yoga and diet in the study group as compared to control group participants. Yoga and diet combined may be an effective adjunct therapy for improving brain health and mental performance, lowering the risk of depression by affecting the neurotransmitter system and raising vagal tone which contributes to learning and memory.

Effectiveness of patisiran after switching from tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real-world outcomes of patients with ATTRv-PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch. This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv-PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12-month patisiran treatment period. Among the 24 patients with ATTRv-PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy. Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv-PN.

Abstract 66: Early-Life Sodium Restriction Programs Salt-Sensitivity of Autonomics and Blood Pressure in Adult C57BL/6J Mice

Extremely premature birth is a risk factor for sodium (Na) depletion due to renal immaturity and urine Na losses. We have proposed that Na depletion in preterm infants mechanistically contributes to their increased risk for cardiovascular and metabolic disease observed in adulthood, potentially due to changes during hypothalamic development. In humans, the hypothalamus matures between 20-25 weeks of gestation; in mice, this developmental window occurs between postnatal day (PD) 21 and PD42. Previously, we demonstrated in mice that dietary Na restriction from PD21 to PD42 induced long-lasting increases in energy expenditure via exaggerated autonomic activity. Therefore, we hypothesized that restricting dietary Na from PD21 to PD42 would similarly induce programmed changes in cardiovascular control via changes in autonomic and neurohypophyseal functions. Male C57BL/6J mice were provided a customized low (0.04%, n=7) or supplemented (0.30%, n=8) Na version of the soy protein-free Teklad 2920x diet from PD21 to PD42, after which they were returned to the standard (0.15% Na) 2920x diet. Radiotelemetric blood pressure (BP) transducers were implanted at 7-8 weeks of age. At 10 weeks of age, no differences in BP or heart rate (HR) were noted between groups. All animals were switched to a high (1%) Na diet at 12 weeks of age. At 16 weeks of age, systolic BP was not altered in the 0.30% Na group but significantly increased in the 0.04% Na group compared to the week 10 baseline (24h avg: +6±2 mmHg, p&lt;0.05). Ganglionic block with chlorisondamine or β-adrenergic block with propranolol reduced heart rate (HR) to a greater extent (each p&lt;0.05) in the 0.04% group. Conversely, muscarinic block with atropine resulted in a smaller increase in HR in this group (p&lt;0.05). Urine elimination rates of aldosterone (0.30%: 1.96±0.44 vs 0.04%: 2.92±0.064 ng/d) and copeptin (0.30%: 0.16±0.03 vs. 0.04%: 0.14±0.02 ng/d) were similar between groups. Finally, at 18 weeks of age, all mice received the angiotensin AT 1 R antagonist losartan in drinking water. This caused a greater BP reduction in the 0.04% group at 20 weeks (24h avg: -12±2 vs -19±2 mmHg, p&lt;0.05). Together, these data indicate that dietary Na restriction during hypothalamic development programs increased salt sensitivity of BP via a mechanism involving AT 1 R and characterized by increased sympathetic yet decreased parasympathetic activity.

Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy: A First-in-Human Randomized Pilot Study. Neuromodulation in Cancer Study (NCAN).

Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD. CTRCD is preceded by increased activation of the sympathetic nervous system and abnormal left ventricular mechanical deformation as measured by abnormal global longitudinal strain (GLS). Low-level tragus stimulation (LLTS) is a new, safe, noninvasive technique that offers great potential to reduce increased sympathetic activation and improve GLS. Here, we describe a study method to examine the effects of LLTS on autonomic balance and cardiac function in breast cancer or lymphoma patients treated with anthracyclines. A first-in-human pilot, randomized, double-blind feasibility study will evaluate 104 patients (age >50y) with breast cancer or lymphoma who receive anthracyclines with one additional CTRCD risk factor. Patients undergo 2 weeks of LLTS daily (1 h/d). Autonomic balance will be measured using heart rate variability metrics. Strain imaging using GLS will be performed pre and post-LLTS. Endothelial inflammation and oxidative stress measures will be performed using in vitro assays at baseline and after 2 weeks. We hypothesize that LLTS stabilizes sympathovagal imbalance and improves cardiac performance in anthracycline-treated patients with breast cancer or lymphoma.

Postural Orthostatic Tachycardia Syndrome (POTS) as a Cause of Dizziness - Expanding the Etiological Spectrum.

Dizziness is a frequent complaint encountered in neurology clinics. Dizziness can be spontaneous or triggered, which includes orthostatic dizziness. Orthostatic dizziness can be acute (reflex/vasovagal syncope), chronic (orthostatic hypotension (OH), or postural orthostatic tachycardia syndrome (POTS). Since dizziness has numerous causes, these patients undergo extensive investigations before a diagnosis is made. Here, we describe five patients who presented with dizziness and were diagnosed to have POTS on evaluation. We conducted a retrospective study of patients who presented to the Department of Neurology from August 2020 to November 2021 with the complaint of dizziness and were diagnosed with POTS. The clinical history, neurological examination, treatment response, routine blood investigations, magnetic resonance imaging (MRI) brain, and autonomic function tests (AFTs) of the patients were reviewed from patients' clinical records. Patients with dizziness and with diagnosis other than POTS were excluded from the study. Among the five patients, males were predominant with a male to female ratio of 3:2. All the patients were in their early fourth decade with a mean age of 35.4 years. The presenting symptom was dizziness, and the key associated symptoms were anxiety and headache. Due to the orthostatic nature of symptoms and absence of orthostatic fall in blood pressure (BP), a detailed AFT was carried out, leading to the diagnosis of POTS. Patients were assessed at 3-6 months after treatment and there was a moderate response in one and no response in the remaining four patients. POTS should be considered a possible etiology when patients present with orthostatic dizziness in the absence of orthostatic fall in BP. Anxiety and headache may be associated with this type of dizziness.

Abstract 47: Deletion of PRR in AgRP Neurons of the Arcuate Nucleus Contributes to the Development of DOCA-Salt Hypertension

Agouti-related protein (AgRP) neurons, a key neuronal population within the arcuate nucleus (ARC), are known for their pivotal roles in regulating energy- and glucose homeostasis. However, their involvement in cardiovascular regulation remains poorly understood. Using RNAscope in situ hybridization, we found that 95.4% of the ARC AgRP neurons express the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system that is crucial for blood pressure (BP) regulation. We therefore hypothesized that PRR signaling in the ARC AgRP neurons plays a regulatory role in the development of hypertension. To test this hypothesis, we selectively deleted PRR in ARC AgRP neurons by crossing AgRP-IRES-Cre mice with PRR fl/fl mice. Using RNAscope, as expected, AgRP Cre+ PRR fl/y mice displayed a significantly lower PRR mRNA in the ARC AgRP neurons than WT mice (76.3 ± 6.1 vs. 127.7 ± 2.9 AFU, p &lt; 0.05), indicating efficient ablation of PRR in ARC AgRP neurons. To examine the impact of PRR deletion in the ARC AgRP neurons on BP, the AgRP Cre+ PRR fl/y and control mice were implanted with telemetry probes to monitor BP continuously. After baseline recording, mice received DOCA-salt treatment (50 mg DOCA + saline as drinking water) for two weeks. BP variability and standard time domain heart rate variability (HRV) parameters, including overall HRV (SDNN) and short-term HRV (rMSSD), were analyzed from beat-to-beat intervals (n = 2-7 mice/group). At baseline, there was no difference between the two groups in BP, BP variability, and HRV. Two weeks of DOCA-salt induced a significantly higher BP in AgRP Cre+ PRR fl/y mice than the controls (156.2 ± 6 vs. 119.4 ± 3 mmHg, p &lt; 0.05), while BP variability did not differ between the two groups. Noteworthy, AgRP Cre+ PRR fl/y mice exhibited lower SDNN than the controls (13.3 ± 4 vs. 19.4 ± 4 ms), indicating increased sympathetic and/or reduced parasympathetic nervous activity. This lower SDNN suggests impaired cardiac autonomic function and adaptability to physiological demands in AgRP Cre+ PRR fl/y mice. Concurrently, AgRP Cre+ PRR fl/y mice showed a lower rMSSD (4.7 ± 0.5 vs. 10.8 ± 3.5 ms), implying reduced parasympathetic activity. In conclusion, deletion of PRR in the ARC AgRP neurons results in compromised cardiac autonomic function associated with the development of hypertension. Our findings underscore a novel protective role of PRR signaling in the ARC AgRP neurons in BP regulation.

A Study of Cardiac Autonomic Neuropathy in Patient with Diabetes Mellitus.

Atherosclerotic coronary artery disease, diabetic cardiomyopathy, and cardiac autonomic neuropathy (CAN) are the three categories into which the cardiovascular consequences of diabetes can be grouped. After all other potential causes have been ruled out, cardiovascular autonomic neuropathy-often referred to as CAN in the literature-is defined as the impairment of autonomic regulation of the cardiovascular system. Finding people with CAN is crucial because, if detected early enough, comprehensive therapies focusing on lifestyle, glucose management, and cardiovascular risk factors can reverse the course of CAN and delay its progression. In order to better understand CAN in individuals with diabetes mellitus (DM) and how it relates to risk factors, the current study was conducted. Sixty consecutive diabetic patients were selected to be included in our study, diagnosed as per the American Diabetes Association (ADA) and the European Association for the Study of Diabetes. The presence of CAN was assessed with the help of Ewing's Battery, composed of five bedside tests. Out of 60 patients, a total of 53 patients (88.3%) with DM had CAN. Of these, 38.3% showed early CAN, 38.3% showed definite CAN, and 7% showed severe CAN. The abnormal E:I (exhalation/inhalation) ratio, noticed in 75% of patients, was the most frequently observed abnormal autonomic function test that tests the parasympathetic nervous system. The ECG's QTc interval prolongation provides good specificity for diagnosing CAN as well as assessing its severity, but the majority of cases showed low sensitivity. Since CAN has a significant association with mortality, every patient diagnosed with DM should be evaluated for CAN at the time of diagnosis as well as on an annual basis thereafter, as recommended by the ADA. Optimal glycemic management and lifestyle modification at the initial stages of diabetes may prevent CAN-related complications.

Intra- and Inter-Rater Reliability of Linear and Nonlinear Measures of Short-Term Heart Rate Variability Following Combat-Related Traumatic Injury.

Heart rate variability (HRV) is a marker of autonomic function. However, the reliability of short-term HRV measurement in individuals with combat-related traumatic injury (CRTI) remains undetermined. An intra- and inter-rater reliability study was conducted using a subsample (n = 35) of British servicemen with CRTI enrolled in the ongoing ADVANCE study. A five-minute epoch of single-lead electrocardiogram data collected during spontaneous breathing was used to measure HRV. HRV analyses were independently performed by two examiners using Kubios. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC), and coefficient of variance were calculated for linear [root mean square of successive difference (RMSSD), standard deviation of NN interval, low-frequency, high-frequency, total power] and nonlinear (SD1-2, acceleration and deceleration capacities, sample entropy) measures. Bland-Altman %plots were used to assess bias in intra- and inter-rater HRV data. The mean age of participants was 39.3 ± 6.3 years. An excellent ICC score of 0.9998 (95% CI 0.9997, 0.9999) was observed for intra-rater analyses of RMSSD, and similar excellent ICC scores were seen for all other HRV measures. The inter-rater reliability analyses produced an excellent ICC score (range 0.97-1.00). Comparatively, frequency-domain measures produced higher MDC% and SEM% scores than time-domain and nonlinear measures in both inter- and intra-rater analyses. The Bland-Altman plots revealed relatively higher bias for frequency-domain and nonlinear measures than time-domain measures. ECG-related short-term HRV measures were reliable in injured servicemen under spontaneous breathing. However, the reliability appeared better with the time-domain measure than frequency-domain and nonlinear measures in this sample.

Effect of Cereal Consumption (Frugra®) on Autonomic Nervous System Function in Healthcare Workers Who Skip Breakfast.

In this study, we aimed to clarify the effects of breakfast intervention on autonomic nerve function in healthcare workers who skip breakfast. This cross-sectional, interventional study was conducted between January 2020 and December 2021. All participants were full-time healthcare workers who completed a self-administered questionnaire on fatigue and subjective symptoms and underwent noninvasive autonomic nerve function tests. "Skippers" were defined as individuals who ate breakfast <4 times per week, and "eaters" were those who ate breakfast >4 times per week. We introduced a cereal, Frugra (Calbee, Inc.), to skippers who opted for the breakfast intervention. Subsequently, they completed the questionnaire again and repeated the autonomic nerve function tests. Among 196 participants (age [mean±SD]: 29.8±7.8 y; 177 women and 19 men), 120 were categorized as skippers and 76 as eaters. In the skipper group, more participants were nurses, lived alone, and worked the night shift than in the eater group. The Chalder Fatigue Scale (CFS) score in the skipper group was higher than that in the eater group, although not significantly. Regarding autonomic nerve function, no significant differences were observed between the groups. In 50 skippers who opted for the breakfast intervention, the CFS score significantly decreased after 4 wk. Log low frequency and log coefficient of component variance total power significantly increased, whereas log high frequency increased, but not significantly, after the intervention. In conclusion, for healthcare workers who were breakfast skippers, the consumption of breakfast cereal reduced their fatigue level and improved their autonomic nervous system activity.

Autonomous UAV navigation using deep learning-based computer vision frameworks: A systematic literature review

The increasing use of unmanned aerial vehicles (UAVs) in both military and civilian applications, such as infrastructure inspection, package delivery, and recreational activities, underscores the importance of enhancing their autonomous functionalities. Artificial intelligence (AI), particularly deep learning-based computer vision (DL-based CV), plays a crucial role in this enhancement. This paper aims to provide a systematic literature review (SLR) of Scopus-indexed research studies published from 2019 to 2024, focusing on DL-based CV approaches for autonomous UAV applications. By analyzing 173 studies, we categorize the research into four domains: sensing and inspection, landing, surveillance and tracking, and search and rescue. Our review reveals a significant increase in research utilizing computer vision for UAV applications, with over 39.5 % of studies employing the You Only Look Once (YOLO) framework. We discuss the key findings, including the dominant trends, challenges, and opportunities in the field, and highlight emerging technologies such as in-sensor computing. This review provides valuable insights into the current state and future directions of DL-based CV for autonomous UAVs, emphasizing its growing significance as legislative frameworks evolve to support these technologies.

Posttraumatic stress disorder increases thrombosis risk: Evidence from a biobank data set.

Depression and anxiety are linked to deep venous thrombosis (DVT) and posttraumatic disorder (PTSD) increases risk of venous thromboembolism in women. However, the mechanisms underlying this relationship remain unknown. We hypothesized that PTSD would associate with increased DVT risk, that neuroimmune mechanisms would mediate the PTSD-DVT link, and that these associations would be stronger in women. This cohort study included N = 106 427 participants from a large biobank. PTSD and DVT were defined using ICD-10 codes. A subset (N = 1520) underwent imaging, from which we assessed stress-associated neural activity (SNA). High-sensitivity C-reactive protein (hs-CRP) levels and heart rate variability (HRV) were used as indicators of systemic inflammation and autonomic activity, respectively. Linear, logistic, and Cox regressions and mediation analyses were used to test our hypotheses. Of 106 427 participants, 4192 (3.9%) developed DVT. PTSD associated with increased DVT risk (HR [95% CI]: 1.66 [1.34, 2.07], p < .001), and this finding remained significant after adjustment for age, sex, and traditional DVT risk factors. When analyzed separately by sex, PTSD was significantly associated with DVT risk in women but not men. Further, heightened SNA and lower HRV mediated the effect of PTSD on DVT risk. Results suggest that individuals with PTSD are at increased risk for DVT, and that risk is higher in women. This relationship was partially driven by alterations in stress-associated neural activity and autonomic function, suggesting potential targets for preventive therapies. Future studies are needed to investigate whether intervening on PTSD-DVT mechanisms has downstream beneficial effects on DVT, especially among women.

Virtual reality improves sleep quality and associated symptoms in patients with chronic insomnia

PurposeThe present study aimed to explore the effectiveness of virtual reality (VR) therapy on sleep quality and associated symptoms, such as depression and anxiety, cognitive decline and autonomic nervous dysfunction, in chronic insomnia patients. MethodsSixty-three chronic insomnia patients were randomly divided into VR group (n = 32) and control group (n = 20) based on a standard drug therapy. Patients were instructed to use VR at home once a day at evening for 6-week treatment. All participants received evaluations of subjective sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS), depression and anxiety symptoms measured with the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), cognitive function, and objective sleep structure and autonomic nerve function examination measured with the sleep respiration monitoring device at baseline and after 6-week treatment. The main objective of this study was sleep quality assessment as the primary outcome. ResultsAfter 6-week treatment, the decreases in PSQI score (−5.60 ± 2.37 vs −4.10 ± 1.80, P = 0.020) and ISI score (−8.81 ± 4.52 vs −6.35 ± 2.89, P = 0.038) of the VR group were significantly greater compared with the control group. The VR group showed more reduction in HAMD score (−9.96 ± 4.41 vs −7.50 ± 2.89, P = 0.035) and HAMA score (−8.96 ± 3.80 vs −6.80 ± 3.22, P = 0.046), and more increase in processing speed (0.54 ± 0.60 vs 0.00 ± 0.79, P = 0.011) than the control group. Moreover, the low-frequency coupling (−10.00 ± 17.40 vs. 8.25 ± 20.03, P = 0.001) was lowered and the high-frequency coupling (9.99 ± 17.40 vs. −8.24 ± 20.03, P = 0.001) was elevated in the VR group relative to the control group. ConclusionOur findings offered preliminary evidence that VR therapy enhanced sleep quality and also lessened depressive and anxious symptoms, and improved cognitive and autonomic functioning in patients with chronic insomnia.

Active Immunotherapy for the Prevention of Alzheimer's and Parkinson's Disease.

Neurodegenerative diseases (ND) give rise to significant declines in motor, autonomic, behavioral, and cognitive functions. Of these conditions, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent, impacting over 55 million people worldwide. Given the staggering financial toll on the global economy and their widespread manifestation, NDs represent a critical issue for healthcare systems worldwide. Current treatment options merely seek to provide symptomatic relief or slow the rate of functional decline and remain financially inaccessible to many patients. Indeed, no therapy has yet demonstrated the potential to halt the trajectory of NDs, let alone reverse them. It is now recognized that brain accumulation of pathological variants of AD- or PD-associated proteins (i.e., amyloid-β, Tau, α-synuclein) begins years to decades before the onset of clinical symptoms. Accordingly, there is an urgent need to pursue therapies that prevent the neurodegenerative processes associated with pathological protein aggregation long before a clinical diagnosis can be made. These therapies must be safe, convenient, and affordable to ensure broad coverage in at-risk populations. Based on the need to intervene long before clinical symptoms appear, in this review, we present a rationale for greater investment to support the development of active immunotherapy for the prevention of the two most common NDs based on their safety profile, ability to specifically target pathological proteins, as well as the significantly lower costs associated with manufacturing and distribution, which stands to expand accessibility to millions of people globally.

New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy.

Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40-86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, P = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing (R = 0.3; P = 0.02) and the small fiber neuropathy screening list (R = 0.3; P = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list (R = 0.3; P = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used.

The Ethics of Artificial Intelligence and Autonomous Systems: Review

Artificial intelligence (AI) and autonomous systems are rapidly advancing technologies that offer significant benefits but also pose new ethical challenges. This review aims to comprehensively analyze the key ethical issues related to AI and autonomy through an expanded discussion of relevant literature. The development of advanced AI and autonomous systems could enable unprecedented capabilities but also risks that are unprecedented in their nature and scale. Ensuring these technologies are developed and applied in an ethical manner will require addressing issues around safety, transparency, accountability, and the prioritization of human values. Researchers have proposed technical and philosophical approaches to building "friendly" or "beneficial" AI that avoids potential harms. However, many open questions remain about how to properly specify and validate ethical constraints for systems that may surpass human levels of intelligence. Autonomous systems like self-driving vehicles also introduce new ethical dilemmas around responsibility and decision- making in safety-critical situations. Standards are needed to help guide the design of autonomous functions to be transparent, predictable, and respectful of human dignity and diversity. Governments and international organizations have begun outlining policy recommendations for developing AI that is trustworthy and compatible with human rights, privacy, and democratic values.