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The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.

Chronic pain and dysautonomic symptoms deteriorate Systemic sclerosis (SSc) patients’ health-related quality of life with serious repercussions on social life and even on sleep. Heart Rate Variability (HRV) analysis can identify cardiovascular autonomic control impairment in subclinical condition. The aim of the present observational cross-sectional study was to assess the relationship between dysautonomic symptoms, quality of life status and cardiovascular autonomic profile. ECG and respiration were recorded at rest in 20 SSc patients. HRV analysis was performed using two different approaches: Linear spectral analysis and non-linear symbolic analysis. Pain was evaluated using the Numeric Rating Scale (NRS) and 3 questionnaires were administered for the evaluation of sleep quality (PSQI), mood tone (PHQ-9) and disability (HAQ). We found that sleep impairment was related to sympathetic predominance at rest measured as low-frequency/high-frequency ratio (LF/HF) (r = 0.48 and p = 0.033); poorer sleep quality was related to higher pain values (r = 0.48 and p = 0.034) and depressive symptoms (r = 0.82 and p < 0.01); higher pain scores were related to higher cardiovascular vagal modulation and higher disability indexes (r = 0.47 and p = 0.038 & r = 0.55 and p = 0.012, respectively). In conclusion dysautonomia and chronic pain showed a severe impact on sleep quality and disability with a consequent worsening of depressive symptom in our cohort of SSc patients.

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) impacts cardiopulmonary systems and exercise capacity serves as a marker of disease severity. While the six-minute walking test (6MWT) is widely used to assess physical performance, its limitations to assess the cardiopulmonary function remain unresolved in SSc-ILD patients. This study aimed to investigate cardiorespiratory adaptations during the 6MWT, hypothesizing that ventilatory inefficiency is related to exercise capacity in SSc-ILD patients. We recruited 23 female SSc-ILD patients and 13 age- and sex-matched healthy controls (HC). Inclusion criteria included SSc diagnosis (limited or diffuse cutaneous subset) with mild-to-moderate associated ILD. Participants performed 6MWT with combined cardiopulmonary exercise testing (CPET) assessment using a wearable metabolic system to measure ventilatory and gas exchange parameters, including minute ventilation (VE), respiratory frequency (Rf), tidal volume (Vt), and ventilatory equivalent for CO 2 (VE/VCO 2 ). SSc-ILD patients exhibited increased Rf and VE during the initial minutes of exercise and during recovery compared to HC. Despite similar walking distances, SSc-ILD demonstrated higher VE/VCO 2 during the 6MWT. VE/VCO 2 was negatively correlated with 6MWT distance (6MWD) in SSc-ILD but not in HC. Patients walking more than 474 m (median) presented higher VE/VCO 2 than HC with same 6MWD. SSc-ILD patients showed a general impaired ventilatory efficiency during 6MWT. The main result suggests that exercise capacity is not only linked to global cardiovascular adaptation but also to ventilatory performance. These findings underscore the importance of incorporating CPET metrics to cardiorespiratory assessments to improve clinical understanding and assessment of SSc-ILD.

Accurate bacterial identification is essential for determining the causative agent of an infection, thus facilitating appropriate treatment and management strategies in both human and animal health contexts. Some species in the Vibrio genus are recognized pathogens, associated with a variety of infections. However, identification of these bacteria is oftentimes controversial. Therefore, we aimed to evaluate different identification approaches in terms of their reliability in distinguishing Vibrio species. To achieve this, we selected a set of 40 Vibrio isolates previously recovered from water and floating plastic samples in a large bay environment and identified them employing MALDI-TOF mass spectrometry, and rrs and pyrH gene sequencing. A subset of isolates was also submitted to whole genome sequencing. Overall, MALDI-TOF was found to be a fast-screening methodology for identification, notably at genus-level. However, for better species discrimination, pyrH gene sequencing stood out as a more reliable tool in contrast to rrs gene sequencing and MALDI-TOF, as corroborated by whole genome sequencing analysis.

PurposeAging impairs the autonomic balance reducing the vagal and increasing the sympathetic components of heart rate variability (HRV) and this could be associated with a decline in physical capacity. Inspiratory muscle training (IMT) is a possible tool to attenuate this physical capacity decline in older women. The aim of this study was to investigate the influence of IMT in the older women on physical capacity and autonomic cardiac modulation at rest and post exercise.Methods20 female participants 60–72 years old were randomly allocated in two groups. One group underwent IMT set at 50% of maximum inspiratory pressure (MIP), every day for 4 weeks (IMT-group). The placebo group performed the same training procedure but with a minimal resistance (5% MIP; PLA-group). Every week, the IMT load was readjusted and the HRV evaluated at rest. The six-minute walk test (6MWT) was performed once pre and post IMT-intervention. The IMT-group and PLA-group performed the same test and intervention procedures.ResultsAfter a 5 weeks intervention, the MIP had significantly improved in the IMT-group but not in the PLA-group (p < 0.01; es = 1.17). The high frequency power of the HRV spectrum had already improved by the second week (p < 0.01; es = 1.13) and remained elevated until the last week of intervention (p < 0.01; es = 1.43). The same positive results were described in 6MWT distance (p = 0.04; es = 0.39) and the change (∆) of heart rate recovery (HRR) from 1 min (p = 0.02; es = 0.68).ConclusionIMT increases HRV, improves 6MWT distance and HRR.

Background: Post-menopausal women have impaired cardiorespiratory responses to exercise compared to young women. Exercise training may counterbalance impairments, but the time-dependent effects of exercise training remain unclear. The current study aims to investigate the effects of rowing training on maximal aerobic capacity and time-course cardiorespiratory adaptations in older women. Methods: Female participants (n = 23) were randomly allocated to the experimental group (EXP; n = 23; 66 ± 5 years old) enrolled in rowing exercise training and control group (CON; n = 10; 64 ± 4 years old). The cardiopulmonary exercise test (CET) was performed in a cycle ergometer pre- and post-interventions. Oxygen uptake (VO2), stroke volume (SV), cardiac output (CO), and HR were recorded during CET and analyzed at the peak of the exercise. HR was monitored during exercise recovery, and the index of HRR was calculated by ΔHRR (HRpeak—HR one-minute recovery). Every two weeks, Rowing Stepwise Exercise (RSE) in a rowing machine was performed to track specific adaptations to the exercise modality. HR was continuously recorded during RSE and corrected for the average power of each step (HR/watts). The rowing training protocol consisted of three weekly sessions of 30 min at an intensity corresponding to 60–80% of peak HR for ten weeks. Results: Rowing exercise training increased VO2, SV, and CO at the peak of the CET, and ΔHRR. Increased workload (W) and reduced HR response to a greater achieved workload (HR/W) during RSE were observed after six weeks of training. Conclusions: Rowing exercise training is a feasible method to improve cardiorespiratory performance, vagal reactivation and heart rate adjustments to exercise in older women.

Evidence from clinical practice suggests that PD patients with the Glucocerebrosidase gene mutation (GBA-PD) are characterized by more severe dysautonomic symptoms than patients with idiopathic PD (iPD). Therefore, an accurate assessment of cardiovascular autonomic control (CAC) is necessary to clarify the role of GBA mutations in the pathophysiology of PD. We evaluated the CAC at rest and during orthostatic challenge of 15 iPD, 15 GBA-PD and 15 healthy controls (CTR). ECG and respiration were recorded in supine position and during active standing. The analysis of Heart Rate Variability (HRV) was performed on ECG recordings using two different approaches, linear spectral analysis and non-linear symbolic analysis. GBA-PD patients presented more frequently an akinetic-rigid phenotype and cognitive disfunction than iPD patients. Both iPD and GBA-PD group were characterized by a lower spectral HRV than CTR group. At rest, the GBA-PD group was characterized by a lower parasympathetic modulation and a shift of the sympathovagal balance towards a sympathetic predominance compared to the CTR group. Moreover, the GBA-PD patients presented a lower HR increment and a lower or absent reduction of the vagal modulation in response to the active standing than iPD patients. Lastly, the cardiovascular autonomic dysfunction in PD patients was associated with longer disease duration, and with the occurrence of REM sleep behavior disorder and constipation. Our findings suggest a more severe impairment in the CAC of PD patients with GBA mutations. These results and further studies on the role of GBA mutations could allow a stratification based on cardiovascular risk in PD patients and the implementation of prevention programs.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

PurposeWe aimed to investigate the effect of inspiratory muscle training (IMT) on, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress, in older women.MethodsFourteen elderly women were assigned to perform IMT at 50% of maximal inspiratory pressure (MIP) (IMT group, n = 8) or placebo training at 5% MIP (Sham group, n = 6), in a counter-balanced order, using an inspiratory threshold device for 4 weeks. During the protocol, MIP was tested weekly once. In a second visit, blood pressure, heart rate, stroke volume, cardiac output, middle cerebral artery blood flow velocity (MCAv), and ventilation parameters were recorded continuously at rest and during orthostatic stress testing, which was conducted on a force plate to measure center-of-pressure (COP) oscillations (postural balance) and the electromyographic activity of the right medial gastrocnemius and tibialis anterior.ResultsIMT increased MIP from second to 4th week. The drops in MCAv, stroke volume, and cardiac output, as well as COP displacements during initial orthostasis decreased post-IMT.ConclusionIMT improves the interplay of the respiratory pump, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress in older women.

ObjectiveSystemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was to perform an add-on device-based non-invasive neuromodulatory treatment through transcutaneous auricular vagal nerve stimulation (tVNS) in patients with SSc, assessing its effects on pain as primary endpoint and on inflammation, cardiovascular autonomic control and HRQoL.MethodsThirty-two patients with SSc were enrolled based on reported pain assessed through Numeric Rating Scale (NRS). Twenty-one (90% with limited cutaneous SSc) completed a randomised, cross-over, patient-blind trial, in which interventional and active control were used in random order for 4 weeks, interspersed with 4 weeks washout. NRS, Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Item4 for pain interference, heart rate variability (HRV), serum cytokines and HRQoL questionnaires (Health Assessment Questionnaire, Patient Health Questionnaire-9, University of California, Los Angeles Gastrointestinal Tract, Pittsburgh Sleep Quality Index) were assessed at baseline, at T1 (after 1 month of tVNS or active control), at T2 (after washout) and at T3 (after 1 month of active control or tVNS). T-test for paired data and Wilcoxon signed-rank test for non-normally distributed parameters were performed to compare the effect of tVNS and active control.ResultsNRS pain was significantly reduced by tVNS and not by active control (Mean±SD: −27.7%±21.3% vs −7.7%±26.3%, p=0.002). Interleukin-6 was downregulated in tVNS versus active control (p=0.029). No significant differences were observed in tVNS versus active control for PROMIS-29 Item4, QoL scales and HRV with both spectral and symbolic analyses.ConclusiontVNS demonstrated to be a safe and non-invasive add-on tool to reduce pain in SSc.