Exercise Challenge Research Articles

Complex Exercises Improve Cognition in People With Parkinson's Disease and Freezing of Gait.

Evidence has suggested that cognitive decline may be a risk factor for freezing of gait (FOG) in Parkinson's disease (PD). Complex and challenging exercises have been suggested as potential rehabilitation strategies to decrease FOG severity and improve cognition; however, it is unknown whether improvement in cognition would explain decreased FOG severity following exercise. In this secondary analysis, we evaluated the effects of the adapted resistance training with instability (ARTI-complex and challenging exercises) compared with traditional motor rehabilitation (TMR-without challenging exercises) on cognitive function in people with FOG of PD. We also verified whether cognitive improvement explains the decrease in FOG previously published. Participants were randomized to either the experimental group (ARTI, n = 17) or the active control group (TMR, n = 15). Both training groups exercised 3 times a week for 12 weeks (80-90 minute each session). FOG severity (FOG ratio from inertial sensors during a 360° turning-in-place task), frontal lobe function (Frontal Assessment Battery [FAB]), global cognition (Montreal Cognitive Assessment [MoCA]), and attention and psychomotor speed (Digit Symbol Substitution Test [DSST]) were evaluated before and after interventions. Only the ARTI group improved FAB, MoCA, and DSST scores at posttraining. In addition, ARTI was more effective than TMR in improving FAB scores at posttraining. The changes in FAB scores explained the changes in FOG ratio following ARTI (R2 = .43, P < .01). This pilot study suggests that ARTI, a complex and challenging training, improves cognition in people with FOG of PD. Improvements in frontal lobe function with ARTI help explain decreased FOG severity.

Correction to “Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials”

Correction to “Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials”

Responsible Religious Freedom: Factual Scrutiny in Free Exercise Doctrine

Abstract The state of the Free Exercise Clause in U.S. constitutional law is uncertain. With an opportunity in Fulton v. Philadelphia to clarify the vitality of the current standard from Employment Division v. Smith, the United States Supreme Court has declined to do so. The lasting impact of Smith has been to move away from directly requiring government justifications for infringing free exercise. Instead, courts now use neutrality and general applicability as heuristics for government justification. Yet, relying solely on neutrality and general applicability to proxy for government justification when infringing religious exercise distracts courts from conducting a fact-based inquiry. This article demonstrates how more scrutiny of the legislative facts in free exercise doctrine may serve as a viable alternative to Smith’s flawed approach for evaluating government justifications. The author first shows empirically how more factual scrutiny—directly requiring the government to justify its actions with evidence—can benefit government and religious claimants and then discusses the normative advantages of a fact-intensive approach to constitutional scrutiny. During a moment of sharp division over religious freedom and other competing rights, factual scrutiny can be a powerful tool for handling free exercise challenges and promoting responsible religious freedom.

How influencers motivate inactive adolescents to be more physically active: a mixed methods study.

Regular physical activity offers numerous health benefits, particularly for adolescents. However, only 14% of school-aged children in Switzerland achieve the World Health Organization's recommendation of 60 min of moderate to vigorous physical activity per day. Changing health behaviors is a complex process in which understanding behavioral and communication patterns is crucial. Because adolescents spend substantial time on social media channels and obtain information from them, these are potential channels for accessing health-related content. This study explores the questions of which influencers and what content motivate adolescents to be more physically active and whether influencers can impact enjoyment and the intention to engage in physical activity. The study employed a convergent mixed methods approach, combining self-assessment questionnaires and semi-structured interviews. Ninety-three adolescents aged 14-20 years who exercised < 1 h per day participated. They followed one of the six participating influencers on Instagram. Over 6 weeks, the questionnaires collected quantitative data, measuring enjoyment, stages of change, and physical activity levels. Furthermore, semi-structured interviews were conducted with 23 adolescents and six influencers to gain in-depth insights. The quantitative findings indicate that adolescent followers enjoyed physical activity more after the social media intervention and at follow-up than at the beginning of the study. The followers' stages of change progressed over time. Compared with those following more athletic influencers, followers of nonathletic influencers (that is, a singer, a journalist, and an eFootballer) showed increased physical activity over time. Qualitative analysis highlighted Instagram factors influencing physical activity, including resonance with influencers' lifestyles and preference for simple, relatable activities. Authentic content was positively associated with increased exercise, particularly among already motivated followers. Unexpectedly, nonathletic influencers, such as a singer, a journalist, and an eFootballer, motivated adolescents best despite their nontraditional focus on physical activity. Their success stems from relatable lifestyles and simple activities that are easily incorporated into their daily routines. Conversely, athletic influencers demonstrated challenging exercises that were fascinating but difficult to adopt. This finding suggests the potential for utilizing nonathletic influencers in future campaigns targeting inactive adolescents.

The Legal Dilemma and Optimization Path of the Jurisdiction of the International Court of Justice in Litigation

The litigation of the International Court of Justice (ICJ) is a vital avenue for peacefully resolving legal disputes between nations and fostering positive international cooperation. ICJs aim is to refine and develop its methodology for properly handling and adjudicating various legal disputes among countries, and to optimize the related codified rule framework accordingly. Concurrently, the ICJ harbors the vision of broadening its jurisdiction and gaining recognition from more countries, striving to better maintain international peace, promote the proper resolution of international disputes, and advance the continuous progress and development of the international judicial system. However, in the context of the evolving and progressing international community, the ICJ has encountered numerous challenges in the actual exercise of its jurisdictional authority. This study examines these challenges in depth, focusing on issues related to admissibility, optional compulsory jurisdiction, and delayed jurisdiction. Through this analysis, a series of targeted recommendations are proposed to address these practical dilemmas and to support the ICJ in fulfilling its crucial mandate more effectively.

Frail Older Adults' Needs and Preferences for Mobile Health Exercise Interventions Guided by Nudge Theory: AQualitative Analysis.

To explore frail older adults' preferences and needs regarding mobile health (mHealth) exercise interventions in China. Additionally, it sought to identify the nudge strategies necessary for initiating and sustaining exercise behaviours among frail older adults. A qualitative study. The semi-structured interviews were conducted between April and May 2024 from two communities in Changsha, China. The data were analysed using a deductive framework analysis aligned to nudge theory, and an inductive thematic analysis to gather relevant needs and preferences. This study involved 14 participants with pre-frailty or frailty, aged 60-82 years (median age of 64 years). While participants were generally receptive to new technologies, lower levels of health literacy and competing priorities often hindered their participation. Three primary functionality requirements were as follows. (1) Profession engagement: tailored exercise prescription, professional and timely feedback and guidance; (2) personalised knowledge encompassing pain management, successful cases and inspiration; (3) beneficial, tailored, dynamic, fragmented, challenging exercise courses. Participants showed positive attitudes towards simplification nudges, gamification nudges, social nudges, trustworthy nudges, reminder nudges, economic nudges, feedback nudges and pre-commitment nudges. Addressing privacy concerns was essential to build trust and acceptance among older adults. These findings emphasised the importance of designing mHealth interventions that address frail older adults' specific needs and preferences while incorporating effective nudge strategies to promote engagement and adherence. Future researchers should explore wearables, ChatGPT language models, virtual coaching assistants, exercise snack to further optimise the experience and analyse the effects of nudges in mHealth exercise interventions among older adults. Exercise systems or app development for frail older adults should meet three basic functionality and essential nudge strategies. The consolidated criteria for reporting qualitative research (COREQ) guidelines were used for reporting. Older adults' engagement and interview data contribute a lot.

Negritude: A Universal Heritage; from the Quartier Latin in France to the City of Chicago in the United States of America

Black is beautiful! Such words from Martin Luther King are much telling about the inner meaning of movements like that of Negritude. Born out of the wings of racism and exclusion, the Negritude movement voiced out the strong need to step out of any form of inferiority complex. With a vision that africanized the notion of Africanity, the movement crossed borders to find roots in the Western and Caribbean lands before fostering around the world. Thus, in this paper, it is targeted to show up how Léopol Sedar Senghor’s and his likes’ positions that splashed away the negative image stuck on the the Black man for centuries, through a cultural crusade. A re-reading of the Negritude is recoursed to to update the other forms of negritude-oriented expressions the African Diaspora has been experiencing so far. Based on the theory of multiculturalism, our analysis has put forwards the challenging exercise to know oneself before any attempt to merge into the main stream of cultural identities.

New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis.

Despite advances in our radiological, histological and microbiological armamentarium, distinguishing between Crohn's disease (CD) and intestinal tuberculosis (ITB), especially in a TB endemic country, continues to be a challenging exercise in a significant number of patients. This review aims to summarize current available evidence on novel diagnostic techniques which have a potential to fill the gap in our knowledge of differentiating between ITB and CD. Both ITB and CD are associated with altered host immune responses, and detection of these altered innate and adaptive immune cells has potential to distinguish ITB from CD. ITB and CD have different epigenetic, proteomic and metabolomic signatures, and recent research has focused on detecting these differences. In addition, the gut microbiome, which is involved in mucosal immunity and inflammatory responses, is considerably altered in both ITB and CD, and is another potential frontier, which can be tapped to discriminate between the two diseases. With technological advancements, we have newer radiological modalities including perfusion CT and dual-layer spectral detector CT enterography and evidence is emerging of their role in differentiating ITB from CD. Finally, time will tell whether the advent of artificial intelligence, with rapidly accumulating data in this field, will be the gamechanger in solving this puzzle of diagnostic dilemma between ITB and Crohn's disease. Recent advances need to be clinically validated before they can be used as novel diagnostic measures to differentiate Intestinal TB from CD.

Exercise-Induced Bronchoconstriction in Children: State of the Art from Diagnosis to Treatment.

Exercise-induced bronchoconstriction (EIB) is a common clinical entity in people with asthma. EIB is characterized by postexercise airway obstruction that results in symptoms such as coughing, dyspnea, wheezing, chest tightness, and increased fatigue. The underlying mechanism of EIB is not completely understood. "Osmotic theory" and "thermal or vascular theory" have been proposed. Initial assessment must include a specific work-up to exclude alternative diagnoses like exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history and clinical examination must be followed by basal spirometry and exercise challenge test. The standardized treadmill running (TR) test, a controlled and standardized method to assess bronchial response to exercise, is the most adopted exercise challenge test for children aged at least 8 years. In the TR test, the goal is to reach the target heart rate in a short period and maintain it for at least 6 min. The test is then followed by spirometry at specific time points (5, 10, 15, and 30 min after exercise). In addition, bronchoprovocation tests like dry air hyperpnea (exercise and eucapnic voluntary hyperpnea) or osmotic aerosols (inhaled mannitol) can be considered when the diagnosis is uncertain. Treatment options include both pharmacological and behavioral approaches. Considering medications, the use of short-acting beta-agonists (SABA) just before exercise is the commonest option strategy, but daily inhaled corticosteroids (ICS) can also be considered, especially when EIB is not controlled with SABA only or when the patients practice physical activity very often. Among the behavioral approaches, warm-up before exercise, breathing through the nose or face mask, and avoiding polluted environments are all recommended strategies to reduce EIB risk. This review summarizes the latest evidence published over the last 10 years on the pathogenesis, diagnosis using spirometry and indirect bronchoprovocation tests, and treatment strategies, including SABA and ICS, of EIB. A specific focus has been placed on EIB management in young athletes, since this condition can not only prevent them from practicing regular physical activity but also competitive sports.

‘Just because I have prostate cancer doesn’t mean that I can’t do things’ – men’s experiences of the acceptability of an exercise intervention for prostate cancer during treatment

BackgroundStructured exercise has an important role in mitigating the extensive side effects caused by ongoing prostate cancer treatments, specifically androgen deprivation therapy (ADT) and radiation therapy (RT). Little is known about men’s experiences of, and preferences for, structured exercise programmes during active cancer treatment. This study aimed to inform the acceptability of a 6-month supervised intervention that emphasised increasing and varied intensities of aerobic and resistance exercise, by exploring the experiences of men who participated.MethodsIndividual semi-structured interviews were conducted with an interviewer independent of the exercise study and data was analysed using a descriptive qualitative design.ResultsTwelve prostate cancer patients were interviewed including participants who completed (n = 9) and withdrew from (n = 3) the intervention. Four main themes captured how men experienced the intervention: (1) Navigating the Unknown: Building confidence amidst vulnerability (subtheme- pushing the limits), (2) Building Trust: The credibility and approach of the exercise instructor (subtheme- appropriateness of supervised vs. independent exercise), (3) Flexibility in Delivery, (4) Finding Purpose: Exercise as a means of escapism and regaining control during treatment.ConclusionWhile an initial lack of self-confidence can be a barrier to exercise participation, exercise programmes have the potential to provide psychosocial benefits, rebuild confidence and empower men throughout their cancer treatment and into recovery. Structured exercise is acceptable during treatment including RT and can offer a form of escapism and sense of control for men navigating their cancer journey. Trust building, flexible delivery and credibility alongside a challenging exercise prescription are important facilitators of acceptability for men. Strategies to embed exercise from the point of diagnosis through ADT and RT should reflect men’s experiences of exercise during treatment.Trial registrationThe trial has been registered on ClinicalTrials.gov as of the 14th of December 2021 (NCT05156424).

Acute cognitively challenging exercise as “cognitive booster” for children: Positive feedback matters!

Background and aimAcute exercise can enhance children's cognition. Heterogeneous effect sizes necessitate investigating exercise task characteristics, contextual factors, and related affective states. The study aimed to test whether different feedback forms during acute cognitively challenging exercise affect children's executive control, alerting, and orienting performances, also considering the potential mediational role of affective states. MethodsIn a within–subjects posttest only design, 100 children (Mage = 11.0, SDage = 0.8, 48% female) participated weekly in one of three exergames with different feedback: no feedback (NO-FB), standard acoustic environment (ST-FB), positive feedback (PO-FB). Acute bouts were designed to keep physical intensity (65% HRmax) and duration (15-min) constant and to have a high cognitive challenge. Valence, arousal, perceived physical exertion, cognitive engagement, and flow were assessed before, during and after exergaming. Each bout was followed by an Attention Network Test. ResultsANOVAs revealed a significant main effect of feedback on executive control (η2p = 0.09) with faster reaction times after PO-FB compared to the other conditions (η2ps > 0.06) and on valence at post–test (η2p = 0.11) with highest values in PO-FB (η2ps > 0.08). In PO-FB, valence was associated with executive control (r = −0.23) but did not mediate feedback effects on executive control (95% CI [–5.25, 4.68]). Alerting and orienting performances were unaffected by feedback (η2ps < 0.08). ConclusionResults suggest that positive feedback during acute cognitively challenging exergaming enhances children's executive control and positive affect, highlighting that exercise task characteristics and contextual factors are essential for cognitive benefits.

Accuracy and Feasibility of a Novel Glucose/Lactate Continuous Multi-Analyte Sensing Platform in Humans.

Continuous glucose monitoring systems (CGMs) have been commercially available since 1999. However, automated insulin delivery systems may benefit from real-time inputs in addition to glucose. Continuous multi-analyte sensing platforms will meet this area of potential growth without increasing the burden of additional devices. We aimed to generate pilot data regarding the safety and function of a first-in-human, single-probe glucose/lactate multi-analyte continuous sensor. The investigational glucose/lactate continuous multi-analyte sensor (PercuSense Inc, Valencia, California) was inserted to the upper arms of 16 adults with diabetes, and data were available for analysis from 11 of these participants (seven female; mean [SD] = age 43 years [16]; body mass index [BMI] = 27 kg/m2 [5]). A commercially available Guardian 3 CGM (Medtronic, Northridge, California) was also inserted into the abdomen for comparison. All participants underwent a meal-test followed by an exercise challenge on day 1 and day 4 of wear. Performance was benchmarked against venous blood YSI glucose and lactate values. The investigational glucose sensor had an overall mean absolute relative difference (MARD) of 14.5% (median = 11.2%) which improved on day 4 compared with day 1 (13.9% vs 15.2%). The Guardian 3 CGM had an overall MARD of 13.9% (median = 9.4%). The lactate sensor readings within 20/20% and 40/40% of YSI values were 59.7% and 83.1%, respectively. Our initial data support safety and functionality of a novel glucose/lactate continuous multi-analyte sensor. Further sensor refinement will improve run-in performance and accuracy.

Diastolic dysfunction: assessment and implications on the single ventricle circulation.

Patients with a functionally single ventricle (SV) are palliated with a series of procedures leading to a Fontan circulation. Over the life span, a substantial proportion of SV patients develop heart failure that can arise from circulatory or ventricular failure. Diastolic dysfunction (DD) is an important determinant of adverse outcomes in SV patients. However, assessment and categorization of DD in the SV remains elusive. We review recent literature and developments in assessment of DD in the SV and its relation to clinical outcomes. DD is prevalent in the SV and associated with worse outcomes. Occult DD can be exposed with provocative testing by exercise or preload challenge during catheterization. Likewise, sensitivity to detect DD may be increased via assessment of atrial function and strain imaging. Recent studies revisiting previous concepts such as incoordinate diastolic wall motion show that these are associated with SV end-diastolic pressures and post-Fontan recovery, yielding accessible DD assessment. Emerging technologies such as ultrafast ultrasound (UFUS) can provide noninvasive assessment of myocardial stiffness, inefficient diastolic flow patterns and intraventricular pressure gradients, thereby yielding new tools and insights into diastolic myocardial and hemodynamic properties. Characterizing DD in the SV continues to have substantial limitations, necessitating synthesis of multiple parameters into an overall assessment, accounting for their change over time, and in the context of the patient's clinical status. New and emerging techniques may help advance DD assessment and the ability to track response to treatment of new targets.

“Bring your worst”: Residents' perspectives on video review of challenging patient communication as a learning tool

ObjectiveTo investigate residents' experiences recording and receiving feedback on a challenging video of a patient encounter. Methods: We used a qualitative design with first year residents who took part in a mandatory communication skills course in which all participants were asked to bring a challenging video of a patient encounter. The methods consisted of brief reflection texts and focus groups related to their perspectives on the use of challenging videos. Results: 106 residents wrote brief reflection texts, and 13 residents participated in four focus groups. Residents mainly expressed positive experiences with the challenging video exercise. Residents reported that the pressure to perform was felt to be less than on previous teaching sessions because the focus was on choosing an encounter which was less than perfect. They also reported that they appreciated the opportunity to see that other doctors were not performing optimally. Conclusion: The use of challenging videos as a teaching method for communication skills was experienced as encouraging by residents and facilitated enhanced learning. InnovationWe recommend adding more focus on challenging situations in video review. This could support learning by providing what our participants found to be a less daunting learning environment.

Examining authorial agency in elementary children’s narratives

ABSTRACT This paper investigates stories written by children and aims to reveal how children resist or neutralise the social and cultural conditions in their writing. We draw on Archer’s critical realist theory of agency and structure and Stephens’ conceptualisation of agency as a relational experience that involves intersubjectivity. Looking at 8 stories written by year 5 and year 6 children, we explore how children exercise agency and challenge the sociocultural conditions. Our analysis explores children’s authorial choices about discourse (language), story (characters, action, and settings) and significance (values and worldviews) and how these choices shape the author’s agency or portray the agency of the characters. Overall, positioning against the sociocultural conditions is achieved and exercised through the child’s position as the author or through the child’s depiction of the characters and the use of ‘subject positions’ in stories. Findings suggest that agency is exercised in relation to a range of conditions including the laws of nature, normative social relations, interpersonal relationships, authoritative or passive parenting, and the socio-political context. The results shed light on narratives as spaces for children to practice agency and calls for pedagogical approaches that position children as active and capable participants of a classroom. Implications are discussed for education.

Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge

BackgroundThe significance of autonomic dysfunction in premature ventricular contraction–induced cardiomyopathy (PVC-CM) remain unknown. ObjectivesUtilizing a novel “dual stressor” provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model. MethodsIn 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling. ResultsExercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload. ConclusionsSympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.

Evaluating the Efficacy of Kinesthesia, Balance, and Vestibulo-Postural Training in Knee Osteoarthritis Management

Background: Knee osteoarthritis (OA) is a common degenerative joint disease that causes pain, reduced mobility, and impaired quality of life. This study compares the efficacy of kinesthesia and balance exercises with isometric strengthening versus vestibulo-postural training using a bipodalic stabilometric platform with isometric strengthening in improving muscle strength and functional independence in knee OA patients. Methods: Thirty subjects with knee OA, aged between 30-60 years, were randomly assigned to two groups. Group 1 (n=15) received kinesthesia and balance exercises along with isometric strengthening exercises, while Group 2 (n=15) received vestibulo-postural training using a bipodalic stabilometric platform combined with isometric strengthening exercises. Both groups performed their respective exercise regimens three times a week for four weeks. Outcomes measured included quadriceps and hamstrings strength using the Manual Muscle Testing (MMT) grading system and functional independence using the Barthel Index score. Results: Group 2 demonstrated significantly greater improvements in quadriceps strength (mean change: 1.34 vs. 0.40; p &lt; 0.001), hamstrings strength (mean change: 1.07 vs. 0.20; p &lt; 0.001), and Barthel Index score (mean change: 20.54 vs. 5.5; p &lt; 0.001) compared to Group 1. The between-group analysis confirmed that vestibulo-postural training with isometric strengthening was significantly more effective in enhancing muscle strength and functional independence in knee OA patients. Conclusion: Vestibulo-postural training using a bipodalic stabilometric platform combined with isometric strengthening exercises significantly improves muscle strength and functional independence in knee OA patients compared to kinesthesia and balance exercises with isometric strengthening. These findings highlight the importance of incorporating dynamic and challenging balance exercises into OA management strategies to optimize patient outcomes and enhance quality of life..

Post mission disposal of Megha-Tropiques-1 through controlled atmospheric Re-entry to be published in: The journal of space safety engineering

Controlled Re-Entry Experiment of Megha-Tropiques 1 (CREEM), an immensely challenging and significant exercise, was successfully executed on 7 March 2023 by Indian Space Research organization (ISRO) as part of its ongoing efforts to improve compliance with internationally accepted space debris mitigation guidelines. In this paper, we present the overall strategy of CREEM which was primarily shaped by the stringent requirements of targeted impact within a pre-designated zone and ensuring visibility during the final de-boosting burns. We specifically address how the strategy was driven by the on-board and operational constraints, the rationale for the selection of the target region, the de-orbiting maneuver performance details, and the operational workarounds to ensure required subsystem performance. The external coordination related aspects and the lessons learnt are also presented.

Revealing functional-molecular parasympathetic dysfunction in PVC-induced cardiomyopathy via dual stressor PVC and exercise

Abstract Background Exercise intolerance is a common presentation of premature ventricular contractions-induced cardiomyopathy (PVC-CM). In a canine PVC-CM model, previous studies have shown cardiac autonomic nervous system remodeling, resulting in persistent sympathetic excess. Nevertheless, the molecular mechanisms and functional implications of this neural remodeling, as well as parasympathetic alterations, remain unclear. Purpose We aim to evaluate the functional-molecular mechanisms of parasympathetic remodeling and its potential contribution to exercise intolerance in an animal model of PVC-CM. Methods We studied 15 canines (8 experimental vs 7 sham controls) chronically instrumented with pacemakers and telemetry devices to deliver 12-weeks of bigeminal PVCs (200ms coupling) to induce PVC-CM and to record sympathetic (SNA), vagal nerve activity (VNA) and heart rate (HR) over this period. Exercise challenge was conducted in sinus rhythm (SR) and in the presence of bigeminal PVCs ("dual stressor") at baseline and after development of PVC-CM. Sympatho-vagal neural and HR responses were assessed during and after exercise at baseline and after PVC-CM development, with and without PVCs, thus comparing baseline SR, baseline with PVCs, CM SR and CM with PVCs. Western Blot was performed on intrinsic and extrinsic cardiac neural tissues to evaluate molecular mechanisms of neural remodeling. Results Compared to baseline, SNA was significantly higher in PVC-CM in all phases of exercise (rest, exercise, recovery, p=0.03). In contrast, VNA was significantly lower in PVC-CM than baseline during exercise recovery (P=0.014). After exercise, HR recovery (HRR) was impaired (p=0.001), VNA lower (p=0.014) and SNA (p=0.03) higher in PVC-CM compared with baseline. Tyrosine hydroxylase (TH) immunoreactivity in the left ventricle (LV, p=0.001) and stellate ganglia (SG, p=0.03) and trans-cardiac plasma NE levels (p=0.03) were higher in PVC-CM compared with sham. Choline Acetyltransferase (CHAT) was not significantly different in either vagus (p=0.33) or LV (p=0.8) between PVC-CM vs sham. Cardiac (LV) Nerve Growth Factor (NGF), Growth Associated Protein (GAP-43) and beta 1-adrenoreceptor levels were lower (p=0.042, p=0.003, p=0.002 respectively) whereas beta 2-adreno- and muscarinic M2-cholinergic receptors were higher (p=0.02, p&amp;lt;0.01 respectively) in PVC-CM compared with sham. Conclusion Neural remodeling in PVC-CM results in an imbalanced sympathetic excess and sympathetic-parasympathetic dysfunction characterized by a loss of sympathetic functional reserve during exercise and impaired parasympathetic activity and HRR after exercise. Adaptive downregulation of NGF might explain this imbalance and dysfunction. These data open the intriguing possibility of neural-targeted therapies to reverse remodeling and restore autonomic function disrupted by chronic PVCs.GraphsMolecular

Association of temperature and absolute humidity with incidence of exercise-induced bronchoconstriction in children.

Exercise test outdoors is widely used to diagnose asthma in children, but it is unclear how much outdoor air factors affect the results. We analysed 321 outdoor exercise challenge tests with spirometry in children 6-16 years conducted due to suspicion of asthma or for assessing the effect of medication on asthma. We studied the association of FEV1 decrease and incidence of exercise-induced bronchoconstriction (EIB) with temperature, relative humidity (RH) and absolute humidity (AH). Asthma was diagnosed in 57% of the subjects. AH ≥5 g/m3, but not RH or temperature, was associated with the EIB incidence (p = 0.035). In multivariable logistic regression, AH ≥5 g/m3 was negatively associated (OR = 0.51, 95% CI [0.28─0.92], p = 0.026) while obstruction before exercise (OR = 2.11, 95% CI [1.16─3.86], p = 0.015) and IgE-mediated sensitisation were positively associated with EIB (OR = 2.24, 95% CI [1.11─4.51], p = 0.025). AH (r = -0.12, p = 0.028) and temperature (r = -0.13, p = 0.023) correlated with decrease in FEV1. In multivariable linear regression, only AH was associated with FEV1 decrease (coefficient = -0.044, 95% CI [-0.085 to -0.004], p = 0.033). AH of outdoor air associates with occurrence and severity of EIB in outdoor exercise tests in children. Care should be taken when interpreting negative outdoor exercise test results if AH of air is high.