Acute Response Research Articles

Acute response to resistance exercise and later development of arm lymphedema in breast cancer survivors: An exploratory follow-up of a randomized cross-over trial

BackgroundIn breast cancer survivors at risk for lymphedema, variation in lymphatic function and arm volume has been observed related to a bout of exercise, with potential for prediction of breast cancer-related arm lymphedema (BCRaL). This novel, exploratory study examined the acute lymphatic response to resistance exercise and later development of BCRaL in women at high risk for BCRaL. MethodsOne year after participation in a cross-over trial evaluating the acute lymphatic response to upper-extremity resistance exercise (low-and heavy-load), participants were assessed for BCRaL (n ​= ​16). The response to exercise was assessed before and after (post, 24- and 72-hrs) each exercise bout as extracellular fluid (L-Dex; bioimpedance spectroscopy (BIS)), interarm volume % difference (IVD; Dual-energy x-ray absorptiometry (DXA)) and symptoms (Numeric rating scale, 0–10 (NRS)). BCRaL at follow-up was defined as presence of one objective indicator (L-Dex >10, change ≥+6.5, IVD >5%) plus one objective or subjective indicator (interarm symptom ≥1 or visual inspection). Descriptive statistics were used to compare the acute response between participants with and without BCRaL at follow-up. ResultsNo trends indicating a similar acute response to exercise was observed in participants who later developed BCRaL (n ​= ​5). There were no observable differences in acute lymphatic response between participants that developed BCRaL and those who did not, both at an individual and group level. ConclusionsFindings from this exploratory study showed no evidence to suggest that the acute response to resistance exercise can predict BCRaL development.

Association between insulin sensitivity and lean mass loss during weight loss.

The study objective was to assess the relationship between insulin sensitivity and changes in total lean mass (LM) and appendicular LM (ALM) during weight loss. Individuals were randomly assigned to either a standard or a moderately reduced carbohydrate diet for 16 weeks. Body composition was assessed using dual-energy x-ray absorptiometry and insulin sensitivity index (SI) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline SI was predictive of changes in total LM and ALM. Participants (n = 57; baseline BMI 32.1 ± 3.8 kg/m2) lost an average of 6.8 ± 3.2 kg of body weight (p < 0.001), with 1.5 ± 2.6 kg coming from LM (p < 0.05) and 0.5 ± 0.73 kg from ALM (p < 0.05). Multiple regression analysis demonstrated that SI was inversely associated with changes in total LM (kilograms; β = 0.481, p < 0.001), after adjusting for baseline LM, fat mass, acute insulin response to glucose, and weight loss. Similar results were seen when assessing ALM loss (β = 0.359, p < 0.05). Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing LM loss.

Targeted delivery of factors and cells for improving cardiac tissue regeneration and heart function following myocardial infarction

Following myocardial infarction (MI), cardiac tissue undergoes irreversible cellular alterations, with cardiomyocytes being replaced by fibrotic tissue. In order to improve tissue regeneration, a previously characterized chitosan-based cryogel, which was designed by our group, was used. The treatment regimen involved the sequential delivery of the cryogel loaded with specific cytokines and growth factors, followed by a separate injection of pre-differentiated cells. Initially, the cryogel loaded with interleukin-10 and transforming growth factor-β was injected into infarcted tissue immediately after MI induction, targeting the acute inflammatory response. On day four post-MI, a second injection was administered, this time utilizing cryogel loaded with vascular endothelial growth factor and fibroblast growth factor-2, aimed at promoting tissue regeneration and angiogenesis. Subsequently, on day six post-MI, the experimental group received cardiomyocyte-like cells, smooth muscle cells, and endothelial cells. The purpose of these cells, in synergy with cytokines and growth factors, was to repopulate the lost cellular populations, thereby enhancing myocardial repair. The treatment improved myocardial tissue regeneration, increased cardiac output, ejection fraction, and reduced fibrotic regions. Thus, the chitosan-based cryogel, enriched with anti-inflammatory and proangiogenic factors and supplemented with pre-differentiated cells, offers a promising platform for controlled release of therapeutics, promoting substantial tissue repair and regeneration following MI.

Large inter-individual variability in force-velocity profile changes in response to acute high-load resistance training.

While the acute effects of high-load resistance training on the force generating capacity of muscles have been widely examined, limited data exist on the relationship with the force-velocity profile (FV). Evidence suggests high sensitivity of the vertical FV profile to monitor changes in the muscle's mechanical properties according to the type of the exercise protocol. However, the interpretation of the findings seems not as straightforward. Therefore, the purpose of this study was to examine the effects of a high-load resistance training protocol on the muscle's mechanical properties during loaded jumps and on the vertical force-velocity profile (FV) in relation to maximal strength. 29 resistance-trained male (mean age±SD: 35.4 ± 7.8 years) and 29 female athletes (mean age±SD: 32.5 ± 7.0 years) participated in the study. Five-repetition maximum (5RM) in back squat, unloaded countermovement jump (CMJ) and FV profile were assessed. Loaded jumps were performed against 25, 50, 75, and 100 percent of body mass. Participants performed exercise protocols corresponding to their 5RM. Immediately after, unloaded CMJ and FV profile measurements were repeated. A significant decrease in CMJ height (∼5-6%) and in average power (∼4%) was recorded for both men and women. The FV profile did not change after the exercise protocol; however, there was a significant decrease in theoretical maximal power (from 4 to 5%) and in theoretical maximal velocity (∼3%). Maximal strength was not associated with the changes in FV profile. Findings suggest that an acute high-load exercise decreased vertical jump performance and maximal power output, but without a concomitant change in FV profile. The large interindividual variability in FV measures indicates a less straightforward connection of the applied exercise with the acute response in the FV profile, highlighting the complexity of the FV profile to monitor changes in response to an acute training load.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

IL-17 in wound repair: bridging acute and chronic responses.

Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17's involvement in chronic wound inflammation and repair.

Accelerated pacing reduces left heart filling pressures: a novel therapy for heart failure with preserved ejection fraction?

Abstract Background The recent MyPACE trial demonstrated significant improvement of quality-of-life, physical activity, and atrial fibrillation (AF) burden with accelerated pacing as compared to the standard 60bpm back-up rate setting in patients with heart failure with preserved ejection fraction (HFpEF) and indication for pacemaker therapy. We hypothesized that a potential working mechanism underlying these improved outcomes lies in the reduction of left heart filling pressures during accelerated pacing, reducing congestion and atrial stretch. Aim To assess the acute effects of accelerated atrial pacing on left heart filling pressures in consecutive AF patients undergoing catheter ablation. Methods Fifty AF patients undergoing catheter ablation were prospectively enrolled for accelerated atrial pacing. As illustrated in Figure 1, pacing was performed proximally in coronary sinus (CS). Pacing rate was increased incrementally from resting heart rate by 10-bpm increments up to Wenckebach rhythm, with 30-sec intervals of pacing on and off for hemodynamic stabilization. Left atrial pressure (LAP) was continuously monitored via a fluid-filled transseptal sheath (SL0 sheath, Abbott). Acute pacing-induced changes in mean LAP and PR-interval were evaluated at each pacing rate and compared between resting heart rate, the patient-specific optimal heart rate (i.e., the rate resulting in the lowest mean LAP), and the maximum pacing rate. Results Atrial pacing acutely decreased mean LAP from 14.8[9.8; 18.4] to 12.8[8.5; 15.8]mmHg (median[IQR], p&amp;lt;0.001) as heart rate increased from 51[47; 61] to 90[70; 100]bpm (p&amp;lt;0.001) (Figure 2, resting versus optimal category). Among the 50 patients included, only 4 did not exhibit a decrease in LAP. Further increasing pacing rate to a maximum of 130[100; 140]bpm resulted in an acute LAP increase to 16.2[12.7; 19.9]mmHg (p&amp;lt;0.001) to values above resting mean LAP. Accelerated pacing induced negative AV dromotropy, i.e., lengthening of the PR-interval from 169[150; 185] to 186[164; 209]ms (p=0.003) and 270[217; 310]ms (p&amp;lt;0.001). Conclusion Our study demonstrated that moderately accelerated atrial pacing reduced mean LAP in AF patients undergoing catheter ablation. While our primary focus was on acute response in AF patients, the reduction in mean LAP during moderate pacing rates may suggest a promising therapeutic approach for managing HFpEF patients. However, caution is warranted as pacing rates beyond the optimal range led to a marked increase in LAP. Additionally, increasing pacing rates were observed to induce varying degrees of AV-node dromotropy, which potentially modulates therapy response.Fig 1. Overview of clinical protocolFig 2. Response to accelerated pacing

Cardiac resynchronization therapy using endocardial versus trans-coronary sinus, epicardial left ventricular pacing: the Epi-Endo study

Abstract Aims Some studies have suggested that cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing (Endo-CRT) is superior to a conventional transvenous, epicardial CRT (Epi-CRT). To determine whether, in CRT recipients, endocardial LV pacing is haemodynamically superior to trans-coronary vein (trans-CV) LV epicardial pacing. Methods and results At implantation patients (n=16; aged 68.9±8.32 years; 13 male) underwent Epi-CRT and Endo-CRT in basal, mid and apical myocardial segments, delivered using the trans-CS lead and an intra-cavitary, roving EP catheter to achieve juxtapositions of the epicardial and endocardial side of the LV free wall respectively. Myocardial scar was quantified using cardiovascular magnetic resonance. An acute haemodynamic response (AHR) was defined as a ≥10% increase in the maximal rate of rise of LV pressure (%LV dP/dtmax) in relation to RV pacing (DOO). When the 84 paired segments were taken together, the %ΔLV dP/dtmax was higher with Endo-CRT than with Epi-CRT (9.9±8,6% vs 7.9±8.3% respectively, p&amp;lt;0.002; 52.3% vs 28.6% responders [p&amp;lt;0.045). However, Endo-CRT was not always superior to epi-CRT in individual patients. For example, in basal segments, only 5/10 (50%) patients were converted from non-responders with epi-CRT to responders with endo-CRT whereas 1/4 (25%) epi-CRT responder was converted to a non-responder with endo-CRT (Figure). There was no difference in ΔLV dP/dtmax between Epi-CRT and endo-CRT in segments with myocardial scar. Conclusions On average, endo-CRT provides a better AHR than epi-CRT. Within patients, however, endo-CRT is not always better.Epicardial versus Endocardial CRT

Multicenter hemodynamic assessment of the LOT-CRT strategy: when is one lead enough for resynchronization?

Abstract Background Left bundle branch area pacing (LBBAP) has been postulated as an alternative to traditional cardiac resynchronization therapy via biventricular pacing (BiV) in heart failure patients with wide QRS. Limited data is available regarding the acute hemodynamic response of LBBAP and the combination of LBBAP and coronary venous (LVcv) pacing (LOT-CRT). Purpose We sought to compare the acute hemodynamic and ECG effects of traditional CRT (BiV or LV-only) versus LBBAP and LOT-CRT in CRT candidates with advanced conduction disease. Methods In this multi-centre study (5 EU and 7 US centres), 48 subjects (mean age 65.8 years, 67% males, LV ejection fraction 29.4%) with either nonspecific interventricular conduction delay (NIVCD, n = 29) or left bundle branch block (LBBB; n =19; based upon strict criteria AHA/ACC/HRS plus Strauss) underwent an acute hemodynamic study to determine the % change in +LV dP/dtmax from baseline atrial pacing versus BiV, LBBAP, or LOT-CRT. Each therapy pacing configuration was applied 4 times at 5 different atrioventricular (AV) delays. QRS shortening was assessed using standard 12-lead ECG. Results Successful LBBAP lead implantation was achieved in 27 patients (56%) using current EHRA criteria. Twenty-one patients (44%) were categorized as deep septal pacing (DSP), due to suboptimal lead penetration or advanced left conduction system disease with broad paced QRS complexes and absent V1-r-wave. The increase in AV-optimized dP/dtmax for the different pacing configurations is displayed in the Figure, left panel. LOT-CRT dP/dtmax % improvement was 25.8%, significantly higher than LBBAP configurations (p&amp;lt;0.01), either unipolar-LBBAP (19.3%), or bipolar-LBBAP (16.4%), but not different from BiV (26.4%). QRS shortening was greater in LOT-CRT (29.5ms) vs. unipolar-LBBAP (11.9ms), bipolar-LBBAP (11.7ms), or BiV (18.5ms), all p&amp;lt;0.01. Sub-group analysis indicated the hemodynamic benefit of adding LVcv pacing when LBBAP strategy was pursued (Figure, right panel) depended on obtaining LBBAP rather than DSP (p &amp;lt; 0.01) and baseline QRS duration (p = 0.03). The largest benefit was observed among subjects with a baseline QRS wider than the observed cohort mean (171ms) and DSP only, where LOT-CRT provided 14.5% (5.0-24.1%) greater dP/dtmax improvement and 20.8ms (12.8-28.8ms) greater QRS duration shortening than unipolar DSP. Conclusions In a CRT cohort with advanced conduction disease, LOT-CRT provided greater acute hemodynamic benefit than LBBAP strategy (i.e. including also DSP cases). Patients with wider QRS or suboptimal outcome of LBBAP strategy (DSP) are more likely to benefit from addition of a LVcv lead to implement LOT-CRT.Figure 1

An innovative label-free electrochemical aptamer sensor: utilizing Ti3C2Tx/MoS2/Au NPs for accurate interleukin-6 detection

In the medical field, changes in interleukin-6 (IL-6) concentration serve as essential biomarkers for monitoring and diagnosing various conditions, including acute inflammatory responses such as those seen in trauma and burns, and chronic illnesses like cancer. This paper detailed a label-free electrochemical aptamer sensor designed for IL-6 quantification. A composite material consisting of Ti3C2Tx and MoS2 was successfully synthesized to fabricate this sensor. The synergistic effect of MoS2's catalytic action on hydrogen peroxide (H2O2), used as a signalling marker, when combined with the exceptional conductivity and large specific surface area of Ti3C2Tx, not only enables an increased loading of MoS2 but also significantly boosts the electrochemical response. The in situ-reduced Au NPs provided stable immobilization sites for DNA aptamers (DNAapt) and facilitated electron transfer, ensuring accurate IL-6 recognition. Under optimal conditions, the aptamer sensor exhibited a wide linear range (5 pg/mL to 100 ng/mL) and a low limit of detection (LOD) of 2.9 pg/mL. Its sensing performance in human serum samples highlights its potential as a promising clinical analysis tool.

#2866 The CompAct-HD trial reports a persistent inflammatory profile in patients undergoing haemodialysis, acutely exacerbated with each treatment

Abstract Background and Aims Inflammation induced by haemodialysis (HD) treatment has been recognised for several decades. Despite significant advances in technology, there is evidence that incompatibility between the dialyser, a foreign surface, and the patients’ blood, results in activation of the immune system. With each session, blood-membrane interaction leads to a repetitive activation of the innate complement system and a subsequent inflammatory response. It is now widely acknowledged that the consequences of long-term inflammation include fibrosis and accelerated cardiovascular disease, a common cause of mortality in patients with renal failure. The aim of the CompAct-HD trial is to characterize complement activation and biomarker response to blood-membrane-circuit interaction during HD. Method For a single session, six timed intradialytic blood samples were collected from HD patients during standard treatment with ultrapure water and high flux “biocompatible” membranes. Complement activity potential was determined from timepoint 1 and inflammatory biomarkers from timepoints 2 to 6. Single time point samples were also collected from 7 healthy donors. Highly multiplexed assays enabled to determine 30 biomarkers of inflammation, including cytokines, chemokines, growth factors and complement proteins, from a single blood sample. Data analysis was performed using Microsoft® Excel Version 16.80 and GraphPad Prism 10.1.0. Results 354 patients were recruited from 8 dialysis units across Greater Manchester, UK. An interim analysis was performed on 150 HD patients receiving standard care as well as 7 healthy donors. Dialysis appears to generate an acute inflammatory response, that is, within 15 minutes of commencing treatment which does not appear to resolve by the end of the session. This heightened inflammatory state was observed in HD patients in comparison to healthy donors (Fig. 1) with most pronounced changes seen in cytokines IL-1β, IL-10, IL-12p40 and TNF-α during dialysis. Established markers such as IL-6 also showed a 6-fold increase at the 75th percentile. Similarly, an exaggerated intradialytic response was observed in complement proteins, including the terminal complement complex (TCC) C5b-9 and anaphylatoxin C5a with spikes of up to 7-fold and 10-fold respectively (Fig. 2). A session of HD was shown to cause a relative increase in complement proteins and inflammatory biomarkers. The magnitude of response seen in patients was variable (Fig. 3) with the greatest rise seen in the top quartile (above the Q3 boundary). Conclusion Our findings evidence a sharp inflammatory response to modern day HD treatment across a large cohort of dialysis patients. When compared to healthy donors, we observed heightened levels of inflammation in dialysis patients that is further exacerbated with each treatment session. This study shows that HD has a significant role to play in the chronic inflammatory state of patients with end stage renal failure. Furthermore, here we describe potential targets, in both cytokine and complement proteins, which could be the key to downregulation of inflammation. Using targeted therapeutics, we have an opportunity to deliver a more biocompatible treatment, improving patient outcomes.

Acute Autonomic Nervous System Response to Direct Sacral Nerve Root Stimulation in Lower Urinary Tract Dysfunction: A New Approach to Understand the Mechanism of Action of Sacral Nerve Modulation.

Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction. In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods. Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA. Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

#220 Acute vascular response to hemodialysis as measured by serum syndecan-1 and endothelin-1 levels, as well as vascular stiffness

Abstract Background and Aims End-stage kidney disease (ESKD) patients on chronic hemodialysis (HD) have very high cardiovascular risk. Acute vascular changes during dialysis mediated partially by factors of the endothelium may have a crucial role in the cardiovascular (CV) disease of HD patients. Aim To study acute vascular changes during HD measured by applanation tonometry and to assess the role of syndecan-1 (SDC-1), endothelin-1 (ET-1), and traditional and non-traditional CV risk factors in these changes. Method 29 consecutive chronic HD patients (median age: 65.6 ± 10.4 years; 52% men) were included in the study. Pre-, mid-, and post-HD plasma SDC-1 and ET-1 levels and routine biochemical parameters were measured. Applanation tonometry (SphygmoCor, AtCor Medical) was performed before HD. Results As assessed by trend analysis, SDC-1 levels increased significantly during HD (p = 0.004). ET-1 levels were decreasing during HD. Male patients had significantly higher ET-1 levels than women. Patients were divided into 2 groups based on their pulse wave velocity (PWV): PWV ≥12 m/s and PWV &amp;lt;12 m/s. Pre-HD and mid-HD SDC-1 levels were significantly higher in the group with PWV ≥12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/ml, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/ml, p = 0.044, respectively). Post-HD ET-1 levels were significantly higher in the patient group having PWV ≥12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients having PWV ≥12 m/s had significantly higher pre-HD peripheral and aortic systolic blood pressure than the patients having lower PWV (147.4 ± 73.3 vs. 134.1 ± 72.2 mmHg, p = 0.038, and 130.7 ± 16.6 vs. 122.5 ± 14.9 mmHg, p = 0.016, respectively). Mid-HD and post-HD blood pressures were not different. We found a positive correlation between total cholesterol and the decrease in SDC-1 levels during HD (r = 0.539; p = 0.008). Pre-, mid-, and post-HD SDC-1 correlated significantly with the ultrafiltration volume during HD (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion SDC-1 and ET-1 may contribute to the vascular changes observed during HD, and they have correlations with some traditional and non-traditional CV risk factors.

Cerebral cortex activation and functional connectivity during low-load resistance training with blood flow restriction: An fNIRS study.

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.

Eco-anxiety among regional Australian youth with mental health problems: A qualitative study.

In Australia, climate-related disasters disproportionately affect rural, regional and remote young people with effects ranging from severe flooding and catastrophic fires to unbearable heat and yet most studies on eco-anxiety are based on reports by urban youth who do not have direct experiences of such impacts. Furthermore, there is a dearth of research on how eco-anxiety impacts those who already experience mental health problems. The present study aims to address this gap by focussing on the lived experiences of regional Australian youth with recent experience of climate-related disasters alongside clinical insights from those involved in their care. Two groups, a clinician and client group, were recruited through headspace Port Macquarie-a primary youth mental health service in a regional city of New South Wales, Australia. In all, 25 participants took part in focus group discussions, including 13 clinicians and 12 clients of the service. Clients and clinicians responded to a version of the same questions: (1) whether the effects of climate change impact on regional youth with mental health problems, (2) how young people cope with eco-anxiety and (3) how regional communities can help young people cope with eco-anxiety better. Group discussions were audio-recorded and transcribed. Transcripts were analysed according to the principles of Interpretative Phenomenological Analysis using a team approach. Three dimensions of eco-anxiety were identified by clinicians and clients-helplessness in the present, hopelessness about the future and acute stress and anxiety related to experiences of severe flooding and fires. Clinicians and clients also thought that a misalignment between young people and older generations, including government, was a source of eco-anxiety and having a collective voice was seen as important for regional youth as was community support through social media sites. Clinicians thought that eco-anxiety was 'in the background' for their clients, whereas the clients who participated were clearly experiencing eco-anxiety. Whereas clinicians could identify potential coping strategies, clients could not. Eco-anxiety can be experienced by regional youth with mental health problems as both an acute response to natural hazards and a more sustained sense of hopelessness about the future. Impacts of acute anxiety and chronic hopelessness, with its associated depression risk, among young people with pre-existing mental health problems warrants further investigation as this study suggests that it may exacerbate their existing conditions. Clinicians and clients in this region would benefit from specific training and resources related to the identification and treatment of eco-anxiety. Future research on climate-related mental health should be inclusive of the perspectives of those who have direct experience of climate-related adverse events.

The biphasic activity of autophagy and heat shock protein response in peripheral blood mononuclear cells following acute resistance exercise in resistance-trained males.

Autophagy and heat shock protein (HSP) response are proteostatic systems involved in the acute and adaptive responses to exercise. These systems may upregulate sequentially following cellular stress including acute exercise, however, currently few data exist in humans. This study investigated the autophagic and HSP responses to acute intense lower body resistance exercise in peripheral blood mononuclear cells (PBMCs) with and without branched-chain amino acids (BCAA) supplementation. Twenty resistance-trained males (22.3 ± 1.5yr; 175.4 ± .7cm; 86.4 ± 15.6kg) performed about of intense lower body resistance exercise and markers of autophagy and HSP70 were measured immediately post- (IPE) and 2, 4, 24, 48, and 72h post-exercise. Prior to resistance exercise, 10 subjects were randomly assigned to BCAA supplementation of 0.22g/kg/d for 5days pre-exercise and up to 72h following exercise while the other 10 subjects consumed a placebo (PLCB). There were no difference in autophagy markers or HSP70 expression between BCAA and PLCB groups. LC3II protein expression was significantly lower 2 and 4h post-exercise compared to pre-exercise. LC3II: I ratio was not different at any time point compared to pre-exercise. Protein expression of p62 was lower IPE, 2, and 4h post-exercise and elevated 24h post-exercise. HSP70 expression was elevated 48 and 72h post-exercise. Autophagy and HSP70 are upregulated in PBMCs following intense resistance exercise with autophagy increasing initially post-exercise and HSP response in the latter period. Moreover, BCAA supplementation did not affect this response.

Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?

An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.

Acute Responses to Traditional and Cluster-Set Squat Training With and Without Blood Flow Restriction.

Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Páez-Maldonado, J, Rodiles-Guerrero, L, Boullosa, D, León-Prados, JA, Wernbom, M, and Pareja-Blanco, F. Acute responses to traditional and cluster-set squat training with and without blood flow restriction. J Strength Cond Res XX(X): 000-000, 2024-To compare the acute responses to different set configurations (cluster [CLU] vs. traditional [TRA]) under distinct blood flow conditions (free vs. restricted) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the set configuration (TRA: continuous repetitions; vs. CLU: 30 seconds of rest every 2 repetitions) and in the blood flow condition (FF: free-flow; vs. blood flow restriction [BFR]: 50% of arterial occlusion pressure). The relative intensity (60% 1RM), volume (3 sets of 8 repetitions), and resting time (2 minutes) were equated. Mean propulsive force (MPF), velocity (MPV) and power (MPP), and electromyography (EMG) parameters were recorded during each repetition. Tensiomyography (TMG), blood lactate, countermovement jump (CMJ) height, maximal voluntary isometric contraction, in SQ, and movement velocity against the load that elicited a 1 m·s-1 velocity at baseline (V1-load) in SQ were assessed at pre- and post-exercise. The CLU protocols allowed a better maintenance of MPF, MPV, MPP, and EMG median frequency during the exercise compared to TRA (clu-time interaction, p < 0.05). The TRA protocols experienced greater impairments post-exercise in TMG- and EMG-derived variables (clu-time interaction, p < 0.05) and SQ and CMJ performance (clu-time interaction, p = 0.08 and p < 0.05, respectively), as well as higher blood lactate concentrations (clu-time interaction, p < 0.001) than CLU. Moreover, BFR displayed decreases in TMG variables (bfr-time interaction, p < 0.01), but BFR-CLU resulted in the greatest reduction in twitch contraction time (p < 0.001). Cluster sets reduced fatigue during and after the training session and BFR exacerbated impairments in muscle mechanical properties; however, the combination of both could improve contraction speed after exercise.

Grape Pomace Polyphenols Reduce Acute Inflammatory Response Induced by Carrageenan in a Murine Model.

Grape pomace (GP), a by-product of wine production, contains bioactive polyphenols with potential health benefits. This study investigates the anti-inflammatory properties of a polyphenolic fraction derived from GP, obtained by ultrasound-microwave hybrid extraction and purified using ion-exchange chromatography. In the inflammation model, mice were divided into six groups: intact, carrageenan, indomethacin, and three GP polyphenols treatment groups. Paw edema was induced by subplantar injection of carrageenan, and the GP polyphenols were administered intraperitoneally at doses of 10, 20, and 40 mg/kg. The anti-inflammatory effect was evaluated by measuring paw volume, and expression of inflammatory markers: cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), and cytokines (IL-1β and IL-6), along with lipid peroxidation levels. The GP polyphenols significantly reduced paw edema and expression levels of COX-2, MPO, and cytokines in a dose-dependent manner effect, with the highest dose showing the greatest reduction. Additionally, lipid peroxidation levels were also decreased by GP polyphenols treatment at doses of 10 and 20 mg/kg. These findings suggest that ultrasound-microwave extraction combined with amberlite purification proved to be effective in obtaining a polyphenolic-rich fraction from GP. Thus, GP polyphenols may serve as a natural anti-inflammatory and antioxidant agent for treating inflammation and oxidative stress-related diseases.

The Utility of High-Intensity, Intermittent Exercise Protocols to Induce Fatigue for Screening Purposes in Jump-Landing Sports

Short-term fatigue protocols simulating sports participation are scarce and not well-documented in jump-landing sports. Therefore, this study investigated physiological and physical responses following high-intensity, intermittent exercise protocols (HIIPs) with a standardized level of subjective exhaustion (Borg ≥18/20) and a modified fixed version of five circuits (HIIP-5) for future inclusion in biomechanical screening protocols. Twenty male volleyball and basketball players participated in this study to complete the HIIP and the HIIP-5. Physiological and physical variables were assessed before and up to 30 min after cessation of both protocols. Regarding physiological variables, heart rate values increased (+104 bpm, p &lt; 0.001) and remained elevated up to 30 min (+34 bpm, p &lt; 0.001), and blood lactate levels increased (+17 mmol/l, p &lt; 0.001) compared to baseline. Regarding physical variables, decreased jump height (−4 cm, p = 0.001–0.009) and quadriceps muscle strength (p = 0.001−0.050) were observed up to 30 min compared to baseline. The type of the fatigue protocol did not have an effect on the investigated variables (p &gt; 0.05). To conclude, both the HIIP and the HIIP-5 seem valuable tools to induce acute and long-lasting responses, providing a sufficiently large time window of 30 min within which biomechanical markers of injury can be assessed under fatigued conditions in future risk factor screenings. In practice, the fatigue protocol can be terminated after only five circuits if athletes had not yet been stopped at that point due to exhaustion (Borg ≥18/20).