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Toxicon : Official Journal of the... Jun 2024Presynaptic- or β-neurotoxicity of secreted phospholipases A (sPLA) is a complex process. For full expression of β-neurotoxicity, the enzymatic activity of the toxin...
Presynaptic- or β-neurotoxicity of secreted phospholipases A (sPLA) is a complex process. For full expression of β-neurotoxicity, the enzymatic activity of the toxin is essential. However, it has been shown that not all toxic effects of a β-neurotoxin depend on its enzymatic activity, for example, the inhibition of mitochondrial cytochrome c oxidase. The main objective of this study was to verify whether it is possible to observe and study the phospholipase-independent actions of β-neurotoxins by a standard ex vivo twitch-tension experimental approach. To this end, we compared the effects of a potent snake venom β-neurotoxin, ammodytoxin A (AtxA), and its enzymatically inactive mutant AtxA(D49S) on muscle contraction of the mouse phrenic nerve-hemidiaphragm preparation. While AtxA significantly affected the amplitude of the indirectly evoked isometric muscle contraction, the resting tension of the neuromuscular (NM) preparation, the amplitude of the end-plate potential (EPP), the EPP half decay time and the resting membrane potential, AtxA(D49S) without enzymatic activity did not. From this, we can conclude that the effects of AtxA independent of enzymatic activity cannot be studied with classical electrophysiological measurements on the isolated NM preparation. Our results also suggest that the inhibition of cytochrome c oxidase activity by AtxA is not involved in the rapid NM blockade by this β-neurotoxin, but that its pathological consequences are rather long-term. Interestingly, in our experimental setup, AtxA upon direct stimulation reduced the amplitude of muscle contraction and induced contracture of the hemidiaphragm, effects that could be interpreted as myotoxic.
PubMed: 38942241
DOI: 10.1016/j.toxicon.2024.107833 -
Scientific Reports Jun 2024In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen....
In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1-10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca channels responsible for the cardiac action potentials depolarization phase. Two types of Ca currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.
Topics: Animals; Bees; ortho-Aminobenzoates; Myocytes, Cardiac; Insecticides; Cardiotoxicity; Calcium; Myocardial Contraction; Heart; Ryanodine Receptor Calcium Release Channel; Diamide
PubMed: 38942905
DOI: 10.1038/s41598-024-65007-2 -
European Journal of Applied Physiology Jun 2024To assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra...
PURPOSE
To assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra torque, progressive increase in torque during stimulation, and estimates of the persistent inward current (PIC) contribution to motoneuron firing in the plantar flexors.
METHODS
Ten participants performed triangular shaped contractions to 20% of maximal plantar flexion torque before and after WPHF NMES with and without a handgrip contraction, and control conditions. Extra torque, the relative difference between the initial and final torque during stimulation, and sustained electromyographic (EMG) activity were assessed. High-density EMG was recorded during triangular shaped contractions to calculate ∆F, an estimate of PIC contribution to motoneuron firing, and its variation before vs after the intervention referred to as ∆F change score.
RESULTS
While extra torque was not significantly increased with remote contraction (WPHF + remote) vs WPHF (+ 37 ± 63%, p = 0.112), sustained EMG activity was higher in this condition than WPHF (+ 3.9 ± 4.3% MVC EMG, p = 0.017). Moreover, ∆F was greater (+ 0.35 ± 0.30 Hz) with WPHF + remote than control (+ 0.03 ± 0.1 Hz, p = 0.028). A positive correlation was found between ∆F change score and extra torque in the WPHF + remote (r = 0.862, p = 0.006).
DISCUSSION
The findings suggest that the addition of remote muscle contraction to WPHF NMES enhances the central contribution to torque production, which may be related to an increased PIC contribution to motoneuron firing. Gaining a better understanding of these mechanisms should enable NMES intervention optimization in clinical and rehabilitation settings, improving neuromuscular function in clinical populations.
PubMed: 38940932
DOI: 10.1007/s00421-024-05538-8 -
Frontiers in Cardiovascular Medicine 2024This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old...
This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old male patient presenting with early-onset heart failure and reduced ejection fraction. DCM is a nonischemic heart condition characterized by left biventricular dilation and systolic dysfunction, with approximately one-third of cases being familial and often linked to genetic mutations. The TTN gene, encoding the largest human protein essential for muscle contraction and sarcomere structure, is implicated in about 25% of DCM cases through mutations, especially truncating variants. Our investigation revealed a previously unreported G > C mutation at the splice acceptor site in intron 356 of TTN, confirmed by Sanger sequencing and not found in population databases, suggesting a novel contribution to the understanding of DCM etiology. The case emphasizes the critical role of the TTN gene in cardiac function and the genetic complexity underlying DCM. A comprehensive literature review highlighted the prevalence and significance of splice variants in the TTN gene, particularly those affecting the titin A-band, which is known for its role in muscle contraction and stability. This variant's identification underscores the importance of genetic screening in patients with DCM, offering insights into the disease's familial transmission and potential therapeutic targets. Our findings contribute to the expanding knowledge of genetic factors in DCM, demonstrating the necessity of integrating genetic diagnostics in cardiovascular medicine. This case supports the growing evidence linking splicing mutations in specific regions of the TTN gene to DCM development and underscores the importance of genetic counseling and testing in managing heart disease.
PubMed: 38938651
DOI: 10.3389/fcvm.2024.1387063 -
BMC Cardiovascular Disorders Jun 2024The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma....
Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.
BACKGROUND
The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.
METHODS
We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.
RESULTS
Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.
CONCLUSIONS
2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
Topics: Humans; Female; Male; Middle Aged; Prospective Studies; Predictive Value of Tests; Aged; Ventricular Function, Left; Radiation Injuries; Risk Assessment; Systole; Cardiotoxicity; Risk Factors; Adult; Time Factors; Thoracic Neoplasms; Radiotherapy; Ventricular Function, Right; Echocardiography; Heart Disease Risk Factors; Stroke Volume
PubMed: 38937716
DOI: 10.1186/s12872-024-03981-1 -
ACS Applied Materials & Interfaces Jun 2024Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle...
Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting patches exhibited excellent electrical conductivity, elasticity, and mechanical and contractile strengths, which are critical parameters for reinforcing weakened cardiac contraction and impulse propagation. Furthermore, the PVA-GA/PEDOT blend is suitable for direct ink writing via a melting extrusion. As a proof of concept, we have proven the efficiency of the patches in propagating the electrical signal in adult mouse cardiomyocytes through recordings of intracellular Ca transients during cell stimulation. Finally, the patches were implanted in healthy mouse hearts to demonstrate their accommodation and biocompatibility. Magnetic resonance imaging revealed that the implants did not affect the essential functional parameters after 2 weeks, thus showing great potential for treating cardiomyopathies.
PubMed: 38936818
DOI: 10.1021/acsami.4c03784 -
JMIR Formative Research Jun 2024Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the...
BACKGROUND
Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the recommended first-line treatment. However, multiple individual and institutional barriers impede women's access to skilled care. Evidence suggests that digital health solutions are acceptable and may be effective in delivering first-line incontinence treatment, although these technologies have not yet been leveraged at scale.
OBJECTIVE
The primary objective is to describe the effectiveness and safety of a prescribed digital health treatment program to guide PFMT for UI treatment among real-world users. The secondary objectives are to evaluate patient engagement following an updated user platform and identify the factors predictive of success.
METHODS
This retrospective cohort study of women who initiated device use between January 1, 2022, and June 30, 2023, included users aged ≥18 years old with a diagnosis of stress, urgency, or mixed incontinence or a score of >33.3 points on the Urogenital Distress Inventory Short Form (UDI-6). Users are prescribed a 2.5-minute, twice-daily, training program guided by an intravaginal, motion-based device that pairs with a smartphone app. Data collected by the device or app include patient-reported demographics and outcomes, adherence to the twice-daily regimen, and pelvic floor muscle performance parameters, including angle change and hold time. Symptom improvement was assessed by the UDI-6 score change from baseline to the most recent score using paired 2-tailed t tests. Factors associated with meeting the UDI-6 minimum clinically important difference were evaluated by regression analysis.
RESULTS
Of 1419 users, 947 met inclusion criteria and provided data for analysis. The mean baseline UDI-6 score was 46.8 (SD 19.3), and the mean UDI-6 score change was 11.3 (SD 19.9; P<.001). Improvement was reported by 74% (697/947) and was similar across age, BMI, and incontinence subtype. Mean adherence was 89% (mean 12.5, SD 2.1 of 14 possible weekly uses) over 12 weeks. Those who used the device ≥10 times per week were more likely to achieve symptom improvement. In multivariate logistic regression analysis, baseline incontinence symptom severity and maximum angle change during pelvic floor muscle contraction were significantly associated with meeting the UDI-6 minimum clinically important difference. Age, BMI, and UI subtype were not associated.
CONCLUSIONS
This study provides real-world evidence to support the effectiveness and safety of a prescribed digital health treatment program for female UI. A digital PFMT program completed with visual guidance from a motion-based device yields significant results when executed ≥10 times per week over a period of 12 weeks. The program demonstrates high user engagement, with 92.9% (880/947) of users adhering to the prescribed training regimen. First-line incontinence treatment, when implemented using this digital program, leads to statistically and clinically substantial symptom improvements across age and BMI categories and incontinence subtypes.
PubMed: 38935967
DOI: 10.2196/58551 -
Medicine and Science in Sports and... Jun 2024This study investigated the magnitude and etiology of neuromuscular fatigue and muscle damage induced by eccentric cycling compared to conventional concentric cycling in...
INTRODUCTION
This study investigated the magnitude and etiology of neuromuscular fatigue and muscle damage induced by eccentric cycling compared to conventional concentric cycling in patients with breast cancer.
METHODS
After a gradual familiarization protocol for eccentric cycling, nine patients with early-stage breast cancer performed three cycling sessions in eccentric or concentric mode. The eccentric cycling session (ECC) was compared to concentric cycling sessions matched for power output (CONpower, 80% of concentric peak power output, 95 ± 23 W) or oxygen uptake (10 ± 2 mL.min.kg-1). Pre- to postexercise changes (30s through 10 min recovery) in knee extensor maximal voluntary contraction force (MVC), voluntary activation, and quadriceps potentiated twitch force (Qtw) were quantified to determine global, central, and peripheral fatigue, respectively. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured in the plasma before and 24 h postexercise as markers of muscle damage.
RESULTS
Compared to CONpower (-11 ± 9%) and (-5 ± 5%), the ECC session resulted in a greater decrease in MVC (-25 ± 12%) postexercise (P < 0.001). Voluntary activation decreased only in ECC (-9 ± 6% postexercise, P < 0.001). The decrease in Qtw was similar postexercise between ECC and CONpower (-39 ± 21% and -40 ± 16%, P > 0.99) but lower in (P < 0.001). The CONpower session resulted in twofold greater compared to the ECC and sessions (P < 0.001). No change in CK or LDH activity was reported from preexercise to 24 h postexercise.
CONCLUSIONS
The ECC session induced greater neuromuscular fatigue compared to the concentric cycling sessions without generating severe muscle damage. ECC is a promising exercise modality for counteracting neuromuscular maladaptation in patients with breast cancer.
PubMed: 38935539
DOI: 10.1249/MSS.0000000000003506 -
Clinical Nutrition ESPEN Jun 2024Aging frequently causes changes in body composition, such as a loss of strength and muscular mass and an increase in fat mass. Exercise training programs have been...
BACKGROUND & AIMS
Aging frequently causes changes in body composition, such as a loss of strength and muscular mass and an increase in fat mass. Exercise training programs have been suggested as effective strategies to mitigate or prevent age-related declines in body composition. Therefore, this study examined the effects of a sixteen-week High-Speed Resistance Training (HSRT) program on body composition parameters in community-dwelling independent older adults.
METHODS
The present clinical trial included 79 older adults, who were divided into two groups: intervention group (IG, N = 40, age, 68.50 ± 3.54 years; weight, 68.65 ± 11.36 kg) and control group (CG, N = 39, age, 72.08 ± 5.89 years; weight, 67.04 ± 10.69 kg). IG performed the supervised HSRT for 16 weeks, with 3 sessions per week of 60-70min, each session of 5-6 exercises, 2-3 sets, and 6-10 reps/exercise, while CG did not perform any exercise training program. Body composition parameters were assessed using a multifrequency tetrapolar bioelectrical impedance analyzer (InBody® S10). The level of physical activity and the dietary intake were evaluated by the International Physical Activity Questionnaire (IPAQ-SF) and the Food Frequency Questionnaire, respectively. Statistical analyses were performed using the analysis of covariance (ANCOVA), and effect size (Cohen's d).
RESULTS
The analysis showed significant effects of the group factor for IG on phase angle (F = 14.39, p < 0.001, η = 0.159). Additionally, results from Δ changes (post-minus pre-values) revealed small and medium effects in favor to IG for body cell mass (t = 1.21, p = 0.230, d = 0.27 [-0.17, 0.71]) and phase angle (t = 2.82, p = 0.006, d = 0.63 [0.18, 1.08]), respectively.
CONCLUSIONS
The HSRT could effectively prevent the decline in cellular health and cell integrity in older adults, as evidenced by the significant improvements in the phase angle.
REGISTRATION
Clinicaltrial.gov (ID: NCT05586087).
PubMed: 38935496
DOI: 10.1016/j.clnesp.2024.06.010 -
IEEE Transactions on Neural Systems and... Jun 2024Robotic rehabilitation has been shown to match the effects of conventional physical therapy on motor function for patients with neurological diseases. Rehabilitation...
Robotic rehabilitation has been shown to match the effects of conventional physical therapy on motor function for patients with neurological diseases. Rehabilitation robots have the potential to reduce therapists' workload in time-intensive training programs as well as perform actions that are not replicable by human therapists. We investigated the effects of one such modality that cannot be achieved by a human therapist: assistance and resistance within the electromechanical delay between muscle activation and muscle contraction during arm extension. We found increased muscle activation when providing robotic assistance within this electromechanical delay. Assistance provided within this delay moves the participant's arm quicker than their own muscle and increases the subsequent peak voluntary muscle activation compared to normal arm extension by 68.97 ± 80.05% (SE = 0.021; p = 0.007). This is surprising since all previous literature shows that muscle activation either decreases or does not change when participants receive robotic assistance. As a consequence, traditional robotic rehabilitation incrementally reduces assistance as the patient improves to maintain levels of muscle activation which is suggested to be important for neuronal repair. The present result may enable therapists to no longer have to choose between providing assistance or increasing muscle activation. Instead, therapists may be able to provide assistance while also increasing muscle activation.
PubMed: 38935467
DOI: 10.1109/TNSRE.2024.3419688