Molecular basis of force-pCa relation in MYL2 cardiomyopathy mice: Role of the super-relaxed state of myosin.

In this study, we investigated the role of the super-relaxed (SRX) state of myosin in the structure-function relationship of sarcomeres in the hearts of mouse models of cardiomyopathy-bearing mutations in the human ventricular regulatory light chain (RLC, MYL2 gene). Skinned papillary muscles from hypertrophic (HCM-D166V) and dilated (DCM-D94A) cardiomyopathy models were subjected to small-angle X-ray diffraction simultaneously with isometric force measurements to obtain the interfilament lattice spacing and equatorial intensity ratios (I11/I10) together with the force-pCa relationship over a full range of [Ca2+] and at a sarcomere length of 2.1 µm. In parallel, we studied the effect of mutations on the ATP-dependent myosin energetic states. Compared with wild-type (WT) and DCM-D94A mice, HCM-D166V significantly increased the Ca2+ sensitivity of force and left shifted the I11/I10-pCa relationship, indicating an apparent movement of HCM-D166V cross-bridges closer to actin-containing thin filaments, thereby allowing for their premature Ca2+ activation. The HCM-D166V model also disrupted the SRX state and promoted an SRX-to-DRX (super-relaxed to disordered relaxed) transition that correlated with an HCM-linked phenotype of hypercontractility. While this dysregulation of SRX ↔ DRX equilibrium was consistent with repositioning of myosin motors closer to the thin filaments and with increased force-pCa dependence for HCM-D166V, the DCM-D94A model favored the energy-conserving SRX state, but the structure/function-pCa data were similar to WT. Our results suggest that the mutation-induced redistribution of myosin energetic states is one of the key mechanisms contributing to the development of complex clinical phenotypes associated with human HCM-D166V and DCM-D94A mutations.

Residual force depression is not related to positive muscle fascicle work during submaximal voluntary dorsiflexion contractions in humans.

Residual force depression (rFD) following active muscle shortening is assumed to correlate most strongly with muscle work, but this has not been tested during voluntary contractions in humans. Using dynamometry, we compared steady-state ankle joint torques (N = 16) following tibialis anterior (TA) muscle-tendon unit (MTU) lengthening and shortening to the time-matched torque during submaximal voluntary fixed-end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. Ultrasound revealed significantly reduced (P < 0.001) TA fascicle shortening amplitudes during MTU lengthening without a preload over small and medium amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large amplitude significantly (P < 0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to MTU lengthening without a preload (P = 0.001). Significant (P = 0.028) steady-state fascicle force enhancement relative to REF was observed following MTU lengthening, and was similar among MTU lengthening-hold conditions (3-5%). MTU shortening with and without a preload over small and large amplitudes significantly (P < 0.001) increased positive fascicle and MTU work relative to REF, but significant (P = 0.006) rFD was observed following MTU shortening with a preload (7-10%) only. rFD was linearly related to positive MTU work [rrm (47) = 0.48, P < 0.001], but not positive fascicle work [rrm (47) = 0.16, P = 0.277]. Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady-state force output, which might arise from less shortening-induced rFD. Our findings also indicate similar rFD following different amounts of positive fascicle/MTU work, which cautions against using work to predict rFD during submaximal voluntary contractions. KEY POINTS: Accurately predicting muscle force is challenging because active muscle shortening depresses force output. The residual force depression (rFD) that exists following active muscle shortening is commonly assumed to correlate strongly and positively with muscle work. We found that tibialis anterior muscle fascicle work and muscle-tendon unit work did not accurately predict rFD during submaximal voluntary dorsiflexion contractions. Fascicle shortening during fixed-end reference contractions also potentially induced rFD of 3-5%, which was similar to the rFD following muscle-tendon unit shortening without a preload. A higher number of active muscle fibres during shortening probably increased rFD, which suggests that motor unit recruitment during shortening might predict rFD.

Age-dependent effects of the ß3 adrenoceptor agonist CL316,243 on human and rat detrusor muscle strips.

Motility of detrusor smooth muscle includes adrenergic relaxation and cholinergic contraction. Since the latter may be deregulated in overactive bladder (OAB) pathophysiology, anticholinergics are the standard therapy but occasionally less tolerated due to side effects such as dry mouth and constipation. ß3 adrenoceptor agonists also alleviate OAB symptoms by relaxing the detrusor muscle. Their age dependence, however, is far from understood. To address this issue, we induced contractions with KCl (60 mM) and carbachol (from 10 nM to 100 µM) in the presence of the ß3 adrenoceptor agonist CL316,243 (from 0.1 to 10 µM) in both human and rat muscle strips. Our results confirmed that both contractions were attenuated by ß3 adrenoceptor activation in both species, but with differing age dependence. In humans, specimens from mid-life subjects showed a significantly more pronounced effect of CL316,243 in attenuating carbachol-induced contractions than those from aged subjects (Cohen's d of maximal attenuation: 1.82 in mid-life versus 0.13 in aged) without altering EC50. Conversely, attenuation of KCl responses by CL316,243 increased during ageing (Spearman correlation coefficient = -0.584, P<0.01). In rats, both KCl- and carbachol-induced contractions were significantly more attenuated by CL316,243 in samples from adolescent as compared to aged samples. Immunohistochemistry in human detrusor sections proved ß3 adrenoreceptor abundance to remain unaltered during ageing. In conclusion, our findings suggest differential age-dependent changes in human ß3 adrenoceptor-dependent attenuation of detrusor contraction in terms of electromechanical versus pharmacomechanical coupling; they may help understand the differential responsiveness of OAB patients to ß3 agents.

Physical Effort Pre-Crastination Determines Preference in an Isometric Task.

How the brain decides when to invest effort is a central question in neuroscience. When asked to walk a mile to a destination, would you choose a path with a hill at the beginning or the end? The traditional view of effort suggests we should be indifferent-all joules are equal so long as it does not interfere with accomplishing the goal. Yet when total joules are equal across movement decisions, the brain's sensitivity to the temporal profile of effort investment remains poorly understood. Here, we sought to parse the interaction of time and physical effort by comparing subjective preferences in an isometric arm-pushing task that varied the duration and timing of high and low effort. Subjects were presented with a series of two-alternative forced choices, where they chose the force profile they would rather complete. Subjects preferred earlier physical effort (i.e., to pre-crastinate) but were idiosyncratic about preference for task timing. A model of subjective utility that includes physical effort costs, task costs, and independent temporal sensitivity factors described subject preferences best. Interestingly, deliberation time and response vigor covary with the same subjective utility model for preference, suggesting a utility that underlies both decision making and motor control. These results suggest physical effort costs are temporally sensitive, with earlier investment of effort preferred to later investment, and that the representation of effort is based not only on the total energy required but when it is required to invest that energy.

Effect of isometric quadriceps exercise on local microcirculation of the infrapatellar fat pad in female patients with knee osteoarthritis.

OBJECTIVE: To elucidate the local microcirculation of the infrapatellar fat pad (IFP) in patients with knee osteoarthritis (KOA) by determining the changes in IFP hardness and hemoglobin concentration during isometric quadriceps exercise (IQE). DESIGN: In this observational cross-sectional study, patients diagnosed with bilateral KOA were included in the KOA group (30 knees), healthy older adults in the control group (20 knees), and younger adults in the young group (20 knees). Ultrasonography was performed at rest and during IQE to measure IFP hardness based on shear wave velocity. Near-infrared spectroscopy was performed to measure oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (cHb) in the IFP before (Baseline), during (IQE task), and after IQE (Post). IFP hardness and O2Hb, HHb, and cHb concentration were analyzed using a linear mixed model for the groups and measurement points. RESULTS: During IQE, IFP hardness changes were significantly less in the KOA group than in the other groups (KOA: 95 % confidence intervals (CIs) [-0.854, 0.028]; control: 95 % CI [-0.941, -0.341]; and young: 95 % CI [-2.305, -1.706]). In the KOA group, O2Hb concentration exhibited no significant changes at Post compared with Baseline; however, significant changes were observed in the other groups (KOA: 95 % CI [-1.176, 0.423]; control: 95 % CI [-1.452, -0.276]; and young: 95 % CI [-4.062, -2.102]). CONCLUSIONS: During IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP.

The effects of muscle starting length on work loop power output of isolated mouse soleus and extensor digitorum longus muscle.

Force-length relationships derived from isometric activations may not directly apply to muscle force production during dynamic contractions. As such, different muscle starting lengths between isometric and dynamic conditions could be required to achieve maximal force and power. Therefore, this study examined the effects of starting length [±5-10% of length corresponding to maximal twitch force (L0)] on work loop (WL) power output (PO), across a range of cycle frequencies, of the soleus (SOL) and extensor digitorum longus muscle (EDL; N=8-10) isolated from ∼8 week old C57 mice. Furthermore, passive work was examined at a fixed cycle frequency to determine the association of passive work and active net work. Starting length affected maximal WL PO of the SOL and EDL across evaluated cycle frequencies (P<0.030, ηp2>0.494). For the SOL, PO produced at -5% L0 was greater than that at most starting lengths (P<0.015, Cohen's d>0.6), except -10% L0 (P=0.135, d<0.4). However, PO produced at -10% L0 versus L0 did not differ (P=0.138, d=0.35-0.49), indicating -5% L0 is optimal for maximal SOL WL PO. For the EDL, WL PO produced at -10% L0 was lower than that at most starting lengths (P<0.032, d>1.08), except versus -5% L0 (P=0.124, d<0.97). PO produced at other starting lengths did not differ (P>0.163, d<1.04). For the SOL, higher passive work was associated with reduced PO (Spearman's r=0.709, P<0.001), but no relationship was observed between passive work and PO of the EDL (Pearson's r=0.191, r2=0.04, P=0.184). This study suggests that starting length should be optimised for both static and dynamic contractions and confirms that the force-length curve during dynamic contractions is muscle specific.

Metaplastic neuromodulation via transcranial direct current stimulation has no effect on corticospinal excitability and neuromuscular fatigue.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing neuromuscular fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter- individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on neuromuscular fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate neuromuscular fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 min. Neuromuscular fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate neuromuscular fatigue in young healthy individuals.

Effects of Operating Mechanical Conditions and Polymer Networks of Nematic Elastomers on Photo-Induced Mechanical Performances.

Photoresponsive liquid-crystalline elastomers (LCEs) are promising candidates for light-controlled soft actuators. Photoinduced stress/strain originates from the changes in mechanical properties after light irradiation. However, the correlation between the photoinduced mechanical performance and in-use conditions such as stress/strain states and polymer network properties (such as effective crosslink density and dangling chain density) remains unexplored for practical applications. Here, isometric photo-induced stress or isotonic strain is investigated at different operating strains or stresses, respectively, on LCEs with polymer network variations, produced by different amounts of solvent during polymerization. As the solvent volume increases, the moduli and photoinduced stresses decrease. However, the photo-induced strain, fracture strain, fracture stress, and viscosity increase. The optical response performance initially increases with the operating strain/stress, peaks at a higher actuation strain/stress, and then, decreases depending on the polymer network. The maximum work densities, which also depend on the operating stress, are in the range of ≈200-300 kJm-3. These findings, highlighting the significant variations in the mechanical performance with the operating stress/strain ranges and amount of solvent used in the synthesis, are critical for designing LCE-based mechanical devices.

How periodic surfaces bend.

A periodic surface is one that is invariant by a two-dimensional lattice of translations. Deformation modes that stretch the lattice without stretching the surface are effective membrane modes. Deformation modes that bend the lattice without stretching the surface are effective bending modes. For periodic piecewise smooth simply connected surfaces, it is shown that the effective membrane modes are, in a sense, orthogonal to effective bending modes. This means that if a surface gains a membrane mode, it loses a bending mode, and conversely, in such a way that the total number of modes, membrane and bending combined, can never exceed 3. Various examples, inspired from curved-crease origami tessellations, illustrate the results.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Effect of muscle stretching and isometric exercises on quality of life in children undergoing regular hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent health issue that can have detrimental effects on the quality of life (QoL) of children. Nevertheless, with adequate management and support, many children with CKD can have satisfying lives. The study aimed to investigate the effect of muscle stretching and isometric exercises on QoL of children undergoing hemodialysis. METHODS: Sixty-eight children aged 6-18 years with kidney failure undergoing hemodialysis at Assiut University Children Hospital were included. They were randomly assigned to two groups. The study group received a 40-min exercise program three times per week for 2 months, while the control group received routine hospital care. For outcome measures, two tools were used: a simple questionnaire sheet for personal and medical data and PedsQL™ scale. RESULTS: After 2 months of exercise, it was shown that most children in the study group (66.7%) had good QoL, in contrast to only 3.3% in the control group, with a highly statistically significant variation between the two examined groups pertaining to the health-related QoL scale (P value = 0.001) after exercise. CONCLUSION: The intensity of care for children on hemodialysis has a distinguished impact upon their quality of life. The implementation of muscle stretching and isometric exercises during hemodialysis represents an important aspect of such care that may be associated with significant improvement in all domains of QoL. Children undergoing hemodialysis need well-organized programs that cover all physical and psychological aspects with smart time manipulation and increased attention from their staff.

Responses to Valsalva's maneuver in spinal cord injury do not broadly relate to vasoconstrictor capacity.

PURPOSE: A blood pressure stabilization during late phase II of Valsalva's maneuver may be utilized to confirm sympathetic vasoconstrictor control after a spinal cord injury. This study investigated whether Valsalva response was predictive of hemodynamics during tilt or isometric handgrip. METHODS: Presence/absence of Valsalva response was compared to heart rate, mean arterial pressure, leg blood flow, and vascular resistance during head-up tilt and isometric handgrip to fatigue in 14 adults with spinal cord injury from C7 to T12 and 14 controls. Statistics were performed with two-way repeated measure analysis of variance (ANOVA), post hoc t-tests for between-group comparisons, and Mann-Whitney U tests for within-group. RESULTS: In total, six participants with spinal cord injury lacked a blood pressure stabilization for Valsalva's maneuver. However, this was not related to vasoconstrictor responses during the other tests. The groups had similar heart rate and blood pressure changes during tilt, though leg blood flow decreases and vascular resistance increases tended to be smaller at 20° tilt in those with spinal cord injury (p = 0.07 and p = 0.11, respectively). Participants with spinal cord injury had lower heart rates and markedly smaller blood pressure increases during handgrip (both p < 0.05). There were no group differences in leg blood flow, but those with spinal cord injury demonstrated a blunted vascular resistance increase by the final 10% of the handgrip (p < 0.01). CONCLUSIONS: Valsalva response was not consistent with hemodynamics during other stimuli, but some individuals evidence increases in sub-lesional vascular resistance to isometric handgrip comparable to controls, suggesting a sympathoexcitatory stimulus may be critical to provoke hemodynamic responses after spinal cord injury.

Isokinetic training of lower extremity during the early stage promote functional restoration in elder patients with disability after Total knee replacement (TKR) - a randomized control trial.

BACKGROUND: Transient progressive weakness and disability of lower limb during the early stage after TKR will increase the risk of fall, but the superior postoperative strength training mode have not been elucidated for functional restoration. This study aimed to compare whether the isokinetic lower limb training is superior to either isotonic or home isometric exercise during early stage after TKR in older people. METHODS: A total of 43 recruited old participants (mean age, 68.40 years old) receiving TKR were divided randomly based on the different four-week training modes into three groups including isokinetic, isotonic, and home isometric exercise (control group). The primary outcome was set as functional performance in terms of Timed Up and Go (TUG) test and the secondary outcomes include the peak torque of knee at 60 and 120 degree/ second, Short-Form 36 Health Survey (SF-36), and Western Ontario and McMaster Universities Arthritis index (WOMAC). RESULTS: All of the peak torque measurements of the knee improved significantly in both the isokinetic and the isotonic group, but not in the control group. Although isotonic training resulted in more strength gains, a significant enhancement in TUG test was observed in the isokinetic group only (p = 0.003). However, there were no significantly improvement of TUG test after training in other two groups. SF-36 and WOMAC improved after training in all three groups, with no significant difference in the degree of improvement between groups. CONCLUSION: Isokinetic training for 4 weeks following TKR effectively improved all the outcome parameters in this study, including the TUG test, lower limb strength, and functional scores. However, both isokinetic and isotonic training modes could be recommended after TKR because of no significant difference in the degree of improvement between these two groups. TRIAL REGISTRATION: Clinical trial registration number: NCT02938416. LEVEL OF EVIDENCE: I.

The mechanisms underpinning the slow component of [Formula: see text] in humans.

PURPOSE: When exercising above the lactic threshold (LT), the slow component of oxygen uptake ([Formula: see text]) appears, mainly ascribed to the progressive recruitment of Type II fibers. However, also the progressive decay of the economy of contraction may contribute to it. We investigated oxygen uptake ([Formula: see text]) during isometric contractions clamping torque (T) or muscular activation to quantify the contributions of the two mechanisms. METHODS: We assessed for 7 min T of the leg extensors, net oxygen uptake ([Formula: see text]) and root mean square (RMS) from vastus lateralis (VL) in 11 volunteers (21 ± 2 yy; 1.73 ± 0.11 m; 67 ± 14 kg) during cyclic isometric contractions (contraction/relaxation 5 s/5 s): (i) at 65% of maximal voluntary contraction (MVC) (FB-Torque) and; (ii) keeping the level of RMS equal to that at 65% of MVC (FB-EMG). RESULTS: [Formula: see text] after the third minute in FB-Torque increased with time ([Formula: see text] = 94 × t + 564; R2 = 0.99; P = 0.001), but not during FB-EMG. [Formula: see text]/T increased only during FB-Torque ([Formula: see text]/T = 1.10 × t + 0.57; R2 = 0.99; P = 0.001). RMS was larger in FB-Torque than in FB-EMG and significantly increased in the first three minutes of exercise to stabilize till the end of the trial, indicating that the pool of recruited MUs remained constant despite [Formula: see text]. CONCLUSION: The analysis of the RMS, [Formula: see text] and T during FB-Torque suggests that the intrinsic mechanism attributable to the decay of contraction efficiency was responsible for an increase of [Formula: see text] equal to 18% of the total [Formula: see text].

The effect of caffeine chewing gum on muscle performance and fatigue after severe-intensity exercise: isometric vs. dynamic assessments in trained cyclists.

This study investigated the effect of caffeinated chewing gum (GUMCAF) on muscle fatigue (isometric vs. dynamic) after severe-intensity cycling bouts. Fifteen trained male cyclists participated in four visits. Each visit involved two severe-intensity cycling bouts (Δ1 and Δ2) lasting 6 min, separated by a 5-min recovery period. Muscle fatigue was assessed by isometric maximal voluntary knee extension contraction (IMVC) with twitch interpolation technique and dynamically by 7 s all-out cycling sprints. Assessments were performed before GUMCAF (Pre-GUM) and after the cycling bouts (Post-Exercise). GUMCAF and placebo gum (GUMPLA) were administered in a randomized double-blind procedure with participants receiving each gum type (GUMCAF and GUMPLA) during two separate visits. The results showed no significant interaction between gum types and time for the isometric and dynamic measurements (p > 0.05). The percentage change in performance from Pre-GUM to Post-Exercise showed no significant difference between GUMCAF and GUMPLA for either the dynamic-derived TMAX (~ -17.8% and -15.1%, respectively; p = 0.551) or isometric IMVC (~ -12.3% and -17.7%, respectively; p = 0.091) measurements. Moderate to large correlations (r = 0.31-0.51) were found between changes in sprint maximal torque and maximal power output measurements and isometric force, for both gum conditions. GUMCAF was not effective in attenuating muscle force decline triggered by severe-intensity cycling exercises, as measured by both isometric and dynamic methods. The correlations between IMVC and cycling maximal torque and power output suggest caution when interpreting isometric force as a direct measure of fatigue during dynamic cycling exercises.

Can isometric testing substitute for the one repetition maximum squat test?

When measuring maximum strength, a high accuracy and precision is required to monitor the training adaptations. Based on available reliability parameters, the literature suggests the replacement of the one repetition maximum (1RM) by isometric testing to save testing time. However, from a statistical point of view, correlation coefficients do not provide the required information when aiming to replace one test by another. Therefore, the literature suggests the inclusion of the mean absolute error (MAE), the mean absolute percentage error (MAPE) for agreement analysis. Consequently, to check the replaceability of 1RM testing methods, the current study examined the agreement of isometric and dynamic testing methods in the squat and the isometric mid-thigh pull. While in accordance with the literature, correlations were classified high r = 0.638-0.828 and ICC = 0.630-0.828, the agreement analysis provided MAEs of 175.75-444.17 N and MAPEs of 16.16-57.71% indicating an intolerable high measurement error between isometric and dynamic testing conditions in the squat and isometric mid-thigh pull. In contrast to previous studies, using MAE, MAPE supplemented by CCC and BA analysis highlights the poor agreement between the included strength tests. The recommendation to replace 1RM testing with isometric testing routines in the squat does not provide suitable concordance and is not recommended.

Measuring critical force in sport climbers: a validation study of the 4 min all-out test on finger flexors.

PURPOSE: The critical force (CF) concept, differentiating steady and non-steady state conditions, extends the critical power paradigm for sport climbing. This study aimed to validate CF for finger flexors derived from the 4 min all-out test as a boundary for the highest sustainable work intensity in sport climbers. METHODS: Twelve participants underwent multiple laboratory visits. Initially, they performed the 4 min intermittent contraction all-out test for CF determination. Subsequent verification visits involved finger-flexor contractions at various intensities, including CF, CF -2 kg, CF -4 kg, and CF -6 kg, lasting for 720 s or until failure, while monitoring muscle-oxygen dynamics of forearm muscles. RESULTS: CF, determined from the mean force of last three contractions, was measured at 20.1 ± 5.7 kg, while the end-force at 16.8 ± 5.2 kg. In the verification trials, the mean time to failure at CF was 440 ± 140 s, with only one participant completing the 720 s task. When the load was continuously lowered (-2 kg, -4 kg, and -6 kg), a greater number of participants (38%, 69%, and 92%, respectively) successfully completed the 720 s task. Changes of muscle-oxygen dynamics showed a high variability and could not clearly distinguish between exhaustive and non-exhaustive trials. CONCLUSIONS: CF, based on the mean force of the last three contractions, failed to reliably predict the highest sustainable work rate. In contrast, determining CF as the end-force of the last three contractions exhibited a stronger link to sustainable work. Caution is advised in interpreting forearm muscle-oxygen dynamics, lacking sensitivity for nuanced metabolic responses during climbing-related tasks.

Effects of lunges inserted in walking (eccentric walking) on lower limb muscle strength, physical and cognitive function of regular walkers.

INTRODUCTION: Walking is a popular exercise but does not increase lower limb muscle strength and balance. We hypothesized that muscle strength, physical and cognitive function would be improved by inserting lunges in conventional walking. METHODS: Eleven regular walkers (54-88 years) who had more than 5000 steps in exercise walking a day at least 5 days a week participated in this study. They walked as usual for the first 4 weeks and included lunges and descending stairs or slope walking (i.e., eccentric walking) for the next 8 weeks. The steps of eccentric walking were gradually increased from 100 to 1000 steps per week over 8 weeks. RESULTS: The average steps per day were 10,535 ± 3516 in the first 4 weeks, and 10,118 ± 3199 in the eccentric walking period without a significant difference. No significant changes in maximal voluntary isometric contraction torque of the knee extensors (MVC), 30-s chair stand (CS), 2-min step, balance assessed by center of pressure movement area with eyes close, sit and reach, a digit symbol substitution test (DSST) for cognitive function were observed in the first 4 weeks. However, significant (P < 0.05) improvements were evident in MVC (18.6 ± 15.7%), CS (24.2 ± 17.3%), balance ( - 45.3 ± 34.5%), and DSST (20.8 ± 16.7%) from weeks 4 to 12. Serum complement component 1q concentration decreased (P < 0.05) from weeks 4 to 12, although no changes in serum glucose, triglyceride, and cholesterol concentrations were observed. CONCLUSION: These results supported the hypothesis, and suggest that eccentric walking provides effects that are not achieved by conventional walking.

The Contractile Machines of the Heart.

This chapter will describe basic structural and functional features of the contractile apparatus of muscle cells of the heart, namely, cardiomyocytes and smooth muscle cells. Cardiomyocytes form the contractile myocardium of the heart, while smooth muscle cells form the contractile coronary vessels. Both muscle types have distinct properties and will be considered with respect to their cellular appearance (brick-like cross-striated versus spindle-like smooth), arrangement of contractile proteins (sarcomeric versus non-sarcomeric organization), calcium activation mechanisms (thin-filament versus thick-filament regulation), contractile features (fast and phasic versus slow and tonic), energy metabolism (high oxygen versus low oxygen demand), molecular motors (type II myosin isoenzymes with high adenosine diphosphate [ADP]-release rate versus myosin isoenzymes with low ADP-release rates), chemomechanical energy conversion (high adenosine triphosphate [ATP] consumption and short duty ratio versus low ATP consumption and high duty ratio of myosin II cross-bridges [XBs]), and excitation-contraction coupling (calcium-induced calcium release versus pharmacomechanical coupling). Part of the work has been published (Neuroscience - From Molecules to Behavior", Chap. 22, Galizia and Lledo eds 2013, Springer-Verlag; with kind permission from Springer Science + Business Media).

Comparing the effects of neck stabilization exercises versus dynamic exercises among patients having nonspecific neck pain with forward head posture: a randomized clinical trial.

BACKGROUND: Nonspecific neck pain (NSNP) is a well-established global burden affecting. It is also a common problem in Pakistan. The burden of neck pain is also increasing day by day due to poor work ergonomics, and increased use of computers and mobiles after the pandemic. An individual's poor posture is often associated with forward head posture (FHP). Limited evidence is available about the effects of neck stabilization (NSE) and dynamic exercises (NDE) for nonspecific neck pain particularly in patients with FHP. This aimed to compare the effects of NSE versus NDE among patients having NSNP with FHP in reducing pain, disability, forward head posture and improving neck range of motion. METHODS: It is a single-blinded randomized clinical trial with 60 patients aged 18-40 years, with moderate intensity NSNP for > 3 weeks and < 6 months along with FHP with a moderate disability on neck disability index (NDI) randomly assigned to the treatment groups. Group 1 was doing NSE and group 2 was doing NDE. Transcutaneous Electical Nerve Stimulation, cold packs, and stretching exercises were given to both groups. A total of 9 sessions (3 sessions/ week) were given to participants. NDI questionnaire, Visual analogue scale (VAS), goniometry, and plumb line measurement tool were used as baseline and assessment at the end of 3rd week. The data was analyzed on SPSS version 21. Descriptive analysis was performed. Independent t-test was used for between group comparison and paired t-test used for within group comparison. A p-value less than 0.05 was considered statistically significant. RESULTS: After treatment within-group analysis of both NSE and NDE showed significant (p < 0.001) improvement in pain on VAS, all ROMs of the neck including flexion, extension, left and right lateral flexion and left rotation, plumb line and NDI score with very large effect size. However, between-group analysis showed non-significant differences (p > 0.05) for post-treatment mean VAS, neck ROM, NDI and plumb line measurement. CONCLUSION: Between NSE and NDE, no one is more beneficial than another. Both are equally effective in alleviating pain, increasing ROM, decreasing functional disability, and improving forward head posture in patients with NSNP. TRIAL REGISTRATION: Registered trial at ClinicalTrials.gov Identifier: NCT05298631, 28/03/2022, prospectively registered.

Adaptive Force of hamstring muscles is reduced in patients with knee osteoarthritis compared to asymptomatic controls.

BACKGROUND: Quadriceps strength deficits are known for patients with knee osteoarthritis (OA), whereas findings on hamstrings are less clear. The Adaptive Force (AF) as a special neuromuscular function has never been investigated in OA before. The maximal adaptive holding capacity (max. isometric AF; AFisomax) has been considered to be especially vulnerable to disruptive stimuli (e.g., nociception). It was hypothesized that affected limbs of OA patients would show clear deficits in AFisomax. METHODS: AF parameters and the maximal voluntary isometric contraction (MVIC) of hamstrings were assessed bilaterally comparing 20 patients with knee OA (ART) vs. controls (CON). AF was measured by a pneumatically driven device. Participants were instructed to maintain a static position despite an increasing load of the device. After reaching AFisomax, the hamstrings merged into eccentric action whereby the force increased further to the maximum (AFmax). MVIC was recorded before and after AF trials. Mixed ANOVA was used to identify differences between and within ART and CON (comparing 1st and 2nd measured sides). RESULTS: AFisomax and the torque development per degree of yielding were significantly lower only for the more affected side of ART vs. CON (p ≤ 0.001). The percentage difference of AFisomax amounted to - 40%. For the less affected side it was - 24% (p = 0.219). MVIC and AFmax were significantly lower for ART vs. CON for both sides (p ≤ 0.001). Differences of MVIC between ART vs. CON amounted to - 27% for the more, and - 30% for the less affected side; for AFmax it was - 34% and - 32%, respectively. CONCLUSION: The results suggest that strength deficits of hamstrings are present in patients with knee OA possibly attributable to nociception, generally lower physical activity/relief of lower extremities or fear-avoidance. However, the more affected side of OA patients seems to show further specific impairments regarding neuromuscular control reflected by the significantly reduced adaptive holding capacity and torque development during adaptive eccentric action. It is assumed that those parameters could reflect possible inhibitory nociceptive effects more sensitive than maximal strengths as MVIC and AFmax. Their role should be further investigated to get more specific insights into these aspects of neuromuscular control in OA patients. The approach is relevant for diagnostics also in terms of severity and prevention.