Microfluidic-based models to address the bone marrow metastatic niche complexity.

Bone marrow (BM) is a preferential metastatic site for solid cancers, contributing to higher morbidity and mortality among millions of oncologic patients worldwide. There are no current efficient therapies to minimize this health burden. Microfluidic based in vitro models emerge as powerful alternatives to animal testing, as well as promising tools for the development of personalized medicine solutions. The complexity associated with the BM metastatic niche originated a wide variety of microfluidic platforms designed to mimic this microenvironment. This review gathers the essential parameters to design an accurate in vitro microfluidic device, based on a comparative analysis of existing models created to address the different steps of the metastatic cascade.

Potential involvement of proline and flavonols in plant responses to ozone.

Ozone is considered to be a major phytotoxic pollutant. It is an oxidizing molecule with harmful effects that can affect human health and vegetation. Due to its phytotoxicity, it constitutes a threat to food security in a context of climate change. Proline accumulation is induced in response to numerous stresses and is assumed to be involved in plant antioxidant defense. We therefore addressed the question of the putative involvement of proline in plant ozone responses by analyzing the responses of two Arabidopsis mutants (obtained in the Col-0 genetic background) altered in proline metabolism and different ecotypes with various degrees of ozone sensitivity, to controlled ozone treatments. Among the mutants, the p5cs1 mutant plants accumulated less proline than the double prodh1xprodh2 (p1p2) mutants. Ozone treatments did not induce accumulation of proline in Col-0 nor in the mutant plants. However, the variation of the photosynthetic parameter Fv/Fm in the p1p2 mutant suggests a positive effect of proline. Proline accumulation induced by ozone was only observed in the most ozone-sensitive ecotypes, Cvi-0 and Ler. Contrary to our expectations, proline accumulation could not be correlated with variations in protein oxidation (carbonylation). On the other hand, flavonols content, measured here, using non-destructive methods, reflected exactly the genotypes ranking according to ozone sensitivity.

Training-intensity Distribution on Middle- and Long-distance Runners: A Systematic Review.

Training-intensity distribution (TID) is considered the key factor to optimize performance in endurance sports. This systematic review aimed to: I) characterize the TID typically used by middle-and long-distance runners; II) compare the effect of different types of TID on endurance performance and its physiological determinants; III) determine the extent to which different TID quantification methods can calculate same TID outcomes from a given training program. The keywords and search strategy identified 20 articles in the research databases. These articles demonstrated differences in the quantification of the different training-intensity zones among quantification methods (i. e. session-rating of perceived exertion, heart rate, blood lactate, race pace, and running speed). The studies that used greater volumes of low-intensity training such as those characterized by pyramidal and polarized TID approaches, reported greater improvements in endurance performance than those which used a threshold TID. Thus, it seems that the combination of high-volume at low-intensity (≥ 70% of overall training volume) and low-volume at threshold and high-intensity interval training (≤ 30%) is necessary to optimize endurance training adaptations in middle-and long-distance runners. Moreover, monitoring training via multiple mechanisms that systematically encompasses objective and subjective TID quantification methods can help coaches/researches to make better decisions.

Effects of Different Types of Resistance Training and Detraining on Functional Capacity, Muscle Strength, and Power in Older Women: A Randomized Controlled Study.

ABSTRACT: Filho, MM, Venturini, GRdO, Moreira, OC, Leitão, L, Mira, PA, Castro, JB, Aidar, FJ, Novaes, JdS, Vianna, JM, and Caputo Ferreira, ME. Effects of different types of resistance training and detraining on functional capacity, muscle strength, and power in older women: A randomized controlled study. J Strength Cond Res 36(4): 984-990, 2022-Resistance training (RT) increases muscle strength, power, and functional capacity (FC) of older women. However, these benefits can be lost partially or totally with detraining. This study aimed to compare the effect of 20 weeks of different types of RT and 4 weeks of detraining on muscle strength, power, and FC in older women. Ninety-five older women were randomly divided into 4 experimental groups (strength endurance, power, absolute strength, and relative strength training) and 1 control group (CG). We assessed muscle strength (10RM test) and muscle power of the lower (countermovement jump) and upper limbs (medicine ball pitch). Functional capacity was assessed by the Senior Fitness Test, which comprises the following tests: 30-second arm curl, 30-second chair stand, back scratch, chair sit and reach, 8-foot up and go, and 6-minute walk. The experiment lasted 24 weeks (familiarization: 2 weeks; neural adaptation: 6 weeks; specific training: 12 weeks; and detraining: 4 weeks). Muscle strength, lower and upper limb power (all p < 0.05), 30-second arm curl, 30-second chair stand, 8-foot up and go, 6-minute walk (all p < 0.001), and lower limb flexibility (p = 0.002) improved in all experimental groups after training and CG showed no differences in any of these variables. After detraining, muscle strength, lower and upper limb power (p < 0.05 for all), and FC decreased in comparison to the end of RT (30-second arm curl, 30-second chair stand, 8-foot up and go, 6-minute walk, and lower limb flexibility, p < 0.05 for all). Although the FC of the subjects has been reduced after 4 weeks of detraining, it was maintained at higher levels in comparison to baseline. These results suggested that older women can be submitted to different types of RT to achieve improvements in general fitness.

The lack of neuropeptide Y-Y1 receptor signaling modulates the chemical and mechanical properties of bone matrix.

Genetic and pharmacological functional studies have provided evidence that the lack of Neuropeptide Y-Y1  receptor (Y1 R) signaling pathway induces a high bone mass phenotype in mice. However, clinical observations have shown that drug or genetic mediated improvement of bone mass might be associated to alterations to bone extracellular matrix (ECM) properties, leading to bone fragility. Hence, in this study we propose to characterize the physical, chemical and biomechanical properties of mature bone ECM of germline NPY-Y1 R knockout (Y1 R-/- ) mice, and compare to their wild-type (WT) littermates. Our results demonstrated that the high bone mass phenotype observed in Y1 R-/- mice involves alterations in Y1 R-/-  bone ECM ultrastructure, as a result of accelerated deposition of organic and mineral fractions. In addition, Y1 R-/- bone ECM displays enhanced matrix maturation characterized by greater number of mature/highly packed collagen fibers without pathological accumulation of immature/mature collagen crosslinks nor compromise of mineral crystallinity. These unique features of Y1 R-/-  bone ECM improved the biochemical properties of Y1 R-/-  bones, reflected by mechanically robust bones with diminished propensity to fracture, contributing to greater bone strength. These findings support the future usage of drugs targeting Y1 R signaling as a promising therapeutic strategy to treat bone loss-related pathologies.

The alliance between nerve fibers and stem cell populations in bone marrow: life partners in sickness and health.

The bone marrow (BM) is the central hematopoietic organ in adult mammals, with great potential to be used as a tool to improve the efficacy of the body's response to a number of malignancies and stressful conditions. The nervous system emerges as a critical regulatory player of the BM both under homeostatic and pathologic settings, with essential roles in cellular anchorage and egress, stem cell differentiation, and endothelial cell permeability. This review collects the current knowledge on the interplay between the nervous system and the BM cell populations, with a focus on how the nervous system modulates hematopoietic stem and progenitor cell, mesenchymal stromal cell, and endothelial progenitor cell activity in BM. We have also highlighted the pathologies that have been associated with disturbances in the neuronal signaling in BM and discussed if targeting the nervous system, either by modulating the activity of specific neuronal circuits or by pharmacologically leveling the activity of sympathetic and sensorial signaling-responsive cells in BM, is a promising therapeutic approach to tackling pathologies from BM origin.-Leitão, L., Alves, C. J., Sousa, D. M., Neto, E., Conceição, F., Lamghari, M. The alliance between nerve fibers and stem cell populations in bone marrow: life partners in sickness and health.

Bone marrow cell response after injury and during early stage of regeneration is independent of the tissue-of-injury in 2 injury models.

Selectively recruiting bone marrow (BM)-derived stem and progenitor cells to injury sites is a promising therapeutic approach. The coordinated action of soluble factors is thought to trigger the mobilization of stem cells from the BM and recruit them to lesions to contribute to tissue regeneration. Nevertheless, the temporal response profile of the major cellular players and soluble factors involved in priming the BM and recruiting BM-derived cells to promote regeneration is unknown. We show that injury alters the BM cellular composition, introducing population-specific fluctuations during tissue regeneration. We demonstrate that injury causes an immediate, transient response of mesenchymal stromal cells and endothelial cells followed by a nonoverlapping increase in hematopoietic stem and progenitor cells. Moreover, BM reaction is identical whether the injury is inflicted on skin and muscle or also involves a bone defect, but these 2 injury paradigms trigger distinct systemic cytokine responses. Together, our results indicate that the BM response to injury in the early stages of regeneration is independent of the tissue-of-injury based on the 2 models used, but the injured tissue dictates the systemic cytokine response.-Leitão, L., Alves, C. J., Alencastre, I. S., Sousa, D. M., Neto, E., Conceição, F., Leitão, C., Aguiar, P., Almeida-Porada, G., Lamghari, M. Bone marrow cell response after injury and during early stage of regeneration is independent of the tissue-of-injury in 2 injury models.

Split-root system optimization based on the survival, growth and development of the model Poaceae Brachypodium distachyon.

Split-root system has been developed to better understand plant response to environmental factors, by exposing two separate parts of a single root system to heterogeneous situations. Surprisingly, there is no study attempting to maximize plant survival, growth and root system structure through a statistically sound comparison of different experimental protocols. Here, we aim at optimizing split-root systems on the model plant for Poaceae and cereals Brachypodium distachyon in terms of plant survival, number of roots and their equal distribution between the two compartments. We tested the effect of hydroponic or soil as growing media, with or without change of media at the transplantation step. The partial or total cutting of roots and/or shoots was also tested in different treatments as it could have an influence on plant access to energy and water and consequently on survival, growth and root development. Growing plants in soil before and after transplantation in split-root system was the best condition to get the highest survival rate, number of coleoptile node axile roots and growth. Cutting the whole root system was the best option to have a high root biomass and length at the end of the experiment. However, cutting shoots was detrimental for plant growth, especially in terms of root biomass production. In well-watered conditions, a plant submitted to a transfer in a split-root system is thus mainly lacking energy to produce new roots thanks to photosynthesis or adaptive autophagy, not water or nutrients.

Correction: Pokotylo, I., et al. Deciphering the Binding of Salicylic Acid to Arabidopsis thaliana Chloroplastic GAPDH-A1. Int. J. Mol. Sci. 2020, 21, 4678.

The authors wish to make the following correction to their published paper [...].

Deciphering the Binding of Salicylic Acid to Arabidopsis thaliana Chloroplastic GAPDH-A1.

Salicylic acid (SA) has an essential role in the responses of plants to pathogens. SA initiates defence signalling via binding to proteins. NPR1 is a transcriptional co-activator and a key target of SA binding. Many other proteins have recently been shown to bind SA. Amongst these proteins are important enzymes of primary metabolism. This fact could stand behind SA's ability to control energy fluxes in stressed plants. Nevertheless, only sparse information exists on the role and mechanisms of such binding. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was previously demonstrated to bind SA both in human and plants. Here, we detail that the A1 isomer of chloroplastic glyceraldehyde 3-phosphate dehydrogenase (GAPA1) from Arabidopsis thaliana binds SA with a KD of 16.7 nM, as shown in surface plasmon resonance experiments. Besides, we show that SA inhibits its GAPDH activity in vitro. To gain some insight into the underlying molecular interactions and binding mechanism, we combined in silico molecular docking experiments and molecular dynamics simulations on the free protein and protein-ligand complex. The molecular docking analysis yielded to the identification of two putative binding pockets for SA. A simulation in water of the complex between SA and the protein allowed us to determine that only one pocket-a surface cavity around Asn35-would efficiently bind SA in the presence of solvent. In silico mutagenesis and simulations of the ligand/protein complexes pointed to the importance of Asn35 and Arg81 in the binding of SA to GAPA1. The importance of this is further supported through experimental biochemical assays. Indeed, mutating GAPA1 Asn35 into Gly or Arg81 into Leu strongly diminished the ability of the enzyme to bind SA. The very same cavity is responsible for the NADP+ binding to GAPA1. More precisely, modelling suggests that SA binds to the very site where the pyrimidine group of the cofactor fits. NADH inhibited in a dose-response manner the binding of SA to GAPA1, validating our data.

Compartmentalized Microfluidic Platforms: The Unrivaled Breakthrough of In Vitro Tools for Neurobiological Research.

Microfluidic technology has become a valuable tool to the scientific community, allowing researchers to study fine cellular mechanisms with higher variable control compared with conventional systems. It has evolved tremendously, and its applicability and flexibility made its usage grow exponentially and transversely to several research fields. This has been particularly noticeable in neuroscience research, where microfluidic platforms made it possible to address specific questions extending from axonal guidance, synapse formation, or axonal transport to the development of 3D models of the CNS to allow pharmacological testing and drug screening. Furthermore, the continuous upgrade of microfluidic platforms has allowed a deeper study of the communication occurring between different neuronal and glial cells or between neurons and other peripheral tissues, both in physiological and pathological conditions. Importantly, the evolution of microfluidic technology has always been accompanied by the development of new computational tools addressing data acquisition, analysis, and modeling.

The grapevine tonoplast aquaporin TIP2;1 is a pressure gated water channel.

In plants, the vacuole is a multifunctional organelle with an important role in the maintenance of the intracellular space. Tonoplast membranes are highly permeable to water due to their content in aquaporins TIPs (Tonoplast Intrinsic Proteins) that allow the rapid water influx creating an internal turgor pressure responsible for cell expansion, elongation and shape. The aim of the present study was to evaluate if the grapevine Vitis vinifera TIP2;1 would operate as a possible volume regulator gated by membrane surface tension. For that, the wild type VvTIP2;1 and a non-functional mutated form were heterologous expressed in yeast. Using an experimental strategy in which cells are incubated in external media that induce an increase in internal hydrostatic pressure and consequently membrane surface tension, we were able to compare the osmotic permeability (Pf) and the activation energy for water transport (Ea) of yeast strains expressing the functional and a non-functional TIP2;1. We found Pf and Ea dependence on internal turgor pressure only for the strain harboring the functional aquaporin indicating that TIP2;1 activity is regulated by membrane tension changing from an open to a closed state in an internal pressure dependent manner. This turgor dependent gating of TIP2;1 might be a mechanism to regulate vacuolar size and shape in plants withstanding hostile drought conditions such as grapevine.

Do Men and Women Differ in Hematological Adaptations to 24 Weeks of Crossfit® Training?

Regular exercise can modulate the immune system functioning through changes in the number and function of leukocytes as well as in red blood cells and other typical blood markers. High intensity exercise promotes increases in cytotoxic activity, phagocytic capacity, chemotaxis and cell apoptosis. The aim of the study was to compare the chronic effects of a 24-week training program using CrossFit® methodology on hematological variables of men vs. women. Twenty-nine CrossFit® athletes (35.3 ± 10.4 years, 175.0 ± 9.2 cm, 79.5 ± 16.4 kg) participated in the study. The blood count, the lipid profile and glucose markers were measured every two months during the study period. The erythrocyte count and hemoglobin concentrations increased in months 4 and 6 in men and women, respectively. Hematocrit levels increased in men in months 2, 4 and 6, while in women only in month 6. Red cell distribution width increased in men in month 6 when compared to the value in month 2. Segmented neutrophils increased in men in month 6 and eosinophil levels increased in women in month 6. Differences between the two sexes were observed in monocytes levels at baseline, as well as in months 2, 4 and 6. Cross-Fit® training increased red cell count indicators in both sexes, which may be related to increased erythropoiesis. Some white blood cell counts were altered and these differed between sexes. The number of lymphocytes remained stable throughout the experiment.

Detraining and Retraining Effects from a Multicomponent Training Program on the Functional Capacity and Health Profile of Physically Active Prehypertensive Older Women.

BACKGROUND: Resuming a physical exercise program after a period of cessation is common in older women. Monitoring the responses during this detraining (DT) and retraining (RT) may allow us to analyze how the body reacts to an increase and a reduction in physical inactivity. Therefore, we conducted a follow-up training, DT, and RT in prehypertensive older women to analyze the response to these periods. METHODS: Twenty-three prehypertensive older women (EG; 68.3 ± 2.8 years; 1.61 ± 0.44 m) performed 36 weeks of the multicomponent training program (MTP) followed by twelve weeks of DT plus eight weeks of RT. Fifteen prehypertensive older women (CG; 66.3 ± 3.2 years; 1.59 ± 0.37 m) maintained their normal routine. Functional capacity (FC), lipid, and hemodynamic profile were assessed before, during 24 and 36 weeks of the MTP, after 4 and 12 weeks of DT, and after 8 weeks of RT. RESULTS: After 24 weeks of the MTP, only SBP did not improve. Four weeks of DT did not affect lower body strength (30-CS), TC, or GL. Eight weeks of RT improved BP (SBP: -2.52%; ES: 0.36; p < 0.00; DBP: -1.45%; ES: 0.44; p < 0.02), handgrip strength (3.77%; ES: 0.51; p < 0.00), and 30-CS (3.17%; ES: 0.38; p < 0.04) compared with 36 weeks of the MTP. CONCLUSIONS: Eight weeks of RT allowed patients to recover the benefits lost with detraining, which after only four weeks affected them negatively, and the systematic practice of exercise contributed to greater regulation of BP since 24 weeks of the MTP proved not to be enough to promote positive effects of SBP.

Follow-Up of Eight-Weeks Detraining Period after Exercise Program on Health Profiles of Older Women.

BACKGROUND: The multicomponent training program (MTP) is a physical exercise strategy used to combat the sedentary lifestyle in older women (OW). However, periods of interruption in training are common in this population. The aim of our study was to analyze the 8-week MTP effects followed by two, four, and eight weeks of interruption on the lipid profile (LP) and functional capacity (FC) of OW. METHODS: Twenty-one OW (experimental group [EG], 67.6 ± 3.1 years; 1.55 ± 0.35 m) were subjected to an 8-week MTP followed by a detraining period, and 14 OW (control group [CG], 69.4 ± 4.7 years; 1.61 ± 0.26 m) maintained their daily routine. FC (i.e., 30-s chair stand [30-CS], 8-foot up and go [8-FUG], 6-min walk [6-MWT], handgrip strength [HGS], and heart-rate peak during 6-WMT [HRPeak]), total cholesterol (TC) and triglycerides (TG) were assessed before and after MTP and two, four, and eight weeks after MTP. RESULTS: 8-week MTP resulted in higher FC and decreased LP values in EG (p < 0.05); two and four weeks of detraining did not promote changes. After eight weeks of detraining TC (ES: 2.74; p = 0.00), TG (ES: 1.93; p = 0.00), HGS (ES: 0.49, p = 0.00), HRPeak (ES: 1.01, p = 0.00), 6-MWT (ES: 0.54, p = 0.04), and 8-FUG (ES: 1.20, p = 0.01) declined significantly. CONCLUSIONS: Periods of more than four weeks of detraining should be avoided to promote a good quality of life and health in OW. If older people interrupt training for a period longer than four weeks, physical-education professionals must outline specific training strategies to maintain the adaptations acquired with MTP. Future studies should establish these criteria based on ideal training volume, intensity, and frequency.

Effects of Moderate Exercise Training on Cancer-Induced Muscle Wasting.

BACKGROUND: Muscle wasting is a common phenomenon in oncology and seems to be attenuated by exercise training. The aim of this study is to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles. It will also determine whether exercise training can attenuate this muscle dysfunction. METHODS: Fifty Sprague Dawley rats were randomly assigned to four experimental groups: two breast cancer model groups (sedentary and exercise) and two control groups (sedentary and exercise). Breast cancer was induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training, animals were sacrificed, and gastrocnemius and soleus muscles harvested for morphometric analysis. RESULTS: In sedentary tumor-bearing animals, a significant reduction in cross-sectional area was found in both muscles (p < 0.05). Interstitial fibrosis was significantly higher in the gastrocnemius muscle of the sedentary tumor-bearing animals (p < 0.05), but not in the soleus muscle. In the gastrocnemius of sedentary tumor-bearing animals, a shift from large to small fibers was observed. This cancer-related muscle dysfunction was prevented by long-term exercise training. CONCLUSIONS: In sedentary animals with tumors, the gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and a marked degree of interstitial fibrosis. There was no difference in collagen deposition between tumor groups, and the soleus muscle showed a less pronounced but significant reduction in cross-sectional area. These contrasting results confirm that cancer-induced muscle wasting can affect specific types of fibers and specific muscles, namely fast glycolytic muscles, and that exercise training can be used to improve it.

Ischemic Preconditioning Improves Handgrip Strength and Functional Capacity in Active Elderly Women.

BACKGROUND: Aging decreases some capacities in older adults, sarcopenia being one of the common processes that occur and that interfered with strength capacity. The present study aimed to verify the acute effect of IPC on isometric handgrip strength and functional capacity in active elderly women. METHODS: In a single-blind, placebo-controlled design, 16 active elderly women (68.1 ± 7.6 years) were randomly performed on three separate occasions a series of tests: (1) alone (control, CON); (2) after IPC (3 cycles of 5-min compression/5-min reperfusion at 15 mmHg above systolic blood pressure, IPC); and (3) after placebo compressions (SHAM). Testing included a handgrip isometric strength test (HIST) and three functional tests (FT): 30 s sit and stand up from a chair (30STS), get up and go time (TUG), and 6 min walk distance test (6MWT). RESULTS: HIST significantly increased in IPC (29.3 ± 6.9 kgf) compared to CON (27.3 ± 7.1 kgf; 7.1% difference; p = 0.01), but not in SHAM (27.7 ± 7.9; 5.5%; p = 0.16). The 30STS increased in IPC (20.1 ± 4.1 repetitions) compared to SHAM (18.5 ± 3.5 repetitions; 8.7%; p = 0.01) and CON (18.5 ± 3.9 repetitions; 8.6%; p = 0.01). TUG was significantly lower in IPC (5.70 ± 1.35 s) compared to SHAM (6.14 ± 1.37 s; -7.2%; p = 0.01), but not CON (5.91 ± 1.45 s; -3.7%; p = 0.24). The 6MWT significantly increased in IPC (611.5 ± 93.8 m) compared to CON (546.1 ± 80.5 m; 12%; p = 0.02), but not in SHAM (598.7 ± 67.6 m; 2.1%; p = 0.85). CONCLUSIONS: These data suggest that IPC can promote acute improvements in handgrip strength and functional capacity in active elderly women.

Three-Month vs. One-Year Detraining Effects after Multicomponent Exercise Program in Hypertensive Older Women.

Background: Chronic diseases are the leading causes of death and disability in older women. Physical exercise training programs promote beneficial effects for health and quality of life. However, exercise interruption periods may be detrimental for the hemodynamic and lipidic profiles of hypertensive older women with dyslipidemia. Methods: Nineteen hypertensive older women with dyslipidemia (exercise group: 67.5 ± 5.4 years, 1.53 ± 3.42 m, 71.84 ± 7.45 kg) performed a supervised multicomponent exercise training program (METP) during nine months, followed by a one-year detraining period (DT), while fourteen hypertensive older women (control group: 66.4 ± 5.2 years, 1.56 ± 3.10 m, 69.38 ± 5.24 kg) with dyslipidemia kept their continued daily routine without exercise. For both groups, hemodynamic and lipidic profiles and functional capacities (FCs) were assessed four times: before and after the METP and after 3 and 12 months of DT (no exercise was carried out). Results: The METP improved hemodynamic and lipidic profiles (p < 0.05), while three months of DT decreased all (p < 0.05) parameters, with the exception of diastolic blood pressure (DBP). One year of DT significantly (p < 0.01) decreased systolic blood pressure (7.85%), DBP (2.29%), resting heart rate (7.95%), blood glucose (19.14%), total cholesterol (10.27%), triglycerides (6.92%) and FC­agility (4.24%), lower- (−12.75%) and upper-body strength (−12.17%), cardiorespiratory capacity (−4.81%) and lower- (−16.16%) and upper-body flexibility (−11.11%). Conclusion: Nine months of the exercise program significantly improved the hemodynamic and lipid profiles as well as the functional capacities of hypertensive older women with dyslipidemia. Although a detraining period is detrimental to these benefits, it seems that the first three months are more prominent in these alterations.

Ischemic Preconditioning with High and Low Pressure Enhances Maximum Strength and Modulates Heart Rate Variability.

Background: The application of ischemic preconditioning (IPC) to resistance exercise has attracted some attention, owing to increases in muscle performance. However, there is still no consensus on the optimal occlusion pressure for this procedure. This study compared the acute effects of IPC with high and low pressure of occlusion on upper and lower limb maximal strength and heart rate variability in recreationally trained individuals. Methods: Sixteen recreationally trained men (25.3 ± 1.7 years; 78.4 ± 6.2 kg; 176.9 ± 5.4 cm; 25.1 ± 1.5 m2 kg−1) were thoroughly familiarized with one repetition maximum (1 RM) testing in the following exercises: bench press (BP), front latissimus pull-down (FLPD), and shoulder press (SP) for upper limbs, and leg press 45º (LP45), hack machine (HM), and Smith Squat (SS) for lower limbs. The 1 RM exercises were then randomly performed on three separate days: after a high pressure (220 mmHg, IPChigh) and a low pressure (20 mmHg, IPClow) IPC protocol and after no intervention (control, CON). Heart rate variability was also measured at rest, during and after the entire IPC protocol, and after the exercises. Results: Maximal strength was significantly (p < 0.05) higher in both IPChigh and IPClow compared with CON in all upper- and lower-limb exercises. There was no difference between the two experimental conditions. No significant differences were found in the comparison across the different experimental conditions for LFnu, HFnu, LF/HF ratio, and RMSSDms. Conclusions: IPC performed with both high and low pressures influenced heart rate variability, which may partly explain the maximal strength enhancement.

Effects of Resistance Training to Muscle Failure on Acute Fatigue: A Systematic Review and Meta-Analysis.

BACKGROUND: Proper design of resistance training (RT) variables is a key factor to reach the maximum potential of neuromuscular adaptations. Among those variables, the use of RT performed to failure (RTF) may lead to a different magnitude of acute fatigue compared with RT not performed to failure (RTNF). The fatigue response could interfere with acute adaptive changes, in turn regulating long-term adaptations. Considering that the level of fatigue affects long-term adaptations, it is important to determine how fatigue is affected by RTF versus RTNF. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the effects of RTF versus RTNF on acute fatigue. METHODS: The search was conducted in January 2021 in seven databases. Only studies with a crossover design that investigated the acute biomechanical properties (vertical jump height, velocity of movement, power output, or isometric strength), metabolic response (lactate or ammonia concentration), muscle damage (creatine kinase activity), and rating of perceived exertion (RPE) were selected. The data (mean ± standard deviation and sample size) were extracted from the included studies and were either converted into the standardized mean difference (SMD) or maintained in the raw mean difference (RMD) when the studies reported the results in the same scale. Random-effects meta-analyses were performed. RESULTS: Twenty studies were included in the systematic review and 12 were included in the meta-analysis. The main meta-analyses indicated greater decrease of biomechanical properties for RTF compared with RTNF (SMD - 0.96, 95% confidence interval [CI] - 1.43 to - 0.49, p < 0.001). Furthermore, there was a larger increase in metabolic response (RMD 4.48 mmol·L-1, 95% CI 3.19-5.78, p < 0.001), muscle damage (SMD 0.76, 95% CI 0.31-1.21, p = 0.001), and RPE (SMD 1.93, 95% CI 0.87-3.00, p < 0.001) for RTF compared with RTNF. Further exploratory subgroup analyses showed that training status (p = 0.92), timepoint (p = 0.89), load (p = 0.10), and volume (p = 0.12) did not affect biomechanical properties; however, greater loss in the movement velocity test occurred on upper limbs compared with lower limbs (p < 0.001). Blood ammonia concentration was greater after RTF than RTNF (RMD 44.66 µmol·L-1, 95% CI 32.27-57.05, p < 0.001), as was 48 h post-exercise blood creatine kinase activity (SMD 0.86, 95% CI 0.33-1.42, p = 0.002). Furthermore, although there was considerable heterogeneity in the overall analysis (I2 = 83.72%; p < 0.01), a significant difference in RPE after RTF compared with RTNF was only found for studies that did not equalize training volumes. CONCLUSIONS: In summary, RTF compared with RTNF led to a greater decrease in biomechanical properties and a simultaneous increase in metabolic response, higher muscle damage, and RPE. The exploratory analyses suggested a greater impairment in the velocity of movement test for the upper limbs, more pronounced muscle damage 48 h post-exercise, and a greater RPE in studies with non-equalized volume after the RTF session compared with RTNF. Therefore, it can be concluded that RTF leads to greater acute fatigue compared with RTNF. The higher acute fatigue after RTF can also have an important impact on chronic adaptive processes following RT; however, the greater acute fatigue following RTF can extend the time needed for recovery, which should be considered when RTF is used. PROTOCOL REGISTRATION: The original protocol was prospectively registered (CRD42020192336) in the International Prospective Register of Systematic Reviews (PROSPERO).