Long-Term Neurophysiological Adaptations to Strength Training: A Systematic Review With Cross-Sectional Studies.

ABSTRACT: Santos, PDG, Vaz, JR, Correia, J, Neto, T, and Pezarat-Correia, P. Long-term neurophysiological adaptations to strength training: a systematic review with cross-sectional studies. J Strength Cond Res 37(10): 2091-2105, 2023-Neuromuscular adaptations to strength training are an extensively studied topic in sports sciences. However, there is scarce information about how neural mechanisms during force production differ between trained and untrained individuals. The purpose of this systematic review is to better understand the differences between highly trained and untrained individuals to establish the long-term neural adaptations to strength training. Three databases were used for the article search (PubMed, Web of Science, and Scopus). Studies were included if they compared groups of resistance-trained with untrained people, aged 18-40 year, and acquired electromyography (EMG) signals during strength tasks. Twenty articles met the eligibility criteria. Generally, strength-trained individuals produced greater maximal voluntary activation, while reducing muscle activity in submaximal tasks, which may affect the acute response to strength training. These individuals also presented lower co-contraction of the antagonist muscles, although it depends on the specific training background. Global intermuscular coordination may be another important mechanism of adaptation in response to long-term strength training; however, further research is necessary to understand how it develops over time. Although these results should be carefully interpreted because of the great disparity of analyzed variables and methods of EMG processing, chronic neural adaptations seem to be decisive to greater force production. It is crucial to know the timings at which these adaptations stagnate and need to be stimulated with advanced training methods. Thus, training programs should be adapted to training status because the same stimulus in different training stages will lead to different responses.

Shear Wave Elastographic Investigation of the Immediate Effects of Slump Neurodynamics in People With Sciatica.

OBJECTIVES: Neurodynamic techniques are often used to treat people with sciatica pain, but their mechanical effects on the sciatic nerve are unknown. Shear wave elastography (SWE) has been shown to effectively estimate the stiffness of peripheral nerves in real time. The aim of this study was to use SWE to assess the effects of slump neurodynamics in the sciatic stiffness of people with sciatica. METHODS: Sixteen participants volunteered for this study. The sciatic stiffness of 8 patients with unilateral chronic sciatica and 8 healthy control participants was measured by SWE, with the participants in a prone position and during a dynamic condition (ie, ankle dorsiflexion). These measurements were performed before and immediately after the neurodynamic intervention, which consisted of a static slump position applied to the symptomatic limb of the patients with sciatica and in a randomly chosen limb of the healthy participants. RESULTS: The 8 patients with sciatica included 6 male and 2 female patients, and the 8 healthy control participants included 5 male and 3 female volunteers. Slump neurodynamics resulted in an immediate decrease in the sciatic nerve stiffness of the symptomatic limb in people with sciatica by 16.1% (effect size = 0.65; P = .019). The intervention showed no significant changes in the sciatic nerve stiffness of the healthy participants (effect size = 0.05; P = .754). CONCLUSIONS: Slump neurodynamics have the potential of decreasing the sciatic nerve stiffness in people with sciatica, and this effect can be quantified by SWE, which may provide valuable information for health professionals.

Noninvasive Measurement of Sciatic Nerve Stiffness in Patients With Chronic Low Back Related Leg Pain Using Shear Wave Elastography.

OBJECTIVES: The purpose of this study was to determine whether sciatic nerve stiffness is altered in people with chronic low back-related leg pain by using shear wave elastography. METHODS: In this cross-sectional study, the sciatic nerve shear wave velocity (ie, an index of stiffness) was measured in both legs of 16 participants (8 with unilateral low back-related leg pain and 8 healthy controls). Sciatic stiffness was measured during a passive ankle dorsiflexion motion performed at 2°/s in an isokinetic dynamometer. The ankle range of motion and passive torque, as well as muscle activity, were also measured. RESULTS: In people with low back-related leg pain, the affected limb showed higher sciatic nerve stiffness compared to the unaffected limb (+11.3%; P = .05). However, no differences were observed between the unaffected limb of people with low back-related leg pain and the healthy controls (P = .34). CONCLUSIONS: People with chronic low back-related leg pain have interlimb differences in sciatic nerve stiffness, as measured by a safe and noninvasive method: shear wave elastography. The changes found may be related to alterations in nerve mechanical properties, which should be confirmed by future investigations.

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16-transgenic mice.

The nuclear factor kappa light chain enhancer of activated B cells (NF-κB) has been implicated in the progression of cancers induced by high-risk human papillomaviruses (HPV). In cancer patients, NF-κB is also thought to drive a chronic systemic inflammatory status, leading to cachexia. This study addressed the ability of dimethylaminoparthenolide (DMAPT), a water-soluble NF-κB inhibitor, to block the development of HPV-induced lesions and wasting syndrome in HPV16-transgenic mice. Mice received DMAPT orally (100 mg/kg/day), once a day, for 6 consecutive weeks. Body weight was monitored weekly along with food and water intake. After 6 weeks the animals were submitted to a grip strength test and sacrificed for specimen collection. Skin samples were analyzed histologically and for expression of NF-κB-regulated genes Bcl2 and Bcl2l1. Gastrocnemius muscles were weighted and analyzed for expression of NF-κB subunits p50, p52, p65, and Rel-B. DMAPT reduced the incidence of epidermal dysplasia (18.2% versus 33.3% in HPV16+/- untreated mice). This was associated with reduced expression of Bcl2 and Bcl2l1 (p = .0003 and p = .0014, respectively) and reduced neutrophilic infiltration (p = .0339). Treated mice also showed partially preserved bodyweight and strength, which were independent of the expression levels of NF-κB subunits in skeletal muscle.These results suggest that NF-κB inhibition may be a valid strategy against HPV-induced lesions in vivo and warrant further preclinical tests particularly in the set of combination therapies. In addition, the data may support the use of DMAPT to prevent wasting syndrome.

Hamstring stiffness pattern during contraction in healthy individuals: analysis by ultrasound-based shear wave elastography.

PURPOSE: To assess the stiffness of hamstring muscles during isometric contractions in healthy individuals, using ultrasound-based shear wave elastography to (1) determine the intra- and inter-day assessment repeatability, (2) characterize the stiffness of semitendinosus (ST) and biceps femoris long head (BFlh) along the contraction intensity, and (3) characterize stiffness distribution among the hamstring muscles and inter-limb symmetry. METHODS: Two experiments were conducted. In experiment I (n = 12), the intra-day repeatability in assessing the BFlh and ST stiffness were determined at intensities between 10-60% of maximal voluntary isometric contraction (MVIC) in a single session. In experiment II (n = 11), the stiffness of the hamstring muscles of both thighs was assessed at 20% of MVIC in the first session; and retested (for one randomly chosen thigh) in a second session. Isometric contraction of knee flexors was performed with the knee flexed at 30° and with the hip in a neutral position. RESULTS: Moderate-to-very-high intra- and inter-day repeatability was found (ICC = 0.69-0.93). The BFlh/ST stiffness ratio increased with contraction intensity. At 20% of MVIC, the ST showed the highest stiffness among the hamstring muscles (p < 0.02), with no differences between the remaining hamstring muscles (p > 0.474). No differences were found between limbs (p = 0.12). CONCLUSIONS: The stiffness distribution among the hamstring muscles during submaximal isometric contractions is heterogeneous, but symmetric between limbs, and changes depending on the contraction intensity. Shear wave elastography is a reliable tool to assess the stiffness of hamstring muscles during contraction.

Thrombosed Aneurysm of the External Jugular Vein: A Rare Cause of Cervical Mass.

BACKGROUND: External jugular vein aneurysm is a rare condition with few cases described in the literature. Complications include thrombus formation, thrombophlebitis, pulmonary embolism, rupture, and cosmetic complaint. METHODS AND RESULTS: The authors present a clinical case and treatment of thrombosed aneurysm of the external jugular vein in a 47-year-old man. CONCLUSIONS: Despite its rarity, external jugular vein aneurysm should be remembered in the differential diagnosis of a cervical mass. Surgical excision is indicated in symptomatic aneurysms and for aesthetic reasons. Excision eliminates the risk of complications and allows for histopathologic diagnosis.

Lehman syndrome: a new syndrome for pierre robin sequence.

Lehman syndrome, or lateral meningocele syndrome, is characterized by facial dysmorphism, multiple lateral meningoceles, and skeletal abnormalities. Only nine cases have been described. We present a case of a 2-year-old boy presenting with micrognathia, glossoptosis, and hypertelorism as well as associated severe obstructive sleep apnea. He was submitted to bilateral mandibular distraction with external nonresorbable devices to correct Pierre Robin sequence (PRS). Later, multiple lateral meningoceles were identified, and a diagnosis of Lehman syndrome was made. Lehman syndrome must be considered in syndromic infants with PRS. Distraction osteogenesis is a safe procedure that is effective as a first choice in the treatment of patients with Lehman syndrome presenting with micrognathia.

Reliability of the Active-Knee-Extension and Straight-Leg-Raise Tests in Subjects With Flexibility Deficits.

CONTEXT: The active-knee-extension test (AKE) and the straight-leg-raise test (SLR) are widely used for flexibility assessment. A number of investigations have tested the reliability of these measures, especially the AKE. However, in most studies, the sample involved subjects with normal flexibility. In addition, few studies have determined the standard error of measurement (SEM) and minimal detectable difference (MDD), which can provide complementary and more clinically relevant information than the intraclass correlation coefficient (ICC) alone. OBJECTIVES: This study aimed to determine the AKE and SLR intrarater (test-retest) reliability in subjects with flexibility deficits, as well as the correlation between the 2 tests. DESIGN: Reliability study, test-retest design. SETTING: Academic laboratory. SUBJECTS: 102 recreationally active participants (48 male, 54 female) with no injury to the lower limbs and with flexibility deficits in the hamstrings muscle group. MAIN OUTCOMES: Intrarater reliability was determined using the ICC, complemented by the SEM and MDD. MEASURES: All participants performed, in each lower limb, 2 trials of the AKE and the SLR. RESULTS: The ICC values found for AKE and SLR tests were, respectively, .87-.94 and .93-.97. The values for SEM were low for both tests (2.6-2.9° for AKE, 2.2-2.6° for SLR), as well as the calculated MDD (7-8° for AKE; 6-7° for SLR). A moderate to strong, and significant, correlation between AKE and SLR was determined for the dominant limb (r = .71) and the nondominant limb (r = .67). CONCLUSIONS: These findings suggest that both AKE and SLR have excellent intrarater reliability. The SEMs and MDDs recorded are also very encouraging for the use of these tests in subjects with flexibility deficits.

Microsurgical reconstruction for radiation- and bisphosphonate-induced mandible osteonecrosis based on patient-specific physiopathologic mechanisms.

BACKGROUND: Radiation- and bisphosphonate-induced mandible osteonecrosis have distinct underlying physiopathologic mechanisms, but both can constitute a serious problem and lead to functional impairment and facial disfigurement. METHODS AND RESULTS: We describe different clinical situations related to several grades of osteonecrosis, where different options of free transfer should be considered based on case-specific physiopathologic mechanisms. We propose a simple clinical grading system to predict the best treatment option. CONCLUSIONS: For patients with advanced refractory disease, pathologic fracture, orocutaneous fistula, and severe osteolysis, resection associated with microvascular reconstruction seems to be a valid option that stops the underlying pathophysiology of overinfected avascular bone necrosis. Physicians who understand the specific physiopathologic mechanisms of each case can incorporate them into the assessment of the required reconstruction and treatment plans.

Using ultrasound shear wave elastography to characterize peripheral nerve mechanics: a systematic review on the normative reference values in healthy individuals.

Ultrasound shear wave elastography (SWE) is an emerging non-invasive imaging technique for peripheral nerve evaluation. Shear wave velocity (SWV), a surrogate measure of stiffness, holds promise as a biomarker for various peripheral nerve disorders. However, to maximize its clinical and biomechanical value, it is important to fully understand the factors that influence nerve SWV measurements. This systematic review aimed to identify the normal range of SWV for healthy sciatic and tibial nerves and to reveal the factors potentially affecting nerve SWV. An electronic search yielded 17 studies eligible for inclusion, involving 548 healthy individuals (age range, 17 to 72 years). Despite very good reliability metrics, the reported SWV values differed considerably across studies for the sciatic (1.9-9.9 m/s) and tibial (2.3-9.1 m/s) nerves. Factors such as measurement proximity to joint regions, limb postures inducing nerve axial stretching, and transducer alignment with nerve fiber orientation were associated with increased SWV. These findings suggest regional-specific nerve mechanical properties, non-linear elastic behaviour, and marked mechanical anisotropy. The impact of age and sex remains unclear and warrants further investigation. These results emphasize the importance of considering these factors when assessing and interpreting nerve SWE. While increased SWV has been linked to pathological changes affecting nerve tissue mechanics, the significant variability observed in healthy nerves highlights the need for standardized SWE assessment protocols. Developing guidelines for enhanced clinical utility and achieving a comprehensive understanding of the factors that influence nerve SWE assessments are critical in advancing the field.

Immediate and short-term effects of eccentric muscle contractions on structural, morphological, mechanical, functional and physiological properties of peripheral nerves: A protocol for a systematic review and meta-analysis.

BACKGROUND: It is widely acknowledged that eccentric muscle contractions may cause skeletal muscle damage. However, there is little knowledge about the impact of eccentric contractions on non-muscular structures. Animal and human studies revealed that eccentric contractions can also induce immediate and short-term nerve dysfunction. The purpose of this review is to examine whether eccentric muscle contractions induce immediate and short-term effects on structural, morphological, mechanical, functional and physiological properties of peripheral nerves, from both animal and human studies. METHODS AND ANALYSIS: A systematic review of randomised (RCTs) and non-randomised controlled trials will be conducted. Four electronic databases (i.e., Medline/Pubmed, Science Direct, PEDro and Cochrane) will be searched using predefined search terms to identify relevant studies. Eligible studies have to comprise any type of eccentric contraction of upper or lower limb muscles. Primary outcomes will include measures related to structure, morphology, mechanical, functional and physiological properties of peripheral nerves. Two independent reviewers will assess eligibility, evaluate risk of bias, and extract relevant data. In human studies, the risk of bias will be assessed by the Cochrane Collaboration risk of bias tool (RoB 2.0 tool) for RCTs and by risk of bias in non-randomised studies of interventions (ROBINS-I) for non-randomised controlled trials; while for animal studies, the risk of bias will be assessed using the SYRCLE's RoB tool. A narrative synthesis will be conducted for all included studies. Also, if appropriate, a meta-analysis will be performed, where the effect size of each outcome will be determined by the standardized mean difference as well as the 95% confidence intervals. I2 statistics will be used to assess heterogeneity. ETHICS AND DISSEMINATION: For this study, no ethical approval is required. Findings will be disseminated widely through peer-reviewed publication and conference presentations. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). Registration number: CRD42021285767.

Pharmacological NF-κB inhibition decreases cisplatin chemoresistance in muscle-invasive bladder cancer and reduces cisplatin-induced toxicities.

Most patients with muscle-invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up-regulation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF-κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF-κB signaling and patient survival. The efficacy of cisplatin plus the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum-naive claudin-low MIBC showed constitutive NF-κB signaling and this was associated with reduced disease-specific survival in TCGA patients. Chemotherapy up-regulated NF-κB signaling and chemoresistance-associated genes, including SPHK1, PLAUR, and SERPINE1. In mice, DMAPT significantly improved the efficacy of cisplatin in both models. The combination preserved body weight, renal function, and morphology, reduced muscle fatigue and IL-6 serum levels, and did not aggravate immuno-hematological toxicity compared with cisplatin alone. These data provide a rationale for combining NF-κB inhibition with platinum-based chemotherapy and conducting a clinical trial in MIBC patients.

Is there a relationship between back squat depth, ankle flexibility, and Achilles tendon stiffness?

This study investigated the relationship between back squat depth capacity, ankle dorsiflexion resistance to stretch and maximal range of motion (ROM), and Achilles tendon stiffness of healthy individuals (n = 20). Squat depth capacity was assessed with 2D kinematic analysis. Ankle dorsiflexion maximal ROM was assessed using a smartphone digital goniometry (lunge test) and isokinetic dynamometry (prone test). Ankle dorsiflexion resistance to stretch was assessed during the prone test. Achilles tendon stiffness was estimated at rest [using shear wave elastography (stiffness-SWE)] and during isometric contraction through tendon force-length relationship (using B-mode sonography). Squat depth was associated only with ankle dorsiflexion ROM in the lunge test (r = 0.69, p = 0.001). Ankle dorsiflexion ROM in the lunge test was associated with the ankle resistance to stretch (r = 0.46, p = 0.050) and Achilles tendon stiffness-SWE (r = 0.62, p = 0.005); and it was the only variable different between individuals with low and high squat depth capacity (p = 0.014). No other statistically significant associations were found. In conclusion, back squat depth is associated with ankle dorsiflexion ROM when the knee is flexed, without evident influence of global joint and Achilles tendon mechanical properties.

A quick and low-intensity method for oral administration to large numbers of mice: A possible alternative to oral gavage.

Oral administration of medication to experimental animals is a cause of significant stress. When coupled to animals who are already under strenuous circumstances due to the disease being modelled, there is a significant risk for increased morbidity and mortality, thus influencing the results. Faced with these constraints, a low-intensity method for oral administration was developed, based solely on the natural behaviour of the animals and minimal conditioning, in which precise doses of medication were administered in a locally available, standard wheat cookie fragment, providing both a palatable vehicle and an absorbent matrix for the medication. Fast administration to large numbers of animals was thus achieved, safeguarding the animals' welfare and ensuring ease of handling. This method is a promising alternative to oral gavage in pre-clinical drug studies with laboratory mice.

Rheumatoid Nodule Simulating a Parotid Tumor.

Rheumatoid nodules are an extra-articular manifestation of rheumatoid arthritis that are rarely found in the maxillofacial region. A 59-year-old woman with rheumatoid arthritis treated with methotrexate, leflunomide, and tocilizumab, presented with an enlarging mass in the left parotid region. Magnetic resonance imaging (MRI) displayed a lesion compatible with a neoplasm. However, an incisional biopsy showed features consistent with a rheumatoid nodule. The patient was managed conservatively, including cessation of methotrexate and initiation of treatment with hydroxychloroquine. At 15-month follow-up, the lesion had a significant reduction in size. To our knowledge, this is the first case report of a rheumatoid nodule in the parotid region. Although it is a rare manifestation, clinicians should consider this a possible differential diagnosis of parotid masses in patients with a history of rheumatoid arthritis or connective tissue disease.

Regional Differences in Biceps Femoris Long Head Stiffness during Isometric Knee Flexion.

This study sought to investigate whether the stiffness of the biceps femoris long head differs between proximal and distal regions during isometric knee flexion at different contraction intensities and muscle lengths. Twelve healthy individuals performed knee flexion isometric contractions at 20% and 60% of maximum voluntary isometric contraction, with the knee flexed at 15 and 45 degrees. Muscle stiffness assessment was performed using ultrasound-based shear wave elastography. Proximal and distal regions of the biceps femoris long head were assessed. Biceps femoris long head muscle showed a greater stiffness (i) in the distal region, (ii) at higher contraction intensity, and (iii) at longer muscle length. The proximal-to-distal stiffness ratio was significantly lower than 1 (i.e., heterogenous) at lower contraction intensity regardless of the muscle length. However, this was not observed at higher contraction intensity. This study is the first to show heterogeneity in the active stiffness of the biceps femoris long head. Given the greater incidence of injury at the proximal region of biceps femoris long head, this study opens new directions for future research. Additionally, the present study results indicate that studies assessing muscle stiffness at one single muscle region should be interpreted with caution.

Ptaquiloside from bracken (Pteridium spp.) promotes oral carcinogenesis initiated by HPV16 in transgenic mice.

Bracken (Pteridium spp.) is a common weed that is consumed as food especially in Asia, and is suspected of promoting carcinogenesis induced by papillomaviruses in the digestive and urinary systems. This is particularly worrying because the incidence of head-and-neck cancers associated with the human papillomavirus (HPV) is rapidly increasing, and HPV co-carcinogens urgently need to be identified. This study tested the hypothesis that two bracken compounds, ptaquiloside and rutin, are able to promote head-and-neck and bladder carcinogenesis in HPV16-transgenic mice. Expression of HPV16 E6 and E7 in oral and bladder tissues was confirmed using quantitative real-time PCR. Mice were exposed orally to ptaquiloside (0.5 mg per animal per week for 10 weeks from 20 weeks-old) or rutin (413 mg kg-1 day-1 for 24 weeks from 6 weeks-old), sacrificed at 30 weeks-old and studied histologically. HPV16 E6 and E7 expression was higher in oral mucosa compared with the bladder (p 0.001). Importantly, ptaquiloside, but not rutin, increased the incidence of oral squamous cell carcinomas (p = 1.2 × 10-8) in HPV16-transgenic mice. Also, cancers of unexposed transgenic mice were restricted to the tongue base, while ptaquiloside-exposed mice showed multifocal lesions throughout the oral cavity. Wild-type controls showed no oral lesions. No bladder lesions were observed in any treated or untreated group. These results indicate that ptaquiloside from bracken is able to promote oral carcinogenesis initiated by HPV16. Rutin did not show any carcinogenic effects in this model. The absence of bladder lesions may reflect an insufficient incubation period or factors related to the specific viral oncogenes present in this model.

Effects of knee flexor submaximal isometric contraction until exhaustion on semitendinosus and biceps femoris long head shear modulus in healthy individuals.

This study examined whether a knee flexor isometric contraction at 20% of maximal voluntary isometric contraction until exhaustion would alter the biceps femoris long head (BFlh) and semitendinosus (ST) active stiffness, assessed using ultrasound-based shear wave elastography. Twelve healthy individuals participated in 2 sessions separated by 7 days. Time to exhaustion was similar in both sessions (day 1: 443.8 ± 192.5 s; day 2: 474.6 ± 131.7 s; p = 0.323). At the start of the fatigue task, the ST showed greater active stiffness than the BFlh (p < 0.001), with no differences between days (p = 0.08). The ST active stiffness then decreased from 40% of the task time to exhaustion (- 2.2 to - 13.3%, p = 0.027) until the end of the task (- 16.1 to - 22.9%, p = 0.012), while no significant changes were noted in the BFlh (p = 0.771). Immediately after the fatigue task, a decrease in active stiffness was observed in the ST (- 11.8 to - 17.8%, p < 0.001), but not in the BFlh (p = 0.551). Results were consistent between the 2 testing sessions (p = 0.07-0.959). The present results indicate that fatigue alters the hamstring active stiffness pattern.

Effects of lower body quadrant neural mobilization in healthy and low back pain populations: A systematic review and meta-analysis.

BACKGROUND: Neural mobilization (NM) is widely used to assess and treat several neuromuscular disorders. However, information regarding the NM effects targeting the lower body quadrant is scarce. OBJECTIVES: To determine the effects of NM techniques targeting the lower body quadrant in healthy and low back pain (LBP) populations. DESIGN: Systematic review with meta-analysis. METHOD: Randomized controlled trials were included if any form of NM was applied to the lower body quadrant. Pain, disability, and lower limb flexibility were the main outcomes. PEDro scale was used to assess methodological quality. RESULTS: Forty-five studies were selected for full-text analysis, and ten were included in the meta-analysis, involving 502 participants. Overall, studies presented fair to good quality, with a mean PEDro score of 6.3 (from 4 to 8). Five studies used healthy participants, and five targeted people with LBP. A moderate effect size (g = 0.73, 95% CI: 0.48-0.98) was determined, favoring the use of NM to increase flexibility in healthy adults. Larger effect sizes were found for the effect of NM in pain reduction (g = 0.82, 95% CI 0.56-1.08) and disability improvement (g = 1.59, 95% CI: 1.14-2.03), in people with LBP. CONCLUSION: Evidence suggests that there are positive effects from the application of NM to the lower body quadrant. Specifically, NM shows moderate effects on flexibility in healthy participants, and large effects on pain and disability in people with LBP. Nevertheless, more studies with high methodological quality are necessary to support these conclusions.