Fine-needle percutaneous muscle microbiopsy technique as a feasible tool to address histological analysis in young children with cerebral palsy and age-matched typically developing children.

Cerebral palsy (CP) is a heterogeneous group of motor disorders attributed to a non-progressive lesion in the developing brain. Knowledge on skeletal muscle properties is important to understand the impact of CP and treatment but data at the microscopic levels are limited and inconsistent. Currently, muscle biopsies are collected during surgery and are restricted to CP eligible for such treatment or they may refer to another muscle or older children in typically developing (TD) biopsies. A minimally invasive technique to collect (repeated) muscle biopsies in young CP and TD children is needed to provide insights into the early muscle microscopic alterations and their evolution in CP. This paper describes the protocol used to 1) collect microbiopsies of the medial gastrocnemius (MG) and semitendinosus (ST) in CP children and age-matched TD children, 2) handle the biopsies for histology, 3) stain the biopsies to address muscle structure (Hematoxylin & Eosin), fiber size and proportion (myosin heavy chain), counting of the satellite cells (Pax7) and capillaries (CD31). Technique feasibility and safety as well as staining feasibility and measure accuracy were evaluated. Two microbiopsies per muscle were collected in 56 CP (5.8±1.1 yr) and 32 TD (6±1.1 yr) children using ultrasound-guided percutaneous microbiopsy technique. The biopsy procedure was safe (absence of complications) and well tolerated (Score pain using Wong-Baker faces). Cross-sectionally orientated fibers were found in 86% (CP) and 92% (TD) of the biopsies with 60% (CP) and 85% (TD) containing more than 150 fibers. Fiber staining was successful in all MG biopsies but failed in 30% (CP) and 16% (TD) of the ST biopsies. Satellite cell staining was successful in 89% (CP) and 85% (TD) for MG and in 70% (CP) and 90% (TD) for ST biopsies, while capillary staining was successful in 88% (CP) and 100% (TD) of the MG and in 86% (CP) and 90% (TD) for the ST biopsies. Intraclass coefficient correlation showed reliable and reproducible measures of all outcomes. This study shows that the percutaneous microbiopsy technique is a safe and feasible tool to collect (repeated) muscle biopsies in young CP and TD children for histological analysis and it provides sufficient muscle tissue of good quality for reliable quantification.

High intensity training improves symptoms of central sensitization at six-month follow-up in persons with chronic nonspecific low back pain: Secondary analysis of a randomized controlled trial.

BACKGROUND: High intensity training (HIT) improves disability and physical fitness in persons with chronic nonspecific low back pain (CNSLBP). However, it remains unclear if HIT affects pain processing and psychosocial factors. OBJECTIVE: To evaluate 1) the effects of HIT on symptoms of central sensitization and perceived stress and 2) the relationship of symptoms of central sensitization and perceived stress with therapy success, at six-month follow-up, in persons with CNSLBP. METHODS: This is a secondary analysis of a previously published randomized controlled trial. Persons with CNSLBP (n = 51, age=43.6y) completed the Central Sensitization Inventory (CSI) and Perceived Stress Scale (PSS) at baseline (PRE) and six months after 12-week of HIT consisting of concurrent exercise therapy (FU). Two groups were formed based on CSI scores (low-CSI/high-CSI). First, linear mixed models were fitted for each outcome, with time and groups as covariates. Multiple comparisons were executed to evaluate group (baseline), time (within-group), and interaction (between-group) effects. Second, correlation and regression analyses were performed to evaluate if baseline and changes in CSI/PSS scores were related to therapy success, operationalized as improvements on disability (Modified Oswestry Disability Index), and pain intensity (Numeric Pain Rating Scale). RESULTS: Total sample analyses showed a decrease in both CSI and PSS. Within-group analyses showed a decrease of CSI only in the high-CSI group and a decrease of PSS only in the low-CSI group. Between-group analyses showed a pronounced decrease favouring high-CSI (mean difference: 7.9; 95%CI: 2.1, 12.7) and no differences in PSS (mean difference: 0.1; 95%CI: -3.0, 3.2). CSI, but not PSS, was weakly related to therapy success. CONCLUSION: HIT improves symptoms of central sensitization in persons with CNSLBP. This effect is the largest in persons with clinically relevant baseline CSI scores. HIT also decreases perceived stress.

Observations of nemaline bodies in muscle biopsies of critically ill patients infected with SARS-CoV-2.

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1-3 and days 5-8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5-8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.

The Role of Skeletal Muscle Mitochondria in Colorectal Cancer Related Cachexia: Friends or Foes?

Up to 60% of colorectal cancer (CRC) patients develop cachexia. The presence of CRC related cachexia is associated with more adverse events during systemic therapy, leading to a high mortality rate. The main manifestation in CRC related cachexia is the loss of skeletal muscle mass, resulting from an imbalance between skeletal muscle protein synthesis and protein degradation. In CRC related cachexia, systemic inflammation, oxidative stress, and proteolytic systems lead to mitochondrial dysfunction, resulting in an imbalanced skeletal muscle metabolism. Mitochondria fulfill an important function in muscle maintenance. Thus, preservation of the skeletal muscle mitochondrial homeostasis may contribute to prevent the loss of muscle mass. However, it remains elusive whether mitochondria play a benign or malignant role in the development of cancer cachexia. This review summarizes current (mostly preclinical) evidence about the role of skeletal muscle mitochondria in the development of CRC related cachexia. Future human research is necessary to determine the physiological role of skeletal muscle mitochondria in the development of human CRC related cachexia.

Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.

Introduction: There is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA). Increasing evidence suggest the presence of autoantibodies in a subset of axSpA patients. The aim of this study was to identify novel IgA antibodies in early axSpA patients and to determine their diagnostic potential in combination with previously determined IgG antibodies against UH (Hasselt University)-axSpA-IgG antigens. Methods: An axSpA cDNA phage display library constructed from axSpA hip synovium, was used to screen for novel IgA antibodies in plasma from early axSpA patients. The presence of these antibodies against novel UH-axSpA-IgA antigens was determined in two independent axSpA cohorts, in healthy controls and in patients with chronic low back pain. Results: We identified antibodies to 7 novel UH-axSpA-IgA antigens, of which 6 correspond to non-physiological peptides and 1 to the human histone deacetylase 3 (HDAC3) protein. IgA antibodies against 2 of these 7 novel UH-axSpA-IgA antigens and IgG antibodies against 2 of the previously identified antigens were significantly more present in early axSpA patients from the UH cohort (18/70, 25.7%) and the (Bio)SPAR cohort (26/164, 15.9%), compared to controls with chronic low back pain (2/66, 3%). Antibodies to this panel of 4 antigens were present in 21.1% (30/142) of patients with early axSpA from the UH and (Bio)SPAR cohorts. The positive likelihood ratio for confirming early axSpA using antibodies to these 4 UH-axSpA antigens was 7.0. So far, no clinical correlation between the novel identified IgA antibodies and inflammatory bowel disease could be identified. Discussion: In conclusion, screening an axSpA cDNA phage display library for IgA reactivity resulted in the identification of 7 novel UH-axSpA-IgA antigens, of which 2 show promising biomarker potential for the diagnosis of a subset of axSpA patients, in combination with previously identified UH-axSpA-IgG antigens.

Certainty-Based Marking on Multiple-Choice Items: Psychometrics Meets Decision Theory.

When a response to a multiple-choice item consists of selecting a single-best answer, it is not possible for examiners to differentiate between a response that is a product of knowledge and one that is largely a product of uncertainty. Certainty-based marking (CBM) is one testing format that requires examinees to express their degree of certainty on the response option they have selected, leading to an item score that depends both on the correctness of an answer and the certainty expressed. The expected score is maximized if examinees truthfully report their level of certainty. However, prospect theory states that people do not always make rational choices of the optimal outcome due to varying risk attitudes. By integrating a psychometric model and a decision-making perspective, the present study looks into the response behaviors of 334 first-year students of physiotherapy on six multiple-choice examinations with CBM in a case study. We used item response theory to model the objective probability of students giving a correct response to an item, and cumulative prospect theory to estimate their risk attitudes when students choose to report their certainty. The results showed that with the given CBM scoring matrix, students' choices of a certainty level were affected by their risk attitudes. Students were generally risk averse and loss averse when they had a high success probability on an item, leading to an under-reporting of their certainty. Meanwhile, they were risk seeking in case of small success probabilities on the items, resulting in the over-reporting of certainty.

The lumbar multifidus is characterised by larger type I muscle fibres compared to the erector spinae.

The metabolic capacity of a muscle is one of the determinants of muscle function. Muscle fiber type characteristics give an indication about this metabolic capacity. Therefore it might be expected that the lumbar multifidus (MF) as a local stabilizer contains higher proportions of slow type I fibers, compared to the erector spinae (ES) as a global mobilizer. The aim of this study is to determine the muscle fiber characteristics of the ES and MF to provide insight into their structural and metabolic characteristics, and thereby the functional capacity of both muscles. Muscle fiber type characteristics in the ES and MF were investigated with an immunofluorescence staining of the myosin heavy chain isoforms. In both the ES and MF, type I muscle fibers are predominantly present. The cross-sectional area (CSA) of type I muscle fibers is significantly larger in the lumbar MF compared to the ES. However, the mean muscle fiber type percentage for type I was not significantly different, which resulted in an insignificant difference in relative cross-sectional area (RCSA) for type I. No significant differences were found for all other muscle fiber types. This may indicate that the MF displays muscle fiber type characteristics that tend to be more appropriate to maintain stability of the spine. However, because we could not demonstrate significant differences in RCSA between ES and MF, we cannot firmly state that there are functional differences between the ES an MF based only on structural characteristics.

High Intensity Training to Treat Chronic Nonspecific Low Back Pain: Effectiveness of Various Exercise Modes.

High-intensity training (HIT) improves rehabilitation outcomes such as functional disability and physical performance in several chronic disorders. Promising results were also found in chronic nonspecific low back pain (CNSLBP). However, the impact of different exercise modes on HIT effectiveness in CNSLBP remains unclear. Therefore, this study evaluated the effectiveness of various HIT exercise modes and compared differences between these modes, on pain intensity, disability, and physical performance, as a therapeutic intervention for persons with CNSLBP. In a randomized comparative trial, consisting of a 12-week program, persons with CNSLBP were divided into four HIT groups, i.e., cardiorespiratory interval training coupled with either general resistance training, core strength training, combined general resistance and core strength training, or mobility exercises. Before and after the program, the Numeric Pain Rating Scale (NPRS), Modified Oswestry Disability Index (MODI), and Patient Specific Functioning Scale (PSFS) were recorded, and a cardiopulmonary exercise test (VO2max, cycling time) and isometric trunk strength test (maximum muscle torque) were performed. Eighty participants (mean age: 44.0 y, 34 males) were included. Improvements were found within all groups after the HIT programs and ranged from -39 to -57% on the NPRS, +27 to +64% on the MODI, +38 to +89% on the PSFS, +7 to +14% on VO2max, and +11 to +18% on cycling time. No differences between groups were found. High-intensity cardiorespiratory interval training improves CNSLBP rehabilitation outcomes when performed with other HIT exercise modes or mobility exercises. Hence, when setting up an exercise therapy program in CNSLBP rehabilitation, various HIT modes can be considered as therapy modalities.

Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts.

OBJECTIVE: This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. METHODS: An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. RESULTS: We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. CONCLUSION: Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.

Unilateral changes of the multifidus in persons with lumbar disc herniation: a systematic review and meta-analysis.

BACKGROUND: Lumbar disc herniation (LDH) is one of the most often diagnosed degenerative pathologies within the lumbar spine. Paraspinal muscle involvement could be a possible mediator in the pathophysiology of disc herniation and influences the course of pain and disability after both surgical or nonsurgical treatment. To potentially improve treatment, it may be important to assess multifidus muscle morphology in patients diagnosed with a LDH. OBJECTIVE: A systematic literature review and meta-analysis regarding the multifidus morphology in patients diagnosed with a LDH was conducted to assess the differences in multifidus muscle morphology between persons with LDH and healthy controls, and between the involved and the uninvolved side within subjects experiencing unilateral LDH. METHODS: A systematic search was conducted of articles published up to and including November 2019 using the Pubmed, Web of Science, EMBASE, and MEDLINE Ovid search engines. The articles obtained from this search were screened based on title and abstract using the predetermined eligibility criteria. Included full text articles were assessed for their methodologic quality using the modified Downs and Black checklist. Heterogeneous data regarding multifidus muscle morphology was included in the descriptive analysis; data that was homogenous was included in the meta-analysis. RESULTS: We identified 3,176 articles. Based on the screening for inclusion/exclusion criteria, 18 articles were included. Studies were either cross sectional or case-control studies assessing side-to-side differences or comparing patients diagnosed with a LDH to a healthy control group. Nine studies investigated whole muscle atrophy, six looked at muscle fat infiltration, seven studies assessed microscopic muscle properties including muscle fiber size, distribution, and muscle fibrosis. From the 18 articles, 10 were included in the meta-analysis. In the meta-analysis, a comparison was made between side-to-side differences for muscle fiber size, distribution, and whole muscle size. Descriptive analysis showed increased fat infiltration and atrophy (muscle and individual fiber) of the multifidus muscle when comparing side-to-side differences or comparing cases to controls. Meta-analysis showed a significant decrease in type I and II muscle fiber size (p=.002, .01, respectively) combined with a significant increase in the number of type I muscle fibers (p=.008) at the side of LDH. Regarding whole muscle size, no significant differences were found. CONCLUSIONS: This study shows the presence of ipsilateral multifidus muscle changes in persons with unilateral LDH.

Disability, kinesiophobia, perceived stress, and pain are not associated with trunk muscle strength or aerobic capacity in chronic nonspecific low back pain.

OBJECTIVES: To investigate to which extent disability, psychological and pain-related factors are associated with the outcomes of an isometric trunk muscle strength test and a cardiopulmonary exercise test in persons with chronic nonspecific low back pain (CNSLBP). DESIGN: Cross-sectional study. SETTING: REVAL Rehabilitation Research Center (Hasselt, Belgium). PARTICIPANTS: Persons with CNSLBP. MAIN OUTCOME MEASURES: Questionnaires concerning disability, patient specific functioning, kinesiophobia, perceived stress, pain intensity, and central sensitization were recorded. Outcomes of an isometric trunk strength test (maximum back and abdominal torque) and cardiopulmonary exercise test (VO2max) were assessed. Multivariate linear regression models determined factors explaining outcome variance. RESULTS: Data of 101 persons (39 males, mean age: 44.2y (SD = 9.6)) was assessed. Neither disability, nor psychological, nor pain-related factors were associated with the assessments. Variance in back muscle strength (R2 = 0.44, F = p < 0.01), abdominal muscle strength (R2 = 0.68, F = p < 0.01), and aerobic capacity (R2 = 0.76, F = p < 0.01) could only be explained through the included demographics covariates (age, gender, weight). CONCLUSION: This study highlighted the lack of biopsychosocial factors in explaining variance in outcomes of abdominal and back strength, and aerobic capacity in persons with CNSLBP with characteristics as depicted in the current sample. This information supports the valid interpretation of the outcomes of these assessments.

Biopsy samples from the erector spinae of persons with nonspecific chronic low back pain display a decrease in glycolytic muscle fibers.

BACKGROUND CONTEXT: Low back pain (LBP) in Western Europe was classified as having the highest disability and overall burden among 291 studied conditions. For an extensive period of time, evidence related to morphological changes (eg, atrophy and fat infiltration) of the paraspinal muscles in persons with LBP has accumulated. Despite this evidence, there is limited knowledge on muscle fiber type composition of these muscles, and their relation to LBP. PURPOSE: The aim of the study is to investigate differences in muscle fiber type composition between persons with nonspecific chronic low back pain (NSCLBP) and healthy controls for the lumbar erector spinae (ES) and multifidus (MF) muscle. STUDY DESIGN AND SETTING: A cross-sectional study took place in the REVAL Rehabilitation Research Center, Hasselt University, Diepenbeek, Belgium. PATIENT SAMPLE: Twenty persons with NSCLBP (age: 44.5±7.42) and 18 healthy controls (age: 39.89±7.90) participated in this study. OUTCOME MEASURES: The primary outcome measure was paraspinal muscle fiber type composition. Secondary outcomes consisted of physiologic measures (maximal aerobic capacity and back muscle strength) and functional measures (activity level). METHODS: Biopsy samples were taken from the lumbar ES and MF muscle at the L4 spinal level. These samples were stained using immunofluorescent antibodies against myosin heavy chains. In each sample, number and size (CSA) of type I, I/IIa, IIa, IIa/x, and IIx muscle fibers were quantified. From these data the relative cross-sectional fiber areas (RCSA) were calculated. To analyze differences in fiber type composition between healthy persons and persons with NSCLBP, a repeated measurements analysis of variance was used. Secondary outcome measures were analyzed using a Student's t test, and Wilcoxon test. This study was supported by the research fund of Hasselt University without potential conflict of interest. RESULTS: There were no significant differences between both groups regarding anthropometric data. There were no significant between group differences for CSA in the ES. Persons with NSCLBP displayed a nonsignificant (p=.0978) increase in the number of type I muscle fibers, and a significant decrease (p=.0019) in the number of type IIx muscle fibers in the ES muscle. Persons with NSCLBP also displayed a trend toward a higher (p=.0596) RCSA for type I fibers and a significantly lower RCSA for type IIx fibers (p=.0411). There were no significant between group differences within the MF. Regarding the secondary outcome measures, there was a significant between group difference in activity level (p=.0004) and isokinetic back muscle strength (p=.0342). CONCLUSIONS: This is the first study to examine muscle fiber type characteristics in both the ES and MF muscle of persons with NSCLBP. Based on muscle fiber characteristics, the paraspinal muscles of persons with NSCLBP seems to display a larger oxidative potential based on an increase of the number type I fibers at the expense of type IIx glycolytic fibers.

Exercise Intensity Matters in Chronic Nonspecific Low Back Pain Rehabilitation.

INTRODUCTION: Exercise therapy (ET) is advocated as a treatment for chronic nonspecific low back pain (CNSLBP). However, therapy effect sizes remain low. In other chronic disorders, training at higher intensity has resulted in greater improvements on both general health related and disease specific outcomes compared to lower-intensity ET. Possibly, high-intensity training also improves effect sizes in CNSLBP. OBJECTIVE: To compare the effects of a high-intensity ET program with a similar moderate-intensity ET program on disability, pain, function, exercise capacity, and abdominal/back muscle strength in persons with CNSLBP. METHODS: In a randomized controlled trial, persons with CNSLBP performed a 12-wk ET program (24 sessions, 1.5 h per session, twice per week) at high-intensity training (HIT) or moderate-intensity training (MIT). Questionnaires to assess disability (Modified Oswestry Index [MODI]), pain intensity (Numeric Pain Rating Scale), and function (Patient Specific Functioning Scale), a cardiopulmonary exercise test to assess exercise capacity (V˙O2max, cycling time), and a maximum isometric muscle strength test to assess abdominal/back muscle strength (maximum muscle torque) were administered at baseline and after the training program. RESULTS: Thirty-eight participants (HIT: n = 19, MIT: n = 19) were included (mean age, 44.1 yr, SD = 9.8, 12 males). Groups did not differ at baseline. Between group differences (P < 0.01) in favor of HIT were found for MODI, V˙O2max, and cycling time. Within group improvements (P < 0.01) were found in both groups on MODI (HIT:-64%, MIT:-33%), Numeric Pain Rating Scale (HIT, -56%; MIT, -39%), Patient-Specific Functioning Scale (HIT:+37%, MIT:+39%), V˙O2max (HIT:+14, MIT:+4%), cycling time (HIT:+18%, MIT:+13%), and back muscle strength (HIT:+10%, MIT:+14%). CONCLUSIONS: High-intensity training proved to be a feasible, well tolerated, and effective therapy modality in CNSLBP. Moreover, it shows greater improvements on disability and exercise capacity than a similar ET performed at moderate intensity.

Chondroid metaplasia of paraspinal connective tissue in the degenerative spine.

A 51-year-old male was routinely biopsied during a paraspinal muscle study. The biopsy sample was taken from the right erector spinae muscle at the fourth lumbar vertebra. The patient had no history of (diagnosed) major back trauma. The obtained sample was histologically analyzed (hematoxylin and eosin, safranin O), and complementary magnetic resonance imaging was performed. The biopsied sample contained chondroid tissue. Based on its location, the biopsy sample was appointed as chondroid metaplasia. Although chondroid metaplasia is not uncommon in humans, this is the first report of chondroid metaplasia within the paraspinal connective tissue. We propose a novel mechanism to explain the paraspinal chrondrogenic changes, related to spinal degeneration.

Reliability and agreement of isometric functional trunk and isolated lumbar strength assessment in healthy persons and persons with chronic nonspecific low back pain.

OBJECTIVES: to assess intra/inter-operator reliability and agreement of maximum isometric abdominal and back muscle strength in a functional trunk and isolated lumbar protocol, using an isokinetic dynamometer, in healthy persons and persons with chronic nonspecific low back pain (CNSLBP). DESIGN: Test-retest. SETTING: Participants performed two assessments consisting of two protocols on the Biodex 3 system, evaluating maximum isometric back and abdominal strength in a functional trunk and isolated lumbar position. During the first assessment, each protocol was executed twice, supported by different operators. PARTICIPANTS: Healthy persons (n = 20) and persons with CNSLBP (n = 20). MAIN OUTCOME MEASURES: Intraclass Correlation (ICC), Standard Error of Measurement (SEM and %SEM), and Minimal Detectable Change (MDC) of muscle strength outcomes and seat positioning characteristics were calculated. RESULTS: Intra/inter reliability of muscle strength outcomes was excellent (ICC: 0.94-0.98), while seat positioning characteristics varied from low to high (ICC: 0-0.94). For muscle strength outcomes, %SEM ranged from 4.7 to 9.2% and MDC ranged from 14.3 to 29.8 Nm in trunk flexion and 39.1-68.5 Nm in trunk extension. CONCLUSIONS: The Biodex 3 system can be used reliably to assess maximum isometric trunk muscle strength with the aforementioned protocols in healthy persons and persons with CNSLBP. All muscle strength outcomes showed comparable agreement (%SEM < 10%).

Feasibility, accuracy and safety of a percutaneous fine-needle biopsy technique to obtain qualitative muscle samples of the lumbar multifidus and erector spinae muscle in persons with low back pain.

The lumbar muscular system, in particular the lumbar multifidus muscle (LM) and the erector spinae muscle (ES), plays an important role in stabilizing and mobilizing the lumbar spine. Based on the topography, the lumbar paraspinal muscles can be classified into local and global muscles. LM is part of the local system, whereas ES is part of the global system. Therefore, it is interesting to investigate the muscle fibre type composition in both muscles. There is accumulating evidence that nonspecific chronic low back pain is associated with lumbar muscle dysfunction. To further elucidate this lumbar paraspinal muscle dysfunction, it is important to understand the structural characteristics of individual muscle fibres of LM and ES. Muscle fibre type composition can be investigated in muscle tissue samples. So far, muscle samples are taken by using invasive procedures that are not well tolerated. The aim of this article was to evaluate the feasibility, accuracy and safety of a percutaneous fine-needle biopsy technique to obtain muscle samples from LM and ES in persons with nonspecific chronic low back pain and to evaluate the feasibility of performing immunofluorescence analysis of myosin heavy chain isoform expression to investigate muscle fibre type composition. Preliminary investigations in cadavers were performed to determine the optimal vertebral level and puncture site to obtain muscle samples of LM and ES through a single skin puncture. In 15 persons with nonspecific chronic low back pain, muscle samples of LM and ES were taken under local anaesthesia with the percutaneous fine-needle biopsy technique, preceded by determination of the puncture site with ultrasonography. Muscle fibre type composition was investigated using immunofluorescence analysis of myosin heavy chain expression. The subjects reported little or no pain and were willing to repeat the procedure. The obtained muscle tissue contained transverse-sectioned muscle fibres in which muscle fibre contractile characteristics of the paraspinal muscles could be evaluated with immunofluorescence analysis of the myosin heavy chains. We can conclude that percutaneous microbiopsy appears to be feasible and accurate, and safe to use to obtain muscle tissue from the paraspinal muscles. The use of ultrasonography to determine the puncture site is necessary to ensure biopsy of the correct muscles and to ensure the safety of the procedure.

Feasibility of high intensity training in nonspecific chronic low back pain: A clinical trial.

BACKGROUND: Although low to moderate intensity exercise therapy is a predominant part of rehabilitation in nonspecific chronic low back pain (NSCLBP), effect sizes are small and optimal exercise modalities/intensities are unclear. Conversely, effects of high intensity training have not yet been investigated in this population. OBJECTIVE: The aim of this study is to investigate the feasibility of high intensity training (HIT) and to explore the magnitude of the effects of a HIT program on exercise capacity and disease related outcome measures compared to conventional therapy for persons with NSCLBP. METHODS: In this non-randomized controlled feasibility study, treatment satisfaction, adherence, disability, pain, physical activity, body composition, exercise capacity and self-reported motivation, were assessed in persons with NSCLBP, before (PRE) and after (POST) 6 weeks (12 sessions, 1.5 hours/session, 2 x/week) of high intensity cardiovascular (100% VO2Max) and high load resistance (80% 1RM) training (HIT, n= 10) and compared to average intensity/load (60% VO2max) conventional physical therapy (CON, n= 10). RESULTS: At PRE, CON and HIT did not differ, except for gender ratio and lean mass. Compared to CON, HIT retained motivation to rehabilitate better (HIT: +3%; CON: -25%) and had higher therapy adherence (+16%) during the study course. No adverse events were noted in both groups. Whereas disability reduced in both groups (HIT: -10.4%; CON: -8.3%), peak workload (+7.0%), time to exhaustion (+9.5%), and activity level (+5.6%) only improved in HIT. CONCLUSIONS: High intensity exercise therapy appears to be a feasible rehabilitation approach in NSCLBP. Outcomes improved following the HIT protocol, warranting the investigation of its effectiveness in future large scale RCT studies.

Time course of diaphragm function recovery after controlled mechanical ventilation in rats.

Controlled mechanical ventilation (CMV) is known to result in rapid and severe diaphragmatic dysfunction, but the recovery response of the diaphragm to normal function after CMV is unknown. Therefore, we examined the time course of diaphragm function recovery in an animal model of CMV. Healthy rats were submitted to CMV for 24-27 h (n = 16), or to 24-h CMV followed by either 1 h (CMV + 1 h SB, n = 9), 2 h (CMV + 2 h SB, n = 9), 3 h (CMV + 3 h SB, n = 9), or 4-7 h (CMV + 4-7 h SB, n = 9) of spontaneous breathing (SB). At the end of the experiment, the diaphragm muscle was excised for functional and biochemical analysis. The in vitro diaphragm force was significantly improved in the CMV + 3 h SB and CMV + 4-7 h SB groups compared with CMV (maximal tetanic force: +27%, P < 0.05, and +59%, P < 0.001, respectively). This was associated with an increase in the type IIx/b fiber dimensions (P < 0.05). Neutrophil influx was increased in the CMV + 4-7 h SB group (P < 0.05), while macrophage numbers remained unchanged. Markers of protein synthesis (phosphorylated Akt and eukaryotic initiation factor 4E binding protein 1) were significantly increased (±40%, P < 0.001, and ±52%, P < 0.01, respectively) in the CMV + 3 h SB and CMV + 4-7 h SB groups and were positively correlated with diaphragm force (P < 0.05). Finally, also the maximal specific force generation of skinned single diaphragm fibers was increased in the CMV + 4-7 h SB group compared with CMV (+45%, P < 0.05). In rats, reloading the diaphragm for 3 h after CMV is sufficient to improve diaphragm function, while complete recovery occurs after longer periods of reloading. Enhanced muscle fiber dimensions, increased protein synthesis, and improved intrinsic contractile properties of diaphragm muscle fibers may have contributed to diaphragm function recovery.

Bortezomib partially protects the rat diaphragm from ventilator-induced diaphragm dysfunction.

OBJECTIVE: Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, bortezomib, would have a protective effect against ventilator-induced diaphragm dysfunction. DESIGN: Randomized, controlled experiment. SETTINGS: Basic science animal laboratory. INTERVENTIONS: Anesthetized rats were submitted for 24 hrs to controlled mechanical ventilation while receiving 0.05 mg/kg bortezomib or saline. Control rats were acutely anesthetized. MEASUREMENTS AND MAIN RESULTS: After 24 hrs, diaphragm force production was significantly lower in mechanically ventilated animals receiving an injection of saline compared to control animals (-36%, p<.001). Importantly, administration of bortezomib improved the diaphragmatic force compared to mechanically ventilated animals receiving an injection of saline (+15%, p<.01), but force did not return to control levels. Compared to control animals, diaphragm cross-sectional area of the type IIx/b fibers was significantly decreased by 28% in mechanically ventilated animals receiving an injection of saline (p<.01) and by 16% in mechanically ventilated animals receiving an injection of bortezomib (p<.05). Diaphragmatic calpain activity was significantly increased in mechanically ventilated animals receiving an injection of saline (+52%, p<.05) and in mechanically ventilated animals receiving an injection of bortezomib (+36%, p<.05). Caspase-3 activity was increased after controlled mechanical ventilation with saline by 55% (p<.05), while it remained similar to control animals in mechanically ventilated animals receiving an injection of bortezomib. Diaphragm 20S proteasome activity was slightly increased in both ventilated groups, and the amount of ubiquitinated proteins was significantly and similarly enhanced in mechanically ventilated animals receiving an injection of saline and mechanically ventilated animals receiving an injection of bortezomib. CONCLUSIONS: These data show that the administration of bortezomib partially protects the diaphragm from controlled mechanical ventilation-induced diaphragm contractile dysfunction without preventing atrophy. The fact that calpain activity was still increased after bortezomib treatment may explain the persistence of atrophy. Part of bortezomib effects might have been due to its ability to inhibit caspase-3 in this model.

N-Acetylcysteine protects the rat diaphragm from the decreased contractility associated with controlled mechanical ventilation.

OBJECTIVE: Controlled mechanical ventilation results in diaphragmatic dysfunction, and oxidative stress has been shown to be an important contributor to ventilator-induced diaphragm dysfunction. We hypothesized that the administration of an antioxidant, N-acetylcysteine, would restore the redox balance in the diaphragm and prevent against the deleterious effects of controlled mechanical ventilation. DESIGN: Randomized, controlled experiment. SETTINGS: Basic science animal laboratory. SUBJECTS: Male Wistar rats, 14 wks old. INTERVENTIONS: Anesthetized rats were submitted for 24 hrs to either spontaneous breathing receiving 150 mg/kg N-acetylcysteine (SBNAC) or saline (SBSAL) or to controlled mechanical ventilation receiving 150 mg/kg N-acetylcysteine (MVNAC) or saline (MVSAL). MEASUREMENTS AND MAIN RESULTS: After 24 hrs of controlled mechanical ventilation, diaphragmatic force production was significantly lower in MVSAL compared with all groups. Importantly, administration of N-acetylcysteine completely abolished this controlled mechanical ventilation-induced diaphragmatic contractile dysfunction. Diaphragmatic protein oxidation was significantly increased after 24 hrs of controlled mechanical ventilation (+53%, p < .01) in MVSAL animals, whereas administration of N-acetylcysteine prevented this controlled mechanical ventilation-induced oxidative stress. Diaphragmatic 20S proteasome activity was increased in MVSAL (+62%, p < .05). Further, compared with SBSAL, diaphragm caspase-3 activity was significantly increased in MVSAL (+279%, p < .001), and N-acetylcysteine treatment provided partial protection against caspase-3 activation. Diaphragmatic calpain activity was significantly increased after controlled mechanical ventilation (+137%, p < .001) in MVSAL animals, but N-acetylcysteine treatment protected against this event. Finally, significant negative correlations existed between calpain activity and diaphragm force production (r from -0.56 to -0.49, p < .05). CONCLUSIONS: These data show that the administration of N-acetylcysteine protects the diaphragm from the deleterious effects of controlled mechanical ventilation. Specifically, N-acetylcysteine prevents against controlled mechanical ventilation-induced diaphragmatic oxidative stress and proteolysis and abolishes controlled mechanical ventilation-induced diaphragmatic contractile dysfunction.