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BACKGROUND: Survival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of muscle status suitable for routine care have not been evaluated for their association with long-term survival and their relation with each other in a large cohort of KTR.METHODS: Data of outpatient KTR ≥ 1 year post-transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height 2 (ASMI) through bio-electrical impedance analysis (BIA), and by 24-h urinary creatinine excretion rate indexed for height 2 (CERI). Muscle strength was determined by hand grip strength indexed for height 2 (HGSI). Secondary analyses were performed using parameters not indexed for height 2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all-cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: We included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m 2), of which 62 (8%) died during a median [interquartile range] follow-up of 3.0 [2.3-5.7] years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m 2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m 2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m 2; P < 0.001). We observed no association between ASMI and all-cause mortality (HR 0.93 per SD increase; 95% confidence interval [CI] [0.72, 1.19]; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI [0.44, 0.81]; P = 0.002 and HR 0.47 per SD increase; 95% CI [0.33, 0.68]; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI [0.47, 0.98]; P = 0.04 and HR 0.53 per SD increase; 95% CI [0.36, 0.76]; P = 0.001, respectively). Similar associations were found for unindexed parameters. CONCLUSIONS: Higher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all-cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24-h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.

Objective: To identify reference values for handgrip strength through a literature search and compare the agreement of reference values from Brazil with others for handgrip strength in a sample of COPD patients in Brazil, as well as to determine which set of reference values is more discriminative regarding differences in clinical characteristics between individuals with low handgrip strength and normal handgrip strength. Methods: To identify reference values for handgrip strength, a literature search was performed; a retrospective cross-sectional analysis of baseline-only data from two unrelated studies was then performed. Individuals were evaluated for handgrip strength, peripheral muscle strength, respiratory muscle strength, pulmonary function, body composition, exercise capacity, dyspnea, and functional status. Results: Of the 45 studies that were initially selected, 9 met the criteria for inclusion in the analysis, which included 99 COPD patients in Brazil (52% of whom were male with GOLD stage II-IV COPD). The prevalence of low handgrip strength varied across studies (from 9% to 55%), the set of reference values for handgrip strength in a sample of individuals in Brazil having classified 9% of the study sample as having low handgrip strength. The level of agreement between the reference values for a sample of individuals in Brazil and the other sets of reference values varied from weak to excellent. The reference values for a sample of individuals in Brazil showed the highest number of significantly different characteristics between individuals with low and normal handgrip strength. Conclusions: The level of agreement between national and international sets of reference values for handgrip strength varied from weak to excellent in COPD patients in Brazil. Reference values for handgrip strength with higher discriminative capacity are not necessarily those that identify more individuals as having low handgrip strength. RESUMO Objetivo: Identificar valores de referência de força de preensão manual por meio de pesquisa bibliográfica e comparar, em pacientes com DPOC no Brasil, o nível de concordância entre valores de referência de força de preensão manual obtidos no Brasil com outros valores de referência, bem como determinar qual conjunto de valores de referência é mais discriminativo em relação a características clínicas em indivíduos com força de preensão manual baixa e normal. Métodos: Para identificar valores de referência de força de preensão manual, foi realizada uma pesquisa bibliográfica. Em seguida, foi realizada uma análise transversal retrospectiva de dados exclusivamente basais provenientes de dois estudos não relacionados. Os indivíduos foram avaliados quanto à força de preensão manual, força muscular periférica, força muscular respiratória, função pulmonar, composição corporal, capacidade de exercício, dispneia e estado funcional. Resultados: Dos 45 estudos inicialmente selecionados, 9 preencheram os critérios de inclusão na análise, que incluiu 99 pacientes com DPOC no Brasil (52% dos quais eram homens com DPOC no estágio II-IV da GOLD). A prevalência de força de preensão manual baixa variou entre os estudos (de 9% a 55%), sendo que os valores de referência de força de preensão manual em indivíduos no Brasil classificaram 9% dos pacientes com DPOC como sendo indivíduos com força de preensão manual baixa. O nível de concordância entre os valores de referência para indivíduos no Brasil e os demais valores de referência variou de fraco a excelente. Os valores de referência para indivíduos no Brasil revelaram o maior número de características significativamente diferentes em indivíduos com força de preensão manual baixa e normal. Conclusões: O nível de concordância entre valores de referência nacionais e internacionais de força de preensão manual variou de fraco a excelente em pacientes com DPOC no Brasil. Os valores de referência de força de preensão manual com maior capacidade discriminativa não são necessariamente aqueles que identificam mais indivíduos como sendo indivíduos com força de preensão manual baixa.

Objectives To provide reference values for handgrip strength, shoulder and ankle range of motion (ROM) and upper-limb and lower limb stability for youth judokas of both sexes and investigate the effects of sex and side dominance. Design Cross-sectional. Methods A total of 137 youth judokas from under-18 (n = 60) and under-21 (n = 77) categories of both sexes were assessed. Handgrip strength was assessed using a Jamar dynamometer, ankle ROM was measured by lunge test, shoulder ROM was assessed by an inclinometer and upper-limb and lower limb stability were assessed by the Closed Kinetic Chain Upper Extremity Stability Test and by the Modified Star Excursion Balance Test (mSEBT). Results In both categories, males had greater handgrip strength. In the under-18 category, the dominant side had greater handgrip strength, the non-dominant side of females had smaller shoulder external rotation ROM than the dominant side and also than both sides of males, and females had greater shoulder IR ROM. In the under-21 category, the dominant side of females had greater ankle dorsiflexion ROM than the dominant side of males, the dominant sides and females had greater shoulder ER ROM, and males had better performance in the mSEBT. Conclusions This study provided reference values for handgrip strength, shoulder and ankle ROM, upper and lower limb stability for youth judokas, which can be used to guide assessment during preseason. Sex influenced on shoulder ER and IR ROM, handgrip strength and lower limb stability. In addition, side dominance influenced on shoulder ER ROM and on handgrip strength.

Objective The purposes of this study were to (1) investigate aspects of construct validity of peak force measurements of crate-and-pitcher tasks using the Task-oriented Arm-hAnd Capacity (TAAC), an instrument designed to measure task-oriented arm and hand strength for cross-sectional and evaluation purposes, and (2) compare TAAC measurements with those of comparative measures using COSMIN guidelines. Methods In this cross-sectional validity study, participants were 105 children (mean age = 12 years 10 months; number of boys = 66) diagnosed with unilateral cerebral palsy (UCP). Ten a priori hypotheses were formulated with peak force of the TAAC as index measure and compared with measures on body functions and structure and activity level of the International Classification of Functioning, Disability and Health for Children and Youth. Strength and direction of the relationship between the TAAC and comparative measures were investigated by calculating Pearson correlation coefficients (r). Results On body functions and structures level, low-to-moderate positive correlations (0.493–0.687) were found. On activity level, low negative and positive correlations (−0.271 to 0.387) were found. Conclusion The construct of peak force measurement of the TAAC is in line with the a priori hypotheses with comparators on body function and structures and activity level, indicating a partial overlap of the construct of the TAAC with both International Classification of Functioning levels. The TAAC appears to be valuable, as it measures functional strength that differs from the constructs of the comparators. More research with a larger population and more comparators is needed. Impact Clinically relevant information is lacking about the use of strength and strength measurement during daily activities in children with UCP. This study shows that the TAAC provides unique information about functional strength in children with UCP.

Hospitalization may induce a decrease of muscle strength and muscle mass in older patients due to physical inactivity, malnutrition and diseases, negatively affecting health outcome. We aimed to examine the literature on change in muscle strength and muscle mass in older patients during hospitalization. A literature search was performed in major electronic databases from inception to March 2016. Studies including hospitalized patients with a mean age ≥ 65 years, describing change of hand grip strength and/or muscle mass were found eligible. Extracted data were divided in hand grip strength or muscle mass and stratified by elective or acute admission. Meta-analysis was conducted using Comprehensive Meta-analysis. Twenty-five studies were included, describing a total of 1789 patients with a mean age range of 65 to 85.8 years and an overall median length of stay of 14.7 days. Pooled hand grip strength and muscle mass were found to significantly decrease in electively admitted older patients during hospitalization (standardized mean difference (95% confidence interval): − 0.42 (− 0.66, − 0.17) and − 0.44 (− 0.61, − 0.27)), but not in acutely admitted older patients (standardized mean difference (95% confidence interval): 0.18 (− 0.02, 0.37) and − 0.25 (− 0.58, 0.09)). In conclusion, decrease in muscle strength and muscle mass in older patients is dependent on the type of admission.

Hospitalization may induce a decrease of muscle strength and muscle mass in older patients due to physical inactivity, malnutrition and diseases, negatively affecting health outcome. We aimed to examine the literature on change in muscle strength and muscle mass in older patients during hospitalization. A literature search was performed in major electronic databases from inception to March 2016. Studies including hospitalized patients with a mean age≥65years, describing change of hand grip strength and/or muscle mass were found eligible. Extracted data were divided in hand grip strength or muscle mass and stratified by elective or acute admission. Meta-analysis was conducted using Comprehensive Meta-analysis. Twenty-five studies were included, describing a total of 1789 patients with a mean age range of 65 to 85.8years and an overall median length of stay of 14.7days. Pooled hand grip strength and muscle mass were found to significantly decrease in electively admitted older patients during hospitalization (standardized mean difference (95% confidence interval): -0.42 (-0.66, -0.17) and -0.44 (-0.61, -0.27)), but not in acutely admitted older patients (standardized mean difference (95% confidence interval): 0.18 (-0.02, 0.37) and -0.25 (-0.58, 0.09)). In conclusion, decrease in muscle strength and muscle mass in older patients is dependent on the type of admission.

Background Decreased grip strength (GS) is predictive of cardiovascular (CV) disease but whether it improves CV risk prediction has not been evaluated. We assessed the predictive value of low GS on incident CV events and overall mortality taking into account CV risk equations in a population-based study from Switzerland. Methods 2707 adults (54.8% women, age range 50–75years) were followed for a median time of 5.4years. GS was assessed using a hydraulic hand dynamometer. CV absolute risk at baseline was assessed using recalibrated SCORE, Framingham and PROCAM risk equations. Incident CV events were adjudicated by an independent committee. Results 160 deaths and 188 incident CV events occurred during follow-up. On bivariate analysis, low GS was associated with increased incident CV events: hazard ratio (HR) and (95% confidence interval) 1.76 (1.13–2.76), p p =0.09. The association between low GS and incident CV events disappeared after adjusting for baseline CV risk: HR=1.23 (0.79–1.94), p =0.36; 1.34 (0.86–2.10), p =0.20 and 1.47 (0.94–2.31), p =0.09 after adjusting for SCORE, Framingham and PROCAM scores, respectively. Conclusion Low GS is not predictive of incident CV events when taking into account CV absolute risk.

In addition to measures already used in clinical practice, molecular measures have been proposed to assess health status, but these have not yet been introduced into clinical practice. We aimed to test the association of functional capacity measures used in current practice and molecular measures with age and health status. The cohort consisted of 178 middle-aged to old participants of the Leiden Longevity Study (range 42-82years). We tested associations between functional capacity measures (physical tests: grip strength, 4-meter walk, chair stand test; cognitive tests: Stroop test, digit symbol substitution test and 15-picture learning test) with age and with cardiovascular or metabolic disease as a measure of the health status. These associations with age and health status were also tested for molecular measures (C reactive protein (CRP), numbers of senescent p16INK4a positive cells in the epidermis and dermis and putative immunosenescence (presence of CD57+ T cells)). All functional capacity measures were associated with age. CRP and epidermal p16INK4a positivity were also associated with age, but with smaller estimates. Grip strength and the Stroop test were associated with cardiovascular or metabolic disease, as was epidermal p16INK4a positivity. All associations with cardiovascular or metabolic disease attenuated when adjusting for age. In conclusion, in middle-aged to old persons, the molecular measures tested here were more weakly associated with age and health status than functional capacity measures. Whether these molecular measures associate more closely with health status in the elderly or in specific groups of patients needs to be explored further.

Background Microglia play a central role in most neurological disorders, but the impact of microgliosis on brain environment and clinical functions is not fully understood. Mice lacking multifunctional protein-2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, develop a fatal disorder characterized by motor problems similar to the milder form of MFP2 deficiency in humans. The hallmark of disease in mice is the chronic proliferation of microglia in the brain, but molecular pathomechanisms that drive rapid clinical deterioration in human and mice remain unknown. In the present study, we identified the effects of specific deletion of MFP2 from microglia in the brain on immune responses, neuronal functioning, and behavior. Methods We created a novel Cx3cr1-Mfp2−/− mouse model and studied the impact of MFP2 deficiency on microglial behavior at different ages using immunohistochemistry and real-time PCR. Pro- and anti-inflammatory responses of Mfp2−/− microglia were assessed in vitro and in vivo after stimulation with IL-1β/INFγ and IL-4 (in vitro) and LPS and IL-4 (in vivo). Facial nerve axotomy was unilaterally performed in Cx3cr1-Mfp2−/− and control mice, and microglial functioning in response to neuronal injury was subsequently analyzed by histology and real-time PCR. Finally, neuronal function, motor function, behavior, and cognition were assessed using brainstem auditory evoked potentials, grip strength and inverted grid test, open field exploration, and passive avoidance learning, respectively. Results We found that Mfp2−/− microglia in a genetically intact brain environment adopt an inflammatory activated and proliferative state. In addition, we found that acute inflammatory and neuronal injury provoked normal responses of Mfp2−/− microglia in Cx3cr1-Mfp2−/− mice during the post-injury period. Despite chronic pro-inflammatory microglial reactivity, Cx3cr1-Mfp2−/− mice exhibited normal neuronal transmission, clinical performance, and cognition. Conclusion Our data demonstrate that MFP2 deficiency in microglia causes intrinsic dysregulation of their inflammatory profile, which is not harmful to neuronal function, motor function, and cognition in mice during their first year of life. Electronic supplementary material The online version of this article (10.1186/s12974-019-1442-3) contains supplementary material, which is available to authorized users.

In a population-based sample of British women aged over 70 years old, lean mass and peak lower limb muscle force were both independently associated with hip strength and fracture risk indices, thereby suggesting a potential benefit of promoting leg muscle strengthening exercise for the prevention of hip fractures in postmenopausal women.INTRODUCTION: To investigate cross-sectional associations of lean mass and physical performance, including lower limb muscle function, with hip strength, geometry and fracture risk indices (FRIs) in postmenopausal women.METHODS: Data were from the Cohort of Skeletal Health in Bristol and Avon. Total hip (TH) and femoral neck (FN) bone mineral density (BMD), hip geometry and total body lean mass (TBLM) were assessed by dual x-ray absorptiometry (DXA). Finite element analysis of hip DXA was used to derive FN, intertrochanteric and subtrochanteric FRIs. Grip strength, gait speed and chair rise time were measured objectively. Lower limb peak muscle force and muscle power were assessed by jumping mechanography.RESULTS: In total, 241 women were included (age = 76.4; SD = 2.6 years). After adjustment for age, height, weight/fat mass and comorbidities, TBLM was positively associated with hip BMD (β TH BMD = 0.36, P ≤ 0.001; β FN BMD = 0.26, P = 0.01) and cross-section moment of inertia (0.24, P ≤ 0.001) and inversely associated with FN FRI (- 0.21, P = 0.03) and intertrochanteric FRI (- 0.11, P = 0.05) (estimates represent SD difference in bone measures per SD difference in TBLM). Lower limb peak muscle force was positively associated with hip BMD (β TH BMD = 0.28, P ≤ 0.001; β FN BMD = 0.23, P = 0.008) and inversely associated with FN FRI (- 0.17, P = 0.04) and subtrochanteric FRI (- 0.18, P = 0.04). Associations of grip strength, gait speed, chair rise time and peak muscle power with hip parameters were close to the null. CONCLUSIONS: Lean mass and lower limb peak muscle force were associated with hip BMD and geometrical FRIs in postmenopausal women. Leg muscle strengthening exercises may therefore help prevent hip fractures in older women.

Background: Accurate assessment of isometric hand grip strength (HGS) and isometric lower limb strength (LS) are often limited to specialized clinics due to high costs and need for specialized equipment and personnel. A mobile and user-friendly device would facilitate a wider use of these measures in the clinical setting. The Nintendo Wii Balance Board (WBB) is a novel and pragmatic tool that has been validated for measuring muscle strength and other clinically relevant physiological variables. However, reference data for HGS and LS are lacking. The purpose of the current study is to establish reference data for HGS and LS in individuals ≥20 years of age using the WBB method, and to characterize the effects of age in these measurements. Method: Healthy participants were recruited at various locations and their HGS and LS were tested by six assessors using the WBB. Reference data were analysed and presented in age-groups, while the age-related change in HGS and LS was tested and characterized with linear regression models. Results: Three hundred and fifty-four participants between 20 and 99 years of age were tested. Data are presented separately according to gender and the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+, and presented in absolute values as well as percentiles. The main findings were; (1) Significantly higher HGS and LS among males compared to females and for the dominant limb compared to the non-dominant limb, (2) a significant decline in strength with increasing age, and (3) the rate of decline increased significantly (i.e. it was non-linear) with age for HGS, but not for LS. Conclusion: This study reported reference data with percentiles for a novel method for assessing HGS and LS. Data were consistent with previously known effects of age and gender on HGS and LS. The presented data may supplement future trials using the WBB in research or in the clinical setting.

Expression of the neuronal kinase DCLK3 is reduced in Huntington’s disease. Galvan et al. report that DCLK3 silencing in the mouse striatum exacerbates the toxicity of mutant huntingtin, whereas DCLK3 overexpression is neuroprotective, and show that DCLK3 regulates the expression of many genes involved in transcription regulation and chromatin remodelling., The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (doublecortin like kinase 3), which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington’s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have an anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington’s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington’s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture. Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodelling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including the transcriptional activator adaptor TADA3, a core component of the Spt-ada-Gcn5 acetyltransferase (SAGA) complex which links histone acetylation to the transcription machinery. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodelling in these brain cells, and show that reduced expression of the kinase in Huntington’s disease could render the striatum highly vulnerable to neurodegeneration.

Purpose To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs). Methods Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized. Results The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension. Conclusions Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment. Type of study/level of evidence Therapeutic III.

Background: It is generally asserted that reliable and intuitive control of upper-limb prostheses requires adequate feedback of prosthetic finger positions and pinch forces applied to objects. Body-powered prostheses (BPPs) provide the user with direct proprioceptive feedback. Currently available BPPs often require high cable operation forces, which complicates control of the forces at the terminal device. The aim of this study is to quantify the influence of high cable forces on object manipulation with voluntary-closing prostheses.Method: Able-bodied male subjects were fitted with a bypass-prosthesis with low and high cable force settings for the prehensor. Subjects were requested to grasp and transfer a collapsible object as fast as they could without dropping or breaking it. The object had a low and a high breaking force setting.Results: Subjects conducted significantly more successful manipulations with the low cable force setting, both for the low (33% more) and high (50%) object's breaking force. The time to complete the task was not different between settings during successful manipulation trials.Conclusion: High cable forces lead to reduced pinch force control during object manipulation. This implies that low cable operation forces should be a key design requirement for voluntary-closing BPPs.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.

Background Mechanisms underlying the association between grip strength and cardiovascular mortality are poorly understood. We aimed to assess the association of grip strength with a panel of cardiovascular risk markers. Design The study was based on a cross-sectional analysis of 3468 adults aged 50-75 years (1891 women) from a population-based sample in Lausanne, Switzerland. Methods Grip strength was measured using a hydraulic hand dynamometer. Cardiovascular risk markers included anthropometry, blood pressure, lipids, glucose, adiposity, inflammatory and other metabolic markers. Results In both genders, grip strength was negatively associated with fat mass (Pearson correlation coefficient: women: -0.170, men: -0.198), systolic blood pressure (women: -0.096, men: -0.074), fasting glucose (women: -0.048, men: -0.071), log-transformed leptin (women: -0.074, men: -0.065), log-transformed high-sensitivity C-reactive protein (women: -0.101, men: -0.079) and log-transformed homocysteine (women: -0.109, men: -0.060). In men, grip strength was also positively associated with diastolic blood pressure (0.068), total (0.106) and low density lipoprotein-cholesterol (0.082), and negatively associated with interleukin-6 (-0.071); in women, grip strength was negatively associated with triglycerides (-0.064) and uric acid (-0.059). After multivariate adjustment, grip strength was negatively associated with waist circumference (change per 5 kg increase in grip strength: -0.82 cm in women and -0.77 cm in men), fat mass (-0.56% in women; -0.27% in men) and high-sensitivity C-reactive protein (-6.8% in women; -3.2% in men) in both genders, and with body mass index (0.22 kg/m javax.xml.bind.JAXBElement@165be361 ) and leptin (-2.7%) in men. Conclusion Grip strength shows only moderate associations with cardiovascular risk markers. The effect of muscle strength as measured by grip strength on cardiovascular disease does not seem to be mediated by cardiovascular risk markers.

Fatigue is a common and highly disabling symptom of multiple sclerosis. Patients experience an effort-independent general subjective feeling of fatigue as well as excessive fatigability when engaging in physical or mental activity. Previous research using functional magnetic resonance imaging (fMRI) has revealed heterogeneous findings, but some evidence implicates the motor system. To identify brain correlates of fatigue, 44 mildly impaired patients with relapsing-remitting multiple sclerosis and 25 age- and gender-matched healthy controls underwent functional magnetic resonance imaging at 3 Tesla, while they performed alternating blocks of rest and a non-fatiguing precision grip task. We investigated neural correlates of fatigue using the motor subscore of Fatigue Scale for Motor and Cognitive Functions (FSMCMOTOR) using the bilateral motor cerebellum, putamen, and dorsal premotor cortex as regions of interest. Patients and healthy controls performed the grip force task equally well without being fatigued. In patients, task-related activity in lobule VI of right motor cerebellum changed in proportion with individual FSMCMOTOR scores. In right dorsal premotor cortex, linear increases in activity across consecutive task blocks scaled with individual FSMCMOTOR scores in healthy controls, but not in patients. In premotor and dorsomedial prefrontal areas, patients were impaired at upscaling task-related activity the more they were affected by motor fatigue. The results support the notion that increased sensorimotor processing in the cerebellum contributes to the experience of motor fatigue and fatigability in multiple sclerosis. Additionally, downscaling of motivational input or sensorimotor processing in prefrontal and premotor areas may constitute an additional pathophysiological factor.

The aim of the study was to determine the impact of an interdisciplinary exercise-based rehabilitation intervention on fatigue and quality of life (QOL) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs). At the Danish Knowledge Centre for Rehabilitation and Palliative Care, a 5-day interdisciplinary exercise-based rehabilitation intervention was carried out on 48 patients with MPN. It was followed by 12 weeks of self-exercising prior to follow-up. Initially and at follow-up, participants filled out validated questionnaires; Brief Fatigue Inventory, Multidimensional Fatigue Inventory, European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire, Myeloproliferative Neoplasm Symptom Assessment Form and Hospital Anxiety and Depression Scale. Maximal oxygen uptake and muscular strength were tested as well. Paired t test was used to compare scores between baseline and follow-up. In total, 45 participants (94%) completed the follow-up. No significant differences were observed on fatigue or QOL when comparing baseline and follow-up. Mean maximal oxygen uptake increased from 27.2 to 33.6 ml O2 · kg−1 ·min−1 (p

Background Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. Methods To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. Results Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2–3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. Conclusions We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0427-0) contains supplementary material, which is available to authorized users.

Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34-99 (N = 10,681). Fisher's test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories. Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34-99 (N = 10,681). Fisher's test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.

Hypovitaminosis D has been associated with poorer physical and cognitive performances in older adults. The objectives of this study were (1) to measure and compare the time to perform (pTUG) and to imagine (iTUG) the Timed "Up & Go" test (TUG) test, and the time difference between these two performances (i.e., TUG delta time) in non-demented community-dwelling older adults with and without lower serum 25-hydroxyvitamin D (25OHD) concentrations and (2) to examine the association between the TUG delta time and serum 25OHD concentrations. Durations of pTUG, iTUG and TUG delta time, and serum 25OHD concentrations (severe insufficiency 30 ng/mL) were measured in 359 non-demented participants (mean age 70.4 ± 4.8 years; 40.7 % women). Participants with severe 25OHD insufficiency (15.6 %) had higher TUG delta time compared to those with moderate insufficiency (P = 0.010) and normal status (P = 0.048). TUG delta time was negatively associated with serum 25OHD concentrations (P

Background The safety of patient-controlled i.v. analgesia (PCA) with remifentanil for obstetrical analgesia remains a matter of concern. The efficacy of remifentanil bolus application, that is, the coincidence between pain and remifentanil effect-site concentration, may be improved by forecasting contractions, but it is not known whether such a technique would also improve safety. Methods We recorded pain intensity during labour continuously using a handheld dynamometer in 43 parturients. Using these data, we compared different models in their ability to predict future contractions. In addition, we modelled remifentanil effect-site concentration using three simulated modes of bolus administration, with and without prediction of future contractions. Results The average duration of pain during contractions recorded by the dynamometer was 45 [14 standard deviation (sd)] s. The time interval between painful contractions was highly variable, with a mean of 151 (31 sd) s during the first and 154 (52 sd) s during the second recording. Using a simple algorithm (three-point moving average), the sd of the difference between predicted and observed inter-contraction intervals can be reduced from 0.95 to 0.79 min. However, the coincidence between remifentanil concentration and pain during contraction is not substantially improved when using these models to guide remifentanil bolus application. Conclusions Because of the large variability of inter-contraction intervals, the use of prediction models will not influence the mean remifentanil concentration in-between contractions. Using models predicting future contractions to improve the timing of remifentanil PCA bolus administration will not diminish the need of continuous clinical surveillance and other safety measures.

When humans and other animals make decisions in their natural environments prospective rewards have to be weighed against costs. It is well established that increasing costs lead to devaluation or discounting of reward. While our knowledge about discount functions for time and probability costs is quite advanced, little is known about how physical effort discounts reward. In the present study we compared three different models in a binary choice task in which human participants had to squeeze a handgrip to earn monetary rewards: a linear, a hyperbolic, and a parabolic model. On the group as well as the individual level, the concave parabolic model explained most variance of the choice data, thus contrasting with the typical hyperbolic discounting of reward value by delay. Research on effort discounting is not only important to basic science but also holds the potential to quantify aberrant motivational states in neuropsychiatric disorders.

International audience; X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells. It was postulated that therapeutically increasing muscle fiber size would cause symptomatic improvement in myotubularin deficiency. Recent studies have elucidated an important role for the activin-receptor type IIB (ActRIIB) in regulation of muscle growth and have demonstrated that ActRIIB inhibition results in significant muscle hypertrophy. To evaluate whether promoting muscle hypertrophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1delta4) mice. Compared with wild-type mice, untreated Mtm1delta4 mice have decreased body weight, skeletal muscle hypotrophy, and reduced survival. Treatment of Mtm1delta4 mice with ActRIIB-mFC produced a 17% extension of lifespan, with transient increases in weight, forelimb grip strength, and myofiber size. Pathologic analysis of Mtm1delta4 mice during treatment revealed that ActRIIB-mFC produced marked hypertrophy restricted to type 2b myofibers, which suggests that oxidative fibers in Mtm1delta4 animals are incapable of a hypertrophic response in this setting. These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency.

We assessed force coordination of the hand in Parkinson's disease and its relationship to motor complications of levodopa therapy, particularly to levodopa-induced dyskinesias (LID). We studied two groups of Parkinson's disease patients with (Parkinson's disease + LID, n = 23) and without levodopa-induced dyskinesias (Parkinson's disease - LID, n = 10), and age-matched healthy controls. The motor score of the Unified Parkinson's Disease Rating Scale, a dyskinesia score and force in a grip-lift paradigm were assessed ON and OFF levodopa. A pathological increase of forces was seen in ON-state in Parkinson's disease + LID only. In Parkinson's disease + LID, the force involved in pressing down the object before lifting was significantly increased by levodopa (by 61%, P < 0.05). An overshooting of peak grip force by 51% (P < 0.05) and of static grip force by 45% (P < 0.01) was observed in the ON- compared with the OFF-drug condition. In contrast, no excessive force was found in Parkinson's disease - LID. Peak grip force in ON-state was 140% (P < 0.05) higher in Parkinson's disease + LID than in Parkinson's disease - LID, while static grip force was increased by 138% (P < 0.01) between groups. Severity of peak-dose dyskinesias was strongly correlated with grip force in ON-state (r = 0.79 with peak force, P < 0.01). No correlation was observed between forces and the motor score as well as with the daily dose of dopaminergic medication. Force excess was only observed in patients with LID and motor fluctuations. A close relationship was seen between the overshooting of forces and dyskinesias in the ON-drug condition. We postulate that both LID and grip force excess share common pathophysiological mechanisms related to motor fluctuations.

Fourteen extension osteotomies were performed in 13 patients with angular metacarpal malunion. Surgery was indicated by the limitation of mobility, the reduction in gripping capacity, and pain following digitopalmar grasping movements. After surgery, the patients regained good articular mobility. However, in 60% of cases a teno-arthrolysis was required upon removal of consolidation hardware to restore digital function. The operation allowed pain relief in two-thirds of the patient population; in the remaining subjects, pain was experienced when making grasping movements. At the final examination, in the majority of cases gripping strength was similar to that of the contralateral hand. In conclusion, correction of angular malunion by extension osteotomy is a demanding procedure, and whenever possible should be avoided by a precise reduction of the metacarpal fracture during initial surgery. A fractured metacarpal with a palmar angulation of over 15 degrees should systematically be reduced and fixed if unstable.

Sagittal intermaxillary changes brought about by functional appliances show large inter-individual variation. One factor that may in part explain these differences is the masticatory musculature and its functional capacity. The aims of this study were to investigate changes in maximal molar bite force during functional appliance treatment and to assess the influence of pre-treatment maximal molar bite force on treatment outcomes with functional appliances used in Class II malocclusion children. Twenty-five children (17 males and 8 females), aged 9-13 years, with a Class II malocclusion and increased overjet were treated with functional appliances for 1-2 years. Dental casts, lateral cephalograms, maximal molar bite force, and finger force measurements were performed before (T1) and after (T2) treatment. These same measurements were also performed 1-2 years before treatment (T0); the intermediate period before starting treatment served as the control. Multiple regression analyses were used to determine possible correlations between initial maximal molar bite force and dental or cephalometric changes during treatment. Maximal molar bite force, which increased pre-treatment (T0-T1), decreased during functional appliance treatment (T1-T2). Children with a weaker T1 maximal molar bite force showed a larger overjet reduction, greater improvement in molar relationship, greater reduction in ANB angle, and greater augmentation in SNB angle from T1 to T2. Treatment of children with Class II malocclusions with functional appliances seems to lead to more favourable treatment outcomes in those with a weaker maximal molar bite force. This was observed both as regards improvements in dental sagittal relationships, namely overjet and molar Class, as well as skeletal changes due to a decrease in ANB and an increase in SNB angles.