Prevalence and Associated Factors of Sarcopenia in Older Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Bastiaanse, Luc P.; Hilgenkamp, Thessa I. M.; Echteld, Michael A.; Evenhuis, Heleen M.

2012-01-01

Sarcopenia is defined as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength. It has hardly been studied in older people with intellectual disabilities (ID). In this study 884 persons with borderline to profound ID aged 50 years and over, were investigated to determine the prevalence of sarcopenia in…

Segregation of striated and smooth muscle lineages by a Notch-dependent regulatory network

PubMed Central

2014-01-01

Background Lineage segregation from multipotent epithelia is a central theme in development and in adult stem cell plasticity. Previously, we demonstrated that striated and smooth muscle cells share a common progenitor within their epithelium of origin, the lateral domain of the somite-derived dermomyotome. However, what controls the segregation of these muscle subtypes remains unknown. We use this in vivo bifurcation of fates as an experimental model to uncover the underlying mechanisms of lineage diversification from bipotent progenitors. Results Using the strength of spatio-temporally controlled gene missexpression in avian embryos, we report that Notch harbors distinct pro-smooth muscle activities depending on the duration of the signal; short periods prevent striated muscle development and extended periods, through Snail1, promote cell emigration from the dermomyotome towards a smooth muscle fate. Furthermore, we define a Muscle Regulatory Network, consisting of Id2, Id3, FoxC2 and Snail1, which acts in concert to promote smooth muscle by antagonizing the pro-myogenic activities of Myf5 and Pax7, which induce striated muscle fate. Notch and BMP closely regulate the network and reciprocally reinforce each other’s signal. In turn, components of the network strengthen Notch signaling, while Pax7 silences this signaling. These feedbacks augment the robustness and flexibility of the network regulating muscle subtype segregation. Conclusions Our results demarcate the details of the Muscle Regulatory Network, underlying the segregation of muscle sublineages from the lateral dermomyotome, and exhibit how factors within the network promote the smooth muscle at the expense of the striated muscle fate. This network acts as an exemplar demonstrating how lineage segregation occurs within epithelial primordia by integrating inputs from competing factors. PMID:25015411

Soft versus hard occlusal splint therapy in the management of temporomandibular disorders (TMDs)

PubMed Central

Seifeldin, Sameh A; Elhayes, Khaled A.

2015-01-01

Aim To compare between soft and hard occlusal splint therapy for the management of myofacial pain dysfunction (MPD) or internal derangement (ID) of the temporomandibular joint (TMJ) with reciprocal clicking. Patients and methods This study included 50 patients (age range: 24–47 years) who had been diagnosed with MPD or ID of the TMJ in the form of reciprocal clicking. Patients were divided into two groups. They were treated for 4 months with either a vacuum-formed soft occlusal splint constructed from 2-mm-thick elastic rubber sheets (soft splint group) or a hard flat occlusal splint fabricated from transparent acrylic resin (hard splint group). Monthly follow-up visits were performed during the treatment period. Before treatment and 1, 2, 3 and 4 months after treatment, the dentist measured all parameters of TMJ function (pain visual analog scores, tenderness of masticatory muscles, clicking and tenderness of the TMJ, and range of mouth opening). Results All parameters of TMJ function showed significant improvement in both groups during the follow-up period, with a statistically significant difference between the two groups at the 4-month follow-up visit. Conclusions Both forms of occlusal splints (soft and hard) improved TMJ symptoms in patients with MPD or ID of the TMJ. However, the soft occlusal splints exhibited superior results after 4 months of use. PMID:26644756

Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein.

PubMed Central

Beech, D. J.; Bolton, T. B.

1989-01-01

1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed. PMID:2590772

Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial.

PubMed

Lonkvist, Camilla K; Lønbro, Simon; Vinther, Anders; Zerahn, Bo; Rosenbom, Eva; Primdahl, Hanne; Hojman, Pernille; Gehl, Julie

2017-06-03

Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects. At the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional. This randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy. Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov ( NCT02557529 ) September 11th 2015.

Executive function in children with intellectual disability--the effects of sex, level and aetiology of intellectual disability.

PubMed

Memisevic, H; Sinanovic, O

2014-09-01

Executive function is very important in the children's overall development. The goal of this study was to assess the executive function in children with intellectual disability (ID) through the use of the Behavior Rating Inventory of Executive Function (BRIEF) teacher version. An additional goal was to examine the differences in executive function in relation to child's sex, level and aetiology of ID. The sample consisted of 90 children with ID attending two special education schools in Sarajevo, Bosnia and Herzegovina. There were 42 children with mild ID and 48 children with moderate ID. Of those, 54 were boys and 36 were girls. Children were classified into three etiological categories: 30 children with Down syndrome, 30 children with other genetic cause or organic brain injury and 30 children with unknown aetiology of ID. Special education teachers, who knew the children for at least 6 months filled the BRIEF. Children with ID had a significant deficit in executive function as measured by the BRIEF. There were no statistically significant differences in executive function in relation to the child's sex. Level of ID had a significant effect on executive function. In relation to the aetiology of ID, the only significant difference was on the Shift scale of the BRIEF. Knowing what executive function is most impaired in children with ID will help professionals design better intervention strategies. More attention needs to be given to the assessment of executive function and its subsequent intervention in the school settings. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Does visual impairment lead to additional disability in adults with intellectual disabilities?

PubMed

Evenhuis, H M; Sjoukes, L; Koot, H M; Kooijman, A C

2009-01-01

This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.

High fat diet rescues disturbances to metabolic homeostasis and survival in the Id2 null mouse in a sex-specific manner

PubMed Central

Zhou, Peng; Hummel, Alyssa D.; Pywell, Cameron M.; Dong, X. Charlie; Duffield, Giles E.

2014-01-01

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have altered expression of circadian genes involved in lipid metabolism, altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. Here we further characterized the Id2−/− mouse metabolic phenotype in a sex-specific context and under low and high fat diets, and examined metabolic and endocrine parameters associated with lipid and glucose metabolism. Under the low-fat diet Id2−/− mice showed decreased weight gain, reduced gonadal fat mass, and a lower survival rate. Under the high-fat diet, body weight and gonadal fat gain of Id2−/− male mice was comparable to control mice and survival rate improved markedly. Furthermore, the high-fat diet treated Id2−/− male mice lost the enhanced glucose tolerance feature observed in the other Id2−/− groups, and there was a sex-specific difference in white adipose tissue storage of Id2−/− mice. Additionally, a distinct pattern of hepatic lipid accumulation was observed in Id2−/− males: low lipids on the low-fat diet and steatosis on the high-fat diet. In summary, these data provides valuable insights into the impact of Id2 deficiency on metabolic homeostasis of mice in a sex-specific manner. PMID:25108156

Comparative Analyses by Sequencing of Transcriptomes during Skeletal Muscle Development between Pig Breeds Differing in Muscle Growth Rate and Fatness

PubMed Central

Li, Anning; Gong, Wen; Xiao, Shuqi; Zhang, Yue; Qin, Limei; Niu, Yuna; Guo, Yunxue; Liu, Xiaohong; Cong, Peiqing; He, Zuyong; Wang, Chong; Li, Jiaqi; Chen, Yaosheng

2011-01-01

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement. The raw data have been submitted to Gene Expression Omnibus (GEO) under series GSE25406. PMID:21637832

Comparative analyses by sequencing of transcriptomes during skeletal muscle development between pig breeds differing in muscle growth rate and fatness.

PubMed

Zhao, Xiao; Mo, Delin; Li, Anning; Gong, Wen; Xiao, Shuqi; Zhang, Yue; Qin, Limei; Niu, Yuna; Guo, Yunxue; Liu, Xiaohong; Cong, Peiqing; He, Zuyong; Wang, Chong; Li, Jiaqi; Chen, Yaosheng

2011-01-01

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement. The raw data have been submitted to Gene Expression Omnibus (GEO) under series GSE25406.

A structured physical activity and fitness programme for older adults with intellectual disabilities: results of a cluster-randomised clinical trial.

PubMed

van Schijndel-Speet, M; Evenhuis, H M; van Wijck, R; van Montfort, K C A G M; Echteld, M A

2017-01-01

The physical activity level of older adults with intellectual disabilities (ID) is extremely low, and their fitness levels are far beneath accepted norms for older people with normal intelligence and comparable with frail older people. A physical activity programme, including an education programme, was developed for older adults with ID using behaviour change techniques. The programme aimed at improving or maintaining adequate levels of physical activity (primary outcome measure) and motor fitness, cardio respiratory fitness, morphologic and metabolic fitness, activities of daily living, cognitive functioning and depressive symptoms (secondary outcome measures). The programme's efficacy was evaluated in a cluster-randomised clinical trial among people aged 43 years and over with mild-moderate levels of ID. Five day-activity centres were randomised to the participation group. In these centres, 81 older adults participated in groups of 8 to 10 in the programme, three times a week during 8 months. The programme was executed by physical activity instructors and staff of day-activity centres. Five other day-activity centres were randomised to the control group; 70 older adults in these centres received care as usual. The generalised linear model with mixed effects was used to test the programme's effectiveness. Significant effects were found on physical activity, muscle strength, systolic and diastolic blood pressure, serum cholesterol level and cognitive functioning, in favour of the programme's participants. No significant improvements were found on balance, serum glucose, weight, waist circumference, walking speed, mobility, depression or instrumental activities of daily living. The physical activity and fitness programme has established small but significant effects in this sample, but generalising the findings to other settings is difficult due to significant participant dropout. Implementation of evidence-based physical activity programmes among older adults with ID is recommended. Further research is needed to investigate the effectiveness of physical activity on daily life functioning and the development on chronic diseases in the long run. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila

PubMed Central

Oortveld, Merel A. W.; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G.; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A.; Schenck, Annette

2013-01-01

Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules. PMID:24204314

Human intellectual disability genes form conserved functional modules in Drosophila.

PubMed

Oortveld, Merel A W; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A; Schenck, Annette

2013-10-01

Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.

Neuropsychological Predictors of Everyday Functioning in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Su, C. Y.; Chen, C. C.; Wuang, Y. P.; Lin, Y. H.; Wu, Y. Y.

2008-01-01

Background: Very little is known about the neuropsychological correlates of adaptive functioning in people with intellectual disabilities (ID). This study examined whether specific cognitive deficits and demographic variables predicted everyday functioning in adults with ID. Method: People with ID (n = 101; ages 19-41 years; mean education = 11…

Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4.

PubMed

Wissmann, Ralph; Bildl, Wolfgang; Oliver, Dominik; Beyermann, Michael; Kalbitzer, Hans-Robert; Bentrop, Detlef; Fakler, Bernd

2003-05-02

Cumulative inactivation of voltage-gated (Kv) K(+) channels shapes the presynaptic action potential and determines timing and strength of synaptic transmission. Kv1.4 channels exhibit rapid "ball-and-chain"-type inactivation gating. Different from all other Kvalpha subunits, Kv1.4 harbors two inactivation domains at its N terminus. Here we report the solution structure and function of this "tandem inactivation domain" using NMR spectroscopy and patch clamp recordings. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, whereas ID2 (residues 40-50) is a 2.5-turn helix made up of small hydrophobic amino acids. Functional analysis suggests that only ID1 may work as a pore-occluding ball domain, whereas ID2 most likely acts as a "docking domain" that attaches ID1 to the cytoplasmic face of the channel. Deletion of ID2 slows inactivation considerably and largely impairs cumulative inactivation. Together, the concerted action of ID1 and ID2 may promote rapid inactivation of Kv1.4 that is crucial for the channel function in short term plasticity.

Putting the Brakes on Muscle Breakdown

NASA Image and Video Library

2018-01-15

Rodent Research-6 is a two-fold investigation aboard the International Space Station into the treatment of muscle loss in spaceflight, which may have implications for patients on Earth with muscle-wasting diseases. The experiment will study the effectiveness of a drug compound as well as the nano-channel drug delivery implant, a device implanted beneath the skin of the patient allowing for a constant, steady delivery of the drug. Rodent Research: https://www.nasa.gov/mission_pages/station/research/experiments/explorer/Investigation.html?#id=7423 HD Download: https://archive.org/details/jsc2018m000072_Putting_the_Brakes_on_Muscle_Breakdown_MXF _______________________________________ FOLLOW THE SPACE STATION! Twitter: https://twitter.com/Space_Station Facebook: https://www.facebook.com/ISS Instagram: https://instagram.com/iss/

The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training.

PubMed

Erskine, R M; Williams, A G; Jones, D A; Stewart, C E; Degens, H

2014-08-01

Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin-I converting enzyme (ACE) and α-actinin-3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (Vm), physiological cross-sectional area (PCSA), maximum isometric force (Ft), specific force (Ft per unit PCSA), maximum isoinertial strength (1-RM), and maximum power (Wmax ; n = 40) before and after 9-week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R-allele carriers had greater Vm, 1-RM, and Wmax than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the "optimal" ACE+ACTN3 genotype combination had greater baseline 1-RM and Wmax compared to those with the "suboptimal" profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human Vm and (independently and in combination with the ACE I/D polymorphism) influences 1-RM and Wmax. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H.; Morton, Derrick J.

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, wemore » examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.« less

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.

PubMed

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H; Morton, Derrick J; Patel, Divya; Joshi, Jugal; Upadhyay, Sunil; Chaudhary, Jaideep

2016-09-09

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. Copyright © 2016 Elsevier Inc. All rights reserved.

Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration.

PubMed

Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

2016-11-18

Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4 , the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration.

Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).

PubMed

Crawford, Jeffrey; Prado, Carla M M; Johnston, Mary Ann; Gralla, Richard J; Taylor, Ryan P; Hancock, Michael L; Dalton, James T

2016-06-01

Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a subject must have ≥10 % improvement in physical function compared to baseline. To meet the definition of response on LBM, a subject must have demonstrated no loss of LBM compared with baseline. Secondary endpoints include durability of response assessed at day 147 in those responding at day 84. A combined overall survival analysis for both studies is considered a key secondary safety endpoint. The POWER trials design was established with extensive clinical input and collaboration with regulatory agencies. The efficacy endpoints are a result of this feedback and discussion of the threshold for clinical benefit in patients at risk for muscle wasting. Full results from these studies will soon be published and will further guide the development of future anabolic trials. Clinical Trial ID: NCT01355484. https://clinicaltrials.gov/ct2/show/NCT01355484 , NCT01355497. https://clinicaltrials.gov/ct2/show/NCT01355497?term=g300505&rank=1 .

The Effect of Aging on Muscular Dynamics Underlying Movement Patterns Changes.

PubMed

Vernooij, Carlijn A; Rao, Guillaume; Berton, Eric; Retornaz, Frédérique; Temprado, Jean-Jacques

2016-01-01

Introduction: Aging leads to alterations not only within the complex subsystems of the neuro-musculo-skeletal system, but also in the coupling between them. Here, we studied how aging affects functional reorganizations that occur both within and between the behavioral and muscular levels, which must be coordinated to produce goal-directed movements. Using unimanual reciprocal Fitts' task, we examined the behavioral and muscular dynamics of older adults (74.4 ± 3.7 years) and compared them to those found for younger adults (23.2 ± 2.0 years). Methods: To achieve this objective, we manipulated the target size to trigger a phase transition in the behavioral regime and searched for concomitant signatures of a phase transition in the muscular coordination. Here, muscular coordination was derived by using the method of muscular synergy extraction. With this technique, we obtained functional muscular patterns through non-negative matrix factorization of the muscular signals followed by clustering the resulting synergies. Results: Older adults showed a phase transition in behavioral regime, although, in contrast to young participants, their kinematic profiles did not show a discontinuity. In parallel, muscular coordination displayed two typical signatures of a phase transition, that is, increased variability of coordination patterns and a reorganization of muscular synergies. Both signatures confirmed the existence of muscular reorganization in older adults, which is coupled with change in dynamical regime at behavioral level. However, relative to young adults, transition occurred at lower index of difficulty (ID) in older participants and the reorganization of muscular patterns lasted longer (over multiple IDs). Discussion: This implies that consistent changes occur in coordination processes across behavior and muscle. Furthermore, the repertoire of muscular patterns was reduced and somewhat modified for older adults, relative to young participants. This suggests that aging is not only related to changes in individual muscles (e.g., caused by dynapenia) but also in their coordination.

SNP ID-info: SNP ID searching and visualization platform.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Cheng, Yu-Huei; Wen, Cheng-Hao; Chang, Phei-Lang; Chang, Hsueh-Wei

2008-09-01

Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.

Increased Cardiac Arrhythmogenesis Associated With Gap Junction Remodeling With Upregulation of RNA-Binding Protein FXR1.

PubMed

Chu, Miensheng; Novak, Stefanie Mares; Cover, Cathleen; Wang, Anne A; Chinyere, Ikeotunye Royal; Juneman, Elizabeth B; Zarnescu, Daniela C; Wong, Pak Kin; Gregorio, Carol C

2018-02-06

Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and posttranscriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of FXR1 (fragile X mental retardation autosomal homolog 1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear. To identify the mechanisms regulating gap junction remodeling in cardiac disease, we sought to identify the functional properties of FXR1 expression, direct targets of FXR1 in human left ventricle dilated cardiomyopathy (DCM) biopsy samples and mouse models of DCM through BioID proximity assay and RNA immunoprecipitation, how FXR1 regulates its targets through RNA stability and luciferase assays, and functional consequences of altering the levels of this important RNA-binding protein through the analysis of cardiac-specific FXR1 knockout mice and mice injected with 3xMyc-FXR1 adeno-associated virus. FXR1 expression is significantly increased in tissue samples from human and mouse models of DCM via Western blot analysis. FXR1 associates with intercalated discs, and integral gap junction proteins Cx43 (connexin 43), Cx45 (connexin 45), and ZO-1 (zonula occludens-1) were identified as novel mRNA targets of FXR1 by using a BioID proximity assay and RNA immunoprecipitation. Our findings show that FXR1 is a multifunctional protein involved in translational regulation and stabilization of its mRNA targets in heart muscle. In addition, introduction of 3xMyc-FXR1 via adeno-associated virus into mice leads to the redistribution of gap junctions and promotes ventricular tachycardia, showing the functional significance of FXR1 upregulation observed in DCM. In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1, namely, that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart. © 2017 American Heart Association, Inc.

The validity and reliability of the Functional Strength Measurement (FSM) in children with intellectual disabilities.

PubMed

Aertssen, W F M; Steenbergen, B; Smits-Engelsman, B C M

2018-06-07

There is lack of valid and reliable field-based tests for assessing functional strength in young children with mild intellectual disabilities (IDs). The aim of this study was to investigate the test-retest reliability and construct validity of the Functional Strength Measurement in children with ID (FSM-ID). Fifty-two children with mild ID (40 boys and 12 girls, mean age 8.48 years, SD = 1.48) were tested with the FSM. Test-retest reliability (n = 32) was examined by a two-way interclass correlation coefficient for agreement (ICC 2.1A). Standard error of measurement and smallest detectable change were calculated. Construct validity was determined by calculating correlations between the FSM-ID and handheld dynamometry (HHD) (convergent validity), FSM-ID, FSM-ID and subtest strength of the Bruininks-Oseretsky test of motor proficiency - second edition (BOT-2) (convergent validity) and the FSM-ID and balance subtest of the BOT-2 (discriminant validity). Test-retest reliability ICC ranged 0.89-0.98. Correlation between the items of the FSM-ID and HHD ranged 0.39-0.79 and between FSM-ID and BOT-2 (strength items) 0.41-0.80. Correlation between items of the FSM-ID and BOT-2 (balance items) ranged 0.41-0.70. The FSM-ID showed good test-retest reliability and good convergent validity with the HHD and BOT-2 subtest strength. The correlations assessing discriminant validity were higher than expected. Poor levels of postural control and core stability in children with mild IDs may be the underlying factor of those higher correlations. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Department of Defense Chemical, Biological, Radiological, and Nuclear Defense Program. FY2003-2005 Performance Plan

DTIC Science & Technology

2004-05-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to...baselined. Long Range Biometric Target ID System Explore technologies for a long range biometric target identification system. 3.5.1.6

Watching proteins function with 150-ps time-resolved X-ray crystallography

NASA Astrophysics Data System (ADS)

Anfinrud, Philip

2007-03-01

We have used time-resolved Laue crystallography to characterize ligand migration pathways and dynamics in wild-type and several mutant forms of myoglobin (Mb), a ligand-binding heme protein found in muscle tissue. In these pump-probe experiments, which were conducted on the ID09B time-resolved beamline at the European Synchrotron and Radiation Facility, a laser pulse photodissociates CO from an MbCO crystal and a suitably delayed X-ray pulse probes its structure via Laue diffraction. Single-site mutations in the vicinity of the heme pocket docking site were found to have a dramatic effect on ligand migration. To visualize this process, time-resolved electron density maps were stitched together into movies that unveil with <2-å spatial resolution and 150-ps time-resolution the correlated protein motions that accompany and/or mediate ligand migration. These studies help to illustrate at an atomic level relationships between protein structure, dynamics, and function.

Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo

PubMed Central

Costamagna, Domiziana; Mommaerts, Hendrik; Sampaolesi, Maurilio; Tylzanowski, Przemko

2016-01-01

Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin−/− mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1. Finally, upon removal of Noggin, the number of mesenchymal Pax7+ muscle precursor cells is reduced and they are more prone to differentiate into adipocytes in vitro. Thus, our results highlight the importance of Noggin/BMP balance for myogenic commitment of early fetal progenitor cells. PMID:27573479

Cross-cultural adaptation, reliability, and validation of the Korean version of the identification functional ankle instability (IdFAI).

PubMed

Ko, Jupil; Rosen, Adam B; Brown, Cathleen N

2017-09-12

To cross-culturally adapt the Identification Functional Ankle Instability for use with Korean-speaking participants. The English version of the IdFAI was cross-culturally adapted into Korean based on the guidelines. The psychometric properties in the Korean version of the IdFAI were measured for test-retest reliability, internal consistency, criterion-related validity, discriminative validity, and measurement error 181 native Korean-speakers. Intra-class correlation coefficients (ICC 2,1 ) between the English and Korean versions of the IdFAI for test-retest reliability was 0.98 (standard error of measurement = 1.41). The Cronbach's alpha coefficient was 0.89 for the Korean versions of IdFAI. The Korean versions of the IdFAI had a strong correlation with the SF-36 (r s  = -0.69, p < .001) and the Korean version of the Cumberland Ankle Instability Tool (r s  = -0.65, p < .001). The cutoff score of >10 was the optimal cutoff score to distinguish between the group memberships. The minimally detectable change of the Korean versions of the IdFAI score was 3.91. The Korean versions of the IdFAI have shown to be an excellent, reliable, and valid instrument. The Korean versions of the IdFAI can be utilized to assess the presence of Chronic Ankle Instability by researchers and clinicians working among Korean-speaking populations. Implications for rehabilitation The high recurrence rate of sprains may result into Chronic Ankle Instability (CAI). The Identification of Functional Ankle Instability Tool (IdFAI) has been validated and recommended to identify patients with Chronic Ankle Instability (CAI). The Korean version of the Identification of Functional Ankle Instability Tool (IdFAI) may be also recommend to researchers and clinicians for assessing the presence of Chronic Ankle Instability (CAI) in Korean-speaking population.

Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration

PubMed Central

Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

2016-01-01

Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4, the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration. DOI: http://dx.doi.org/10.7554/eLife.19484.001 PMID:27855784

Visual local and global processing in low-functioning deaf individuals with and without autism spectrum disorder.

PubMed

Maljaars, J P W; Noens, I L J; Scholte, E M; Verpoorten, R A W; van Berckelaer-Onnes, I A

2011-01-01

The ComFor study has indicated that individuals with intellectual disability (ID) and autism spectrum disorder (ASD) show enhanced visual local processing compared with individuals with ID only. Items of the ComFor with meaningless materials provided the best discrimination between the two samples. These results can be explained by the weak central coherence account. The main focus of the present study is to examine whether enhanced visual perception is also present in low-functioning deaf individuals with and without ASD compared with individuals with ID, and to evaluate the underlying cognitive style in deaf and hearing individuals with ASD. Different sorting tasks (selected from the ComFor) were administered from four subsamples: (1) individuals with ID (n = 68); (2) individuals with ID and ASD (n = 72); (3) individuals with ID and deafness (n = 22); and (4) individuals with ID, ASD and deafness (n = 15). Differences in performance on sorting tasks with meaningful and meaningless materials between the four subgroups were analysed. Age and level of functioning were taken into account. Analyses of covariance revealed that results of deaf individuals with ID and ASD are in line with the results of hearing individuals with ID and ASD. Both groups showed enhanced visual perception, especially on meaningless sorting tasks, when compared with hearing individuals with ID, but not compared with deaf individuals with ID. In ASD either with or without deafness, enhanced visual perception for meaningless information can be understood within the framework of the central coherence theory, whereas in deafness, enhancement in visual perception might be due to a more generally enhanced visual perception as a result of auditory deprivation. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Influence of coronary artery diameter on eNOS protein content

NASA Technical Reports Server (NTRS)

Laughlin, M. H.; Turk, J. R.; Schrage, W. G.; Woodman, C. R.; Price, E. M.

2003-01-01

The purpose of this study was to test the hypothesis that the content of endothelial nitric oxide synthase (eNOS) protein (eNOS protein/g total artery protein) increases with decreasing artery diameter in the coronary arterial tree. Content of eNOS protein was determined in porcine coronary arteries with immunoblot analysis. Arteries were isolated in six size categories from each heart: large arteries [301- to 2,500-microm internal diameter (ID)], small arteries (201- to 300-microm ID), resistance arteries (151- to 200-microm ID), large arterioles (101- to 150-microm ID), intermediate arterioles (51- to 100-microm ID), and small arterioles(<50-microm ID). To obtain sufficient protein for analysis from small- and intermediate-sized arterioles, five to seven arterioles 1-2 mm in length were pooled into one sample for each animal. Results establish that the number of smooth muscle cells per endothelial cell decreases from a number of 10 to 15 in large coronary arteries to 1 in the smallest arterioles. Immunohistochemistry revealed that eNOS is located only in endothelial cells in all sizes of coronary artery and in coronary capillaries. Contrary to our hypothesis, eNOS protein content did not increase with decreasing size of coronary artery. Indeed, the smallest coronary arterioles had less eNOS protein per gram of total protein than the large coronary arteries. These results indicate that eNOS protein content is greater in the endothelial cells of conduit arteries, resistance arteries, and large arterioles than in small coronary arterioles.

Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle.

PubMed

Paulino, Niraldo; Dantas, Andreia Pires; Bankova, Vassya; Longhi, Daniela Taggliari; Scremin, Amarilis; de Castro, Solange Lisboa; Calixto, João Batista

2003-11-01

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

PubMed Central

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke HM; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-01-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification. PMID:26757981

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila.

PubMed

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke Hm; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-08-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

PubMed Central

Vaughan, David; Brogioli, Michael; Maier, Thomas; White, Andy; Waldron, Sarah; Rittweger, Jörn; Toigo, Marco; Wettstein, Jessica; Laczko, Endre; Flück, Martin

2016-01-01

Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism. PMID:26982073

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

PubMed

Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

2012-05-01

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina

PubMed Central

2012-01-01

Background Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina’s stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. Results The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. Conclusions These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins. PMID:23111152

Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina.

PubMed

Luo, Jing; Uribe, Rosa A; Hayton, Sarah; Calinescu, Anda-Alexandra; Gross, Jeffrey M; Hitchcock, Peter F

2012-10-30

Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina's stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins.

Intrinsic disorder in scaffold proteins: Getting more from less

PubMed Central

Cortese, Marc S.; Uversky, Vladimir N.; Dunker, A. Keith

2008-01-01

Regulation, recognition and cell signaling involve the coordinated actions of many players. Signaling scaffolds, with their ability to bring together proteins belonging to common and/or interlinked pathways, play crucial roles in orchestrating numerous events by coordinating specific interactions among signaling proteins. This review examines the roles of intrinsic disorder (ID) in signaling scaffold protein function. Several well-characterized scaffold proteins with structurally and functionally characterized ID regions are used here to illustrate the importance of ID for scaffolding function. These examples include scaffolds that are mostly disordered, only partially disordered or those in which the ID resides in a scaffold partner. Specific scaffolds discussed include RNase, voltage-activated potassium channels, axin, BRCA1, GSK-3β, p53, Ste5, titin, Fus3, BRCA1, Titin, MAP2, D-AKAP2 and AKAP250. Among the mechanisms discussed are: molecular recognition features, fly-casting, ease of encounter complex formation, structural isolation of partners, modulation of interactions between bound partners, masking of intramolecular interaction sites, maximized interaction surface per residue, toleration of high evolutionary rates, binding site overlap, allosteric modification, palindromic binding, reduced constraints for alternative splicing, efficient regulation via posttranslational modification, efficient regulation via rapid degradation, protection of normally solvent-exposed sites, enhancing the plasticity of interaction and molecular crowding. We conclude that ID can enhance scaffold function by a diverse array of mechanisms. In other words, scaffold proteins utilize several ID-facilitated mechanisms to enhance function, and by doing so, get more functionality from less structure. PMID:18619997

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PubMed

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Sutarni, Sri; Bawono, Rheza Gandi; Bayuangga, Halwan Fuad; Gofir, Abdul; Setyopranoto, Ismail

2017-12-29

Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = -0.232, p = 0.024). This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development.

PubMed

Ahuja, Suchit; Dogra, Deepika; Stainier, Didier Y R; Reischauer, Sven

2016-04-01

The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and spp1. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. Copyright © 2016 Elsevier Inc. All rights reserved.

Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe.

PubMed

Necci, Marco; Piovesan, Damiano; Tosatto, Silvio C E

2016-12-01

Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large-scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence-based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. © 2016 The Protein Society.

Large‐scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe

PubMed Central

Necci, Marco; Piovesan, Damiano

2016-01-01

Abstract Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large‐scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence‐based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. PMID:27636733

Adaptation and validation of the Tower of London test of planning and problem solving in people with intellectual disabilities.

PubMed

Masson, J D; Dagnan, D; Evans, J

2010-05-01

There is a need for validated, standardised tools for the assessment of executive functions in adults with intellectual disabilities (ID). This study examines the validity of a test of planning and problem solving (Tower of London) with adults with ID. Participants completed an adapted version of the Tower of London (ToL) while day-centre staff completed adaptive function (Adaptive Behaviour Scale - Residential and Community: Second Edition, modified version) and dysexecutive function (DEX-Independent Rater) questionnaires for each participant. Correlation analyses of test and questionnaire variables were undertaken. The adapted ToL has a robust structure and shows significant associations with independent living skills, challenging behaviour and behaviours related to dysexecutive function. The adapted ToL is a valid test for use with people with ID. However, there is also a need to develop other ecologically valid tools based on everyday planning tasks undertaken by people with ID.

Frontal Brain Electrical Activity (EEG) and Heart Rate in Response to Affective Infant-Directed (ID) Speech in 9-Month-Old Infants

ERIC Educational Resources Information Center

Santesso, Diane L.; Schmidt, Louis A.; Trainor, Laurel J.

2007-01-01

Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective…

Functional properties of behaviour problems depending on level of intellectual disability.

PubMed

Medeiros, K; Rojahn, J; Moore, L L; van Ingen, D J

2014-02-01

Behaviour problems are common among individuals with intellectual disabilities (ID) especially in those with more severe forms. The determination of the functional profile of a targeted behaviour has important implications for the design of customised behavioural interventions. We investigated the relationship between the level of ID and the functional profile of aggression, stereotypy and self-injurious behaviour (SIB) using the Questions about Behavioural Function (QABF). Two staff members at two time points completed the QABF for each of 115 adults with varying levels of ID participating in a day training and habilitation programme. Our results suggest that there is a differential relationship between the functions of behaviour problems and level of ID. While SIB is more often seen by raters to be maintained by escape of social demands and by attaining access to tangible items with the decline of the intellectual level, aggressive and stereotypic behaviours were identified more often as serving multiple functions equally across functioning level. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Executive Functioning in Individuals with Intellectual Disabilities and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Roelofs, R. L.; Visser, E. M.; Berger, H. J. C.; Prins, J. B.; Van Schrojenstein Lantman-De Valk, H. M. J.; Teunisse, J. P.

2015-01-01

Background: Executive functioning (EF) is important for adequate behavioural functioning and crucial for explaining symptoms of autism spectrum disorders (ASD) in individuals with normal intelligence, but is scarcely studied in individuals with ASD and intellectual disabilities (ID). We therefore study EF in an ID population by comparing…

Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.

PubMed

Willemsen, Marjolein H; Ba, Wei; Wissink-Lindhout, Willemijn M; de Brouwer, Arjan P M; Haas, Stefan A; Bienek, Melanie; Hu, Hao; Vissers, Lisenka E L M; van Bokhoven, Hans; Kalscheuer, Vera; Nadif Kasri, Nael; Kleefstra, Tjitske

2014-07-01

Kinesin superfamily (KIF) genes encode motor proteins that have fundamental roles in brain functioning, development, survival and plasticity by regulating the transport of cargo along microtubules within axons, dendrites and synapses. Mouse knockout studies support these important functions in the nervous system. The role of KIF genes in intellectual disability (ID) has so far received limited attention, although previous studies have suggested that many ID genes impinge on synaptic function. By applying next-generation sequencing (NGS) in ID patients, we identified likely pathogenic mutations in KIF4A and KIF5C. To further confirm the pathogenicity of these mutations, we performed functional studies at the level of synaptic function in primary rat hippocampal neurons. Four males from a single family with a disruptive mutation in the X-linked KIF4A (c.1489-8_1490delins10; p.?- exon skipping) showed mild to moderate ID and epilepsy. A female patient with a de novo missense mutation in KIF5C (c.11465A>C; p.(Glu237Lys)) presented with severe ID, epilepsy, microcephaly and cortical malformation. Knock-down of Kif4a in rat primary hippocampal neurons altered the balance between excitatory and inhibitory synaptic transmission, whereas the mutation in Kif5c affected its protein function at excitatory synapses. Our results suggest that mutations in KIF4A and KIF5C cause ID by tipping the balance between excitatory and inhibitory synaptic excitability. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

IRON DEFICIENCY AND INFANT MOTOR DEVELOPMENT

PubMed Central

Shafir, Tal; Angulo-Barroso, Rosa; Jing, Yuezhou; Lu Angelilli, Mary; Jacobson, Sandra W.; Lozoff, Betsy

2011-01-01

Background Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models. Aims To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function. Study design Observational study. Subjects Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS). Outcome measures Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects. Results There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval. Conclusions Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA. PMID:18272298

CK-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise.

PubMed

Heled, Yuval; Bloom, Michael S; Wu, T John; Stephens, Quiona; Deuster, Patricia A

2007-08-01

Exertional rhabdomyolysis (ERB) is a syndrome of severe skeletal muscle breakdown. Blood levels of creatine kinase (CK) are widely used as a marker to reflect muscle breakdown. Some individuals exhibit extreme increases in blood CK after exercise and have been characterized as high responders (HR), but no clinical definition of HR exists and reasons for the HR phenomenon are not understood. This study investigated possible associations between the magnitude of the CK response to exercise and polymorphisms of two genes: muscle-specific creatine kinase (CK-MM) NcoI and angiotensin-converting enzyme (ACE) I/D. An exercise test for defining HR was also investigated. Participants (n = 88) underwent an exercise test that included stepping up and down two stairs for 5 min followed by 15 squats while wearing a backpack weighted at 30% of their body weight. CK levels were measured before, immediately after, and 48 and 72 h after the test. Nine participants (10.2%) were defined as HR. Participants with the CK-MM NcoI AA genotype had a sixfold higher risk of being HR compared with GG and AG genotypes (P = 0.031). No significant differences were found for the ACE I/D polymorphism. Percent body fat was an independent predictor of being a HR. We conclude that the CK-MM AA genotype and percent body fat may be part of the constellation of mechanisms that explain susceptibility to ERB. A physiological test that may assist in predicting ERB is also presented.

Microgravity

NASA Image and Video Library

2001-05-15

Lisa Freed and Gordana Vunjak-Novakovic, both of the Massachusetts Institute of Technology (MIT), have taken the first steps toward engineering heart muscle tissue that could one day be used to patch damaged human hearts. Cells isolated from very young animals are attached to a three-dimensional polymer scaffold, then placed in a NASA bioreactor. The cells do not divide, but after about a week start to cornect to form a functional piece of tissue. Here, a transmission electron micrograph of engineered tissue shows a number of important landmarks present in functional heart tissue: (A) well-organized myofilaments (Mfl), z-lines (Z), and abundant glycogen granules (Gly); and (D) intercalcated disc (ID) and desmosomes (DES). The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: MIT

Heart tissue grown in NASA Bioreactor

NASA Technical Reports Server (NTRS)

2001-01-01

Lisa Freed and Gordana Vunjak-Novakovic, both of the Massachusetts Institute of Technology (MIT), have taken the first steps toward engineering heart muscle tissue that could one day be used to patch damaged human hearts. Cells isolated from very young animals are attached to a three-dimensional polymer scaffold, then placed in a NASA bioreactor. The cells do not divide, but after about a week start to cornect to form a functional piece of tissue. Here, a transmission electron micrograph of engineered tissue shows a number of important landmarks present in functional heart tissue: (A) well-organized myofilaments (Mfl), z-lines (Z), and abundant glycogen granules (Gly); and (D) intercalcated disc (ID) and desmosomes (DES). The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: MIT

Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells.

PubMed

Gimpel, Petra; Lee, Yin Loon; Sobota, Radoslaw M; Calvi, Alessandra; Koullourou, Victoria; Patel, Rutti; Mamchaoui, Kamel; Nédélec, François; Shackleton, Sue; Schmoranzer, Jan; Burke, Brian; Cadot, Bruno; Gomes, Edgar R

2017-10-09

The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to the accumulation of centrosomal proteins and microtubule (MT) nucleation activity at the nuclear envelope (NE) [1-4]. The relocalization of centrosomal proteins, including Pericentrin, Pcm1, and γ-tubulin, depends on Nesprin-1, an outer nuclear membrane (ONM) protein that connects the nucleus to the cytoskeleton via its N-terminal region [5-7]. Nesprins are also involved in the recruitment of kinesin to the NE and play a role in nuclear positioning in skeletal muscle cells [8-12]. However, a function for MT nucleation from the NE in nuclear positioning has not been established. Using the proximity-dependent biotin identification (BioID) method [13, 14], we found several centrosomal proteins, including Akap450, Pcm1, and Pericentrin, whose association with Nesprin-1α is increased in differentiated myotubes. We show that Nesprin-1α recruits Akap450 to the NE independently of kinesin and that Akap450, but not other centrosomal proteins, is required for MT nucleation from the NE. Furthermore, we demonstrate that this mechanism is disrupted in congenital muscular dystrophy patient myotubes carrying a nonsense mutation within the SYNE1 gene (23560 G>T) encoding Nesprin-1 [15, 16]. Finally, using computer simulation and cell culture systems, we provide evidence for a role of MT nucleation from the NE on nuclear spreading in myotubes. Our data thus reveal a novel function for Nesprin-1α/Nesprin-1 in nuclear positioning through recruitment of Akap450-mediated MT nucleation activity to the NE. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

PubMed Central

Ruiz de Garibay, Gorka; Herranz, Carmen; Llorente, Alicia; Boni, Jacopo; Serra-Musach, Jordi; Mateo, Francesca; Aguilar, Helena; Gómez-Baldó, Laia; Petit, Anna; Vidal, August; Climent, Fina; Hernández-Losa, Javier; Cordero, Álex; González-Suárez, Eva; Sánchez-Mut, José Vicente; Esteller, Manel; Llatjós, Roger; Varela, Mar; López, José Ignacio; García, Nadia; Extremera, Ana I.; Gumà, Anna; Ortega, Raúl; Plà, María Jesús; Fernández, Adela; Pernas, Sònia; Falo, Catalina; Morilla, Idoia; Campos, Miriam; Gil, Miguel; Román, Antonio; Molina-Molina, María; Ussetti, Piedad; Laporta, Rosalía; Valenzuela, Claudia; Ancochea, Julio; Xaubet, Antoni; Casanova, Álvaro; Pujana, Miguel Angel

2015-01-01

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM. PMID:26167915

Clinical outcomes of a specialised inpatient unit for adults with mild to severe intellectual disability and mental illness.

PubMed

Lunsky, Y; White, S E; Palucka, A M; Weiss, J; Bockus, S; Gofine, T

2010-01-01

Limitations of general psychiatric services have led to the development of specialised psychiatric programmes for patients with intellectual disability (ID) and mental health needs. Few studies have examined treatment outcomes of specialised inpatient units, and no studies have explored how the effects of intervention may differ for individuals at varying levels of cognitive ability. The present study examined clinical outcomes of inpatients with mild ID in contrast to inpatients with moderate to severe ID within the same service. Thirty-three patients (17 with mild ID and 16 with moderate to severe ID) discharged between 2006 and 2008 from a specialised inpatient unit in Canada for adults with ID and mental illness were studied. In addition to examining change in scores on clinical measures, outcomes with regard to length of stay, diagnostic change, residential change and re-admission to hospital were explored. Both groups demonstrated clinical improvement from admission to discharge. However, only patients with mild ID demonstrated improvements on the Global Assessment of Functioning. This study is one of the first to consider outcomes of higher and lower functioning individuals with ID on a specialised inpatient unit. Results suggest that outcomes may be different for these groups, and some clinical measures may be more sensitive to changes in patients with more severe disabilities.

Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

PubMed Central

Morton, Derrick; Sharma, Pankaj; Gorantla, Yamini; Joshi, Jugal; Nagappan, Perri; Pallaniappan, Ravi; Chaudhary, Jaideep

2016-01-01

ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4. PMID:27487149

Congenital hypopituitarism due to POU1F1 gene mutation.

PubMed

Lee, Ni-Chung; Tsai, Wen-Yu; Peng, Shinn-Forng; Tung, Yi-Ching; Chien, Yin-Hsiu; Hwu, Wuh-Liang

2011-01-01

POU1F1 (Pit-1; Gene ID 5449) is an anterior pituitary transcriptional factor, and POU1F1 mutation is known to cause anterior pituitary hypoplasia, growth hormone and prolactin deficiency and various degree of hypothyroidism. We report here a patient who presented with growth failure and central hypothyroidism since early infancy. However, treatment with thyroxine gave no effect and he subsequently developed calf muscle pseudohypertrophy (Kocher-Debre-Semelaigne syndrome), elevation of creatinine kinase, dilated cardiomyopathy and pericardial effusion. Final diagnosis was made by combined pituitary function test and sequencing analysis that revealed POU1F1 gene C.698T > C (p.F233S) mutation. The rarity of the disease can result in delayed diagnosis and treatment. Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Psychometric Comparison of the Motivation Assessment Scale (MAS) and the Questions about Behavioral Function (QABF)

ERIC Educational Resources Information Center

Koritsas, S.; Iacono, T.

2013-01-01

Background: The Motivation Assessment Scale (MAS) and the Questions About Behavioral Function (QABF) are frequently used to assess the learned function of challenging behaviour in people with intellectual disability (ID). The aim was to explore and compare the psychometric properties of the MAS and the QABF. Method: Seventy adults with ID and…

Investigation of injection dose and camera integration time on quantifying pharmacokinetics of a Cy5.5-GX1 probe with dynamic fluorescence imaging in vivo

NASA Astrophysics Data System (ADS)

Dai, Yunpeng; Chen, Xueli; Yin, Jipeng; Kang, Xiaoyu; Wang, Guodong; Zhang, Xianghan; Nie, Yongzhan; Wu, Kaichun; Liang, Jimin

2016-08-01

The aim of this article is to investigate the influence of a tracer injection dose (ID) and camera integration time (IT) on quantifying pharmacokinetics of Cy5.5-GX1 in gastric cancer BGC-823 cell xenografted mice. Based on three factors, including whether or not to inject free GX1, the ID of Cy5.5-GX1, and the camera IT, 32 mice were randomly divided into eight groups and received 60-min dynamic fluorescence imaging. Gurfinkel exponential model (GEXPM) and Lammertsma simplified reference tissue model (SRTM) combined with a singular value decomposition analysis were used to quantitatively analyze the acquired dynamic fluorescent images. The binding potential (Bp) and the sum of the pharmacokinetic rate constants (SKRC) of Cy5.5-GX1 were determined by the SRTM and EXPM, respectively. In the tumor region, the SKRC value exhibited an obvious trend with change in the tracer ID, but the Bp value was not sensitive to it. Both the Bp and SKRC values were independent of the camera IT. In addition, the ratio of the tumor-to-muscle region was correlated with the camera IT but was independent of the tracer ID. Dynamic fluorescence imaging in conjunction with a kinetic analysis may provide more quantitative information than static fluorescence imaging, especially for a priori information on the optimal ID of targeted probes for individual therapy.

Glucagon-like peptide-1 binding to rat skeletal muscle.

PubMed

Delgado, E; Luque, M A; Alcántara, A; Trapote, M A; Clemente, F; Galera, C; Valverde, I; Villanueva-Peñacarrillo, M L

1995-01-01

We have found [125I]glucagon-like peptide-1(7-36)-amide-specific binding activity in rat skeletal muscle plasma membranes, with an estimated M(r) of 63,000 by cross-linking and SDS-PAGE. The specific binding was time and membrane protein concentration dependent, and displaceable by unlabeled GLP-1(7-36)-amide with an ID50 of 3 x 10(-9) M of the peptide; GLP-1(1-36)-amide also competed, whereas glucagon and insulin did not. GLP-1(7-36)-amide did not modify the basal adenylate cyclase activity in skeletal muscle plasma membranes. These data, together with our previous finding of a potent glycogenic effect of GLP-1(7-36)-amide in rat soleus muscle, and also in isolated hepatocytes, which was not accompanied by a rise in the cell cyclic AMP content, lead use to believe that the insulin-like effects of this peptide on glucose metabolism in the muscle could be mediated by a type of receptor somehow different to that described for GLP-1 in pancreatic B cells, where GLP-1 action is mediated by the cyclic AMP-adenylate cyclase system.

Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

PubMed

Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

2003-08-15

DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation--effects on physical function: study protocol for a randomized controlled trial: a substudy of the NONSEDA trial.

PubMed

Nedergaard, Helene Korvenius; Jensen, Hanne Irene; Lauridsen, Jørgen T; Sjøgaard, Gisela; Toft, Palle

2015-07-23

Critically ill patients rapidly loose much of their muscle mass and strength. This can be attributed to prolonged admission, prolonged mechanical ventilation and increased mortality, and it can have a negative impact on the degree of independence and quality of life. In the NONSEDA trial we randomize critically ill patients to non-sedation or sedation with a daily wake-up trial during mechanical ventilation in the intensive care unit. It has never been assessed whether non-sedation affects physical function. The aim of this study is to assess the effects of non-sedation versus sedation with a daily wake-up trial on physical function after discharge from intensive care unit. Investigator-initiated, randomized, clinical, parallel-group, superiority trial, including 700 patients in total, with a substudy concerning 200 of these patients. Inclusion criteria will be intubated, mechanically ventilated patients with expected duration of mechanical ventilation >24 h. Exclusion criteria will be patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2<9 where sedation might be necessary to ensure sufficient oxygenation or placing the patient in a prone position. The experimental intervention will be non-sedation supplemented with pain management during mechanical ventilation. The control intervention will be sedation with a daily wake-up trial. The co-primary outcome will be quality of life regarding physical function (SF-36, physical component) and degree of independence in activities of daily living (Barthel Index), and this will be assessed for all 700 patients participating in the NONSEDA trial. The secondary outcomes, which will be assessed for the subpopulation of 200 NONSEDA patients in the trial site, Kolding, will be 6-min walking distance, handgrip strength, muscle size (ultrasonographic measurement of the rectus femoris muscle cross-sectional area) and biomechanical data on lower extremity function (maximal voluntary contraction, rate of force development and endurance). This study is the first to investigate the effect of no sedation during critical illness on physical function. If an effect is found, it will add important information on how to prevent muscle weakness following critical illness. The study has been approved by the relevant scientific ethics committee and is registered at ClinicalTrials.gov (ID: NCT02034942, 9 January 2014).

Aspects of Cognitive Functioning in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Perkins, Elizabeth A.; Small, Brent J.

2006-01-01

Recently, more attention is being given to identifying aging-related and dementia-related pathological changes in performance and cognition among persons with intellectual disabilities (ID). This literature review examines age-related differences in specific aspects of cognitive functioning and cognitive performance of people with ID and…

Profiles and Cognitive Predictors of Motor Functions among Early School-Age Children with Mild Intellectual Disabilities

ERIC Educational Resources Information Center

Wuang, Y.-P.; Wang, C.-C.; Huang, M.-H.; Su, C.-Y.

2008-01-01

Background: The purpose of the study was to describe sensorimotor profile in children with mild intellectual disability (ID), and to examine the association between cognitive and motor function. Methods: A total of 233 children with mild ID aged 7 to 8 years were evaluated with measures of cognitive, motor and sensory integrative functioning.…

Department of Defense Chemical and Biological Defense Program. FY2004-2006 Performance Plan

DTIC Science & Technology

2005-03-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to identify...Range Biometric Target ID System Explore technologies for a long range biometric target identification system. Air Containment Monitoring System...Continue development of systems for contained air monitoring for chemical agents.Long Range Biometric Air Containment Monitoring System Continued

XSIM Final Report: Modelling the Past and Future of Identity Management for Scientific Collaborations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowles, Robert; Jackson, Craig; Welch, Von

The eXtreme Science Identity Management (XSIM1) research project: collected and analyzed real world data on virtual organization (VO) identity management (IdM) representing the last 15+ years of collaborative DOE science; constructed a descriptive VO IdM model based on that data; used the model and existing trends to project the direction for IdM in the 2020 timeframe; and provided guidance to scientific collaborations and resource providers that are implementing or seeking to improve IdM functionality. XSIM conducted over 20 semi­structured interviews of representatives from scientific collaborations and resource providers, both in the US and Europe; the interviewees supported diverse set ofmore » scientific collaborations and disciplines. We developed a definition of “trust,” a key concept in IdM, to understand how varying trust models affect where IdM functions are performed. The model identifies how key IdM data elements are utilized in collaborative scientific workflows, and it has the flexibility to describe past, present and future trust relationships and IdM implementations. During the funding period, we gave more than two dozen presentations to socialize our work, encourage feedback, and improve the model; we also published four refereed papers. Additionally, we developed, presented, and received favorable feedback on three white papers providing practical advice to collaborations and/or resource providers.« less

Psychiatric Disorders in Outpatients With Borderline Intellectual Functioning: Comparison With Both Outpatients From Regular Mental Health Care and Outpatients With Mild Intellectual Disabilities

PubMed Central

Wieland, Jannelien; Haan, Sara Kapitein-de; Zitman, Frans G

2014-01-01

Objective: In the Netherlands, patients with borderline intellectual functioning are eligible for specialized mental health care. This offers the unique possibility to examine the mix of psychiatric disorders in patients who, in other countries, are treated in regular outpatient mental health care clinics. Our study sought to examine the rates of all main Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I psychiatric diagnoses in outpatients with borderline intellectual functioning of 2 specialized regional psychiatric outpatient departments and to compare these with rates of the same disorders in outpatients from regular mental health care (RMHC) and outpatients with mild intellectual disabilities (IDs). Method: Our study was a cross-sectional, anonymized medical chart review. All participants were patients from the Dutch regional mental health care provider Rivierduinen. Diagnoses of patients with borderline intellectual functioning (borderline intellectual functioning group; n = 235) were compared with diagnoses of patients from RMHC (RMHC group; n = 1026) and patients with mild ID (mild ID group; n = 152). Results: Compared with the RMHC group, psychotic and major depressive disorders were less common in the borderline intellectual functioning group, while posttraumatic stress disorder and V codes were more common. Compared with the mild ID group, psychotic disorders were significantly less common. Conclusion: Mental health problems in people with borderline intellectual functioning may not be well addressed in general psychiatry, or by standard psychiatry for patients with ID. Specific attention to this group in clinical practice and research may be warranted lest they fall between 2 stools. PMID:25007114

Psychiatric disorders in outpatients with borderline intellectual functioning: comparison with both outpatients from regular mental health care and outpatients with mild intellectual disabilities.

PubMed

Wieland, Jannelien; Kapitein-de Haan, Sara; Zitman, Frans G

2014-04-01

In the Netherlands, patients with borderline intellectual functioning are eligible for specialized mental health care. This offers the unique possibility to examine the mix of psychiatric disorders in patients who, in other countries, are treated in regular outpatient mental health care clinics. Our study sought to examine the rates of all main Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I psychiatric diagnoses in outpatients with borderline intellectual functioning of 2 specialized regional psychiatric outpatient departments and to compare these with rates of the same disorders in outpatients from regular mental health care (RMHC) and outpatients with mild intellectual disabilities (IDs). Our study was a cross-sectional, anonymized medical chart review. All participants were patients from the Dutch regional mental health care provider Rivierduinen. Diagnoses of patients with borderline intellectual functioning (borderline intellectual functioning group; n = 235) were compared with diagnoses of patients from RMHC (RMHC group; n = 1026) and patients with mild ID (mild ID group; n = 152). Compared with the RMHC group, psychotic and major depressive disorders were less common in the borderline intellectual functioning group, while posttraumatic stress disorder and V codes were more common. Compared with the mild ID group, psychotic disorders were significantly less common. Mental health problems in people with borderline intellectual functioning may not be well addressed in general psychiatry, or by standard psychiatry for patients with ID. Specific attention to this group in clinical practice and research may be warranted lest they fall between 2 stools.

Motor competency and social communication skills in preschool children with autism spectrum disorder.

PubMed

Craig, Francesco; Lorenzo, Alessandro; Lucarelli, Elisabetta; Russo, Luigi; Fanizza, Isabella; Trabacca, Antonio

2018-06-01

This study aimed to investigate the association between motor competency and social communication in children with Autism Spectrum Disorder (ASD) compared with children with Intellectual Disabilities (ID) and typically developing (TD) children. Motor competency, ASD symptoms, and nonverbal Intelligent Quotient (IQ) were investigated through the following tests: Movement Assessment Battery for Children, second edition (MABC-2), Social Communication Questionnaire (SCQ), Autism Classification System of Functioning: Social Communication (ACSF:SC) and Leiter International Performances Scale Revised (Leiter-R). The ASD + ID and ID groups had lower MABC-2-manual dexterity mean scores, MABC-2-aiming and catching mean scores, MABC-2-static and dynamic balance mean scores and MABC-2-TTS compared with the TD group (P < 0.05). In addition, the ASD + ID group had lower MABC-2-aiming and catching mean scores compared with the ID group. In the ASD + ID group, we found a significant negative correlation (P < 0.001) between MABC-2-aiming and catching scores with SCQ scores, nonverbal IQ and ACSF:SC levels. Our findings provide new insight into the common neuropsychological mechanisms underlying social communication and motor deficits in ASD. Multiple deficits in motor functioning may be present in ASD and ID, however deficits involving the ability to integrate motor and social cues are somewhat specific to ASD. Autism Res 2018, 11: 893-902. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. This study highlighted the specificity of motor impairment in ASD comparing performances on a frequently used measure of motor impairment between clinical groups (ASD + ID and ID) and a non-clinical group. While previous research has suggested that multiple deficits in motor functioning may be present in ASD, our findings suggest that deficits in tasks involving the ability to integrate visual and motor cues (aiming and catching task) are somewhat specific to ASD. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

A review of cognitive impairments in children with intellectual disabilities: Implications for cognitive behaviour therapy.

PubMed

Hronis, Anastasia; Roberts, Lynette; Kneebone, Ian I

2017-06-01

Nearly half of children with intellectual disability (ID) have comorbid affective disorders. These problems are chronic if left untreated and can significantly impact upon future vocational, educational, and social opportunities. Despite this, there is a paucity of research into effective treatments for this population. Notably, one of the most supported of psychological therapies, cognitive behaviour therapy (CBT), remains largely uninvestigated in children with ID. The current review considers the neuropsychological profile of children and adolescents with mild to moderate ID, with a view to informing how CBT might best be adapted for children and adolescents with ID. Narrative review of literature considering the neuropsychological profiles of children and adolescents with ID, with specific focus upon attention, memory, learning, executive functioning, and communication. Studies were identified through SCOPUS, PsycINFO, and PubMed databases, using combinations of the key words 'intellectual disability', 'learning disability', 'neuropsychology', 'attention', 'learning', 'memory', 'executive function', 'language', and 'reading'. Children with ID have significant deficits in attention, learning, memory, executive functions, and language. These deficits are likely to have a negative impact upon engagement in CBT. Suggestions for adapting therapy to accommodate these wide ranging deficits are proposed. There are multiple cognitive factors which need to be considered when modifying CBT for children who have ID. Furthermore, research is required to test whether CBT so modified is effective in this population. Clinical implications Effective ways of providing cognitive behavioural therapy (CBT) to children with intellectual disability (ID) is unclear. This study provides a framework of potential adaptations for clinical practice As rates of mental illness for children with intellectual disability are high, and rates of treatment provision low, it is hoped that the recommendations provided in this study will encourage more mental health practitioners to provide CBT to children with ID. Limitations These recommendations are based only upon neuropsychological literature. Trialling the effectiveness of an adapted form of CBT for children and adolescents with ID is required. There are varying causes of intellectual disability, with differences in cognitive profiles. The utility of the recommendations made here may vary according to specific aetiologies. © 2017 The British Psychological Society.

Prenatal Iron Deficiency, Neonatal Ferritin, and Infant Cognitive Function

PubMed Central

Davidson, Leslie L.; Boivin, Michael J.; Zoumenou, Romeo; Massougbodji, Achille; Cot, Michel; Bodeau-Livinec, Florence

2016-01-01

OBJECTIVE: To investigate the impact of prenatal maternal iron deficiency (ID) on cord blood serum ferritin (CBSF) concentration and infant cognitive and motor development. METHODS: Our prospective cohort study included 636 mother-singleton child pairs from 828 eligible pregnant women who were enrolled during their first antenatal care (ANC) visit in Allada, Benin, into a clinical trial comparing the efficacy of mefloquine and sulfadoxine-pyrimethamine. Venous blood samples of women were assessed for ferritin and hemoglobin concentrations at the first and second ANC visits (occurring at least 1-month apart) and at delivery. Women were prescribed daily iron and folic acid supplements throughout pregnancy. Hematologic examinations were repeated for cord blood at birth. At age 1 year, cognitive and motor functions of children were assessed by using the Mullen Scales of Early Learning. RESULTS: The prevalence of prenatal ID at first and second ANC visits, and at delivery was 30.5%, 34.0%, and 28.4%, respectively. CBSF concentrations were similar between ID and non-ID pregnant women. Neither prenatal ID nor CBSF concentration was associated with poor cognitive or gross motor function of children at age 1 year. CBSF concentrations were lower among mothers who had ID anemia (IDA) at delivery compared with non-IDA pregnant women (adjusted mean difference: –0.2 [95% confidence interval: –0.4 to –0.0]). CONCLUSIONS: In a malaria-endemic region, ID in pregnancy in the context of iron supplementation is neither associated with CBSF concentration nor with infant cognitive and motor development. Prenatal IDA around the time of delivery is associated with lower CBSF concentrations. PMID:27940685

Absolute and functional iron deficiency in professional athletes during training and recovery.

PubMed

Reinke, Simon; Taylor, William R; Duda, Georg N; von Haehling, Stephan; Reinke, Petra; Volk, Hans-Dieter; Anker, Stefan D; Doehner, Wolfram

2012-04-19

Iron deficiency (ID) is one of the most important metabolic dysfunctions. Athletic performance depends on oxygen transport and mitochondrial efficiency, thus on optimal iron balance. We hypothesised that physical extremes result in ID in elite athletes and that the short recovery period may be insufficient to allow a lasting replenishment of iron reserves. Iron metabolism was examined in 20 elite rowing athletes and 10 professional soccer players at the end of a competitive season, after recuperation and during pre-season training. Absolute ID values were defined as ferritin <30 μg/L, functional ID as ferritin 30-99 μg/L or 100-299 μg/L+transferrin saturation <20%. At the end of season, 27% of all athletes had absolute ID and 70% showed functional ID. Absolute iron depletion was not generally restored after recuperation and observed at all time points in 14% of the athletes. Although athletes with initially low ferritin levels showed a slight increase during recuperation (p<0.09), these increases remained within borderline levels. Furthermore, 10% showed borderline haemoglobin levels, suggestive of mild anaemia, as defined by the World Health Organisation. A significant proportion of professional athletes have ID, independent of the training mode. Although recuperation seems to allow a certain recovery of iron storage, particularly in athletes with initially low ferritin levels, this retrieval was insufficient to fully normalise reduced iron levels. Therefore, iron status should be carefully monitored during the various training and competitive periods in elite athletes. An adequate iron supplementation may be needed to maintain balanced iron stores. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Sleep and Daytime Functioning: A Short-Term Longitudinal Study of Three Preschool-Age Comparison Groups

ERIC Educational Resources Information Center

Anders, Thomas; Iosif, Ana-Maria; Schwichtenberg, A. J.; Tang, Karen; Goodlin-Jones, Beth

2012-01-01

This study examined sleep, sleepiness, and daytime performance in 68 children with autism, 57 children with intellectual disability (ID), and 69 typically developing preschool children. Children in the autism and ID groups had poorer daytime performance and behaviors than the typically developing children. Children in the ID group also were…

Parents' Perceptions of the Supports Received for Their Children's Problem Behaviors

ERIC Educational Resources Information Center

Schofield, Dean Alexander

2012-01-01

Individuals with significant intellectual disabilities (ID) are more likely to engage in problem behaviors than are people with milder disabilities or with no disability. It is widely considered that behavior problems serve a communicative function for individuals with severe ID and limited communication skills. Among people with significant ID,…

Dental care among young adults with intellectual disability

PubMed Central

Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn

2015-01-01

Dental care among young adults with intellectual disability (ID) is poorly documented and largely unmet. By using population-based data from the Metropolitan Atlanta Developmental Disabilities Follow-Up Study, we assessed factors associated with at least one or two dental visits per year among young adults with and without ID. Significantly fewer young adults with ID (45%) visited a dentist at least once per year, compared with those without ID (58%). ID severity and the presence of co-occurring developmental disabilities predicted dental care use. Sociodemographics, daily functioning, societal participation, dental services, and dental health factors were examined as predictors of dental care frequency. Our findings can help focus efforts toward improving the frequency of dental care visits among young adults with ID. PMID:23501584

Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton.

PubMed

Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

2017-01-01

Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T 4 ) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T 4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.

Safety, Pharmacokinetic, and Functional Effects of the Nogo-A Monoclonal Antibody in Amyotrophic Lateral Sclerosis: A Randomized, First-In-Human Clinical Trial

PubMed Central

Meininger, Vincent; Pradat, Pierre-François; Corse, Andrea; Al-Sarraj, Safa; Rix Brooks, Benjamin; Caress, James B.; Cudkowicz, Merit; Kolb, Stephen J.; Lange, Dale; Leigh, P. Nigel; Meyer, Thomas; Milleri, Stefano; Morrison, Karen E.; Orrell, Richard W.; Peters, Gary; Rothstein, Jeffrey D.; Shefner, Jeremy; Lavrov, Arseniy; Williams, Nicola; Overend, Phil; Price, Jeffrey; Bates, Stewart; Bullman, Jonathan; Krull, David; Berges, Alienor; Abila, Bams; Meno-Tetang, Guy; Wurthner, Jens

2014-01-01

The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS); it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK) and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1) to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg) or placebo. In Part 2, 36 subjects were randomized (3∶1) to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg) or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG), and clinical laboratory tests). Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological), and biomarker parameters. Overall, ozanezumab treatment (0.01–15 mg/kg) was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab) showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated co-localization at the site of action. These findings support future studies with ozanezumab in ALS. Trial Registration ClinicalTrials.gov NCT00875446 GSK-ClinicalStudyRegister.com GSK ID 111330 PMID:24841795

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD.

PubMed

Zhang, Xiaolei; Wang, Chen; Dai, Huaping; Lin, Yingxiang; Zhang, Jun

2008-09-01

Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD. Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification. Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups. The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.

Carbohydrate degrading polypeptide and uses thereof

DOEpatents

Sagt, Cornelis Maria Jacobus; Schooneveld-Bergmans, Margot Elisabeth Francoise; Roubos, Johannes Andries; Los, Alrik Pieter

2015-10-20

The invention relates to a polypeptide having carbohydrate material degrading activity which comprises the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 4, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional protein and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Sex-Specific Automatic Responses to Infant Cries: TMS Reveals Greater Excitability in Females than Males in Motor Evoked Potentials

PubMed Central

Messina, Irene; Cattaneo, Luigi; Venuti, Paola; de Pisapia, Nicola; Serra, Mauro; Esposito, Gianluca; Rigo, Paola; Farneti, Alessandra; Bornstein, Marc H.

2016-01-01

Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event-related transcranial magnetic stimulation (TMS). Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs) from the biceps brachii (BB) and interosseus dorsalis primus (ID1) muscles as produced by TMS delivered from 0 to 250 ms after sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was attenuated to stimuli increasingly different from natural cry and absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100-ms latency of this response is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. PMID:26779061

Id-1 promotes osteosarcoma cell growth and inhibits cell apoptosis via PI3K/AKT signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Liang; Liao, Qi; Tang, Qiang

2016-02-12

Accumulating evidence reveals that Id-1 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the role of Id-1 in osteosarcoma (OS) is unknown. In present study, we found that Id-1 expression was elevated in OS tissues than adjacent normal bone tissues. More importantly, we demonstrated that overexpression of Id-1 is significantly correlated with tumor progression and poor survival in OS patients. Furthermore, increased expression of Id-1 was observed in OS cell lines and ectopic expression of Id-1 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas knockdown of Id-1 suppressed OS cellsmore » growth. Moreover, our experimental data revealed that Id-1 promotes cell proliferation by facilitating cell cycle progression and inhibits cell apoptosis. Mechanistically, the effects of Id-1 in OS cells is at least partly through activation of PI3K/Akt signaling pathway. Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients. - Highlights: • Id-1 expression is positively correlated in OS patients with poor prognosis. • Overexpression of Id-1 promotes OS cell growth in vitro and in vivo. • Id-1induces cell cycle progression and inhibits cell apoptosis. • PI3K/Akt signaling pathway contributed to the oncogenic effects of Id-1 in OS cells.« less

R&D100: IC ID

ScienceCinema

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

2018-06-25

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Timing, duration, and severity of iron deficiency in early development and motor outcomes at 9 months

PubMed Central

Santos, Denise CC; Angulo-Barroso, Rosa M; Li, Ming; Bian, Yang; Sturza, Julie; Richards, Blair; Lozoff, Betsy

2017-01-01

BACKGROUND/OBJECTIVES Poorer motor development is reported in infants with iron deficiency (ID). The role of timing, duration and severity is unclear. We assessed relations between ID timing, duration, and severity and gross motor scores, neurological integrity, and motor behavior quality at 9 months. METHODS Iron status was determined at birth and 9 months in otherwise healthy term Chinese infants. The 9-month motor evaluation included the Peabody Developmental Motor Scale (PDMS-2), Infant Neurological International Battery (INFANIB), and motor quality factor. Motor outcomes were analyzed by ID timing (fetal-neonatal, infancy), duration, and severity. For severity, we also considered maternal iron status. RESULTS Data were available for 1194 infants. Iron status was classified as fetal-neonatal and infancy ID (n=253), fetal-neonatal ID (n=256), infancy ID (n=288), and not ID (n=397). Compared with not ID, infants with fetal-neonatal or infancy ID had lower locomotion scores (effect size ds=0.19, 0.18) and those with ID in both periods (longer duration) had lower locomotion and overall PDMS-2 gross motor scores (ds=0.20, 0.18); ID groups did not differ. More severe ID in late pregnancy was associated with lower INFANIB Vestibular function (p=0.01), and total score (p=0.03). More severe ID in infancy was associated with lower scores for locomotion (p=0.03), overall gross motor (p=0.05). CONCLUSIONS Fetal-neonatal and/or infancy ID was associated with lower overall gross motor development and locomotion test scores at 9 months. Associations with ID severity varied by ID timing: more severe ID in late pregnancy, poorer neurological integrity; more severe ID in infancy, poorer gross motor development. PMID:29235557

On the relationship between motor performance and executive functioning in children with intellectual disabilities.

PubMed

Hartman, E; Houwen, S; Scherder, E; Visscher, C

2010-05-01

It has been suggested that children with intellectual disabilities (ID) have motor problems and higher-order cognitive deficits. The aim of this study was to examine the motor skills and executive functions in school-age children with borderline and mild ID. The second aim was to investigate the relationship between the two performance domains. Sixty-one children aged between 7 and 12 years diagnosed with borderline ID (33 boys and 28 girls; 71 < IQ < 79) and 36 age peers with mild ID (24 boys and 12 girls; 54 < IQ < 70) were assessed. Their abilities were compared with those of 97 age- and gender-matched typically developing children. Qualitative motor skills, i.e. locomotor ability and object control, were evaluated with the Test of Gross Motor Development (TGMD-2). Executive functioning (EF), in terms of planning ability, strategic decision-making and problem solving, was gauged with the Tower of London (TOL) task. Compared with the reference group, the full ID cohort scored significantly lower on all assessments. For the locomotor skills, the children with mild ID scored significantly lower than the children with borderline ID, but for the object control skills and the TOL score, no significant differences between the two groups were found. Motor performance and EF correlated positively. At the most complex level, the TOL showed decision time to be a mediator between motor performance and EF: the children with the lower motor scores had significantly shorter decision times and lower EF scores. Analogously, the children with the lower object control scores had longer execution times and lower EF scores. The current results support the notion that besides being impaired in qualitative motor skills intellectually challenged children are also impaired in higher-order executive functions. The deficits in the two domains are interrelated, so early interventions boosting their motor and cognitive development are recommended.

Muscle activation patterns in acceleration-based phases during reach-to-grasp movement.

PubMed

Tokuda, Keisuke; Lee, Bumsuk; Shiihara, Yasufumi; Takahashi, Kazuhiro; Wada, Naoki; Shirakura, Kenji; Watanabe, Hideomi

2016-11-01

[Purpose] An earlier study divided reaching activity into characteristic phases based on hand velocity profiles. By synchronizing muscle activities and the acceleration profile, a phasing approach for reaching movement, based on hand acceleration profiles, was attempted in order to elucidate the roles of individual muscle activities in the different phases of the acceleration profile in reaching movements. [Subjects and Methods] Ten healthy volunteer subjects participated in this study. The aim was to electromyographically evaluate muscles around the shoulder, the upper trapezius, the anterior deltoid, the biceps brachii, and the triceps brachii, most of which have been used to evaluate arm motion, as well as the acceleration of the upper limb during simple reaching movement in the reach-to-grasp task. [Results] Analysis showed the kinematic trajectories of the acceleration during a simple biphasic profile of the reaching movement could be divided into four phases: increasing acceleration (IA), decreasing acceleration (DA), increasing deceleration (ID), and decreasing deceleration (DD). Muscles around the shoulder showed different activity patterns, which were closely associated with these acceleration phases. [Conclusion] These results suggest the important role of the four phases, derived from the acceleration trajectory, in the elucidation of the muscular mechanisms which regulate and coordinate the muscles around the shoulder in reaching movements.

Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling.

PubMed

Snijders Blok, Lot; Madsen, Erik; Juusola, Jane; Gilissen, Christian; Baralle, Diana; Reijnders, Margot R F; Venselaar, Hanka; Helsmoortel, Céline; Cho, Megan T; Hoischen, Alexander; Vissers, Lisenka E L M; Koemans, Tom S; Wissink-Lindhout, Willemijn; Eichler, Evan E; Romano, Corrado; Van Esch, Hilde; Stumpel, Connie; Vreeburg, Maaike; Smeets, Eric; Oberndorff, Karin; van Bon, Bregje W M; Shaw, Marie; Gecz, Jozef; Haan, Eric; Bienek, Melanie; Jensen, Corinna; Loeys, Bart L; Van Dijck, Anke; Innes, A Micheil; Racher, Hilary; Vermeer, Sascha; Di Donato, Nataliya; Rump, Andreas; Tatton-Brown, Katrina; Parker, Michael J; Henderson, Alex; Lynch, Sally A; Fryer, Alan; Ross, Alison; Vasudevan, Pradeep; Kini, Usha; Newbury-Ecob, Ruth; Chandler, Kate; Male, Alison; Dijkstra, Sybe; Schieving, Jolanda; Giltay, Jacques; van Gassen, Koen L I; Schuurs-Hoeijmakers, Janneke; Tan, Perciliz L; Pediaditakis, Igor; Haas, Stefan A; Retterer, Kyle; Reed, Patrick; Monaghan, Kristin G; Haverfield, Eden; Natowicz, Marvin; Myers, Angela; Kruer, Michael C; Stein, Quinn; Strauss, Kevin A; Brigatti, Karlla W; Keating, Katherine; Burton, Barbara K; Kim, Katherine H; Charrow, Joel; Norman, Jennifer; Foster-Barber, Audrey; Kline, Antonie D; Kimball, Amy; Zackai, Elaine; Harr, Margaret; Fox, Joyce; McLaughlin, Julie; Lindstrom, Kristin; Haude, Katrina M; van Roozendaal, Kees; Brunner, Han; Chung, Wendy K; Kooy, R Frank; Pfundt, Rolph; Kalscheuer, Vera; Mehta, Sarju G; Katsanis, Nicholas; Kleefstra, Tjitske

2015-08-06

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common causes of ID, accounting for 1%-3% of unexplained ID in females. Although no de novo DDX3X mutations were identified in males, we present three families with segregating missense mutations in DDX3X, suggestive of an X-linked recessive inheritance pattern. In these families, all males with the DDX3X variant had ID, whereas carrier females were unaffected. To explore the pathogenic mechanisms accounting for the differences in disease transmission and phenotype between affected females and affected males with DDX3X missense variants, we used canonical Wnt defects in zebrafish as a surrogate measure of DDX3X function in vivo. We demonstrate a consistent loss-of-function effect of all tested de novo mutations on the Wnt pathway, and we further show a differential effect by gender. The differential activity possibly reflects a dose-dependent effect of DDX3X expression in the context of functional mosaic females versus one-copy males, which reflects the complex biological nature of DDX3X mutations. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Rest but busy: Aberrant resting-state functional connectivity of triple network model in insomnia.

PubMed

Dong, Xiaojuan; Qin, Haixia; Wu, Taoyu; Hu, Hua; Liao, Keren; Cheng, Fei; Gao, Dong; Lei, Xu

2018-02-01

One classical hypothesis among many models to explain the etiology and maintenance of insomnia disorder (ID) is hyperarousal. Aberrant functional connectivity among resting-state large-scale brain networks may be the underlying neurological mechanisms of this hypothesis. The aim of current study was to investigate the functional network connectivity (FNC) among large-scale brain networks in patients with insomnia disorder (ID) during resting state. In the present study, the resting-state fMRI was used to evaluate whether patients with ID showed aberrant FNC among dorsal attention network (DAN), frontoparietal control network (FPC), anterior default mode network (aDMN), and posterior default mode network (pDMN) compared with healthy good sleepers (HGSs). The Pearson's correlation analysis was employed to explore whether the abnormal FNC observed in patients with ID was associated with sleep parameters, cognitive and emotional scores, and behavioral performance assessed by questionnaires and tasks. Patients with ID had worse subjective thought control ability measured by Thought Control Ability Questionnaire (TCAQ) and more negative affect than HGSs. Intriguingly, relative to HGSs, patients with ID showed a significant increase in FNC between DAN and FPC, but a significant decrease in FNC between aDMN and pDMN. Exploratory analysis in patients with ID revealed a significantly positive correlation between the DAN-FPC FNC and reaction time (RT) of psychomotor vigilance task (PVT). The current study demonstrated that even during the resting state, the task-activated and task-deactivated large-scale brain networks in insomniacs may still maintain a hyperarousal state, looking quite similar to the pattern in a task condition with external stimuli. Those results support the hyperarousal model of insomnia.

The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis.

PubMed

Antoniak, Anneka Elizabeth; Greig, Carolyn A

2017-07-20

In older adults, there is a blunted responsiveness to resistance training and reduced muscle hypertrophy compared with younger adults. There is evidence that both exercise training and vitamin D supplementation may benefit musculoskeletal health in older adults, and it is plausible that in combination their effects may be additive. The aim of this systematic review was to evaluate the effectiveness of combined resistance exercise training and vitamin D 3 supplementation on musculoskeletal health in older adults. A comprehensive search of electronic databases, including Science Direct, Medline, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (Cochrane CENTRAL accessed by Wiley Science) was conducted. Eligible studies were randomised controlled trials including men and women (aged ≥65 years or mean age ≥65 years); enlisting resistance exercise training and vitamin D 3 supplementation; including outcomes of muscle strength, function, muscle power, body composition, serum vitamin D/calcium status or quality of life comparing results with a control group. The review was informed by a preregistered protocol (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015020157). Seven studies including a total of 792 participants were identified. Studies were categorised into two groups; group 1 compared vitamin D 3 supplementation and exercise training versus exercise alone (describing the additive effect of vitamin D 3 supplementation when combined with resistance exercise training) and group 2 compared vitamin D 3 supplementation and exercise training versus vitamin D 3 supplementation alone (describing the additive effect of resistance exercise training when combined with vitamin D 3 supplementation).Meta-analyses for group 1 found muscle strength of the lower limb to be significantly improved within the intervention group (0.98, 95% CI 0.73 to 1.24, p<0.001); all other outcomes showed small but non-significant positive effects for the intervention group. The short physical performance battery (SPPB), timed up and go (TUG), muscle strength of the lower limb and femoral neck bone mineral density showed significantly greater improvements in the intervention group for group 2 comparisons. This review provides tentative support for the additive effect of resistance exercise and vitamin D 3 supplementation for the improvement of muscle strength in older adults. For other functional variables, such as SPPB and TUG, no additional benefit beyond exercise was shown. Further evidence is required to draw firm conclusions or make explicit recommendations regarding combined exercise and vitamin D 3 supplementation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Visual-Motor Integration in Children With Mild Intellectual Disability: A Meta-Analysis.

PubMed

Memisevic, Haris; Djordjevic, Mirjana

2018-01-01

Visual-motor integration (VMI) skills, defined as the coordination of fine motor and visual perceptual abilities, are a very good indicator of a child's overall level of functioning. Research has clearly established that children with intellectual disability (ID) have deficits in VMI skills. This article presents a meta-analytic review of 10 research studies involving 652 children with mild ID for which a VMI skills assessment was also available. We measured the standardized mean difference (Hedges' g) between scores on VMI tests of these children with mild ID and either typically developing children's VMI test scores in these studies or normative mean values on VMI tests used by the studies. While mild ID is defined in part by intelligence scores that are two to three standard deviations below those of typically developing children, the standardized mean difference of VMI differences between typically developing children and children with mild ID in this meta-analysis was 1.75 (95% CI [1.11, 2.38]). Thus, the intellectual and adaptive skill deficits of children with mild ID may be greater (perhaps especially due to their abstract and conceptual reasoning deficits) than their relative VMI deficits. We discuss the possible meaning of this relative VMI strength among children with mild ID and suggest that their stronger VMI skills may be a target for intensive academic interventions as a means of attenuating problems in adaptive functioning.

Needs among persons with human immunodeficiency virus and intellectual and developmental disabilities in community mental health care: a cross-sectional study.

PubMed

Durbin, A; Sirotich, F; Lunsky, Y; Roesslein, K; Durbin, J

2017-03-01

The experience of having human immunodeficiency virus (HIV) is often associated with co-occurring mental health issues. Community mental health services are an important source of support for persons with HIV living in the community. Persons with intellectual disability (ID) are vulnerable to HIV and may have unique support needs beyond those without ID receiving community care. This study compared support needs of men with HIV in community mental health programmes, with and without ID. The sample was composed of 138 HIV-positive men with and without ID receiving mental health case management from one community organisation in Ontario, Canada, on 31 March 2013. Staff-rated needs across 16 domains grouped into four clusters were measured using the Camberwell Assessment of Need: Basic needs (accommodation, food, public transportation, money and benefits); self-care/functional needs (looking after the home, self-care and daytime activities); health/safety needs (physical health, psychological distress, psychotic symptoms, safety to self and safety to others); and social needs (company, intimate relationships and sexual expression). Adjusted logistic regression models examined the association between ID and each need domain. One-quarter of the sample (n = 34/138, 24.6%) had co-occurring ID. Those with ID were more likely to have needs in the basic cluster [odds ratios: food 4.05 (1.14, 14.44), P:0.031; benefits 2.58 (1.05, 6.32), P:0.038)] and self-care/functional cluster [looking after the home (2.75 (1.17, 6.49), P:0.021); self-care (2.72 (1.18, 6.27), P:0.019)], but were less likely to have need for sexual expression: 0.35 (0.14,0.90), P:0.030) (social cluster). There were no differences in the domains in the health/safety cluster. Despite elevated cognitive needs in the basic and self-care/functional clusters for the ID group, limited other differences suggest that with moderate additional targeting, community mental health programmes for persons with HIV may be appropriate for men with ID. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Clinical context and mechanism of functional tricuspid regurgitation in patients with and without pulmonary hypertension.

PubMed

Topilsky, Yan; Khanna, Amber; Le Tourneau, Thierry; Park, Soon; Michelena, Hector; Suri, Rakesh; Mahoney, Douglas W; Enriquez-Sarano, Maurice

2012-05-01

Functional tricuspid regurgitation (FTR) with structurally normal valve is of poorly defined mechanisms. Prevalence and clinical context of idiopathic FTR (Id-FTR) (without overt TR cause) are unknown. To investigate prevalence, clinical context, and mechanisms specific to FTR types, Id-FTR versus pulmonary hypertension-related (PHTN-FTR, systolic pulmonary pressure ≥50 mm Hg), we analyzed 1161 patients with prospectively quantified TR. Id-FTR (prevalence 12%) was associated with aging and atrial fibrillation. For mechanistic purposes, we measured valvular and right ventricular (RV) remodeling in 141 Id-FTR matched to 140 PHTN-FTR and to 99 controls with trivial TR for age, sex, atrial fibrillation, and ejection fraction. PHTN-FTR and Id-FTR were also matched for TR effective-regurgitant-orifice (ERO). Id-FTR valvular alterations (versus controls) were largest annular area (3.53±0.6 versus 2.74±0.4 cm(2), P<0.0001) and lowest valvular/annular coverage ratio (1.06±0.1 versus 1.45±0.2, P<0.0001) but normal valve tenting height. PHTN-FTR had mild annular enlargement but excessive valve tenting height (0.8±0.3 versus 0.35±0.1 cm, P<0.0001). Valvular changes were linked to specific RV changes, largest basal dilatation, and normal length (RV conical deformation) in Id-FTR versus longest RV with elliptical/spherical deformation in PHTN-FTR. With increasing FTR severity (ERO ≥40 mm(2)), changes specific to each FTR type were accentuated, and RV function (index of myocardial performance) was consistently reduced. Id-FTR is frequent, linked to aging and atrial fibrillation, can be severe, and is of unique mechanism. In Id-FTR, excess annular and RV-basal enlargement exhausts valvular/annular coverage reserve, and RV conical deformation does not cause notable valvular tenting. Conversely, PHTN-FTR is determined by valvular tethering with tenting linked to RV elongation and elliptical/spherical deformation. These specific FTR-mechanisms may be important in considering surgical correction in FTR.

Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655.

PubMed

Chandrasekar Rajendran, S C; Chamlagain, B; Kariluoto, S; Piironen, V; Saris, P E J

2017-06-01

Lactococcus lactis N8 and Saccharomyces boulardii SAA655 were investigated for their ability to synthesize B-vitamins (riboflavin and folate) and their functional role as microbial starters in idli fermentation. In this study, ultra-high performance liquid chromatography and microbiological assay were used to determine the total riboflavin and folate content respectively. Increased levels of folate were evident in both L. lactis N8 and S. boulardii SAA655 cultivated medium. Enhanced riboflavin levels were found only in S. boulardii SAA655 grown medium, whereas decreased riboflavin level was found in L. lactis N8 cultivated medium. To evaluate the functional role of microbial starter strains, L. lactis N8 and S. boulardii SAA655 were incorporated individually and in combination into idli batter, composed of wet grounded rice and black gram. For the experiments, naturally fermented idli batter was considered as control. The results indicated that natural idli fermentation did not enhance the riboflavin level and depleted folate levels by half. In comparison with control, L. lactis N8 and S. boulardii SAA655 incorporated idli batter (individually and in combination) increased riboflavin and folate levels by 40-90%. Apart from compensating the folate loss caused by natural fermentation, S. boulardii SAA655 fermented idli batter individually and in combination with L. lactis N8 also showed the highest leavening character. Moreover, the microbial starter incorporation did not significantly influence the pH of idli batter. Incorporation of L. lactis N8 and S. boulardii SAA655 can evidently enhance the functional and technological characteristics of idli batter. UN General Assembly declared 2016 the International Year of pulses emphasizing the importance of legumes as staple food. Furthermore, this is the first experimental report of in situ biofortifcation of riboflavin and folate using microbes in pulse based fermented staple food. The current study suggests possible avenues for research towards an economical strategy to reduce B-vitamin deficiency among the consuming population. © 2017 The Society for Applied Microbiology.

Initial value problem of space dynamics in universal Stumpff anomaly

NASA Astrophysics Data System (ADS)

Sharaf, M. A.; Dwidar, H. R.

2018-05-01

In this paper, the initial value problem of space dynamics in universal Stumpff anomaly ψ is set up and developed in analytical and computational approach. For the analytical expansions, the linear independence of the functions U_{j} (ψ;σ); {j=0,1,2,3} are proved. The differential and recurrence equations satisfied by them and their relations with the elementary functions are given. The universal Kepler equation and its validations for different conic orbits are established together with the Lagrangian coefficients. Efficient representations of these functions are developed in terms of the continued fractions. For the computational developments we consider the following items: 1. Top-down algorithm for continued fraction evaluation. 2. One-point iteration formulae. 3. Determination of the coefficients of Kepler's equation. 4. Derivatives of Kepler's equation of any integer order. 5. Determination of the initial guess for the solution of the universal Kepler equation. Finally we give summary on the computational design for the initial value problem of space dynamics in universal Stumpff anomaly. This design based on the solution of the universal Kepler's equation by an iterative schemes of quadratic up to any desired order ℓ.

Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).

PubMed

Grant, Sheena; Cross, Elaine; Wraith, James Edmond; Jones, Simon; Mahon, Louise; Lomax, Michelle; Bigger, Brian; Hare, Dougal

2013-03-01

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of four enzymes involved in the catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative disorder, with a progressive decline in children's intellectual and physical functioning. There is currently no cure for the disorder. To date there is a paucity of research on how this disorder impacts parents psychological functioning. Specifically, research in the area has failed to employ adequate control groups to assess if the impact of this disorder on parents psychological functioning differs from parenting a child with intellectual disability (ID). The current study examined child behaviour and parental psychological functioning in 23 parents of children with MPS III and 23 parents of children with ID. Parents completed postal questionnaires about their child's behaviour and abilities and their own psychological functioning. Parents of children with MPS III reported fewer behavioural difficulties as their child aged, more severe level of intellectual disability, and similar levels of perceived social support, coping techniques, stress, anxiety and depression levels as parents of children with ID. Both groups of parents scored above the clinical cut off for anxiety and depression. Parents of children with MPS III rated themselves as significantly less future-orientated and goal directed than parents of children with ID. Services should develop support packages for parents of children with MPS III that incorporate an understanding of the unique stressors and current-difficulty approach of this population. Future research should examine gender differences between parental psychological functioning, using mixed qualitative and quantitative approaches, and utilise matched developmental level and typically developing control groups.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Long; Shi, Songting; Zhang, Juan

Highlights: Black-Right-Pointing-Pointer Expression of Id3 but not Id1 is induced by Wnt3a stimulation in C2C12 cells. Black-Right-Pointing-Pointer Wnt3a induces Id3 expression via canonical Wnt/{beta}-catenin pathway. Black-Right-Pointing-Pointer Wnt3a-induced Id3 expression does not depend on BMP signaling activation. Black-Right-Pointing-Pointer Induction of Id3 expression is critical determinant in Wnt3a-induced cell proliferation and differentiation. -- Abstract: Canonical Wnt signaling plays important roles in regulating cell proliferation and differentiation. In this study, we report that inhibitor of differentiation (Id)3 is a Wnt-inducible gene in mouse C2C12 myoblasts. Wnt3a induced Id3 expression in a {beta}-catenin-dependent manner. Bone morphogenetic protein (BMP) also potently induced Id3 expression. However,more » Wnt-induced Id3 expression occurred independent of the BMP/Smad pathway. Functional studies showed that Id3 depletion in C2C12 cells impaired Wnt3a-induced cell proliferation and alkaline phosphatase activity, an early marker of osteoblast cells. Id3 depletion elevated myogenin induction during myogenic differentiation and partially impaired Wnt3a suppressed myogenin expression in C2C12 cells. These results suggest that Id3 is an important Wnt/{beta}-catenin induced gene in myoblast cell fate determination.« less

Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

DTIC Science & Technology

2015-09-01

and PET images. Figure 2 highlights the dynamic uptake of TSPO as compared to muscle. Across 60 minutes the %ID/cc continues to increase which is...p53 double null mutant mouse model. Towards that end, we have successfully acquired anatomic MRI and PET data in orthotopic tumors within the Pten...castration resistant prostate cancer, MRI, PET , FDHT, image optimization 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

On the Relationship between Motor Performance and Executive Functioning in Children with Intellectual Disabilities

ERIC Educational Resources Information Center

Hartman, E.; Houwen, S.; Scherder, E.; Visscher, C.

2010-01-01

Background: It has been suggested that children with intellectual disabilities (ID) have motor problems and higher-order cognitive deficits. The aim of this study was to examine the motor skills and executive functions in school-age children with borderline and mild ID. The second aim was to investigate the relationship between the two performance…

A Pilot Study of a Test for Visual Recognition Memory in Adults with Moderate to Severe Intellectual Disability

ERIC Educational Resources Information Center

Pyo, Geunyeong; Ala, Tom; Kyrouac, Gregory A.; Verhulst, Steven J.

2010-01-01

Objective assessment of memory functioning is an important part of evaluation for Dementia of Alzheimer Type (DAT). The revised Picture Recognition Memory Test (r-PRMT) is a test for visual recognition memory to assess memory functioning of persons with intellectual disabilities (ID), specifically targeting moderate to severe ID. A pilot study was…

A Preliminary Study of the Validity of Memory Tests Recommended by the Working Group for Individuals with Moderate to Severe Intellectual Disability

ERIC Educational Resources Information Center

Pyo, G.; Kripakaran, K.; Curtis, K.; Curtis, R.; Markwell, S.

2007-01-01

Background: Normal aging and Dementia of Alzheimer's Type (DAT) among higher functioning individuals with intellectual disability (ID) have been relatively well studied using a variety of cognitive tests. However, cognitive studies for lower functioning individuals with ID are scarce in the literature. The Working Group recommended the Test…

A matter of life and death: knowledge about the body and concept of death in adults with intellectual disabilities.

PubMed

McEvoy, J; Treacy, B; Quigley, J

2017-01-01

An increased awareness of how people with intellectual disabilities (ID) understand death and dying is necessary in supporting life-long learning, post-bereavement support and planning end-of-life care. Previous research suggests that adults with ID have a limited or 'patchy' understanding of the basic biological components of death. However, the relationship between biological understanding of how the body works and conceptualisation of death remains unexplored in this population. Thirty adults with ID were interviewed to assess their knowledge of human body function and their understanding of the concept of death. Using pictures, participants were asked if they recognised certain organs, asked to explain the function of various body parts and what would happen if certain body parts were missing or did not work. Participants who referred to 'life' or 'not dying' as the goal of body function were categorised as 'Life Theorisers'. In addition, participants were asked about the causes of death, whether all things die and the status of the body after death. The results support previous studies suggesting that understanding of death in adults with ID varies from partial to full comprehension and is associated with level of ID. Also, death comprehension was positively correlated with total body interview scores and 'Life Theorisers' who understood that body parts maintain life and who spontaneously appealed to 'vitalistic' concepts when reasoning about the human body were also more sophisticated in their understanding of death. The study highlights the relationship between knowledge about the goal of human body functioning and death comprehension in adults with ID. The potential that learning to adopt a 'vitalistic' approach to human functioning may have on the acquisition of a greater understanding of death and dying, understanding illness and supporting end-of-life planning is discussed. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Physical fitness is predictive for a decline in daily functioning in older adults with intellectual disabilities: results of the HA-ID study.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Schoufour, Josje D; Evenhuis, Heleen M

2014-10-01

A high incidence of limitations in daily functioning is seen in older adults with intellectual disabilities (ID), along with poor physical fitness levels. The aim of this study was to assess the predictive value of physical fitness for daily functioning after 3 years, in 602 older adults with borderline to profound ID (≥ 50 years). At baseline, physical fitness levels and daily functioning (operationalized as basic activities of daily living [ADL] and mobility) were assessed. After 3 years, the measurements of daily functioning were repeated. At follow-up, 12.6% of the participants were completely independent in ADL and 48.5% had no mobility limitations. More than half of the participants (54.8%) declined in their ability to perform ADL and 37.5% declined in their mobility. Manual dexterity, visual reaction time, balance, comfortable and fast gait speed, muscular endurance, and cardiorespiratory fitness were significant predictors for a decline in ADL. For a decline in mobility, manual dexterity, balance, comfortable and fast walking speed, grip strength, muscular endurance, and cardiorespiratory fitness were all significant predictors. This proves the predictive validity of these physical fitness tests for daily functioning and stresses the importance of using physical fitness tests and implementing physical fitness enhancing programs in the care for older adults with ID. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polypeptide having or assisting in carbohydrate material degrading activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Los, Alrik Pieter

2016-02-16

The invention relates to a polypeptide which comprises the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 76% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 76% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having beta-glucosidase activity and uses thereof

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoonneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; De Jong, Rene Marcel

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 96% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well asmore » the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.« less

Polypeptide having swollenin activity and uses thereof

DOEpatents

Schoonneveld-Bergmans, Margot Elizabeth Francoise; Heijne, Wilbert Herman Marie; Vlasie, Monica D; Damveld, Robbertus Antonius

2015-11-04

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having beta-glucosidase activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; De Jong, Rene Marcel; Damveld, Robbertus Antonius

2015-09-01

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 70% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 70% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having cellobiohydrolase activity and uses thereof

DOEpatents

Sagt, Cornelis Maria Jacobus; Schooneveld-Bergmans, Margot Elisabeth Francoise; Roubos, Johannes Andries; Los, Alrik Pieter

2015-09-15

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 93% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 93% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having acetyl xylan esterase activity and uses thereof

DOEpatents

Schoonneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Los, Alrik Pieter

2015-10-20

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Polypeptide having carbohydrate degrading activity and uses thereof

DOEpatents

Schooneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Vlasie, Monica Diana; Damveld, Robbertus Antonius

2015-08-18

The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 73% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

Detection of anti-liver cytosol antibody type 1 (anti-LC1) by immunodiffusion, counterimmunoelectrophoresis and immunoblotting: comparison of different techniques.

PubMed

Muratori, L; Cataleta, M; Muratori, P; Manotti, P; Lenzi, M; Cassani, F; Bianchi, F B

1995-12-01

Liver cytosol specific antibody type 1 (anti-LC1) was first described in a proportion of patients with liver/kidney microsomal antibody type 1 (anti-LKM1)-positive autoimmune hepatitis (AIH) and is routinely evaluated by immunodiffusion (ID). Using human liver cytosol as the source of antigen, we have used ID, counterimmunoelectrophoresis (CIE) and immunoblotting (IB), to test sera from 167 patients with documented chronic liver diseases of different etiology. 15 patients had antinuclear antibody (ANA) and/or smooth muscle antibody (SMA)-positive AIH, 13 had anti-LKM1-positive AIH, four had ANA/SMA/anti-LKM1-negative AIH, 76 had anti-LKM1-positive hepatitis C (recently renamed unclassified chronic hepatitis-UCH), 40 had chronic hepatitis C, 15 had chronic hepatitis B, and 4 had chronic hepatitis D. A precipitin line of identity with an anti-LC1 reference serum was detected both by ID and CIE in 16 patients: six with anti-LKM1-positive 'definite' AIH, four with ANA/SMA/anti-LKM1-negative 'definite' AIH, and six with anti-LKM1-positive UCH. By IB, 14 out of the 16 anti-LC1-positive sera (87.5%) reacted with a 58 kDa human liver cytosolic polypeptide, whereas three out of 16 (19%) recognised an additional 60 kDa band. Compared to ID, CIE is more economical in terms of both time and reagents and provides more clear-cut results. The 58 kDa reactivity by IB was detectable in nearly all CIE/ID anti-LC1-positive patients, was not found among CIE/ID anti-LC1-negative patients. In conclusion, CIE is the ideal screening test for the detection of anti-LC1, an autoantibody that can be regarded as an additional serological marker of AIH and is especially useful in ANA/SMA/anti-LKM1 negative cases.

Progressive mobility program and technology to increase the level of physical activity and its benefits in respiratory, muscular system, and functionality of ICU patients: study protocol for a randomized controlled trial.

PubMed

Schujmann, Debora Stripari; Lunardi, Adriana Claudia; Fu, Carolina

2018-05-10

Enhanced mobility in the Intensive Care Unit (ICU) could minimize the negative effects of critical illness, such as declines in cognitive, muscular, respiratory, and functional capacity. We aim to compare the functional status at ICU discharge of patients who underwent a progressive mobilization protocol versus patients who received conventional physiotherapy. We also examine the level of physical activity in the ICU, the degree of pulmonary and muscle function, and the length of stay to analyze correlations between these variables. This is a protocol for a randomized controlled trial with blind evaluation. Ninety-six ICU patients will be recruited from a single center and randomly assigned to a control group or an intervention group. To determine the level of protocol activity the patient will receive, the patients' ability to participate actively and their muscle strength will be considered. The protocol consists of five phases, ranging from passive therapies to walking and climbing stairs. The primary outcome will be the functional status at ICU discharge, measured with the Barthel Index and the ICU Mobility Scale (IMS). Measured secondary outcomes will include the level of physical activity, maximal inspiratory and expiratory pressures, forced expiratory volume in 1 second, maximum voluntary ventilation, handgrip strength, surface electromyography of the lower limb muscles, and results of the Timed Up and Go and 2-Minute Walk tests. Evaluations will be made within 2 days of ICU discharge except for the level of activity, which will be evaluated daily. Physiological variables and activity level will be analyzed by chi-square and t tests, according to the intention-to-treat paradigm. Mobility and exercise in the ICU should be undertaken with intensity, quantity, duration, and frequency adjusted according to the patients' status. The results of this study may contribute to new knowledge of early mobility in the ICU, activity level, and varying benefits in critical patients, directing new approaches to physiotherapeutic interventions in these patients. Recruitment will begin in February 2017, and the expected completion date is August 2018. Patients are already being recruited. ClinicalTrials.gov, ID: NCT02889146 . Registered on 3 March 2016.

Array-CGH in children with mild intellectual disability: a population-based study.

PubMed

Coutton, Charles; Dieterich, Klaus; Satre, Véronique; Vieville, Gaëlle; Amblard, Florence; David, Marie; Cans, Christine; Jouk, Pierre-Simon; Devillard, Francoise

2015-01-01

Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.

The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon.

PubMed

Rodriguez Viales, Rebecca; Diotel, Nicolas; Ferg, Marco; Armant, Olivier; Eich, Julia; Alunni, Alessandro; März, Martin; Bally-Cuif, Laure; Rastegar, Sepand; Strähle, Uwe

2015-03-01

The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury. id1 expression was mapped to quiescent type I neural stem cells in the adult telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated that Id1 promotes stem cell quiescence. The increased id1 expression observed in neural stem cells in response to injury appeared independent of inflammatory signals, suggesting multiple antagonistic pathways in the regulation of reactive neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell pool by counteracting neurogenesis-promoting signals. © 2014 AlphaMed Press.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Navy Information Dominance Corps: Human Capital Strategy 2012-2017

DTIC Science & Technology

2012-01-01

Information Dominance (ID) is the operational advantage gained from fully integrating information functions, capabilities, resources and people to...and information domains. The human component of ID is the Information Dominance Corps (IDC) and it has three core functions in this mission. First, it...processes, delivery of a Corps-wide learning continuum, and cultivation of an identifiable, inclusive Information Dominance culture and ethos. This

Health Status and ADL Functioning of Older Persons with Intellectual Disability: Community Residence versus Residential Care Centers

ERIC Educational Resources Information Center

Lifshitz, Hefziba; Merrick, Joav; Morad, Mohammed

2008-01-01

The objective of the study was to study differences in aging phenomena among adults with intellectual disability (ID), who live in community residence versus their peers in residential care centers and to determine the contribution of health status, age, gender, etiology and level of ID to the decline in ADL function with age. Our study was based…

Evaluation of body posture in individuals with internal temporomandibular joint derangement.

PubMed

Munhoz, Wagner Cesar; Marques, Amélia Pasqual; de Siqueira, José Tadeu Tesseroli

2005-10-01

Temporomandibular dysfunctions (TMD) comprise a great number of disruptions that may affect the temporomandibular joint (TMJ), the masticatory muscles, or both. TMJ internal derangement is a specific type of TMD, of which the etiology and physiopathology are broadly unknown, but have been suggested to be linked to head, neck, and body posture factors. This study aimed at verifying possible relationships between body posture and TMJ internal derangements (TMJ-id), by comparing 30 subjects presenting typical TMJ-id signs to 20 healthy subjects. Subjects' clinical evaluations included anamnesis, stomatognatic system evaluation, and plotting analysis on body posture photographs. No statistically significant differences were found between the groups. Results do not support the assertion that body posture plays a role in causing or enhancing TMD; however, these results should be cautiously considered because of the small number of subjects evaluated and the many posture variables submitted to statistical procedures that lead to high standard deviations.

Long-term effect of losartan administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats.

PubMed

KOPRDOVA, R; CEBOVA, M; KRISTEK, F

2009-01-01

Alterations in geometry and structure of coronary arteries have marked consequences on blood flow to the respective area. We evaluated long-term effect of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry and structure of septal branch of coronary artery (RS) of young SHR and Wistar rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20 mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by plethysmographic method. Cardiovascular system was perfused with a fixative (120 mm Hg). RS was processed for electron microscopy. Wall thickness of intima + media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA), volume densities (VD) of endothelial cells (EC), extracellular matrix (ECM) of intima, smooth muscle cells (SMC) and ECM of media were evaluated. BP of 4-week-old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs of SMC, ECM of media were increased in 9-week-old SHR, whereas their VD and CSA of EC were decreased. Losartan administration decreased BP and HW/BW in both groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and increased of ID, circumferential tension, VD and CSA of EC). Losartan administration reduced BP and myocardial mass in both groups and beneficially affected geometry and structure of coronary artery in SHR.

Three Methods for Estimating the Middle-Ear Muscle Reflex (MEMR) Using Otoacoustic Emission (OAE) Measurement Systems

DTIC Science & Technology

2014-10-01

sensitive MEMR measurement using the OAE and MOCR measurement modules in the Mimosa Acoustics HeariD system. All three methods can sensitively detect...three related methods for making this sensitive MEMR measurement using the OAE and MOCR measurement modules in the Mimosa Acoustics HearID system...without buying additional equipment or software. The purpose of this report is to document the methodology we have used since 2007 with Mimosa Acoustics

Scaling of muscle architecture and fiber types in the rat hindlimb.

PubMed

Eng, Carolyn M; Smallwood, Laura H; Rainiero, Maria Pia; Lahey, Michele; Ward, Samuel R; Lieber, Richard L

2008-07-01

The functional capacity of a muscle is determined by its architecture and metabolic properties. Although extensive analyses of muscle architecture and fiber type have been completed in a large number of muscles in numerous species, there have been few studies that have looked at the interrelationship of these functional parameters among muscles of a single species. Nor have the architectural properties of individual muscles been compared across species to understand scaling. This study examined muscle architecture and fiber type in the rat (Rattus norvegicus) hindlimb to examine each muscle's functional specialization. Discriminant analysis demonstrated that architectural properties are a greater predictor of muscle function (as defined by primary joint action and anti-gravity or non anti-gravity role) than fiber type. Architectural properties were not strictly aligned with fiber type, but when muscles were grouped according to anti-gravity versus non-anti-gravity function there was evidence of functional specialization. Specifically, anti-gravity muscles had a larger percentage of slow fiber type and increased muscle physiological cross-sectional area. Incongruities between a muscle's architecture and fiber type may reflect the variability of functional requirements on single muscles, especially those that cross multiple joints. Additionally, discriminant analysis and scaling of architectural variables in the hindlimb across several mammalian species was used to explore whether any functional patterns could be elucidated within single muscles or across muscle groups. Several muscles deviated from previously described muscle architecture scaling rules and there was large variability within functional groups in how muscles should be scaled with body size. This implies that functional demands placed on muscles across species should be examined on the single muscle level.

Individual and combined influence of ACE and ACTN3 genes on muscle phenotypes in Polish athletes.

PubMed

Orysiak, Joanna; Mazur-Różycka, Joanna; Busko, Krzysztof; Gajewski, Jan; Szczepanska, Beata; Malczewska-Lenczowska, Jadwiga

2017-02-08

The aim of this study was to examine the association between ACE and ACTN3 genes, independently or in combination, and muscle strength and power in male and female athletes. The study involved 398 young male (n=266) and female (n=132) athletes representing various sport disciplines (ice hockey, canoeing, swimming, volleyball). All were Caucasians. The following measurements were taken: height of jump and mechanical power in countermovement jump (CMJ) and spike jump (SPJ), and muscle strength of 10 muscle groups (flexors and extensors of the elbow, shoulder, hip, knee and trunk). The ID polymorphism of ACE and the R577X polymorphism of ACTN3 were typed using PCR (polymerase chain reaction) and PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), respectively. The genotype distribution of the ACE and ACTN3 genes did not differ significantly between groups of athletes for either sex. There was no association between ACE and ACTN3 genotypes (alone or in combination) and sum of muscle strength, height of jump or mechanical power in both jump tests (CMJ and SPJ) for male and female athletes. These findings do not support an influential role of the ACE and ACTN3 genes in determining power/strength performance of elite athletes.

Techniques for studying the effects of microgravity on model particle/cell systems

NASA Technical Reports Server (NTRS)

Young, Ronald B.

1988-01-01

To study the direct effects of a low gravity environment on skeletal and cardiac muscle cells, experiments were initiated to determine whether skeletal and/or cardiac muscule cells would grow within the lumen of XM-80 hollow fibers (i.d. = 0.5 mm). Cells were prepared from skeletal or cardiac muscle tissue of 12 day embryos and were cultured for up to 7 days in the hollow fiber environment. Light microscopy revealed that cells proliferated to confluency over this period of time and fusion was apparent in the skeletal muscle cells. Once it was verified that cells would grow to confluency, additional XM-80 fibers containing cells were placed in a Clinostat in the horizontal position at 100 rpm. Fibers were stretched by a built-in spring mechanism to hold the fiber tightly at the center of rotation. Under these conditions, the gravity vector approaches zero and the cells are in an environment that simulates microgravity. Examination of skeletal muscle cells by electron microscopy revealed that myoblast fusion and myofibril accumulation were extensive. Although data obtained thus far are preliminary, they suggest that myofibril organization in chicken skeletal muscle cultures is somewhat more poorly defined in Clinostat rotated cultures than in controls that were not subjected to Clinostat conditions.

Managing Weight: What Do People with an Intellectual Disability Want from Mobile Technology?

PubMed

Smyth, Phil; McDowell, Claire; Leslie, Julian C; Leader, Geraldine; Donnelly, Mark; Simpson, Elizabeth; Skelly, Laura

2017-01-01

Obesity is a significant health challenge. People with Intellectual Disability (ID) are particularly vulnerable to developing obesity. Mobile technology has been developed to support the management of weight and obesity in the form of apps, although not with people with an ID in mind. As a result existing off-the-shelf weight management apps currently available may not be functional in supporting weight reduction within this population. This paper presents the results of consultations with people with ID regarding weight management, comfort with mobile technology and desired characteristics in apps designed for people with ID that target weight management.

Working memory impairment and recovery in iron deficient children.

PubMed

Otero, Gloria A; Pliego-Rivero, F Bernardo; Porcayo-Mercado, Rosario; Mendieta-Alcántara, Gustavo

2008-08-01

Iron is an important oligoelement participating in multiple metabolic processes, including the synthesis of catecholamines, and its deficiency (ID) throughout development is particularly insidious on brain maturation and the emergence of cognitive functions during school age. A working memory (WM) study in 8-10-year-old ID children is presented. It is hypothesized that an impairment in WM exists in ID school-age children and a substantial restoration of this mental ability should occur after iron supplementation. Event-related potentials (ERPs) were recorded during the completion of a Sternberg-type task in control, ID and ID-iron supplemented children. ID children showed less correct answers and diminished ERP amplitude in frontal, central, parietal and temporal regions compared to control children. After iron supplementation and normalizing bodily iron stores, behavioral and ERP differences disappeared between ID and control children. Considering that WM is fundamentally related to attention ability, the results presented here confirm and reinforce previous observations: ID severely diminishes attention [Otero GA, Pliego-Rivero FB, Contreras G, Ricardo J, Fernandez T. Iron supplementation brings up a lacking P300 in iron deficient children. Clin Neurophysiol 2004;115:2259-66] and WM while iron supplementation substantially restores the cognitive capabilities tested. This is one of very few reports using ERP showing a diminished WM capability in ID school-age children.

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability

PubMed Central

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-01-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID. PMID:27457812

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

PubMed

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-11-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Idea density measured in late life predicts subsequent cognitive trajectories: implications for the measurement of cognitive reserve.

PubMed

Farias, Sarah Tomaszewski; Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-11-01

The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve.

An RNAi based screen in Drosophila larvae identifies fascin as a regulator of myoblast fusion and myotendinous junction structure.

PubMed

Camuglia, Jaclyn M; Mandigo, Torrey R; Moschella, Richard; Mark, Jenna; Hudson, Christine H; Sheen, Derek; Folker, Eric S

2018-04-06

A strength of Drosophila as a model system is its utility as a tool to screen for novel regulators of various functional and developmental processes. However, the utility of Drosophila as a screening tool is dependent on the speed and simplicity of the assay used. Here, we use larval locomotion as an assay to identify novel regulators of skeletal muscle function. We combined this assay with muscle-specific depletion of 82 genes to identify genes that impact muscle function by their expression in muscle cells. The data from the screen were supported with characterization of the muscle pattern in embryos and larvae that had disrupted expression of the strongest hit from the screen. With this assay, we showed that 12/82 tested genes regulate muscle function. Intriguingly, the disruption of five genes caused an increase in muscle function, illustrating that mechanisms that reduce muscle function exist and that the larval locomotion assay is sufficiently quantitative to identify conditions that both increase and decrease muscle function. We extended the data from this screen and tested the mechanism by which the strongest hit, fascin, impacted muscle function. Compared to controls, animals in which fascin expression was disrupted with either a mutant allele or muscle-specific expression of RNAi had fewer muscles, smaller muscles, muscles with fewer nuclei, and muscles with disrupted myotendinous junctions. However, expression of RNAi against fascin only after the muscle had finished embryonic development did not recapitulate any of these phenotypes. These data suggest that muscle function is reduced due to impaired myoblast fusion, muscle growth, and muscle attachment. Together, these data demonstrate the utility of Drosophila larval locomotion as an assay for the identification of novel regulators of muscle development and implicate fascin as necessary for embryonic muscle development.

The Atypical Cadherin Dachsous Controls Left-Right Asymmetry in Drosophila.

PubMed

González-Morales, Nicanor; Géminard, Charles; Lebreton, Gaëlle; Cerezo, Delphine; Coutelis, Jean-Baptiste; Noselli, Stéphane

2015-06-22

Left-right (LR) asymmetry is essential for organ development and function in metazoans, but how initial LR cue is relayed to tissues still remains unclear. Here, we propose a mechanism by which the Drosophila LR determinant Myosin ID (MyoID) transfers LR information to neighboring cells through the planar cell polarity (PCP) atypical cadherin Dachsous (Ds). Molecular interaction between MyoID and Ds in a specific LR organizer controls dextral cell polarity of adjoining hindgut progenitors and is required for organ looping in adults. Loss of Ds blocks hindgut tissue polarization and looping, indicating that Ds is a crucial factor for both LR cue transmission and asymmetric morphogenesis. We further show that the Ds/Fat and Frizzled PCP pathways are required for the spreading of LR asymmetry throughout the hindgut progenitor tissue. These results identify a direct functional coupling between the LR determinant MyoID and PCP, essential for non-autonomous propagation of early LR asymmetry. Copyright © 2015 Elsevier Inc. All rights reserved.

ADHD and Challenging behaviour in People with Intellectual Disability: should we screen for ADHD?

PubMed

Perera, Bhathika; Courtenay, Ken

2017-09-01

People with Intellectual Disability (ID) have cognitive impairments that affect their level of functioning the causes of which are multiple and often unknown. Behavioural difficulties are common among people with ID. Attention Deficit Hyperactivity Disorder (ADHD) is recognised more among people with Intellectual Disability and could be a cause of problem behaviours. Screening and assessing for ADHD in people with ID is difficult because of the paucity of robust assessment tools and diagnostic criteria.

Relationship between function of masticatory muscle in mouse and properties of muscle fibers.

PubMed

Abe, Shinichi; Hiroki, Emi; Iwanuma, Osamu; Sakiyama, Koji; Shirakura, Yoshitaka; Hirose, Daiki; Shimoo, Yoshiaki; Suzuki, Masashi; Ikari, Yasutoyo; Kikuchi, Ryusuke; Ide, Yoshinobu; Yoshinari, Masao

2008-05-01

Mammals exhibit marked morphological differences in the muscles surrounding the jaw bone due to differences in eating habits. Furthermore, the myofiber properties of the muscles differ with function. Since the muscles in the oral region have various functions such as eating, swallowing, and speech, it is believed that the functional role of each muscle differs. Therefore, to clarify the functional role of each masticatory muscle, the myofiber properties of the adult mouse masticatory muscles were investigated at the transcriptional level. Expression of MyHC-2b with a fast contraction rate and strong force was frequently noted in the temporal and masseter muscles. This suggests that the temporal and masseter muscles are closely involved in rapid antero-posterior masticatory movement, which is characteristic in mice. Furthermore, expression of MyHC-1 with a low contraction rate and weak continuous force was frequently detected in the lateral pterygoid muscle. This suggests that, in contrast to other masticatory muscles, mouse lateral pterygoid muscle is not involved in fast masticatory movement, but is involved in functions requiring continuous force such as retention of jaw position. This study revealed that muscles with different roles function comprehensively during complicated masticatory movement.

Iron assessment to protect the developing brain.

PubMed

Georgieff, Michael K

2017-12-01

Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction. © 2017 American Society for Nutrition.

ID2 collaborates with ID3 to suppress iNKT and innate-like tumors1

PubMed Central

Li, Jia; Roy, Sumedha; Kim, Young-Mi; Li, Shibo; Zhang, Baojun; Love, Cassandra; Reddy, Anupama; Rajagopalan, Deepthi; Dave, Sandeep; Diehl, Anna Mae; Zhuang, Yuan

2017-01-01

Inhibitor of DNA binding (ID) proteins, including ID1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins has been associated with a broad spectrum of tumors, recent studies have identified that ID3 plays a tumor suppressor role in the development of Burkitt’s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. Here, we report rapid lymphoma development in Id2/Id3 double knockout (L-DKO) mice caused by unchecked expansion of either invariant Natural Killer T (iNKT) cells, or a unique subset of innate-like, CD1d-independent T cells. These populations started expansion in neonatal mice and, upon malignant transformation, caused fatality at age between 3–11 months. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability, along with upregulation of several different signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the NF-kB pathway were found to be shared between L-DKO lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumoriogenic pathways caused by loss function of ID2 and ID3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. PMID:28258199

Intellectual disabilities, neuronal posttranscriptional RNA metabolism, and RNA-binding proteins: three actors for a complex scenario.

PubMed

Bardoni, Barbara; Abekhoukh, Sabiha; Zongaro, Samantha; Melko, Mireille

2012-01-01

Intellectual disability (ID) is the most frequent cause of serious handicap in children and young adults and interests 2-3% of worldwide population, representing a serious problem from the medical, social, and economic points of view. The causes are very heterogeneous. Genes involved in ID have various functions altering different pathways important in neuronal function. Regulation of mRNA metabolism is particularly important in neurons for synaptic structure and function. Here, we review ID due to alteration of mRNA metabolism. Functional absence of some RNA-binding proteins--namely, FMRP, FMR2P, PQBP1, UFP3B, VCX-A--causes different forms of ID. These proteins are involved in different steps of RNA metabolism and, even if a detailed analysis of their RNA targets has been performed so far only for FMRP, it appears clear that they modulate some aspects (translation, stability, transport, and sublocalization) of a subset of RNAs coding for proteins, whose function must be relevant for neurons. Two other proteins, DYRK1A and CDKL5, involved in Down syndrome and Rett syndrome, respectively, have been shown to have an impact on splicing efficiency of specific mRNAs. Both proteins are kinases and their effect is indirect. Interestingly, both are localized in nuclear speckles, the nuclear domains where splicing factors are assembled, stocked, and recycled and influence their biogenesis and/or their organization. Copyright © 2012 Elsevier B.V. All rights reserved.

Id1 expression promotes peripheral CD4{sup +} T cell proliferation and survival upon TCR activation without co-stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chen; Jin, Rong; Wang, Hong-Cheng

2013-06-21

Highlights: •Id1 expression enables naïve T cell proliferation without anti-CD28 co-stimulation. •Id1 expression facilitates T cells survival when stimulated with anti-CD3. •Elevation of IL-2 production by Id1 contributes increased proliferation and survival. •Id1 potentiates NF-κB activation by anti-CD3 stimulation. -- Abstract: Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïvemore » CD4{sup +} cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.« less

Intellectual disability in young people in custody in New South Wales, Australia - prevalence and markers.

PubMed

Haysom, L; Indig, D; Moore, E; Gaskin, C

2014-11-01

Intellectual disability (ID) is known to be more common in incarcerated groups, especially incarcerated youth. Aboriginal young people have higher rates of ID, and make up half of all youth in juvenile custody in New South Wales (NSW), Australia. We aimed to describe the prevalence of possible ID and borderline intellectual functioning (BIF) in young people in NSW custody, and to describe the association between possible ID and Aboriginality after adjusting for the inequalities in social disadvantage. Baseline study of all youth in NSW Custodial Centres between August and October 2009, with 18-month follow-up. Using Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) and Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) cognitive assessments, possible ID was defined as Extremely Low Intellectual Quotient range (Full Scale Intellectual Quotient, FSIQ < 70), and possible BIF was defined as Borderline IQ range (FSIQ < 80). Risk factors for possible ID and BIF included age, gender, Aboriginality, socio-economic disadvantage, offending history and psychological disorders. N = 295 (65%) of all young people in NSW custody completed cognitive and psychological assessments (87% male, 50% Aboriginal, average age 17 years). Almost one half (45.8%) of young people had borderline or lower intellectual functioning (by IQ assessment), and 14% had an IQ in the extremely low range (FSIQ < 70), indicating a possible ID. Aboriginal participants were three times more likely than non-Aboriginal participants to have a possible ID, but after accounting for the excess disadvantage in the Aboriginal group, Aboriginality was no longer a marker of ID. Incarceration from a young age and psychosis were significantly associated with possible ID in Aboriginal participants, compared with Aboriginal participants first incarcerated at a later age, and Aboriginal participants without psychosis. The inequalities in criminal justice between Aboriginal and non-Aboriginal youth may exacerbate or contribute to the intellectual impairment of those incarcerated from a young age. Aboriginal young people with psychosis are also at high risk of cognitive impairments that might indicate a possible co-morbid ID, and these patients should be diverted at court into community assessment services, rather than incarcerated. These results highlight a need for better and earlier identification of young people (particularly Aboriginal youth) at risk of ID and other co-morbidities in the juvenile justice system. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Operational Art and the Sustainment Warfighting Function

DTIC Science & Technology

2011-12-01

Infantry Division (ID) a continuous sustainment line of operation. The leap- frogging of Forward Logisitics Bases provided 3rd Infantry Division (ID...victims. A C-17 Globemaster III departed North Carolina and delivered 14,000 Meals Ready-to- Eat , or MREs, and 14,000 quarts of water in a 7-hour round

Intellectual disability and homelessness.

PubMed

Mercier, C; Picard, S

2011-04-01

The association between poverty and intellectual disability (ID) has been well documented. However, little is known about persons with ID who face circumstances of extreme poverty, such as homelessness. This paper describes the situation of persons with ID who were or are homeless in Montreal and are currently receiving services from a team dedicated to homeless persons. (1) To describe the characteristics, history and current situation of these persons; and (2) to report within-group differences as a function of gender and current residential status. The data were collected from files using an anonymous chart summary. Descriptive statistics on the whole sample (n = 68) and inferential statistics on cross-tabulations by gender and residential status were performed. Persons with ID exhibited several related problems. Some of these persons, primarily women, experienced relatively short periods of homelessness and their situations stabilised once they were identified and followed up. Other persons with ID experienced chronic homelessness that appeared to parallel the number and severity of their other problems. When compared with a previous epidemiological study of the homeless in Montreal, the population of homeless persons with ID differed from the overall homeless population in a number of respects. The results suggest prevention and intervention targets. The need for epidemiological research appears particularly clear in light of the fact that below-average intellectual functioning has been identified as a risk factor for homelessness and a predisposing factor for vulnerability among street people. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Idea Density Measured in Late Life Predicts Subsequent Cognitive Trajectories: Implications for the Measurement of Cognitive Reserve

PubMed Central

Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-01-01

Objective. The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. Method. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Results. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Discussion. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve. PMID:22357642

Iron supplementation until 6 months protects marginally low-birth-weight infants from iron deficiency during their first year of life.

PubMed

Berglund, Staffan K; Westrup, Björn; Domellöf, Magnus

2015-03-01

Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg · kg(-1) · day(-1) of iron supplements from 6 weeks to 6 months of age. At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.006). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Iron supplements with 2 mg · kg(-1) · day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

Effects of whole body vibration exercise on neuromuscular function for individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

PubMed

Lai, Zhangqi; Wang, Xueqiang; Lee, Seullee; Hou, Xihe; Wang, Lin

2017-09-20

Knee osteoarthritis (KOA) is a leading cause of public disability. Neuromuscular function contributes to the development and/or progression of KOA. Whole body vibration (WBV) exercise improve the neuromuscular function of patients with neurological disorders and even that of older patients with limited exercise options. Therefore, WBV exercise may offer an efficient and alternative treatment for individuals with KOA. However, the effects of WBV training on the neuromuscular function of individuals with KOA remain unclear. Therefore, this study attempts to investigate the effect of a 12-week WBV exercise on the neuromuscular function of individuals with KOA. We will conduct a prospective, single-blind randomized controlled trial on 180 KOA patients. Participants will be randomly assigned to the WBV exercise, lower extremity resistance training, and health education groups. The WBV exercise group will participate in a 12-week WBV training. The lower extremity resistance training group will undergo a 12-week lower extremity resistance training of both lower limbs. The control group will receive health education for 12 weeks. After the intervention, the participants will be followed up for 3 months with no active intervention. Primary outcome measures will include anthropometric measurements, gait analysis during walking and stair climbing, muscle strength test of the knee and ankle, proprioception test of the knee and ankle, and neuromuscular response of the leg muscles. Secondary outcome measures will include self-reported pain and physical functional capacity, and physical performance measures. Furthermore, adverse events will be recorded and analyzed. If any participant withdraws from the trial, intention-to-treat analysis will be performed. Important features of this trial mainly include intervention setting, outcome measure selection, and study duration. This study is intended for estimating the effect of WBV intervention on neuromuscular control outcomes. Study results may provide evidence to support the beneficial effects of WBV exercise on the physical performance and neuromuscular control of individuals with KOA to fill the research gap on the efficacy of WBV. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009234 . Registered on 21 September 2016.

Genetic influence on exercise-induced changes in physical function among mobility-limited older adults

PubMed Central

Hsu, Fang-Chi; Brinkley, Tina E.; Carter, Christy S.; Church, Timothy S.; Dodson, John A.; Goodpaster, Bret H.; McDermott, Mary M.; Nicklas, Barbara J.; Yank, Veronica; Johnson, Julie A.; Pahor, Marco

2014-01-01

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors. PMID:24423970

Synaptic dysfunction and intellectual disability.

PubMed

Valnegri, Pamela; Sala, Carlo; Passafaro, Maria

2012-01-01

Intellectual disability (ID) is a common and highly heterogeneous paediatric disorder with a very severe social impact. Intellectual disability can be caused by environmental and/or genetic factors. Although in the last two decades a number of genes have been discovered whose mutations cause mental retardation, we are still far from identifying the impact of these mutations on brain functions. Many of the genes mutated in ID code for several proteins with a variety of functions: chromatin remodelling, pre-/post-synaptic activity, and intracellular trafficking. The prevailing hypothesis suggests that the ID phenotype could emerge from abnormal cellular processing leading to pre- and/or post-synaptic dysfunction. In this chapter, we focus on the role of small GTPases and adhesion molecules, and we discuss the mechanisms through which they lead to synaptic network dysfunction.

High-throughput sequencing technology to reveal the composition and function of cecal microbiota in Dagu chicken.

PubMed

Xu, Yunhe; Yang, Huixin; Zhang, Lili; Su, Yuhong; Shi, Donghui; Xiao, Haidi; Tian, Yumin

2016-11-04

The chicken gut microbiota is an important and complicated ecosystem for the host. They play an important role in converting food into nutrient and energy. The coding capacity of microbiome vastly surpasses that of the host's genome, encoding biochemical pathways that the host has not developed. An optimal gut microbiota can increase agricultural productivity. This study aims to explore the composition and function of cecal microbiota in Dagu chicken under two feeding modes, free-range (outdoor, OD) and cage (indoor, ID) raising. Cecal samples were collected from 24 chickens across 4 groups (12-w OD, 12-w ID, 18-w OD, and 18-w ID). We performed high-throughput sequencing of the 16S rRNA genes V4 hypervariable regions to characterize the cecal microbiota of Dagu chicken and compare the difference of cecal microbiota between free-range and cage raising chickens. It was found that 34 special operational taxonomic units (OTUs) in OD groups and 4 special OTUs in ID groups. 24 phyla were shared by the 24 samples. Bacteroidetes was the most abundant phylum with the largest proportion, followed by Firmicutes and Proteobacteria. The OD groups showed a higher proportion of Bacteroidetes (>50 %) in cecum, but a lower Firmicutes/Bacteroidetes ratio in both 12-w old (0.42, 0.62) and 18-w old groups (0.37, 0.49) compared with the ID groups. Cecal microbiota in the OD groups have higher abundance of functions involved in amino acids and glycan metabolic pathway. The composition and function of cecal microbiota in Dagu chicken under two feeding modes, free-range and cage raising are different. The cage raising mode showed a lower proportion of Bacteroidetes in cecum, but a higher Firmicutes/Bacteroidetes ratio compared with free-range mode. Cecal microbiota in free-range mode have higher abundance of functions involved in amino acids and glycan metabolic pathway.

Iron deficiency in a tertiary gastroenterology center in Romania: prevalence and significancy.

PubMed

Preda, Carmen Monica; Proca, Doina; Sandra, Irina; Horeanga, Boroka Claudia; Fulger, Larisa Elena; Manuc, Teodora; Bancila, Ion; Balas, Oana Elena; Manuc, Mircea; Diculescu, Mircea; Baicus, Cristian; Tieranu, Cristian; Constantinescu, Ileana

2018-01-01

Introduction: Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods: We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results: The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions: Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal.

Iron deficiency in a tertiary gastroenterology center in Romania: prevalence and significancy

PubMed Central

Preda, Carmen Monica; Proca, Doina; Sandra, Irina; Horeanga, Boroka Claudia; Fulger, Larisa Elena; Manuc, Teodora; Bancila, Ion; Balas, Oana Elena; Manuc, Mircea; Diculescu, Mircea; Baicus, Cristian; Tieranu, Cristian; Constantinescu, Ileana

2018-01-01

Introduction:Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods:We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results:The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions:Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal PMID:29696062

Characterization of Strength and Function in Ambulatory Adults With GNE Myopathy.

PubMed

Argov, Zohar; Bronstein, Faye; Esposito, Alicia; Feinsod-Meiri, Yael; Florence, Julaine M; Fowler, Eileen; Greenberg, Marcia B; Malkus, Elizabeth C; Rebibo, Odelia; Siener, Catherine S; Caraco, Yoseph; Kolodny, Edwin H; Lau, Heather A; Pestronk, Alan; Shieh, Perry; Skrinar, Alison M; Mayhew, Jill E

2017-09-01

To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM. Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS). Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning. The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function.

POWERS forID: Personalized Online Weight and Exercise Response System for Individuals with Intellectual Disability: study protocol for a randomized controlled trial.

PubMed

Neumeier, William H; Guerra, Nichole; Thirumalai, Mohanraj; Geer, Betty; Ervin, David; Rimmer, James H

2017-10-23

Intellectual disability (ID) is characterized by limitations in intellectual functioning and adaptive behavior. Adults with ID exhibit higher rates of obesity and poorer health status compared to the general population. Continuity of care and barriers to health-related activities may contribute to the poorer health status observed in this population. To address this problem, a tailored weight management online health information and communication technology platform, known as POWERS forID , was developed and is being tested to determine if this delivery mechanism can improve weight maintenance/weight loss in adults with ID. Obese adults with mild-to-moderate ID (n = 70) are randomized to the POWERS forID intervention or control group for a 24-week trial. Each group undergoes an assessment that includes body weight, waist circumference, and percent body fat at baseline and at weeks 6, 12, and 24. Physical activity barriers, healthy eating barriers, food frequency, and psychosocial wellbeing are measured at baseline and at weeks 12 and 24. Blood lipids are assessed at baseline and 24 weeks. Participants randomized to POWERS forID receive access to the POWERS forID website and calls from a health coach (weekly during weeks 1-12, biweekly during weeks 13-24). The health coach employs motivational interviewing techniques adapted for individuals with ID to promote behavior change. Participants randomized to the control group receive standard clinical weight-loss care. Differences in weight, waist circumference, blood lipids, percent body fat, and psychosocial self-report will be assessed. Barriers and facilitators of implementation as well as perception of study outcomes will be conducted via qualitative analysis. POWERS forID is a novel information and communication technology platform designed to address health needs for adults with ID. This article describes the development and components of POWERS forID . The overall aim is to assess usability and feasibility of POWERS forID for promoting weight loss for obese adults with ID over the course of a 24-week randomized control trial. Clinicaltrials.gov, NCT03139760 . Registered on XXX.

The co-occurrence of mental disorders in children and adolescents with intellectual disability/intellectual developmental disorder

PubMed Central

Munir, Kerim M.

2016-01-01

Purpose of review The study summarizes supportive epidemiological data regarding the true co-occurrence (comorbidity) and course of mental disorders in children with intellectual disability/intellectual developmental disorders (ID/IDD) across the lifespan. Recent findings Published studies involving representative populations of children and adolescents with ID/IDD have demonstrated a three to four-fold increase in prevalence of co-occurring mental disorders. The effect of age, sex, and severity (mild, moderate, severe, and profound) and socioeconomic status on prevalence is currently not clearly understood. To date there are no prevalence estimates of co-occurring mental disorders in youth identified using the new DSM-5 (and proposed ICD-11) definition of ID/IDD using measures of intellectual functions and deficits in adaptive functioning with various severity levels defined on the basis of adaptive functioning, and not intellectual quotient scores. Summary The true relationship between two forms of morbidity remains complex and causal relationships that may be true for one disorder may not apply to another. The new conceptualization of ID/IDD offers a developmentally better informed psychobiological approach that can help distinguish co-occurrence of mental disorders within the neurodevelopmental section with onset during the developmental period as well as the later onset of other mental disorders. PMID:26779862

The co-occurrence of mental disorders in children and adolescents with intellectual disability/intellectual developmental disorder.

PubMed

Munir, Kerim M

2016-03-01

The study summarizes supportive epidemiological data regarding the true co-occurrence (comorbidity) and course of mental disorders in children with intellectual disability/intellectual developmental disorders (ID/IDD) across the lifespan. Published studies involving representative populations of children and adolescents with ID/IDD have demonstrated a three to four-fold increase in prevalence of co-occurring mental disorders. The effect of age, sex, and severity (mild, moderate, severe, and profound) and socioeconomic status on prevalence is currently not clearly understood. To date there are no prevalence estimates of co-occurring mental disorders in youth identified using the new DSM-5 (and proposed ICD-11) definition of ID/IDD using measures of intellectual functions and deficits in adaptive functioning with various severity levels defined on the basis of adaptive functioning, and not intellectual quotient scores. The true relationship between two forms of morbidity remains complex and causal relationships that may be true for one disorder may not apply to another. The new conceptualization of ID/IDD offers a developmentally better informed psychobiological approach that can help distinguish co-occurrence of mental disorders within the neurodevelopmental section with onset during the developmental period as well as the later onset of other mental disorders.

Muscle function may depend on model selection in forward simulation of normal walking

PubMed Central

Xiao, Ming; Higginson, Jill S.

2008-01-01

The purpose of this study was to quantify how the predicted muscle function would change in a muscle-driven forward simulation of normal walking when changing the number of degrees of freedom in the model. Muscle function was described by individual muscle contributions to the vertical acceleration of the center of mass (COM). We built a two-dimensional (2D) sagittal plane model and a three-dimensional (3D) model in OpenSim and used both models to reproduce the same normal walking data. Perturbation analysis was applied to deduce muscle function in each model. Muscle excitations and contributions to COM support were compared between the 2D and 3D models. We found that the 2D model was able to reproduce similar joint kinematics and kinetics patterns as the 3D model. Individual muscle excitations were different for most of the hip muscles but ankle and knee muscles were able to attain similar excitations. Total induced vertical COM acceleration by muscles and gravity was the same for both models. However, individual muscle contributions to COM support varied, especially for hip muscles. Although there is currently no standard way to validate muscle function predictions, a 3D model seems to be more appropriate for estimating individual hip muscle function. PMID:18804767

The Transcription Factors Islet and Lim3 Combinatorially Regulate Ion Channel Gene Expression

PubMed Central

Wolfram, Verena; Southall, Tony D.; Günay, Cengiz; Prinz, Astrid A.; Brand, Andrea H.

2014-01-01

Expression of appropriate ion channels is essential to allow developing neurons to form functional networks. Our previous studies have identified LIM-homeodomain (HD) transcription factors (TFs), expressed by developing neurons, that are specifically able to regulate ion channel gene expression. In this study, we use the technique of DNA adenine methyltransferase identification (DamID) to identify putative gene targets of four such TFs that are differentially expressed in Drosophila motoneurons. Analysis of targets for Islet (Isl), Lim3, Hb9, and Even-skipped (Eve) identifies both ion channel genes and genes predicted to regulate aspects of dendritic and axonal morphology. Significantly, some ion channel genes are bound by more than one TF, consistent with the possibility of combinatorial regulation. One such gene is Shaker (Sh), which encodes a voltage-dependent fast K+ channel (Kv1.1). DamID reveals that Sh is bound by both Isl and Lim3. We used body wall muscle as a test tissue because in conditions of low Ca2+, the fast K+ current is carried solely by Sh channels (unlike neurons in which a second fast K+ current, Shal, also contributes). Ectopic expression of isl, but not Lim3, is sufficient to reduce both Sh transcript and Sh current level. By contrast, coexpression of both TFs is additive, resulting in a significantly greater reduction in both Sh transcript and current compared with isl expression alone. These observations provide evidence for combinatorial activity of Isl and Lim3 in regulating ion channel gene expression. PMID:24523544

Holographic calculation for large interval Rényi entropy at high temperature

NASA Astrophysics Data System (ADS)

Chen, Bin; Wu, Jie-qiang

2015-11-01

In this paper, we study the holographic Rényi entropy of a large interval on a circle at high temperature for the two-dimensional conformal field theory (CFT) dual to pure AdS3 gravity. In the field theory, the Rényi entropy is encoded in the CFT partition function on n -sheeted torus connected with each other by a large branch cut. As proposed by Chen and Wu [Large interval limit of Rényi entropy at high temperature, arXiv:1412.0763], the effective way to read the entropy in the large interval limit is to insert a complete set of state bases of the twist sector at the branch cut. Then the calculation transforms into an expansion of four-point functions in the twist sector with respect to e-2/π T R n . By using the operator product expansion of the twist operators at the branch points, we read the first few terms of the Rényi entropy, including the leading and next-to-leading contributions in the large central charge limit. Moreover, we show that the leading contribution is actually captured by the twist vacuum module. In this case by the Ward identity the four-point functions can be derived from the correlation function of four twist operators, which is related to double interval entanglement entropy. Holographically, we apply the recipe in [T. Faulkner, The entanglement Rényi entropies of disjoint intervals in AdS/CFT, arXiv:1303.7221] and [T. Barrella et al., Holographic entanglement beyond classical gravity, J. High Energy Phys. 09 (2013) 109] to compute the classical Rényi entropy and its one-loop quantum correction, after imposing a new set of monodromy conditions. The holographic classical result matches exactly with the leading contribution in the field theory up to e-4 π T R and l6, while the holographical one-loop contribution is in exact agreement with next-to-leading results in field theory up to e-6/π T R n and l4 as well.

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.

PubMed

Contini, Mauro; Compagnino, Elisa; Cattadori, Gaia; Magrì, Damiano; Camera, Marina; Apostolo, Anna; Farina, Stefania; Palermo, Pietro; Gertow, Karl; Tremoli, Elena; Fiorentini, Cesare; Agostoni, Piergiuseppe

2016-04-01

The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3 ± 1.3 vs. -0.8 ± 1.9 and -0.6 ± 1 mL/mmHg/min, p < 0.0001 and p < 0.01; Dm -7 ± 5 vs. -3.2 ± 7.4 and -1.3 ± 5 mL/mmHg/min, p < 0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 ± 1.9 vs. -0.8 ± 2.3, p = 0.01). ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

Decreased Respiratory Muscle Function Is Associated with Impaired Trunk Balance among Chronic Stroke Patients: A Cross-sectional Study.

PubMed

Lee, Kyeongbong; Cho, Ji-Eun; Hwang, Dal-Yeon; Lee, WanHee

2018-06-01

The abdominal muscles play a role in trunk balance. Abdominal muscle thickness is asymmetrical in stroke survivors, who also have decreased respiratory muscle function. We compared the thickness of the abdominal muscles between the affected and less affected sides in stroke survivors. In addition, the relationship between respiratory muscle function and trunk balance was evaluated. Chronic stroke patients (18 men, 15 women; mean age, 58.94 ± 12.30 years; Mini-Mental Status Examination score ≥ 24) who could sit without assist were enrolled. Abdominal muscle thickness during rest and contraction was measured with ultrasonography, and the thickening ratio was calculated. Respiratory muscle function assessment included maximum respiratory pressure, peak flow, and air volume. Trunk function was evaluated using the Trunk Impairment Scale, and trunk balance was estimated based on the center of pressure velocity and path length within the limit of stability in sitting posture. Abdominal muscles were significantly thinner on the affected side, and the thickening ratio was lower in the affected side (P < 0.05). In addition, the higher thickening ratio of the affected side showed significant relationship with higher trunk function. Moreover, higher respiratory muscle function was significantly correlated with higher level of trunk function and balance in stroke patients (P < 0.05). Thus, chronic stroke survivors have decreased abdominal muscle thickness on the affected side, and respiratory muscle function has positive correlation with trunk function and balance. We propose that respiratory muscle training should be included as part of trunk balance training in chronic stroke patients.

Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery.

USDA-ARS?s Scientific Manuscript database

Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion (ID) in obesity is thought to be mediated by an inflammation-induced increase in the body’s main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in ID as it prevents the release...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Executive Functions and Adaptive Behaviour in Autism Spectrum Disorders with and without Intellectual Disability

PubMed Central

Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Genitori D'Arrigo, Valentina; Elia, Maurizio

2014-01-01

Executive functions (EF) in autism spectrum disorders (ASD) have been often investigated, although results seem to be rather inconsistent. The first aim of this study was to detect which EF components are common to the ASD continuum (from high- to low-functioning ASD) and identify a possible EF profile for ASD people. Planning, mental flexibility, inhibition of response, generativity, and ecologic EF were investigated. This study was extended not only to high-functioning ASD, but also to ASD with intellectual disability (ID). The second aim was to find EF aspects correlating with adaptive skills in ASD. A total of 61 children participated in the study (27 ASD with and without ID and 34 controls). Results highlight an executive profile characterised by impaired flexibility and deficient planning; these deficits are associated with decreased adaptive ability, particularly socialization, and a deficient shifting in ecologic conditions. These features are present in all ASD subgroups with and without ID; for this reason, they might be assumed as being specific features in ASD. PMID:24829905

[Electroencephalographic effects of chlorphenesin carbamate, a new central muscle relaxant, in rabbits (author's transl)].

PubMed

Watanabe, S; Araki, H; Kawasaki, H; Ueki, S

1977-05-01

Electroencephalographic (EEG) effects of chlorphenesin carbamate were investigated in rabbits with chronic electrode implants, and compared with those of chlormezanone and methocarbamol. Chlorphenesin carbamate (50 mg/kg i.v., 100 mg/kg i.d.) induced a drowsy pattern of spontaneous EEG consisting of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal theta waves. Chlormezanone also elicited similar EEG changes but such were much more potent than chlorphenesin carbamate. Methocarbamol showed no effect on spontaneous EEG. Chlorphenesin carbamate caused sedation in this period and muscle relaxation was more potent than that of chlormezanone. The EEG arousal response to auditory stimulation and to electric stimulation of the posterior hypothalamus, centromedian thalamus and mesencephalic reticular formation was slightly depressed by chlorphenesin carbamate. Chlorphenesin carbamate, as with chlormezanone, markedly depressed the limbic afterdischarges elicited by hippocampal stimulation. These EEG effects of chlorphenesin carbamate were qualitatively similar to but much weaker than those of chlormezanone, whereas the muscle relaxant effect of chlorphenesin carbamate was more potent than that of chlormezanone.

Problem solving ability in children with intellectual disability as measured by the Raven's colored progressive matrices.

PubMed

Goharpey, Nahal; Crewther, David P; Crewther, Sheila G

2013-12-01

This study investigated the developmental trajectory of problem solving ability in children with intellectual disability (ID) of different etiologies (Down Syndrome, Idiopathic ID or low functioning Autism) as measured on the Raven's Colored Progressive Matrices test (RCPM). Children with typical development (TD) and children with ID were matched on total correct performance (i.e., non-verbal mental age) on the RCPM. RCPM total correct performance and the sophistication of error types were found to be associated with receptive vocabulary in all participants, suggesting that verbal ability plays a role in more sophisticated problem solving tasks. Children with ID made similar errors on the RCPM as younger children with TD as well as more positional error types. This result suggests that children with ID who are deficient in their cognitive processing resort to developmentally immature problem solving strategies when unable to determine the correct answer. Overall, the findings support the use of RCPM as a valid means of matching intellectual capacity of children with TD and ID. Copyright © 2013 Elsevier Ltd. All rights reserved.

Grief and its Complications in Individuals with Intellectual Disability

PubMed Central

Brickell, Claire; Munir, Kerim

2011-01-01

Bereavement and loss have significant impact on the lives of individuals with intellectual disability (ID). Although there is a growing impetus to define the symptoms of grief that predict long-term functional impairment, little is known about maladaptive grieving among individuals with ID. We examine the literature concerning the phenomenology of traumatic grief (TG) in the general population, along with what is known about the manifestations of grief in individuals with ID. We then apply modern theories of grief and grief resolution to individuals with ID in order to highlight potential areas of vulnerability in this population and to lay the groundwork for interventions that will facilitate their adaptation to loss. We provide a theoretical framework for the proposition that individuals (including children and adults) with ID are more susceptible to TG, based on an increased risk of secondary loss, barriers to communicating about the loss, and difficulty finding meaning in the loss. We conclude that individuals with ID should be considered as potential candidates for targeted bereavement interventions. Further research is required, however, in order to develop population-appropriate measurement scales for testing these hypotheses. PMID:18306095

Lower Cognitive Function in Older Patients with Lower Muscle Strength and Muscle Mass.

PubMed

van Dam, Romee; Van Ancum, Jeanine M; Verlaan, Sjors; Scheerman, Kira; Meskers, Carel G M; Maier, Andrea B

2018-06-18

Low muscle strength and muscle mass are associated with adverse outcomes in older hospitalized patients. The aim of this study was to assess the association between cognitive functioning and muscle strength and muscle mass in hospitalized older patients. This prospective inception cohort included 378 patients aged 70 years or older. At admission patients were assessed for cognitive functioning by use of the Six-Item Cognitive Impairment Test (6-CIT). Muscle strength and muscle mass were assessed using handheld dynamometry and segmental multifrequency bioelectrical impedance analysis, within 48 h after admission and on day 7, or earlier on the day of discharge. The data of 371 patients (mean age ± standard deviation 80.1 ± 6.4 years, 49.3% female) were available for analyses. The median (interquartile range) 6-CIT score was 4 (0-8) points. At admission, lower cognitive functioning was associated with lower muscle strength, lower skeletal muscle mass (SMM), lower appendicular lean mass, and lower SMM index. Cognitive functioning was not associated with change in muscle strength and muscle mass during hospitalization. This study further strengthens evidence for an association between lower cognitive functioning and lower muscle strength and muscle mass, but without a further decline during hospitalization. © 2018 The Author(s) Published by S. Karger AG, Basel.

Characterization of Strength and Function in Ambulatory Adults With GNE Myopathy

PubMed Central

Argov, Zohar; Bronstein, Faye; Esposito, Alicia; Feinsod-Meiri, Yael; Florence, Julaine M.; Fowler, Eileen; Greenberg, Marcia B.; Malkus, Elizabeth C.; Rebibo, Odelia; Siener, Catherine S.; Caraco, Yoseph; Kolodny, Edwin H.; Lau, Heather A.; Pestronk, Alan; Shieh, Perry; Mayhew, Jill E.

2017-01-01

Abstract Objective: To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM. Methods: Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS). Results: Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning. Conclusions: The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function. PMID:28827485

Evaluation of jaw and neck muscle activities while chewing using EMG-EMG transfer function and EMG-EMG coherence function analyses in healthy subjects.

PubMed

Ishii, Tomohiro; Narita, Noriyuki; Endo, Hiroshi

2016-06-01

This study aims to quantitatively clarify the physiological features in rhythmically coordinated jaw and neck muscle EMG activities while chewing gum using EMG-EMG transfer function and EMG-EMG coherence function analyses in 20 healthy subjects. The chewing side masseter muscle EMG signal was used as the reference signal, while the other jaw (non-chewing side masseter muscle, bilateral anterior temporal muscles, and bilateral anterior digastric muscles) and neck muscle (bilateral sternocleidomastoid muscles) EMG signals were used as the examined signals in EMG-EMG transfer function and EMG-EMG coherence function analyses. Chewing-related jaw and neck muscle activities were aggregated in the first peak of the power spectrum in rhythmic chewing. The gain in the peak frequency represented the power relationships between jaw and neck muscle activities during rhythmic chewing. The phase in the peak frequency represented the temporal relationships between the jaw and neck muscle activities, while the non-chewing side neck muscle presented a broad range of distributions across jaw closing and opening phases. Coherence in the peak frequency represented the synergistic features in bilateral jaw closing muscles and chewing side neck muscle activities. The coherence and phase in non-chewing side neck muscle activities exhibited a significant negative correlation. From above, the bilateral coordination between the jaw and neck muscle activities is estimated while chewing when the non-chewing side neck muscle is synchronously activated with the jaw closing muscles, while the unilateral coordination is estimated when the non-chewing side neck muscle is irregularly activated in the jaw opening phase. Thus, the occurrence of bilateral or unilateral coordinated features in the jaw and neck muscle activities may correspond to the phase characteristics in the non-chewing side neck muscle activities during rhythmical chewing. Considering these novel findings in healthy subjects, EMG-EMG transfer function and EMG-EMG coherence function analyses may also be useful to diagnose the pathologically in-coordinated features in jaw and neck muscle activities in temporomandibular disorders and whiplash-associated disorders during critical chewing performance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

PubMed

Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

2018-03-14

The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

Feasibility and outcomes of the Berg Balance Scale in older adults with intellectual disabilities.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Evenhuis, Heleen M

2013-09-01

High incidence of falls and increased risk of fall-related injuries are seen in individuals with intellectual disabilities (ID). The Berg Balance Scale (BBS) is a reliable instrument for balance assessment in the population of (older) adults with ID. The aims of this study were to assess the balance capacities of a large group of older adults with ID with the BBS and look for gender and age effects, as well as reasons for drop-out on separate items, and to identify feasible subtests for subgroups in which the complete BBS is not feasible. The balance capacities of 1050 older clients with borderline to profound ID of three Dutch care-provider services (mean age 61.6 [sd=8.0]) were assessed with the BBS. The participants who completed all items of the BBS (n=508) were the functionally more able part of the study sample. Results showed that even this functionally more able part had poor balance capacities, with a mean BBS score of 47.2, 95% CI [46.3, 48.0], similar to adults in the general population aged around 20 years older. Balance capacities decreased with increasing age and females had poorer balance capacities than males. Difficulties understanding the task and physical limitations were most often the reasons for drop-out. Feasible subtests were identified for the subgroups with very low cognitive levels and wheelchair users. Low balance capacities of older adults with ID show the need for regular screening and the urge for fall prevention programs for individuals with ID. Copyright © 2013 Elsevier Ltd. All rights reserved.

Drug burden index to define the burden of medicines in older adults with intellectual disabilities: An observational cross-sectional study.

PubMed

O'Connell, Juliette; Burke, Éilish; Mulryan, Niamh; O'Dwyer, Claire; Donegan, Clare; McCallion, Philip; McCarron, Mary; Henman, Martin C; O'Dwyer, Máire

2018-03-01

The drug burden index (DBI) is a dose-related measure of anticholinergic and sedative drug exposure. This cross-sectional study described DBI in older adults with intellectual disabilities (ID) and the most frequently reported therapeutic classes contributing to DBI and examined associations between higher DBI scores and potential adverse effects as well as physical function. This study analysed data from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a representative study on the ageing of people with ID in Ireland. Self- and objectively-reported data were collected on medication use and physical health, including health conditions. The Barthel index was the physical function measure. The study examined 677 individuals with ID, of whom 644 (95.1%) reported taking medication and 78.6% (n = 532) were exposed to medication with anticholinergic and/or sedative activity. 54.2% (n = 367) were exposed to high DBI score (≥1). Adjusted multivariate regression analysis revealed no significant association between DBI score and daytime dozing, constipation or falls. After adjusting for confounders (sex, age, level of ID, comorbidities, behaviours that challenge, history of falls), DBI was associated with significantly higher dependence in the Barthel index (P = 0.002). This is the first time DBI has been described in older adults with ID. Scores were much higher than those observed in the general population and higher scores were associated with higher dependence in Barthel index activities of daily living. © 2017 The British Pharmacological Society.

Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites.

PubMed

Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J

2013-04-01

Intrinsically disordered (ID) proteins function in the absence of a unique stable structure and appear to challenge the classic structure-function paradigm. The extent to which ID proteins take advantage of subtle conformational biases to perform functions, and whether signals for such mechanism can be identified in proteome-wide studies is not well understood. Of particular interest is the polyproline II (PII) conformation, suggested to be highly populated in unfolded proteins. We experimentally determine a complete calorimetric propensity scale for the PII conformation. Projection of the scale into representative eukaryotic proteomes reveals significant PII bias in regions coding for ID proteins. Importantly, enrichment of PII in ID proteins, or protein segments, is also captured by other PII scales, indicating that this enrichment is robustly encoded and universally detectable regardless of the method of PII propensity determination. Gene ontology (GO) terms obtained using our PII scale and other scales demonstrate a consensus for molecular functions performed by high PII proteins across the proteome. Perhaps the most striking result of the GO analysis is conserved enrichment (P < 10(-8) ) of phosphorylation sites in high PII regions found by all PII scales. Subsequent conformational analysis reveals a phosphorylation-dependent modulation of PII, suggestive of a conserved "tunability" within these regions. In summary, the application of an experimentally determined polyproline II (PII) propensity scale to proteome-wide sequence analysis and gene ontology reveals an enrichment of PII bias near disordered phosphorylation sites that is conserved throughout eukaryotes. Copyright © 2013 The Protein Society.

Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.

The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

PubMed

Du, Bing-Li; Li, Jiang-Ning; Guo, Hong-Ming; Li, Song; Liu, Biao

2017-09-01

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

Infectious Disease Stigmas: Maladaptive in Modern Society

PubMed Central

Smith, Rachel A.; Hughes, David

2014-01-01

At multiple times in human history people have asked if there are good stigmas. Is there some useful function stigmas serve in the context of our evolutionary history; is stigma adaptive? This essay discusses stigmas as a group-selection strategy and the human context in which stigmas likely appeared. The next section explores how human patterns have changed in modern society and the consequences for infectious disease (ID) stigmas in the modern age. The concluding section suggests that while social-living species may be particularly apt to create and communicate ID stigmas and enact ID-related stigmatization, such stigma-related processes no longer function to protect human communities. Stigmas do not increase the ability of modern societies to survive infectious diseases, but in fact may be important drivers of problematic disease dynamics and act as catalysts for failures in protecting public health. PMID:25477728

Physical Fitness Profile in Adults with Intellectual Disabilities: Differences between Levels of Sport Practice

ERIC Educational Resources Information Center

Cuesta-Vargas, Antonio Ignacio; Paz-Lourido, Berta; Rodriguez, Alejandro

2011-01-01

Neuromuscular and aerobic capacity can be reduced in people with intellectual disabilities (ID). Previous studies suggest these individuals might be particularly susceptible to losing basic functions because of poor physical fitness. The aim of this study is to describe the physical fitness profile of adult athletes with ID and identify whether…

Schizophrenia-Spectrum Psychoses in People With and Without Intellectual Disability

ERIC Educational Resources Information Center

Bouras, N.; Martin, G.; Leese, M.; Vanstraelen, M.; Holt, G.; Thomas, C.; Hindler, C.; Boardman, J.

2004-01-01

Although there is an increased risk of schizophrenia-spectrum psychoses (SSP) in people with intellectual disability (ID), there is a paucity of research evidence into clinical presentation of the disorder in comparison with research into SSP in people without ID. Aims The aims of the study were to compare clinical, functional, and social factors…

The Diagnosis of Depression in People with Severe Limitations in Intellectual Functioning

ERIC Educational Resources Information Center

Scott, Haleigh; Havercamp, Susan M.

2015-01-01

People with intellectual disability (ID) were once considered immune to developing psychopathology, including affective disorders such as depression. Now research has shown that people with ID do suffer from depression, and the focus is on understanding how to best diagnose and provide treatment. Research has come a long way in adapting the…

Frontal brain electrical activity (EEG) and heart rate in response to affective infant-directed (ID) speech in 9-month-old infants.

PubMed

Santesso, Diane L; Schmidt, Louis A; Trainor, Laurel J

2007-10-01

Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective content (i.e., love/comfort, surprise, fear) in a group of typically developing 9-month-old infants. Regional EEG and heart rate were collected continuously during stimulus presentation. We found the pattern of overall frontal EEG power was linearly related to affective intensity of the ID speech, such that EEG power was greatest in response to fear, than surprise than love/comfort; this linear pattern was specific to the frontal region. We also noted that heart rate decelerated to ID speech independent of affective content. As well, infants who were reported by their mothers as temperamentally distressed tended to exhibit greater relative right frontal EEG activity during baseline and in response to affective ID speech, consistent with previous work with visual stimuli and extending it to the auditory modality. Findings are discussed in terms of how increases in frontal EEG power in response to different affective intensity may reflect the cognitive aspects of emotional processing across sensory domains in infancy.

Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

PubMed

Segura-Ortí, E; Gordon, P L; Doyle, J W; Johansen, K L

2018-06-01

The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.

Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

NASA Astrophysics Data System (ADS)

Gao, Yingxin; Zhang, Chi

2015-03-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

Gene expression profiling in patients with polymyalgia rheumatica before and after symptom-abolishing glucocorticoid treatment.

PubMed

Kreiner, Frederik Flindt; Borup, Rehannah; Nielsen, Finn Cilius; Schjerling, Peter; Galbo, Henrik

2017-08-07

The pathophysiology, including the impact of gene expression, of polymyalgia rheumatica (PMR) remains elusive. We profiled the gene expression in muscle tissue in PMR patients before and after glucocorticoid treatment. Gene expression was measured using Affymetrix Human Genome U133 Plus 2.0 arrays in muscle biopsies from 8 glucocorticoid-naive patients with PMR and 10 controls before and after prednisolone-treatment for 14 days. For 14 genes, quantitative real-time PCR (qRT-PCR, n = 9 in both groups) was used to validate the microarray findings and to further investigate the expression of genes of particular interest. Prednisolone normalized erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in PMR patients. A total of 165 putatively clinically relevant, differentially expressed genes were identified (cut-off: fold difference > ±1.2, difference of mean > 30, and p < 0.05); of these, 78 genes differed between patients and controls before treatment, 131 genes responded to treatment in a given direction only in patients, and 44 fulfilled both these criteria. In 43 of the 44 genes, treatment counteracted the initial difference. Functional clustering identified themes of biological function, including regulation of protein biosynthesis, and regulation of transcription and of extracellular matrix processes. Overall, qRT-PCR confirmed the microarray findings: Microarray-detected group differences were confirmed for 9 genes in 17 of 18 comparisons (same magnitude and direction of change); lack of group differences in microarray testing was confirmed for 5 genes in 8 of 10 comparisons. Before treatment, using qRT-PCR, expression of interleukin 6 (IL-6) was found to be 4-fold higher in patients (p < 0.05). This study identifies genes in muscle, the expression of which may impact the pathophysiology of PMR. Moreover, the study adds further evidence of the importance of IL-6 in the disease. Follow-up studies are needed to establish the exact pathophysiological relevance of the identified genes. The study was retrospectively listed on the ISRCTN registry with study ID ISRCTN69503018 and date of registration the 26th of July 2017.

Absolute Reliability and Concurrent Validity of Hand Held Dynamometry and Isokinetic Dynamometry in the Hip, Knee and Ankle Joint: Systematic Review and Meta-analysis

PubMed Central

Chamorro, Claudio; Armijo-Olivo, Susan; De la Fuente, Carlos; Fuentes, Javiera; Javier Chirosa, Luis

2017-01-01

Abstract The purpose of the study is to establish absolute reliability and concurrent validity between hand-held dynamometers (HHDs) and isokinetic dynamometers (IDs) in lower extremity peak torque assessment. Medline, Embase, CINAHL databases were searched for studies related to psychometric properties in muscle dynamometry. Studies considering standard error of measurement SEM (%) or limit of agreement LOA (%) expressed as percentage of the mean, were considered to establish absolute reliability while studies using intra-class correlation coefficient (ICC) were considered to establish concurrent validity between dynamometers. In total, 17 studies were included in the meta-analysis. The COSMIN checklist classified them between fair and poor. Using HHDs, knee extension LOA (%) was 33.59%, 95% confidence interval (CI) 23.91 to 43.26 and ankle plantar flexion LOA (%) was 48.87%, CI 35.19 to 62.56. Using IDs, hip adduction and extension; knee flexion and extension; and ankle dorsiflexion showed LOA (%) under 15%. Lower hip, knee, and ankle LOA (%) were obtained using an ID compared to HHD. ICC between devices ranged between 0.62, CI (0.37 to 0.87) for ankle dorsiflexion to 0.94, IC (0.91to 0.98) for hip adduction. Very high correlation were found for hip adductors and hip flexors and moderate correlations for knee flexors/extensors and ankle plantar/dorsiflexors. PMID:29071305

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

PubMed

Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

2010-01-01

Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo

PubMed Central

Juhas, Mark; Engelmayr, George C.; Fontanella, Andrew N.; Palmer, Gregory M.; Bursac, Nenad

2014-01-01

Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration. PMID:24706792

FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end

PubMed Central

Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi

2016-01-01

The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. PMID:27694619

Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells

PubMed Central

Sharma, Bal Krishan; Kolhe, Ravindra; Black, Stephen M.; Keller, Jonathan R.; Mivechi, Nahid F.; Satyanarayana, Ande

2016-01-01

Reprograming of metabolism is one of the central hallmarks of cancer. The majority of cancer cells depend on high rates of glycolysis and glutaminolysis for their growth and survival. A number of oncogenes and tumor suppressors have been connected to the regulation of altered glucose and glutamine metabolism in cancer cells. For example, the oncogene c-Myc plays vital roles in cancer cell metabolic adaptation by directly regulating various genes that participate in aerobic glycolysis and glutaminolysis. Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation, differentiation, and cell fate determination. Overexpression of Id1 causes intestinal adenomas and thymic lymphomas in mice, suggesting that Id1 could function as an oncogene. Despite it being an oncogene, whether Id1 plays any prominent role in cancer cell metabolic reprograming is unknown. Here, we demonstrate that Id1 is strongly expressed in human and mouse liver tumors and in hepatocellular carcinoma (HCC) cell lines, whereas its expression is very low or undetectable in normal liver tissues. In HCC cells, Id1 expression is regulated by the MAPK/ERK pathway at the transcriptional level. Knockdown of Id1 suppressed aerobic glycolysis and glutaminolysis, suggesting that Id1 promotes a metabolic shift toward aerobic glycolysis. At the molecular level, Id1 mediates its metabolic effects by regulating the expression levels of c-Myc. Knockdown of Id1 resulted in down-regulation (∼75%) of c-Myc, whereas overexpression of Id1 strongly induced (3-fold) c-Myc levels. Interestingly, knockdown of c-Myc resulted in down-regulation (∼60%) of Id1, suggesting a positive feedback-loop regulatory mechanism between Id1 and c-Myc. Under anaerobic conditions, both Id1 and c-Myc are down-regulated (50–70%), and overexpression of oxygen-insensitive hypoxia-inducible factor 1α (Hif1α) or its downstream target Mxi1 resulted in a significant reduction of c-Myc and Id1 (∼70%), suggesting that Hif1α suppresses Id1 and c-Myc under anaerobic conditions via Mxi1. Together, our findings indicate a prominent novel role for Id1 in liver cancer cell metabolic adaptation.—Sharma, B. K., Kolhe, R., Black, S. M., Keller, J. R., Mivechi, N. F., Satyanarayana, A. Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells. PMID:26330493

Predicting Functional Capacity From Measures of Muscle Mass in Postmenopausal Women.

PubMed

Orsatti, Fábio Lera; Nunes, Paulo Ricardo Prado; Souza, Aletéia de Paula; Martins, Fernanda Maria; de Oliveira, Anselmo Alves; Nomelini, Rosekeila Simões; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-06-01

Menopause increases body fat and decreases muscle mass and strength, which contribute to sarcopenia. The amount of appendicular muscle mass has been frequently used to diagnose sarcopenia. Different measures of appendicular muscle mass have been proposed. However, no studies have compared the most salient measure (appendicular muscle mass corrected by body fat) of the appendicular muscle mass to physical function in postmenopausal women. To examine the association of 3 different measurements of appendicular muscle mass (absolute, corrected by stature, and corrected by body fat) with physical function in postmenopausal women. Cross-sectional descriptive study. Outpatient geriatric and gynecological clinic. Forty-eight postmenopausal women with a mean age (standard deviation [SD]) of 62.1 ± 8.2 years, with mean (SD) length of menopause of 15.7 ± 9.8 years and mean (SD) body fat of 43.6% ± 9.8%. Not applicable. Appendicular muscle mass measure was measured with dual-energy x-ray absorptiometry. Physical function was measured by a functional capacity questionnaire, a short physical performance battery, and a 6 minute-walk test. Muscle quality (leg extensor strength to lower-body mineral-free lean mass ratio) and sum of z scores (sum of each physical function tests z score) were performed to provide a global index of physical function. The regression analysis showed that appendicular muscle mass corrected by body fat was the strongest predictor of physical function. Each increase in the standard deviation of appendicular muscle mass corrected by body fat was associated with a mean sum of z score increase of 59% (standard deviation), whereas each increase in absolute appendicular muscle mass and appendicular muscle mass corrected by stature were associated with a mean sum of z scores decrease of 23% and 36%, respectively. Muscle quality was associated with appendicular muscle mass corrected by body fat. These findings indicate that appendicular muscle mass corrected by body fat is a better predictor of physical function than the other measures of appendicular muscle mass in postmenopausal women. I. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

PubMed Central

Cho, Yoshitake; Hazen, Bethany C.; Gandra, Paulo G.; Ward, Samuel R.; Schenk, Simon; Russell, Aaron P.; Kralli, Anastasia

2016-01-01

Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1- and ESRR-induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno-associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4-wk-old mice. Compared to control vector, AAV1-Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40–80%). Moreover, AAV1-Perm1–transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31%, respectively), without prominent changes in fiber-type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.—Cho, Y., Hazen, B. C., Gandra, P. G., Ward, S. R., Schenk, S., Russell, A. P., Kralli, A. Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle. PMID:26481306

Preparation and evaluation of the tumor-specific antigen-derived synthetic mucin 1 peptide: A potential candidate for the targeting of breast carcinoma.

PubMed

Okarvi, Subhani M; Al Jammaz, Ibrahim

2016-07-01

The goal of this study was to prepare a synthetic peptide derived from breast tumor associated antigen and to evaluate its potential as a breast cancer imaging agent. A mucin 1 derived peptide was synthesized by solid-phase peptide synthesis and examined for its radiochemical and metabolic stability. The tumor cell binding affinity of (99m)Tc-MUC1 peptide was investigated on MUC1-positive T47D and MCF7 breast cancer cell lines. In vivo biodistribution was studied in normal Balb/c mice and in vivo tumor targeting and imaging in MCF7 and T47D tumor-bearing nude mice. The synthesized MUC1-derived peptide displayed high radiochemical and metabolic stability. In vitro tumor cell-binding on T47D and MCF7 cell lines demonstrated high affinity of (99m)Tc-MUC1 peptide towards human breast cancer cells (binding affinities in nanomolar range). Pharmacokinetic studies performed on Balb/c mice are characterized by an efficient clearance from the blood and excretion predominantly through the urinary system. In vivo tumor uptake in nude mice with MCF7 tumor xenografts was 2.77±0.63% ID/g as early as 1h p.i. whereas in nude mice with T47D human ductal breast epithelial cancer cells, the accumulation in the tumor was found to be 2.65±0.54% ID/g at 1h p.i. Also tumor lesion was detectable in γ-camera imaging. The tumor uptake values were always higher than the blood and muscle uptake, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios. A low to moderate (<5% ID/g) accumulation and retention of (99m)Tc-MUC1 was found in the major organs (i.e., lungs, stomach, liver, intestines, kidneys, etc.) in both normal and tumor-bearing mice. This study suggests that (99m)Tc-MUC1 tumor-antigen peptide may be a potential candidate for the targeted imaging of MUC1-positive human tumors and warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology and inflammatory reaction.

PubMed

Arnardottir, Snjolaug; Alexanderson, Helene; Lundberg, Ingrid E; Borg, Kristian

2003-01-01

To evaluate the safety and effect of a home training program on muscle function in 7 patients with sporadic inclusion body myositis. The patients performed exercise 5 days a week over a 12-week period. Safety was assessed by clinical examination, repeated muscle biopsies and serum levels of creatine kinase. Muscle strength was evaluated by clinical examination, dynamic dynamometer and by a functional index in myositis. Strength was not significantly improved after the exercise, however none of the patients deteriorated concerning muscle function. The histopathology was unchanged and there were no signs of increased muscle inflammation or of expression of cytokines and adhesion molecules in the muscle biopsies. Creatine kinase levels were unchanged. A significant decrease was found in the areas that were positively stained for EN-4 (a marker for endothelial cells) in the muscle biopsies after training. The home exercise program was considered as not harmful to the muscles regarding muscle inflammation and function. Exercise may prevent loss of muscle strength due to disease and/or inactivity.

Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity

PubMed Central

Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.

2016-01-01

Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory. PMID:27669335

Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

PubMed Central

Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-01-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social–emotional functioning. White and Black youth (n = 64; ages 6–17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation. PMID:26439481

Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

PubMed

Ratto, Allison B; Anthony, Bruno J; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-03-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.

Preliminary findings of serum creatinine and estimated glomerular filtration rate (eGFR) in adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile - serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents with ID who participated in annual health examinations as they enrolled into special education schools in Taiwan. We used serum samples to determine participants' creatinine profiles, and the Cockcroft-Gault formula to calculate the data of eGFR to present the chronic kidney disease. The results found 22% of the participants have abnormal serum creatinine value (creatinine>1.0mg/dl) and 59.6%, 36.4% and 4.0% at chronic kidney disease (CKD) stage 1, 2 and 3 cases accordingly based on the Cockcroft-Gault formula. No CKD stage 4 and 5 cases in this study. That is, there were 4% CKD cases (eGFR <60 mL/min/1.73 m(2); CKD stage 3, 4 and 5) in adolescents with ID in this study. The results also indicated that gender and BMI could significantly predict abnormal creatinine condition in multivariate logistic regression analysis. Those boys with ID were more likely to have abnormal creatinine value than girls with ID (OR=10.13, 95% CI=5.96-17.23). In term of BMI, those underweight adolescents with ID were less likely to have high creatinine value compared to normal weight group (OR=0.45, 95% CI=0.28-0.72). In summary, this study provides the preliminary information of creatinine and estimated GFR in people with ID; we suggest the public health policy should initiate appropriate management strategies to monitor kidney function and to improve treatment outcomes of chronic kidney disease for this vulnerable population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Caregivers' reported functional limitations in activities of daily living among middle-aged adults with intellectual disabilities.

PubMed

Lin, Lan-Ping; Hsia, Yi-Chen; Hsu, Shang-Wei; Loh, Ching-Hui; Wu, Chia-Ling; Lin, Jin-Ding

2013-12-01

This study was conducted to describe the functioning of Activities of Daily Living (ADL) and to examine socio-economic effects on ADL functioning among adults with intellectual disabilities (ID) aged 45 years and older (N=480) in Taiwan. The Barthel Index (BI) was used to determine a baseline level of ADL functioning in the study participants. There are five categories of functional impairment using the following cut-off values in Taiwan: total dependence (BI score 0-20), severe (BI score 21-60), moderate (BI score 61-90), mild (BI score 91-99), and total independence (BI score 100) (Taiwan Department of Health, 2012). The results revealed that 2.3% of adults with ID were in total dependence, 11.9% were in severe dependence, 27.9% were in moderate dependence, 8.1% had a mild dependence, and 49.8% were totally independent. In the multiple linear regression model of the ADL score, we determined that educational level, comorbid Down's syndrome, and disability level are the variables able to significantly predict ADL score (R(2)=0.190) after controlling for the factors of age, marital status, and other comorbidity conditions. Those ID adults with a lower education level (primary vs. literate, β=4.780, p=0.031; intermediate vs. literate, β=6.642, p=0.030), with comorbid Down's syndrome (β=-7.135, p=0.063), and with a more severe disability condition (severe vs. mild, β=-7.650, p=0.007; profound vs. mild, β=-19.169, p<0.001) had significantly lower ADL scores. The present study highlights the need to support mobility in older adults with ID as much as possible to optimize independence in this group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Insomnia Disorder and Brain's Default-Mode Network.

PubMed

Marques, Daniel Ruivo; Gomes, Ana Allen; Caetano, Gina; Castelo-Branco, Miguel

2018-06-09

Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI). The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia. A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

Defense system shortcuts and limits of scope.

PubMed

Rewald, E; Francischetti, M M

2000-10-01

Defense, as a key factor of life, shares the biological tendencies of simplicity and energy saving. We propose that, like the mind, defense tends to rely on shortcuts via immune memes. Also, response repetition may induce the formation of virtual 'modules' [toolkits] to simplify and perfect performance. Engaged modules may expand by proliferating or by capturing immune components from the 'dormant' and even perhaps from active ones. With regard to recovery and/or survival, complexity of the integrated defense system (IDS) (1) requires to be inside of what we call the 'functional window'. In contrast to the physiological and common disease repair, energy is squandered when IDS perceives real danger. Our concern is the uncertain transition to conditions that do not fit into the IDS routine and, even worse, that are outside the functional window where the system is lacking. Copyright 2000 Harcourt Publishers Ltd.

Social Skills Training for Adolescents With Intellectual Disabilities: A School-Based Evaluation.

PubMed

O'Handley, Roderick D; Ford, W Blake; Radley, Keith C; Helbig, Kate A; Wimberly, Joy K

2016-07-01

Individuals with intellectual disabilities (ID) often demonstrate impairments in social functioning, with deficits becoming more apparent during adolescence. This study evaluated the effects of the Superheroes Social Skills program, a program that combines behavioral skills training and video modeling to teach target social skills, on accurate demonstration of three target social skills in adolescents with ID. Skills taught in the present study include Expressing Wants and Needs, Conversation, and Turn Taking. Four adolescents with ID participated in a 3-week social skills intervention, with the intervention occurring twice per week. A multiple baseline across skills design was used to determine the effect of the intervention on social skill accuracy in both a training and generalization setting. All participants demonstrated substantial improvements in skill accuracy in both settings, with teacher ratings of social functioning further suggesting generalization of social skills to nontraining settings. © The Author(s) 2016.

[14C]-beta-phenethylamine, its distribution after administration by various routes to cats, and the effects of monoamine oxidase inhibitors.

PubMed Central

Garcha, G.; Imrie, P. R.; Marley, E.; Thomas, D. V.

1985-01-01

[14C]-beta-phenethylamine [( 14C]-PEA) was instilled intragastrically, intraduodenally (i.d.) or infused into the portal vein or femoral artery of cats, anaesthetized with chloralose, to investigate its distribution in the body. [14C]-PEA and phenylacetic acid (PAA) accounted for approximately 85% of radioactivity recovered in blood from control cats or those pretreated with deprenyl or mebanazine. Progressively greater portal venous (PV), cranial mesenteric arterial (CMA) and PV-CMA concentrations of PEA and PAA were observed with increase in amount of PEA instilled intraduodenally (i.d.); PAA predominated over PEA, more so in CMA than PV blood. Radioactivity was not recovered from blood following intragastric instillation of PEA. When histamine 1.7 mumol kg-1, i.d., was combined with PEA 1.7 mumol kg-1, i.d., or tyramine 8.5 mumol kg-1, i.d., was combined with PEA 8.5 mumol kg-1, i.d., PV-CMA values for PEA were significantly augmented. Arterial concentrations of PEA were increased 3.5 to 5 fold compared to controls by pretreatment with mebanazine or deprenyl plus clorgyline; arterial concentrations of PAA were reduced. PEA blood concentrations were not significantly altered by clorgyline or deprenyl pretreatment. Infusion of PEA 680, 1020 or 1360 nmol kg-1 min-1 for 20 min into the portal vein raised blood pressure 60 to 100 mmHg (at a PEA concentration of ca, 2 nmol ml-1) but lacked effect on the nictitating membrane despite peak arterial PEA concentrations of 20 nmol ml-1; in cats pretreated with mebanazine or clorgyline plus deprenyl, half-maximum contraction of the nictitating membrane occurred with arterial PEA concentrations of 4.8 to 9 nmol ml-1. In cats pretreated with mebanazine or deprenyl plus clorgyline, half maximum contraction of the nictitating membrane was elicited also by intraduodenal PEA 8.5 mumol kg-1 at arterial PEA concentrations of ca. 2 nmol ml-1, despite lack of effect of PEA 17 mumol kg-1, i.d., in control cats with a peak arterial PEA concentration of 1.8 nmol ml-1. [14C]-PEA and PAA were recovered from liver, kidney, distal small intestine, lung, arterial vessel walls, skeletal muscle, brain, foetus and amniotic liquor, after PEA instilled i.d., overall concentration of PEA exceeding that of PAA except in the kidney. The combined amount of PEA and PAA in kidney was 7 to 20 fold that in other tissues. PEA content of tissues was significantly elevated and that of PAA diminished by pretreatment with deprenyl plus clorgyline, and to a lesser extent after mebanazine. PMID:4075021

A mini-overview of single muscle fibre mechanics: the effects of age, inactivity and exercise in animals and humans.

PubMed

Jee, Hyunseok; Kim, Jong-Hee

2017-09-05

Many basic movements of living organisms are dependent on muscle function. Muscle function allows for the coordination and harmonious integrity of movement that is necessary for various biological processes. Gross and fine motor skills are both regulated at the micro-level (single muscle fibre level), controlled by neuronal regulation, and it is therefore important to understand muscle function at both micro- and macro-levels to understand the overall movement of living organisms. Single muscle mechanics and the cellular environment of muscles fundamentally allow for the harmonious movement of our bodies. Indeed, a clear understanding of the functionality of muscle at the micro-level is indispensable for explaining muscular function at the macro-(whole gross muscle) level. By investigating single muscle fibre mechanics, we can also learn how other factors such Ca2+ kinetics, enzyme activity and contractile proteins can contribute to muscle mechanics at the micro- and macro-levels. Further, we can also describe how aging affects the capacity of skeletal muscle cells, as well as how exercise can prevent aging-based sarcopenia and frailty. The purpose of this review is to introduce and summarise the current knowledge of single muscle fibre mechanics in light of aging and inactivity. We then describe how exercise mitigates negative muscle adaptations that occur under those circumstances. In addition, single muscle fibre mechanics in both animal and human models are discussed.

Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma.

PubMed

Cook, Peter J; Thomas, Rozario; Kingsley, Philip J; Shimizu, Fumiko; Montrose, David C; Marnett, Lawrence J; Tabar, Viviane S; Dannenberg, Andrew J; Benezra, Robert

2016-10-01

In glioblastoma (GBM), Id1 serves as a functional marker for self-renewing cancer stem-like cells. We investigated the mechanism by which cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and increases GBM self-renewal and radiation resistance. Mouse and human GBM cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to test for Id1 induction. To elucidate the signal transduction pathway governing the increase in Id1, a combination of short interfering RNA knockdown and small molecule inhibitors and activators of PGE2 signaling were used. Western blotting, quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were employed. Sphere formation and radiation resistance were measured in cultured primary cells. Immunohistochemical analyses were carried out to evaluate the Cox-2-Id1 axis in experimental GBM. In GBM cells, dmPGE2 stimulates the EP4 receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to upregulation of the early growth response1 (Egr1) transcription factor and enhanced Id1 expression. Activation of this pathway increases self-renewal capacity and resistance to radiation-induced DNA damage, which are dependent on Id1. In GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated induction of Id1 is required for optimal tumor cell self-renewal and radiation resistance. Collectively, these findings identify Id1 as a key mediator of PGE2-dependent modulation of radiation response and lend insight into the mechanisms underlying radiation resistance in GBM patients. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A 3D Faraday Shield for Interdigitated Dielectrometry Sensors and Its Effect on Capacitance

PubMed Central

Risos, Alex; Long, Nicholas; Hunze, Arvid; Gouws, Gideon

2016-01-01

Interdigitated dielectrometry sensors (IDS) are capacitive sensors investigated to precisely measure the relative permittivity (ϵr) of insulating liquids. Such liquids used in the power industry exhibit a change in ϵr as they degrade. The IDS ability to measure ϵr in-situ can potentially reduce maintenance, increase grid stability and improve safety. Noise from external electric field sources is a prominent issue with IDS. This paper investigates the novelty of applying a Faraday cage onto an IDS as a 3D shield to reduce this noise. This alters the spatially distributed electric field of an IDS affecting its sensing properties. Therefore, dependency of the sensor’s signal with the distance to a shield above the IDS electrodes has been investigated experimentally and theoretically via a Green’s function calculation and FEM. A criteria of the shield’s distance s = s0 has been defined as the distance which gives a capacitance for the IDS equal to 1 − e−2=86.5% of its unshielded value. Theoretical calculations using a simplified geometry gave a constant value for s0/λ = 1.65, where λ is the IDS wavelength. In the experiment, values for s0 were found to be lower than predicted as from theory and the ratio s0/λ variable. This was analyzed in detail and it was found to be resulting from the specific spatial structure of the IDS. A subsequent measurement of a common insulating liquid with a nearby noise source demonstrates a considerable reduction in the standard deviation of the relative permittivity from σunshielded=±9.5% to σshielded=±0.6%. The presented findings enhance our understanding of IDS in respect to the influence of a Faraday shield on the capacitance, parasitic capacitances of the IDS and external noise impact on the measurement of ϵr. PMID:28042868

A 3D Faraday Shield for Interdigitated Dielectrometry Sensors and Its Effect on Capacitance.

PubMed

Risos, Alex; Long, Nicholas; Hunze, Arvid; Gouws, Gideon

2016-12-31

Interdigitated dielectrometry sensors (IDS) are capacitive sensors investigated to precisely measure the relative permittivity ( ϵ r ) of insulating liquids. Such liquids used in the power industry exhibit a change in ϵ r as they degrade. The IDS ability to measure ϵ r in-situ can potentially reduce maintenance, increase grid stability and improve safety. Noise from external electric field sources is a prominent issue with IDS. This paper investigates the novelty of applying a Faraday cage onto an IDS as a 3D shield to reduce this noise. This alters the spatially distributed electric field of an IDS affecting its sensing properties. Therefore, dependency of the sensor's signal with the distance to a shield above the IDS electrodes has been investigated experimentally and theoretically via a Green's function calculation and FEM. A criteria of the shield's distance s = s 0 has been defined as the distance which gives a capacitance for the IDS equal to 1 - e - 2 = 86.5 % of its unshielded value. Theoretical calculations using a simplified geometry gave a constant value for s 0 / λ = 1.65, where λ is the IDS wavelength. In the experiment, values for s 0 were found to be lower than predicted as from theory and the ratio s 0 / λ variable. This was analyzed in detail and it was found to be resulting from the specific spatial structure of the IDS. A subsequent measurement of a common insulating liquid with a nearby noise source demonstrates a considerable reduction in the standard deviation of the relative permittivity from σ unshielded = ± 9.5% to σ shielded = ± 0.6%. The presented findings enhance our understanding of IDS in respect to the influence of a Faraday shield on the capacitance, parasitic capacitances of the IDS and external noise impact on the measurement of ϵ r .

Alterations in CDH15 and KIRREL3 in Patients with Mild to Severe Intellectual Disability

PubMed Central

Bhalla, Kavita; Luo, Yue; Buchan, Tim; Beachem, Michael A.; Guzauskas, Gregory F.; Ladd, Sydney; Bratcher, Shelly J.; Schroer, Richard J.; Balsamo, Janne; DuPont, Barbara R.; Lilien, Jack; Srivastava, Anand K.

2008-01-01

Cell-adhesion molecules play critical roles in brain development, as well as maintaining synaptic structure, function, and plasticity. Here we have found the disruption of two genes encoding putative cell-adhesion molecules, CDH15 (cadherin superfamily) and KIRREL3 (immunoglobulin superfamily), by a chromosomal translocation t(11;16) in a female patient with intellectual disability (ID). We screened coding regions of these two genes in a cohort of patients with ID and controls and identified four nonsynonymous CDH15 variants and three nonsynonymous KIRREL3 variants that appear rare and unique to ID. These variations altered highly conserved residues and were absent in more than 600 unrelated patients with ID and 800 control individuals. Furthermore, in vivo expression studies showed that three of the CDH15 variations adversely altered its ability to mediate cell-cell adhesion. We also show that in neuronal cells, human KIRREL3 colocalizes and interacts with the synaptic scaffolding protein, CASK, recently implicated in X-linked brain malformation and ID. Taken together, our data suggest that alterations in CDH15 and KIRREL3, either alone or in combination with other factors, could play a role in phenotypic expression of ID in some patients. PMID:19012874

Mutations in two large pedigrees highlight the role of ZNF711 in X-linked intellectual disability.

PubMed

van der Werf, Ilse M; Van Dijck, Anke; Reyniers, Edwin; Helsmoortel, Céline; Kumar, Ajay Anand; Kalscheuer, Vera M; de Brouwer, Arjan Pm; Kleefstra, Tjitske; van Bokhoven, Hans; Mortier, Geert; Janssens, Sandra; Vandeweyer, Geert; Kooy, R Frank

2017-03-20

Intellectual disability (ID) affects approximately 1-2% of the general population and is characterized by impaired cognitive abilities. ID is both clinically as well as genetically heterogeneous, up to 2000 genes are estimated to be involved in the emergence of the disease with various clinical presentations. For many genes, only a few patients have been reported and causality of some genes has been questioned upon the discovery of apparent loss-of-function mutations in healthy controls. Description of additional patients strengthens the evidence for the involvement of a gene in the disease and can clarify the clinical phenotype associated with mutations in a particular gene. Here, we present two large four-generation families with a total of 11 males affected with ID caused by mutations in ZNF711, thereby expanding the total number of families with ID and a ZNF711 mutation to four. Patients with mutations in ZNF711 all present with mild to moderate ID and poor speech accompanied by additional features in some patients, including autistic features and mild facial dysmorphisms, suggesting that ZNF711 mutations cause non-syndromic ID. Copyright © 2016 Elsevier B.V. All rights reserved.

Muscle Strength and Changes in Physical Function in Women With Systemic Lupus Erythematosus.

PubMed

Andrews, James S; Trupin, Laura; Schmajuk, Gabriela; Barton, Jennifer; Margaretten, Mary; Yazdany, Jinoos; Yelin, Edward H; Katz, Patricia P

2015-08-01

Cross-sectional studies have observed that muscle weakness is associated with worse physical function among women with systemic lupus erythematosus (SLE). The present study examines whether reduced upper and lower extremity muscle strength predict declines in function over time among adult women with SLE. One hundred forty-six women from a longitudinal SLE cohort participated in the study. All measures were collected during in-person research visits approximately 2 years apart. Upper extremity muscle strength was assessed by grip strength. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion. Physical function was assessed using the Short Physical Performance Battery (SPPB). Regression analyses modeled associations of baseline upper and lower extremity muscle strength with followup SPPB scores controlling for baseline SPPB, age, SLE duration, SLE disease activity (Systemic Lupus Activity Questionnaire), physical activity level, prednisone use, body composition, and depression. Secondary analyses tested whether associations of baseline muscle strength with followup in SPPB scores differed between intervals of varying baseline muscle strength. Lower extremity muscle strength strongly predicted changes over 2 years in physical function even when controlling for covariates. The association of reduced lower extremity muscle strength with reduced physical function in the future was greatest among the weakest women. Reduced lower extremity muscle strength predicted clinically significant declines in physical function, especially among the weakest women. Future studies should test whether therapies that promote preservation of lower extremity muscle strength may prevent declines in function among women with SLE. © 2015, American College of Rheumatology.

Visual Local and Global Processing in Low-Functioning Deaf Individuals with and without Autism Spectrum Disorder

ERIC Educational Resources Information Center

Maljaars, J. P. W.; Noens, I. L. J.; Scholte, E. M.; Verpoorten, R. A. W.; van Berckelaer-Onnes, I. A.

2011-01-01

Background: The ComFor study has indicated that individuals with intellectual disability (ID) and autism spectrum disorder (ASD) show enhanced visual local processing compared with individuals with ID only. Items of the ComFor with meaningless materials provided the best discrimination between the two samples. These results can be explained by the…

Iron Deficiency Is a Determinant of Functional Capacity and Health-related Quality of Life 30 Days After an Acute Coronary Syndrome.

PubMed

Meroño, Oona; Cladellas, Mercè; Ribas-Barquet, Núria; Poveda, Paula; Recasens, Lluis; Bazán, Víctor; García-García, Cosme; Ivern, Consol; Enjuanes, Cristina; Orient, Salvador; Vila, Joan; Comín-Colet, Josep

2017-05-01

Iron deficiency (ID) is a prevalent condition in patients with ischemic heart disease and heart failure. Little is known about the impact of ID on exercise capacity and quality of life (QoL) in the recovery phase after an acute coronary syndrome (ACS). Iron status and its impact on exercise capacity and QoL were prospectively evaluated in 244 patients 30 days after the ACS. QoL was assessed by the standard EuroQoL-5 dimensions, EuroQoL visual analogue scale, and Heart-QoL questionnaires. Exercise capacity was analyzed by treadmill/6-minute walk tests. The effect of ID on cardiovascular mortality and readmission rate was also investigated. A total of 46% of the patients had ID. These patients had lower exercise times (366±162 vs 462±155seconds; P<.001), metabolic consumption rates (7.9±2.9 vs 9.3±2.6 METS; P=.003), and EuroQoL-5 dimensions (0.76±0.25 vs 0.84±0.16), visual analogue scale (66±16 vs 72±17), and Heart-QoL (1.9±0.6 vs 2.2±0.6) scores (P<.05). ID independently predicted lower exercise times (OR, 2.9; 95%CI, 1.1-7.6; P=.023) and worse QoL (OR, 1.9; 95%CI, 1.1-3.3; P<.001) but had no effect on cardiovascular morbidity or mortality. ID, a prevalent condition in ACS patients, results in a poorer mid-term functional recovery, as measured by exercise capacity and QoL. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.

PubMed

Trembley, Michael A; Quijada, Pearl; Agullo-Pascual, Esperanza; Tylock, Kevin M; Colpan, Mert; Dirkx, Ronald A; Myers, Jason R; Mickelsen, Deanne M; de Mesy Bentley, Karen; Rothenberg, Eli; Moravec, Christine S; Alexis, Jeffrey D; Gregorio, Carol C; Dirksen, Robert T; Delmar, Mario; Small, Eric M

2018-05-01

Background -Hypertrophic cardiomyocyte (CM) growth and dysfunction accompanies various forms of heart disease. The mechanisms responsible for transcriptional changes that impact cardiac physiology and the transition to heart failure (HF) are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling CM electrical activity and force transmission, and is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy. Methods -Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy (SMLM) were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor-A (MRTF-A) and -B specifically in adult CMs to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling. Results -We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure (HF). Although mice lacking MRTFs in adult CMs display normal cardiac physiology at baseline, pressure overload leads to rapid HF characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and CM adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by SMLM may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target. Conclusions -Taken together, our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates crosstalk between the actin and microtubule cytoskeleton and maintains ID integrity and CM homeostasis in heart disease.

Id2 Complexes with the SNAG Domain of Snai1 Inhibiting Snai1-Mediated Repression of Integrin β4

PubMed Central

Chang, Cheng; Yang, Xiaofang; Pursell, Bryan

2013-01-01

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as α6β4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits β4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress β4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the β4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated β4 repression with a concomitant increase in H3K27Me3 modification on the β4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression. PMID:23878399

Inductive learning of thyroid functional states using the ID3 algorithm. The effect of poor examples on the learning result.

PubMed

Forsström, J

1992-01-01

The ID3 algorithm for inductive learning was tested using preclassified material for patients suspected to have a thyroid illness. Classification followed a rule-based expert system for the diagnosis of thyroid function. Thus, the knowledge to be learned was limited to the rules existing in the knowledge base of that expert system. The learning capability of the ID3 algorithm was tested with an unselected learning material (with some inherent missing data) and with a selected learning material (no missing data). The selected learning material was a subgroup which formed a part of the unselected learning material. When the number of learning cases was increased, the accuracy of the program improved. When the learning material was large enough, an increase in the learning material did not improve the results further. A better learning result was achieved with the selected learning material not including missing data as compared to unselected learning material. With this material we demonstrate a weakness in the ID3 algorithm: it can not find available information from good example cases if we add poor examples to the data.

Recovery of peripheral muscle function from fatiguing exercise and daily physical activity level in patients with multiple sclerosis: a case-control study.

PubMed

Ickmans, Kelly; Simoens, Fauve; Nijs, Jo; Kos, Daphne; Cras, Patrick; Willekens, Barbara; Meeus, Mira

2014-07-01

Delayed recovery of muscle function following exercise has been demonstrated in the lower limbs of patients with multiple sclerosis (MS). However, studies examining this in the upper limbs are currently lacking. This study compared physical activity level (PAL) and recovery of upper limb muscle function following exercise between MS patients and healthy inactive controls. Furthermore, the relationship between PAL and muscle recovery was examined. PAL of 19 MS patients and 32 controls was measured using an accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was assessed by performing a fatiguing upper limb exercise test with subsequent recovery measures. Muscle recovery of the upper limb muscles was similar in both groups. Average activity counts were significantly lower in MS patients than in the control group. MS patients spent significantly more time being sedentary and less time on activities of moderate intensity compared with the control group. No significant correlation between PAL and recovery of muscle function was found in MS patients. Recovery of upper limb muscle function following exercise is normal in MS patients. MS patients are less physically active than healthy inactive controls. PAL and recovery of upper limb muscle function appear unrelated in MS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Friction massage versus kinesiotaping for short-term management of latent trigger points in the upper trapezius: a randomized controlled trial.

PubMed

Mohamadi, Marzieh; Piroozi, Soraya; Rashidi, Iman; Hosseinifard, Saeed

2017-01-01

Latent trigger points in the upper trapezius muscle may disrupt muscle movement patterns and cause problems such as cramping and decreased muscle strength. Because latent trigger points may spontaneously become active trigger points, they should be addressed and treated to prevent further problems. In this study we compared the short-term effect of kinesiotaping versus friction massage on latent trigger points in the upper trapezius muscle. Fifty-eight male students enrolled with a stratified sampling method participated in this single-blind randomized clinical trial (Registration ID: IRCT2016080126674N3) in 2016. Pressure pain threshold was recorded with a pressure algometer and grip strength was recorded with a Collin dynamometer. The participants were randomly assigned to two different treatment groups: kinesiotape or friction massage. Friction massage was performed daily for 3 sessions and kinesiotape was used for 72 h. One hour after the last session of friction massage or removal of the kinesiotape, pressure pain threshold and grip strength were evaluated again. Pressure pain threshold decreased significantly after both friction massage (2.66 ± 0.89 to 2.25 ± 0.76; P  = 0.02) and kinesiotaping (2.00 ± 0.74 to 1.71 ± 0.65; P  = 0.01). Grip strength increased significantly after friction massage (40.78 ± 9.55 to 42.17 ± 10.68; P  = 0.03); however there was no significant change in the kinesiotape group (39.72 ± 6.42 to 40.65 ± 7.3; P  = 0.197). There were no significant differences in pressure pain threshold (2.10 ± 0.11 & 1.87 ± 0.11; P  = 0.66) or grip strength (42.17 ± 10.68 & 40.65 ± 7.3; P  = 0.53) between the two study groups. Friction massage and kinesiotaping had identical short-term effects on latent trigger points in the upper trapezius. Three sessions of either of these two interventions did not improve latent trigger points. Registration ID in IRCT: IRCT2016080126674N3.

Stability and trapping of magnetic resonance imaging contrast agents during high-intensity focused ultrasound ablation therapy.

PubMed

Hijnen, Nicole M; Elevelt, Aaldert; Grüll, Holger

2013-07-01

The purpose of this study was to investigate the use of Gd-DTPA shortly before magnetic resonance guided high-intensity focused ultrasound MR-HIFU thermal ablation therapy with respect to dissociation, trapping, and long-term deposition of gadolinium (Gd) in the body. Magnetic resonance-HIFU ablation treatment was conducted in vivo on both rat muscle and subcutaneous tumor (9L glioma) using a clinical 3T MR-HIFU system equipped with a small-animal coil setup. A human equivalent dose of gadopentetate dimeglumine (Gd-DTPA) (0.6 mmol/kg of body weight) was injected via a tail vein catheter just before ablation (≤5 minutes). Potential trapping of the contrast agent in the ablated area was visualized through the acquisition of R1 maps of the target location before and after therapy. The animals were sacrificed 2 hours or 14 days after the injection (n = 4 per group, a total of 40 animals). Subsequently, the Gd content in the tissue and carcass was determined using inductively coupled plasma techniques to investigate the biodistribution. Temporal trapping of Gd-DTPA in the coagulated tissue was observed on the R1 maps acquired within 2 hours after the ablation, an effect confirmed by the inductively coupled plasma analysis (3 times more Gd was found in the treated muscle volume than in the control muscle tissue). Two weeks after the therapy, the absolute amount of Gd present in the coagulated tissue was low compared with the amount present in the kidneys 14 days after the injection (ablated muscle, 0.009% ± 0.002% ID/g; kidney, 0.144% ± 0.165% ID/g). There was no significant increase in Gd content in the principal target organs for translocated Gdions (liver, spleen, and bone) or in the entire carcasses between the HIFU- and sham-treated animals. Finally, an in vivo relaxivity of 4.6 mmols was found in the HIFU-ablated volume, indicating intact Gd-DTPA. Magnetic resonance-HIFU treatment does not induce the dissociation of Gd-DTPA. In small-tissue volumes, no significant effect on the long-term in vivo Gd retention was found. However, care must be taken with the use of proton resonance frequency shift-based MR thermometry for HIFU guidance in combination with Gd because the susceptibility artifact induced by Gd can severely influence treatment outcome.

DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans.

PubMed

Butler, R; Morris, A D; Burchell, B; Struthers, A D

1999-05-01

A polymorphism within the angiotensin-converting enzyme (ACE) gene may increase the risk of myocardial infarction in individuals previously thought to be at low cardiovascular risk. The mechanism through which it exerts this effect is unknown but may be due to increased angiotensin II-induced nitric oxide (NO) breakdown and/or reduced bradykinin-mediated NO release. We investigated whether endothelial function was different between different ACE genotypes. We performed a cross-sectional study comparing the endothelial function of the 3 genotypes (II: n=25; ID: n=31; DD: n=12). Mean+/-SD ages of the subjects were 24+/-4 (II), 25+/-6 (ID), and 25+/-6 (DD) years. We assessed the impact of the genotypes on endothelial function and found that the DD genotype was associated with a significant blunting in endothelial-dependent vasodilatation (forearm blood flow data are presented as mean+/-SD ratio of blood flow in response to 3 incrementally increasing doses of each vasoactive agent in the test arm to blood flow in the control arm; the comparison is between DD versus ID versus II; the P value is an expression of an overall difference by ANOVA, and the 95% CIs are of a pairwise comparison between genotypes): acetylcholine, 2.88+/-1.45 versus 3.81+/-1.93 versus 4.23+/-2.37 (P=0.002; 95% CI [II versus ID], -0.19 to 0.91; 95% CI [II versus DD], 0.36 to 1.80; 95% CI [ID versus DD], 0.02 to 1.42). There was also a significant difference with the endothelial-independent vasodilator sodium nitroprusside, with values of 2.11+/-1.00 versus 2.55+/-1.36 versus 2.75+/-1.18 (P<0.05; 95% CI [II versus ID], -0.15 to 0.51; 95% CI [II versus DD], 0.03 to 0.89; 95% CI [ID versus DD], -0.13 to 0.71), but not with verapamil. There was no effect of the ACE genotype on endothelial-dependent or -independent vasoconstrictors NG-monomethyl-L-arginine or norepinephrine. Investigating the effects of cigarette smoking on each genotype demonstrated that for II and DD genotypes, acetylcholine responses were further blunted if subjects smoked. These data demonstrate that the DD ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses but not to non-NO vasodilators or vasoconstrictors.

Vascular delay improves latissimus dorsi muscle perfusion and muscle function for use in cardiomyoplasty.

PubMed

Carroll, S M; Heilman, S J; Stremel, R W; Tobin, G R; Barker, J H

1997-04-01

Ischemia of the distal portion of the latissimus dorsi muscle occurs in muscle transfer for cardiomyoplasty and reduces distal muscle contractility and thus the mechanical effectiveness of cardiomyoplasty. We hypothesized that muscle function would be improved by a vascular delay procedure that increases distal muscle perfusion of the latissimus dorsi muscle. The latissimus dorsi muscles of 10 adult mongrel dogs were subjected to a vascular delay procedure on one side and a sham procedure on the other. Following 10 days of vascular delay, muscle perfusion was measured with a laser-Doppler perfusion imager before and after elevation of the muscles as flaps based only on their thoracodorsal neurovascular pedicles. The muscles were wrapped and sutured around silicone chambers (simulating cardiomyoplasty), a stimulating electrode was placed around each thoracodorsal nerve, and the muscles were stimulated to contract in both rhythmic and tetanic fashion. Circumferential (distal and middle latissimus dorsi muscle function) force generation and fatigue rates were measured independently. Circumferential muscle force, circumferential and longitudinal fatigue rate, and distal, middle, and overall perfusion were significantly (p < 0.05) improved in delayed muscle compared with nondelayed muscle. We found that a vascular delay procedure and a 10-day delay adaptation period significantly improve latissimus dorsi muscle flap perfusion and function, particularly in the distal and middle portions of the muscle. Delay should be considered as a means of improving the clinical outcome in cardiomyoplasty.

3D finite element models of shoulder muscles for computing lines of actions and moment arms.

PubMed

Webb, Joshua D; Blemker, Silvia S; Delp, Scott L

2014-01-01

Accurate representation of musculoskeletal geometry is needed to characterise the function of shoulder muscles. Previous models of shoulder muscles have represented muscle geometry as a collection of line segments, making it difficult to account for the large attachment areas, muscle-muscle interactions and complex muscle fibre trajectories typical of shoulder muscles. To better represent shoulder muscle geometry, we developed 3D finite element models of the deltoid and rotator cuff muscles and used the models to examine muscle function. Muscle fibre paths within the muscles were approximated, and moment arms were calculated for two motions: thoracohumeral abduction and internal/external rotation. We found that muscle fibre moment arms varied substantially across each muscle. For example, supraspinatus is considered a weak external rotator, but the 3D model of supraspinatus showed that the anterior fibres provide substantial internal rotation while the posterior fibres act as external rotators. Including the effects of large attachment regions and 3D mechanical interactions of muscle fibres constrains muscle motion, generates more realistic muscle paths and allows deeper analysis of shoulder muscle function.

3D Finite Element Models of Shoulder Muscles for Computing Lines of Actions and Moment Arms

PubMed Central

Webb, Joshua D.; Blemker, Silvia S.; Delp, Scott L.

2014-01-01

Accurate representation of musculoskeletal geometry is needed to characterize the function of shoulder muscles. Previous models of shoulder muscles have represented muscle geometry as a collection of line segments, making it difficult to account the large attachment areas, muscle-muscle interactions, and complex muscle fiber trajectories typical of shoulder muscles. To better represent shoulder muscle geometry we developed three-dimensional finite element models of the deltoid and rotator cuff muscles and used the models to examine muscle function. Muscle fiber paths within the muscles were approximated, and moment arms were calculated for two motions: thoracohumeral abduction and internal/external rotation. We found that muscle fiber moment arms varied substantially across each muscle. For example, supraspinatus is considered a weak external rotator, but the three-dimensional model of supraspinatus showed that the anterior fibers provide substantial internal rotation while the posterior fibers act as external rotators. Including the effects of large attachment regions and three-dimensional mechanical interactions of muscle fibers constrains muscle motion, generates more realistic muscle paths, and allows deeper analysis of shoulder muscle function. PMID:22994141

Transplantated mesenchymal stem cells derived from embryonic stem cells promote muscle regeneration and accelerate functional recovery of injured skeletal muscle.

PubMed

Ninagawa, Nana Takenaka; Isobe, Eri; Hirayama, Yuri; Murakami, Rumi; Komatsu, Kazumi; Nagai, Masataka; Kobayashi, Mami; Kawabata, Yuka; Torihashi, Shigeko

2013-08-01

We previously established that mesenchymal stem cells originating from mouse embryonic stem (ES) cells (E-MSCs) showed markedly higher potential for differentiation into skeletal muscles in vitro than common mesenchymal stem cells (MSCs). Further, the E-MSCs exhibited a low risk for teratoma formation. Here we evaluate the potential of E-MSCs for differentiation into skeletal muscles in vivo and reveal the regeneration and functional recovery of injured muscle by transplantation. E-MSCs were transplanted into the tibialis anterior (TA) muscle 24 h following direct clamping. After transplantation, the myogenic differentiation of E-MSCs, TA muscle regeneration, and re-innervation were morphologically analyzed. In addition, footprints and gaits of each leg under spontaneous walking were measured by CatWalk XT, and motor functions of injured TA muscles were precisely analyzed. Results indicate that >60% of transplanted E-MSCs differentiated into skeletal muscles. The cross-sectional area of the injured TA muscles of E-MSC-transplanted animals increased earlier than that of control animals. E-MSCs also promotes re-innervation of the peripheral nerves of injured muscles. Concerning function of the TA muscles, we reveal that transplantation of E-MSCs promotes the recovery of muscles. This is the first report to demonstrate by analysis of spontaneous walking that transplanted cells can accelerate the functional recovery of injured muscles. Taken together, the results show that E-MSCs have a high potential for differentiation into skeletal muscles in vivo as well as in vitro. The transplantation of E-MSCs facilitated the functional recovery of injured muscles. Therefore, E-MSCs are an efficient cell source in transplantation.

Transplantated Mesenchymal Stem Cells Derived from Embryonic Stem Cells Promote Muscle Regeneration and Accelerate Functional Recovery of Injured Skeletal Muscle

PubMed Central

Ninagawa, Nana Takenaka; Isobe, Eri; Hirayama, Yuri; Murakami, Rumi; Komatsu, Kazumi; Nagai, Masataka; Kobayashi, Mami; Kawabata, Yuka

2013-01-01

Abstract We previously established that mesenchymal stem cells originating from mouse embryonic stem (ES) cells (E-MSCs) showed markedly higher potential for differentiation into skeletal muscles in vitro than common mesenchymal stem cells (MSCs). Further, the E-MSCs exhibited a low risk for teratoma formation. Here we evaluate the potential of E-MSCs for differentiation into skeletal muscles in vivo and reveal the regeneration and functional recovery of injured muscle by transplantation. E-MSCs were transplanted into the tibialis anterior (TA) muscle 24 h following direct clamping. After transplantation, the myogenic differentiation of E-MSCs, TA muscle regeneration, and re-innervation were morphologically analyzed. In addition, footprints and gaits of each leg under spontaneous walking were measured by CatWalk XT, and motor functions of injured TA muscles were precisely analyzed. Results indicate that >60% of transplanted E-MSCs differentiated into skeletal muscles. The cross-sectional area of the injured TA muscles of E-MSC–transplanted animals increased earlier than that of control animals. E-MSCs also promotes re-innervation of the peripheral nerves of injured muscles. Concerning function of the TA muscles, we reveal that transplantation of E-MSCs promotes the recovery of muscles. This is the first report to demonstrate by analysis of spontaneous walking that transplanted cells can accelerate the functional recovery of injured muscles. Taken together, the results show that E-MSCs have a high potential for differentiation into skeletal muscles in vivo as well as in vitro. The transplantation of E-MSCs facilitated the functional recovery of injured muscles. Therefore, E-MSCs are an efficient cell source in transplantation. PMID:23914336

Genetic ablation of P65 subunit of NF-κB in mdx mice to improve muscle physiological function.

PubMed

Yin, Xi; Tang, Ying; Li, Jian; Dzuricky, Anna T; Pu, Chuanqiang; Fu, Freddie; Wang, Bing

2017-10-01

Duchenne muscular dystrophy (DMD) is a genetic muscle disease characterized by dystrophin deficiency. Beyond gene replacement, the question of whether ablation of the p65 gene of nuclear factor-kappa B (NF-κB) in DMD can improve muscle physiology function is unknown. In this study, we investigated muscle physiological improvement in mdx mice (DMD model) with a genetic reduction of NF-κB. Muscle physiological function and histology were studied in 2-month-old mdx/p65 +/- , wild-type, mdx, and human minidystrophin gene transgenic mdx (TghΔDys/mdx) mice. Improved muscle physiological function was found in mdx/p65 +/- mice when compared with mdx mice; however, it was similar to TghΔDys/mdx mice. The results indicate that genetic reduction of p65 levels diminished chronic inflammation in dystrophic muscle, thus leading to amelioration of muscle pathology and improved muscle physiological function. The results show that inhibition of NF-κB may be a promising therapy when combined with gene therapy for DMD. Muscle Nerve 56: 759-767, 2017. © 2016 Wiley Periodicals, Inc.

Parameters and functional analysis of the deep epaxial muscles in the thoracic, lumbar and sacral regions of the equine spine.

PubMed

García Liñeiro, J A; Graziotti, G H; Rodríguez Menéndez, J M; Ríos, C M; Affricano, N O; Victorica, C L

2018-07-01

The epaxial muscles produce intervertebral rotation in the transverse, vertical and axial axes. These muscles also counteract the movements induced by gravitational and inertial forces and movements produced by antagonistic muscles and the intrinsic muscles of the pelvic limb. Their fascicles are innervated by the dorsal branch of the spinal nerve, which corresponds to the metamere of its cranial insertion in the spinous process. The structure allows the function of the muscles to be predicted: those with long and parallel fibres have a shortening function, whereas the muscles with short and oblique fibres have an antigravity action. In the horse, the multifidus muscle of the thoracolumbar region extends in multiple segments of two to eight vertebral motion segments (VMS). Functionally, the multifidus muscle is considered a spine stabiliser, maintaining VMS neutrality during spine rotations. However, there is evidence of the structural and functional heterogeneity of the equine thoracolumbar multifidus muscle, depending on the VMS considered, related to the complex control of the required neuromuscular activity. Osteoarticular lesions of the spine have been directly related to asymmetries of the multifidus muscle. The lateral (LDSM) and medial (MDSM) dorsal sacrocaudal muscles may be included in the multifidus complex, the function of which is also unclear in the lumbosacral region. The functional parameters of maximum force (F max ), maximum velocity of contraction (V max ) and joint moment (M) of the multifidus muscles inserted in the 4th, 9th, 12th and 17th thoracic and 3rd and 4th lumbar vertebrae of six horses were studied postmortem (for example: 4MT4 indicates the multifidus muscle that crosses four metameres with cranial insertion in the T4 vertebra). Furthermore, the structural and functional characteristics of LDSM and MDSM were determined. Data were analysed by analysis of variance (anova) in a randomised complete block design (P ≤ 0.05). For some muscles, the ordering of V max values was almost opposite to that of F max values, generally indicating antigravity or dynamic functions, depending on the muscle and VMS. The muscles 3MT12, 3ML3 and 4ML4 exhibited high F max and low V max values, indicating a stabilising action. The very long 7MT4 and 8MT4 multifidus had low F max and high V max values, suggesting a shortening action. However, some functional characteristics of interest did not fall within these general observations, also indicating a dual action. In summary, the results of the analysis of various structural and functional parameters confirm the structural and functional heterogeneity of the equine thoracolumbar multifidus complex, depending on the VMS, regardless of the number of metameres crossing each fascicle. To clarify the functions of the equine multifidus muscle complex, this study aimed to assess its functional parameters in thoracolumbar VMSs with different movement characteristics and in the MDSM and LDSM muscles, hypothesising that the functional parameters vary significantly when the VMS is considered. © 2018 Anatomical Society.

Enhanced ID Pit Sizing Using Multivariate Regression Algorithm

NASA Astrophysics Data System (ADS)

Krzywosz, Kenji

2007-03-01

EPRI is funding a program to enhance and improve the reliability of inside diameter (ID) pit sizing for balance-of plant heat exchangers, such as condensers and component cooling water heat exchangers. More traditional approaches to ID pit sizing involve the use of frequency-specific amplitude or phase angles. The enhanced multivariate regression algorithm for ID pit depth sizing incorporates three simultaneous input parameters of frequency, amplitude, and phase angle. A set of calibration data sets consisting of machined pits of various rounded and elongated shapes and depths was acquired in the frequency range of 100 kHz to 1 MHz for stainless steel tubing having nominal wall thickness of 0.028 inch. To add noise to the acquired data set, each test sample was rotated and test data acquired at 3, 6, 9, and 12 o'clock positions. The ID pit depths were estimated using a second order and fourth order regression functions by relying on normalized amplitude and phase angle information from multiple frequencies. Due to unique damage morphology associated with the microbiologically-influenced ID pits, it was necessary to modify the elongated calibration standard-based algorithms by relying on the algorithm developed solely from the destructive sectioning results. This paper presents the use of transformed multivariate regression algorithm to estimate ID pit depths and compare the results with the traditional univariate phase angle analysis. Both estimates were then compared with the destructive sectioning results.

Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection.

PubMed

Pettis, Ronald J; Ginsberg, Barry; Hirsch, Laurence; Sutter, Diane; Keith, Steven; McVey, Elaine; Harvey, Noel G; Hompesch, Marcus; Nosek, Leszek; Kapitza, Christoph; Heinemann, Lutz

2011-04-01

This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.

Evaluation of Intradermal and Subcutaneous Infusion Set Performance Under 24-Hour Basal and Bolus Conditions

PubMed Central

McVey, Elaine; Keith, Steven; Herr, Joshua K.; Sutter, Diane; Pettis, Ronald J.

2015-01-01

Background: This study sought to assess the function and delivery reliability of intradermal (ID) infusion sets used with commercial insulin pumps. Method: Healthy subjects (n = 43) were randomized to either ID or subcutaneous (SC) arms, and received basal/bolus placebo delivery for 24 hours. Subjects received 4 of 8 infusion set combinations (ID: microneedle design A or B, with 2 pump brands [Animas or MiniMed]; SC: Teflon Quickset or steel Rapid-D, Animas pump only, with or without overtaping) and were evaluated for pump occlusion alarms, fluid leakage, pain, and tissue tolerability. A novel algorithm was developed to determine flow consistency based on fluid pressure, and the duration and occurrence rate for periods of unalarmed but interrupted flow (“silent occlusions’”) were compared. Results: ID delivery was successfully maintained over the 24-hour infusion period. The number of silent occlusions was lower for ID microneedle cannula design B than A (P < .01) and lower for Rapid-D SC device compared to Quick-set (P = .03). There was no significant difference in the number of occlusion alarms between the ID and SC devices with the Animas pump. However, the pumps tested with ID devices had significantly different alarm rates (MiniMed 29.5%, Animas 0%, P < .001). Leakage and tissue tolerability were comparable across devices. Conclusion: The ID infusion set reliably delivered diluent for an extended 24-hour period in healthy subjects and was well tolerated. Silent occlusion flow interruptions could be detected in both ID and SC infusion sets using a proprietary algorithm. This algorithm is a promising method for quantitatively evaluating infusion set flow performance. PMID:26319228

Design of Distortion-Invariant Optical ID Tags for Remote Identification and Verification of Objects

NASA Astrophysics Data System (ADS)

Pérez-Cabré, Elisabet; Millán, María Sagrario; Javidi, Bahram

Optical identification (ID) tags [1] have a promising future in a number of applications such as the surveillance of vehicles in transportation, control of restricted areas for homeland security, item tracking on conveyor belts or other industrial environment, etc. More specifically, passive optical ID tag [1] was introduced as an optical code containing a signature (that is, a characteristic image or other relevant information of the object), which permits its real-time remote detection and identification. Since their introduction in the literature [1], some contributions have been proposed to increase their usefulness and robustness. To increase security and avoid counterfeiting, the signature was introduced in the optical code as an encrypted function [2-5] following the double-phase encryption technique [6]. Moreover, the design of the optical ID tag was done in such a way that tolerance to variations in scale and rotation was achieved [2-5]. To do that, the encrypted information was multiplexed and distributed in the optical code following an appropriate topology. Further studies were carried out to analyze the influence of different sources of noise. In some proposals [5, 7], the designed ID tag consists of two optical codes where the complex-valued encrypted signature was separately introduced in two real-valued functions according to its magnitude and phase distributions. This solution was introduced to overcome some difficulties in the readout of complex values in outdoors environments. Recently, the fully phase encryption technique [8] has been proposed to increase noise robustness of the authentication system.

Modernization of Defense Logistics Standard Systems. Establishing the Functional Baseline. Volume 2. Appendix H

DTIC Science & Technology

1991-09-01

and "DD" is the numeric value of the day (01-31). [61 Time ( TM ). The time type is symbolized by the representation " TM ." Format for this type is...VERSION ID M DT 06/06 M TM 04/04 M ID 01/01 M ID 05/05 ISA13 112 ISA14 113 ISA15 114 ISA16 115INTERCHANGE *ACKNOWLEDG. * S1TEST 14 * SUBELEMENT N CTRL...Max - 6 Date of the interchange. DLMS Usage: As above. 109 Interchange Time Type - TM Min - 4 Max - 4 Time of the interchange. DLMS Usage: As above

Excretion and toxicity evaluation of 131I-Sennoside A as a necrosis-avid agent.

PubMed

Yin, Zhiqi; Sun, Lidan; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Liao, Hong; Ni, Yicheng; Zhang, Jian; Liu, Wei

2017-11-01

1. Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound, 131 I-Sennoside A ( 131 I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity. 2. To further verify excretion pathway and examine nephrotoxicity of 131 I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of 131 I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg. 3. Excretion data revealed that 131 I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that 131 I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48 h post injection, which further verified the necrosis avidity of 131 I-SA. Pharmacokinetic parameters showed that 131 I-SA had fast blood clearance with an elimination half-life of 6.7 h. Various functional indexes were no significant difference (p > 0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage. 4. These data suggest 131 I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy.

Sensitivity of estimated muscle force in forward simulation of normal walking

PubMed Central

Xiao, Ming; Higginson, Jill

2009-01-01

Generic muscle parameters are often used in muscle-driven simulations of human movement estimate individual muscle forces and function. The results may not be valid since muscle properties vary from subject to subject. This study investigated the effect of using generic parameters in a muscle-driven forward simulation on muscle force estimation. We generated a normal walking simulation in OpenSim and examined the sensitivity of individual muscle to perturbations in muscle parameters, including the number of muscles, maximum isometric force, optimal fiber length and tendon slack length. We found that when changing the number muscles included in the model, only magnitude of the estimated muscle forces was affected. Our results also suggest it is especially important to use accurate values of tendon slack length and optimal fiber length for ankle plantarflexors and knee extensors. Changes in force production one muscle were typically compensated for by changes in force production by muscles in the same functional muscle group, or the antagonistic muscle group. Conclusions regarding muscle function based on simulations with generic musculoskeletal parameters should be interpreted with caution. PMID:20498485

Soluble Milk Proteins Improve Muscle Mass Recovery after Immobilization-Induced Muscle Atrophy in Old Rats but Do not Improve Muscle Functional Property Restoration.

PubMed

Verney, J; Martin, V; Ratel, S; Chavanelle, V; Bargetto, M; Etienne, M; Chaplais, E; Le Ruyet, P; Bonhomme, C; Combaret, L; Guillet, C; Boisseau, N; Sirvent, P; Dardevet, D

2017-01-01

Effect of 3 different dairy protein sources on the recovery of muscle function after limb immobilization in old rats. Longitudinal animal study. Institut National de la Recherche Agronomique (INRA). The study took part in a laboratory setting. Old rats were subjected to unilateral hindlimb immobilization for 8 days and then allowed to recover with 3 different dietary proteins: casein, soluble milk proteins or whey proteins for 49 days. Body weight, muscle mass, muscle fibre size, isometric, isokinetic torque, muscle fatigability and muscle oxidative status were measured before and at the end of the immobilization period and during the recovery period i.e 7, 21, 35 and 49 days post immobilization. In contrast to the casein diet, soluble milk proteins and whey proteins were efficient to favor muscle mass recovery after cast immobilization during aging. By contrast, none of the 3 diary proteins was able to improve muscle strength, power and fatigability showing a discrepancy between the recovery of muscle mass and function. However, the soluble milk proteins allowed a better oxidative capacity in skeletal muscle during the rehabilitation period. Whey proteins and soluble milk proteins improve muscle mass recovery after immobilization-induced muscle atrophy in old rats but do not allow muscle functional property restoration.

Adaptation and Validation of the Tower of London Test of Planning and Problem Solving in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Masson, J. D.; Dagnan, D.; Evans, J.

2010-01-01

Background: There is a need for validated, standardised tools for the assessment of executive functions in adults with intellectual disabilities (ID). This study examines the validity of a test of planning and problem solving (Tower of London) with adults with ID. Method: Participants completed an adapted version of the Tower of London (ToL) while…

Mediation between Staff and Elderly Persons with Intellectual Disability with Alzheimer Disease as a Means of Enhancing Their Daily Functioning

ERIC Educational Resources Information Center

Lifshitz, Hefziba; Klein, Pnina S.

2011-01-01

This study presents a new way of mediation between staff and elderly persons with intellectual disability (ID) and Alzheimer type dementia (AD), i.e., the MISC (Mediational Intervention for Sensitizing Caregivers (Klein, 1988, 2003) model. The MISC was adopted for interactions between staff and adults with ID and AD based on observations of…

Population-based cross-sectional study on insulin resistance and insulin-secretory capacity in Japanese school children.

PubMed

Nishimura, Rimei; Sano, Hironari; Onda, Yoshiko; Tsujino, Daisuke; Ando, Kiyotaka; Ebara, Futoshi; Matsudaira, Toru; Ishikawa, Shinichiro; Sakamoto, Takuya; Tajima, Naoko; Utsunomiya, Kazunori

2017-09-01

Little information is available regarding the status of insulin resistance (IR) and insulin deficiency (ID), as well as their relationship with obesity in children using the homeostasis model assessment (HOMA) in a population-based setting. The study included a total of 445 ninth-grade children participating in health check-up programs implemented in Tsunan Town, Niigata, Japan (boys/girls, 252/193 [participation rates: 98.1/95.5%]). HOMA of insulin resistance ≥2.5 was defined as IR, and HOMA of β-cell function <40 defined as ID. The medians (25-75th percentiles) of HOMA of insulin resistance, HOMA of β-cell function, Disposition Index and body mass index in boys were 1.2 (0.8-1.7), 64 (44-93), 52 (43-64) and 19.2 (18.0-20.7) kg/m 2 , respectively, vs 1.5 (1.0-2.0), 86 (63-120), 60 (50-74) and 20.4 (18.9-22.0) kg/m 2 , respectively, in girls. The HOMA of insulin resistance, HOMA of β-cell function and Disposition Index values were significantly higher in the girls (P = 0.002, P < 0.001 and P < 0.001, respectively). Those with IR accounted for a significantly higher proportion of girls than boys (15.5/8.7%; P = 0.027); those with obesity accounted for 9.9/10.7% (boys/girls); and those with IR and obesity accounted for 2.4/4.7%. Those with ID accounted for a significantly higher proportion of boys than girls (20.6/8.8%; P = 0.001), whereas those with ID and obesity accounted for a very small proportion of either group (0.4/0.5%). The presence of IR was higher among the girls. In contrast, ID was more frequent among the boys. The infrequent presence of ID among children might support the presence of non-obese type 2 diabetes adults in Japan. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Semantic Domains and Denotational Semantics

DTIC Science & Technology

1989-02-14

are continuous functions PL N -* PN FL :PN -PN such that IL 0 %FL = id and T1/L o IL -- id. Then the function RL (r,s) = TLo 4L represents the constant...would actually reduce the abstractness of denotations. The popularity of continuations seems to be partly due to the accompanying notational convenience...R.L ’ES.(~’ , r) s’)] ( rl (s))) (ext~ rl , _L R ,S’ E S). (g(r’, r2), ’]r( )) (S[Sile)(SIS1Je) S[ < S > =Ae E Env. fix(Ah R -, R. Ar E R. ext[As E S

Function and position determine relative proportions of different fiber types in limb muscles of the lizard Tropidurus psammonastes.

PubMed

Pereira, Anieli G; Abdala, Virginia; Kohlsdorf, Tiana

2015-02-01

Skeletal muscles can be classified as flexors or extensors according to their function, and as dorsal or ventral according to their position. The latter classification evokes their embryological origin from muscle masses initially divided during limb development, and muscles sharing a given position do not necessarily perform the same function. Here, we compare the relative proportions of different fiber types among six limb muscles in the lizard Tropidurus psammonastes. Individual fibers were classified as slow oxidative (SO), fast glycolytic (FG) or fast oxidative-glycolytic (FOG) based on mitochondrial content; muscles were classified according to position and function. Mixed linear models considering one or both effects were compared using likelihood ratio tests. Variation in the proportion of FG and FOG fibers is mainly explained by function (flexor muscles have on average lower proportions of FG and higher proportions of FOG fibers), while variation in SO fibers is better explained by position (they are less abundant in ventral muscles than in those developed from a dorsal muscle mass). Our results clarify the roles of position and function in determining the relative proportions of the various muscle fibers and provide evidence that these factors may differentially affect distinct fiber types. Copyright © 2014. Published by Elsevier GmbH.

Muscle abnormalities in osteogenesis imperfecta

PubMed Central

Veilleux, L-N.; Trejo, P.; Rauch, F.

2017-01-01

Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research. PMID:28574406

Bipolar Latissimus Dorsi Transfer for Restoration of Pectoralis Major Function in Poland Syndrome.

PubMed

Buchanan, Patrick; Leyngold, Mark; Mast, Bruce A

2016-01-01

Poland syndrome typically presents as a unilateral congenital complete or partial absence of the pectoralis major muscle, variably with other associated anomalies. Reconstruction of the defect typically concentrates on aesthetic restoration with functional outcomes being unsuccessful or limited. We present an innovative means of true muscle transfer that provided functional benefit to increase upper extremity strength. A 16-year-old adolescent boy with Poland syndrome manifesting as left pectoralis major muscle agenesis wished to undergo functional reconstruction. He wanted to play on his high school football team, but could not meet the minimum weightlifting requirements. An ipsilateral latissimus dorsi muscle bipolar functional transfer was done with bone-anchored inset into the sternum and humerus so that muscle flexion would replace the absent pectoralis major. A progressive weight training program was then instituted postoperatively. At 9 months, a significant increase in left upper extremity strength was confirmed. The patient ultimately was able to surpass the weightlifting requirements for his high school football team, and joined the team. Our highlighted procedure restored functional outcome using both plastic surgical principles and orthopedic techniques for muscle and tendon repair: bipolar muscle transfer and load-bearing muscle inset. Heretofore, transfer of the latissimus for provision of pectoralis major function has not been reported. Functional reconstruction was possible due to stable, bipolar muscle transfer with load-bearing muscle attachments into cortical bone of the anterior sternum and anteromedial aspect of the humerus. The techniques described should be within the skill set of most plastic surgeons, so that functional restoration for those with Poland syndrome is possible and accessible.

Comparative studies on troponin, a Ca²⁺-dependent regulator of muscle contraction, in striated and smooth muscles of protochordates.

PubMed

Obinata, Takashi; Sato, Naruki

2012-01-01

Troponin is well known as a Ca(2+)-dependent regulator of striated muscle contraction and it has been generally accepted that troponin functions as an inhibitor of muscle contraction or actin-myosin interaction at low Ca(2+) concentrations, and Ca(2+) at higher concentrations removes the inhibitory action of troponin. Recently, however, troponin became detectable in non-striated muscles of several invertebrates and in addition, unique troponin that functions as a Ca(2+)-dependent activator of muscle contraction has been detected in protochordate animals, although troponin in vertebrate striated muscle is known as an inhibitor of the contraction in the absence of a Ca(2+). Further studies on troponin in invertebrate muscle, especially in non-striated muscle, would provide new insight into the evolution of regulatory systems for muscle contraction and diverse function of troponin and related proteins. The methodology used for preparation and characterization of functional properties of protochordate striated and smooth muscles will be helpful for further studies of troponin in other invertebrate animals. Copyright © 2011. Published by Elsevier Inc.

Respiratory muscle involvement in sarcoidosis.

PubMed

Schreiber, Tina; Windisch, Wolfram

2018-07-01

In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.

Skill-related physical fitness versus aerobic fitness as a predictor of executive functioning in children with intellectual disabilities or borderline intellectual functioning.

PubMed

Hartman, Esther; Smith, Joanne; Houwen, Suzanne; Visscher, Chris

2017-05-01

Children with intellectual disabilities (ID) or borderline intellectual disabilities (BIF) often demonstrate impairments in executive functioning (EF). Studies in typically developing children show that aerobic fitness (AF) is positively related with EF. Skill-related physical fitness (SF) might, however, be a stronger predictor of EF than AF, as cognitive challenges are inherent in application of these skills. In this study, AF and SF were examined simultaneously in relationship with domains of EF in children with ID or BIF. Seventy-three children (age range 8-11; 51 boys) with ID (IQ range 56-79) or BIF (IQ range 71-79) were measured annually over a period of 4 years on AF (20-m endurance shuttle run test) and SF (plate tapping and 10×5m run). EF was measured with the Stroop Color-Word test (inhibition), Trailmaking and Fluency test (cognitive flexibility), Self-ordered pointing task (working memory) and the Tower of London (planning). Multilevel models showed that SF was significantly associated with inhibition and both measures of cognitive flexibility, but in the same models no significant associations between AF and EF were found. In addition, age was significantly related to working memory and cognitive flexibility, favouring the older children. In children with ID or BIF, SF is of greater importance than AF in relationship with core domains of EF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engineering functional and histological regeneration of vascularized skeletal muscle.

PubMed

Gilbert-Honick, Jordana; Iyer, Shama R; Somers, Sarah M; Lovering, Richard M; Wagner, Kathryn; Mao, Hai-Quan; Grayson, Warren L

2018-05-01

Tissue engineering strategies to treat patients with volumetric muscle loss (VML) aim to recover the structure and contractile function of lost muscle tissue. Here, we assessed the capacity of novel electrospun fibrin hydrogel scaffolds seeded with murine myoblasts to regenerate the structure and function of damaged muscle within VML defects to the mouse tibialis anterior muscle. The electrospun fibrin scaffolds provide pro-myogenic alignment and stiffness cues, myomimetic hierarchical structure, suturability, and scale-up capabilities. Myoblast-seeded scaffolds enabled remarkable muscle regeneration with high myofiber and vascular densities after 2 and 4 weeks, mimicking that of native skeletal muscle, while acellular scaffolds lacked muscle regeneration. Both myoblast-seeded and acellular scaffolds fully recovered muscle contractile function to uninjured values after 2 and 4 weeks. Electrospun scaffolds pre-vascularized with co-cultured human endothelial cells and human adipose-derived stem cells implanted into VML defects for 2 weeks anastomosed with host vasculature and were perfused with host red blood cells. These data demonstrate the significant potential of electrospun fibrin scaffolds seeded with myoblasts to fully regenerate the structure and function of volumetric muscle defects and these scaffolds offer a promising treatment option for patients with VML. Copyright © 2018 Elsevier Ltd. All rights reserved.

Respiratory muscle function and exercise limitation in patients with chronic obstructive pulmonary disease: a review.

PubMed

Charususin, Noppawan; Dacha, Sauwaluk; Gosselink, Rik; Decramer, Marc; Von Leupoldt, Andreas; Reijnders, Thomas; Louvaris, Zafeiris; Langer, Daniel

2018-01-01

Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

Characterization of the in vitro expressed autoimmune rippling muscle disease immunogenic domain of human titin encoded by TTN exons 248-249

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelinka, L.; McCann, S.; Budde, J.

2011-08-05

Highlights: {yields} Affinity purification of the autoimmune rippling muscle disease immunogenic domain of titin. {yields} Partial sequence analysis confirms that the peptides is in the I band region of titin. {yields} This region of the human titin shows high degree of homology to mouse titin N2-A. -- Abstract: Autoimmune rippling muscle disease (ARMD) is an autoimmune neuromuscular disease associated with myasthenia gravis (MG). Past studies in our laboratory recognized a very high molecular weight skeletal muscle protein antigen identified by ARMD patient antisera as the titin isoform. These past studies used antisera from ARMD and MG patients as probes tomore » screen a human skeletal muscle cDNA library and several pBluescript clones revealed supporting expression of immunoreactive peptides. This study characterizes the products of subcloning the titin immunoreactive domain into pGEX-3X and the subsequent fusion protein. Sequence analysis of the fusion gene indicates the cloned titin domain (GenBank ID: (EU428784)) is in frame and is derived from a sequence of N2-A spanning the exons 248-250 an area that encodes the fibronectin III domain. PCR and EcoR1 restriction mapping studies have demonstrated that the inserted cDNA is of a size that is predicted by bioinformatics analysis of the subclone. Expression of the fusion protein result in the isolation of a polypeptide of 52 kDa consistent with the predicted inferred amino acid sequence. Immunoblot experiments of the fusion protein, using rippling muscle/myasthenia gravis antisera, demonstrate that only the titin domain is immunoreactive.« less

Techniques for studying the effects of microgravity on model particle/cell systems

NASA Technical Reports Server (NTRS)

Young, Ronald B.

1989-01-01

In an effort to learn more about the effects of a simulated low gravity environment on skeletal muscle, skeletal muscle cell cultures were grown within the lumen of XM-80 hollow fibers (i.d. = 0.5 mm) in a Clinostat rotating at 100 rpm. Cells were isolated from the thigh muscle tissue of 12 day embryos and were cultured for up to 14 days in the hollow fiber environment. Cells proliferated to confluency within several days, and fusion into multinucleated myotubes was then apparent. Fibers were stretched by a built-in spring mechanism to hold the fiber tightly at the center of rotation, and sections of the fiber were removed at 3, 7 and 14 days for electron microscopic analysis. When the Clinostat is rotated in the horizontal position, the gravity vector approaches zero and the cells are in an environment that simulates microgravity. Control experiments consist of one fiber rotated in the vertical position in the clinostat and another fiber that is held in a horizontal configuration in a comparable sized tube that is not rotated at all. Examination of skeletal muscle cells by electron microscopy revealed that myoblast fusion and myofibril accumulation were extensive. Two general conclusions were apparent. First, muscle cells undergo the normal progression of proliferation, fusion, and myofibril assembly in the presence of simulated microgravity for the first week in culture. After 14 days, however, many muscle fibers undergo degeneration such that myofibrillar structures are not extensive or well organized. Second, although no major abnormalities in myofibril assembly were detected in Clinostat-rotated cultures in comparison to controls that were not rotated in a Clinostat, the myofibrils in non-rotated controls tend to be more highly organized than those in either horizontally or vertically rotated Clinostat samples.

New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration

PubMed Central

Pasteuning-Vuhman, Svitlana; Boertje-van der Meulen, Johanna W.; van Putten, Maaike; Overzier, Maurice; ten Dijke, Peter; Kiełbasa, Szymon M.; Arindrarto, Wibowo; Wolterbeek, Ron; Lezhnina, Ksenia V.; Ozerov, Ivan V.; Aliper, Aleksandr M.; Hoogaars, Willem M.; Aartsma-Rus, Annemieke; Loomans, Cindy J. M.

2017-01-01

Skeletal muscle fibrosis and impaired muscle regeneration are major contributors to muscle wasting in Duchenne muscular dystrophy (DMD). Muscle growth is negatively regulated by myostatin (MSTN) and activins. Blockage of these pathways may improve muscle quality and function in DMD. Antisense oligonucleotides (AONs) were designed specifically to block the function of ALK4, a key receptor for the MSTN/activin pathway in skeletal muscle. AON-induced exon skipping resulted in specific Alk4 down-regulation, inhibition of MSTN activity, and increased myoblast differentiation in vitro. Unexpectedly, a marked decrease in muscle mass (10%) was found after Alk4 AON treatment in mdx mice. In line with in vitro results, muscle regeneration was stimulated, and muscle fiber size decreased markedly. Notably, when Alk4 was down-regulated in adult wild-type mice, muscle mass decreased even more. RNAseq analysis revealed dysregulated metabolic functions and signs of muscle atrophy. We conclude that ALK4 inhibition increases myogenesis but also regulates the tight balance of protein synthesis and degradation. Therefore, caution must be used when developing therapies that interfere with MSTN/activin pathways.—Pasteuning-Vuhman, S., Boertje-van der Meulen, J. W., van Putten, M., Overzier, M., ten Dijke, P., Kiełbasa, S. M., Arindrarto, W., Wolterbeek, R., Lezhnina, K. V., Ozerov, I. V., Aliper, A. M., Hoogaars, W. M., Aartsma-Rus, A., Loomans, C. J. M. New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration. PMID:27733450

No beneficial effects of vitamin D supplementation on muscle function or quality of life in primary hyperparathyroidism: results from a randomized controlled trial.

PubMed

Rolighed, Lars; Rejnmark, Lars; Sikjaer, Tanja; Heickendorff, Lene; Vestergaard, Peter; Mosekilde, Leif; Christiansen, Peer

2015-05-01

Impairments of muscle function and strength in patients with primary hyperparathyroidism (PHPT) are rarely addressed, although decreased muscle function may contribute to increased fracture risk. We aimed to assess the changes in muscle strength, muscle function, postural stability, quality of life (QoL), and well-being during treatment with vitamin D or placebo before and after parathyroidectomy (PTX) in PHPT patients. A randomized placebo-controlled trial. We included 46 PHPT patients, mean age 58 (range 29-77) years and 35 (76%) were women. Daily treatment with 70 μg (2800 IU) cholecalciferol or placebo for 52 weeks. Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX. Changes in QoL and measures of muscle strength and function. Preoperatively, 25-hydroxyvitamin D (25OHD) increased significantly (50-94 nmol/l) compared with placebo (57-52 nmol/l). We did not measure any beneficial effects of supplementation with vitamin D compared with placebo regarding well-being, QoL, postural stability, muscle strength, or function. In all patients, we measured marked improvements in QoL, well-being (P<0.01), muscle strength in the knee flexion and extension (P<0.001), and muscle function tests (P<0.01) after surgical cure. Postural stability improved during standing with eyes closed (P<0.05), but decreased with eyes open (P<0.05). Patients with PHPT and 25OHD levels around 50 nmol/l did not benefit from vitamin D supplementation concerning muscle strength, muscle function, postural stability, well-being, or QoL. Independent of preoperative 25OHD levels, PTX improved these parameters. © 2015 European Society of Endocrinology.

Skeletal muscle mitochondria: a major player in exercise, health and disease.

PubMed

Russell, Aaron P; Foletta, Victoria C; Snow, Rod J; Wadley, Glenn D

2014-04-01

Maintaining skeletal muscle mitochondrial content and function is important for sustained health throughout the lifespan. Exercise stimulates important key stress signals that control skeletal mitochondrial biogenesis and function. Perturbations in mitochondrial content and function can directly or indirectly impact skeletal muscle function and consequently whole-body health and wellbeing. This review will describe the exercise-stimulated stress signals and molecular mechanisms positively regulating mitochondrial biogenesis and function. It will then discuss the major myopathies, neuromuscular diseases and conditions such as diabetes and ageing that have dysregulated mitochondrial function. Finally, the impact of exercise and potential pharmacological approaches to improve mitochondrial function in diseased populations will be discussed. Exercise activates key stress signals that positively impact major transcriptional pathways that transcribe genes involved in skeletal muscle mitochondrial biogenesis, fusion and metabolism. The positive impact of exercise is not limited to younger healthy adults but also benefits skeletal muscle from diseased populations and the elderly. Impaired mitochondrial function can directly influence skeletal muscle atrophy and contribute to the risk or severity of disease conditions. Pharmacological manipulation of exercise-induced pathways that increase skeletal muscle mitochondrial biogenesis and function in critically ill patients, where exercise may not be possible, may assist in the treatment of chronic disease. This review highlights our understanding of how exercise positively impacts skeletal muscle mitochondrial biogenesis and function. Exercise not only improves skeletal muscle mitochondrial health but also enables us to identify molecular mechanisms that may be attractive targets for therapeutic manipulation. This article is part of a Special Issue entitled Frontiers of mitochondrial research. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of Real and Simulated Microgravity on Muscle Function

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JA3, the discussion focuses on the following topics: Changes in Calf Muscle Performance, Energy Metabolism, and Muscle Volume Caused by Long Term Stay on Space Station MIR; Vibrografic Signs of Autonomous Muscle Tone Studied in Long Term Space Missions; Reduction of Muscle Strength After Long Duration Space Flights is Associated Primarily with Changes in Neuromuscular Function; The Effects of a 115-Day Spaceflight on Neuromuscular Function in Crewman; Effects of 17-Day Spaceflight on Human Triceps Surae Electrically-Evoked Contractions; Effects of Muscle Unloading on EMG Spectral Parameters; and Myofiber Wound-Mediated FGF Release and Muscle Atrophy During Bedrest.

Resistance training alters skeletal muscle structure and function in human heart failure: effects at the tissue, cellular and molecular levels

PubMed Central

Toth, Michael J; Miller, Mark S; VanBuren, Peter; Bedrin, Nicholas G; LeWinter, Martin M; Ades, Philip A; Palmer, Bradley M

2012-01-01

Reduced skeletal muscle function in heart failure (HF) patients may be partially explained by altered myofilament protein content and function. Resistance training increases muscle function, although whether these improvements are achieved by correction of myofilament deficits is not known. To address this question, we examined 10 HF patients and 14 controls prior to and following an 18 week high-intensity resistance training programme. Evaluations of whole muscle size and strength, single muscle fibre size, ultrastructure and tension and myosin–actin cross-bridge mechanics and kinetics were performed. Training improved whole muscle isometric torque in both groups, although there were no alterations in whole muscle size or single fibre cross-sectional area or isometric tension. Unexpectedly, training reduced the myofibril fractional area of muscle fibres in both groups. This structural change manifested functionally as a reduction in the number of strongly bound myosin–actin cross-bridges during Ca2+ activation. When post-training single fibre tension data were corrected for the loss of myofibril fractional area, we observed an increase in tension with resistance training. Additionally, training corrected alterations in cross-bridge kinetics (e.g. myosin attachment time) in HF patients back to levels observed in untrained controls. Collectively, our results indicate that improvements in myofilament function in sedentary elderly with and without HF may contribute to increased whole muscle function with resistance training. More broadly, these data highlight novel cellular and molecular adaptations in muscle structure and function that contribute to the resistance-trained phenotype. PMID:22199163

Intellectual Disability in Children Aged Less than Seven Years Born Moderately and Late Preterm Compared with Very Preterm and Term-Born Children--A Nationwide Birth Cohort Study

ERIC Educational Resources Information Center

Hirvonen, M.; Ojala, R.; Korhonen, P.; Haataja, P.; Eriksson, K.; Rantanen, K.; Gissler, M.; Luukkaala, T.; Tammela, O.

2017-01-01

Background: Prematurity has been shown to be associated with an increased risk of intellectual disability (ID). Method: The aim was to establish whether the prevalence of ID, defined as significant limitations in both intellectual (intelligence quotient below 70) and adaptive functioning among moderately preterm (MP; 32[superscript + 0]-33…

Perceptual-motor coordination in persons with mild intellectual disability.

PubMed

Carmeli, Eli; Bar-Yossef, Tamar; Ariav, Claudette; Levy, Ran; Liebermann, Dario G

2008-01-01

There is limited experimental evidence to support the view that individuals with intellectual disabilities (ID) have a deficit in motor control. This work is a first attempt to evaluate their motor coordination. The study assessed the relationship between cognitive ability and sensorimotor integration. The clinical hypothesis is that adults with ID fall below non-ID adults in motor skills that involve hand-eye coordination. A group of 42 adults with ID (ID group) was compared to 48 age-matched typical adults (TA) using a mixed experimental design ('Task' as the within-subjects factor and 'Group' as the between-subjects factor). Participants performed the following tests twice: Box-and-Blocks, 25-Grooved-Pegboard, Stick Catching and overhead Beanbag-Throw. Pearson correlations and ANOVAs were used to test the hypothesis (p < or = 0.05). As expected, TA outperformed the ID group in all tests regardless of the hand used during for the assessment. However, TA individuals scored significantly better with one hand (i.e., the preferred and dominant hand) as opposed to persons with ID, who exhibited no hand preference. Test-retest correlations among the first and second assessment scores yielded moderate-strong coefficients, depending on the type of test (Box-and-Blocks = 0.92 and 0.96, 25-Grooved-Pegboard = 0.69 and 0.83, Stick-Catching = 0.88 and 0.94, Beanbag-Throw = 0.58 and 0.91 for ID and TA, respectively). Difficulties in the integration of perceptual information into motor action may result in inadequate solutions to daily motor problems. As it stems from our results, intellectual disability relates to inability to integrate visual inputs and hand movements. In people with mild ID such inability is observed using both hands (i.e., they show no hand preferences). Poor perceptual-motor coordination might have a functional significance in that it may lead to exclusion from vocational and recreational activities, and a decreasing competence of ADL. Assessing coordination in adults with ID may contribute to understanding the nature of the ID condition and may encourage an early rehabilitation.

Dipicolinate salt of imidazole: Discovering its structure and properties using different experimental methodologies and quantum chemical investigations

NASA Astrophysics Data System (ADS)

Thirumurugan, R.; Anitha, K.

2018-03-01

A novel organic proton transfer complex of imidazolium dipicolinate (ID) has been synthesized and it was grown as single crystals using slow evaporation method. The molecular structure of synthesized compound and vibrational modes of its functional groups were confirmed by (1H and 13C) NMR, FTIR and FT-Raman spectroscopic studies, respectively. Single crystal X-ray diffraction (SCXRD) analysis confirmed the orthorhombic system with noncentrosymmetric (NCS), P212121, space group of grown ID crystal. UV-Vis-NIR spectral study confirmed its high optical transparency within the region of 285-1500 nm. Powder second harmonic generation (SHG) efficiency of ID crystal was confirmed and it was 6.8 times that of KDP crystal. TG-DTA and DSC analysis revealed the higher thermal stability of grown crystal as 249 °C. The dielectric response and mechanical behaviour of grown crystal were studied effectively. Density functional theory calculations were performed to probe the relationship between the structure and its properties including molecular optimization, Mulliken atomic charge distribution, frontier molecular orbital (FMOs) and molecular electrostatic potential map (MEP) analysis and first hyperpolarizability. All these experimental and computational results were discussed in this communication and it endorsed the ID compound as a potential NLO candidate could be employed in optoelectronics device applications in near future.

Iron isotopic composition of blood serum in anemia of chronic kidney disease.

PubMed

Anoshkina, Yulia; Costas-Rodríguez, Marta; Speeckaert, Marijn; Van Biesen, Wim; Delanghe, Joris; Vanhaecke, Frank

2017-05-24

Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with CKD and/or iron disorders showed a heavier serum Fe isotopic composition than controls. Many clinical parameters used for the diagnosis and follow-up of anemia correlated significantly with the serum Fe isotopic composition. In contrast, no relation was observed between the serum Fe isotopic composition and the estimated glomerular filtration rate as a measure of kidney function. Among the CKD patients, the serum Fe isotopic composition was substantially heavier in the occurrence of ID anemia, while erythropoietin-related anemia did not exert this effect. The Fe isotopic composition can thus be useful for distinguishing these different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin-related anemia.

A study on the relationship between muscle function, functional mobility and level of physical activity in community-dwelling elderly.

PubMed

Garcia, Patrícia A; Dias, João M D; Dias, Rosângela C; Santos, Priscilla; Zampa, Camila C

2011-01-01

to evaluate the relationship between lower extremity muscle function, calf circumference (CC), handgrip strength (HG), functional mobility and level of physical activity among age groups (65-69, 70-79, 80+) of older adults (men and women) and to identify the best parameter for screening muscle function loss in the elderly. 81 community-dwelling elderly (42 women and 39 men) participated. Walking speed (Multisprint Kit), HG (Jamar dynamometer), hip, knee and ankle muscle function (Biodex isokinetic dynamometer), level of physical activity (Human Activity Profile) and CC (tape measure) were evaluated. ANOVA, Pearson correlation and ROC curves were used for statistical analysis. Dominant CC (34.9±3 vs 37.7±3.6), habitual (1.1±0.2 vs 1.2±0.2) and fast (1.4±0.3 vs 1.7±0.3) walking speed, HG (23.8±7.5 vs 31.8±10.3), average peak torque and average hip, knee and ankle power (p<0.05) were lower for the 80+ group than for the 65-69 year-olds. There were no differences in physical activity level among age groups. Moderate significant correlations were found between muscle function parameters, walking speed and HG; a fair degree of relationship was found between muscle function parameters, CC and level of physical activity (p<0.05). The ROC curve analysis suggested a cutoff point of 14.51 Kgf for screening muscle function loss in elderly women (p=0.03). This study demonstrated an association between muscle function, HG and fast walking speed, a decrease in these parameters with age and the possibility of using HG to screen for muscle function of the lower extremities.

The assessment and impact of sarcopenia in lung cancer: a systematic literature review.

PubMed

Collins, Jemima; Noble, Simon; Chester, John; Coles, Bernadette; Byrne, Anthony

2014-01-02

There is growing awareness of the relationship between sarcopenia (loss of muscle mass and function), and outcomes in cancer, making it a potential target for future therapies. In order to inform future research and practice, we undertook a systematic review of factors associated with loss of muscle mass, and the relationship between muscle function and muscle mass in lung cancer, a common condition associated with poor outcomes. We conducted a computerised systematic literature search on five databases. Studies were included if they explored muscle mass as an outcome measure in patients with lung cancer, and were published in English. Secondary care. Patients with lung cancer. Factors associated with loss of muscle mass and muscle function, or sarcopenia, and the clinical impact thereof in patients with lung cancer. We reviewed 5726 citations, and 35 articles were selected for analysis. Sarcopenia, as defined by reduced muscle mass alone, was found to be very prevalent in patients with lung cancer, regardless of body mass index, and where present was associated with poorer functional status and overall survival. There were diverse studies exploring molecular and metabolic factors in the development of loss of muscle mass; however, the precise mechanisms that contribute to sarcopenia and cachexia remain uncertain. The effect of nutritional supplements and ATP infusions on muscle mass showed conflicting results. There are very limited data on the correlation between degree of sarcopenia and muscle function, which has a non-linear relationship in older non-cancer populations. Loss of muscle mass is a significant contributor to morbidity in patients with lung cancer. Loss of muscle mass and function may predate clinically overt cachexia, underlining the importance of evaluating sarcopenia, rather than weight loss alone. Understanding this relationship and its associated factors will provide opportunities for focused intervention to improve clinical outcomes.

Preserving Healthy Muscle during Weight Loss123

PubMed Central

Cava, Edda; Yeat, Nai Chien; Mittendorfer, Bettina

2017-01-01

Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers. The potential health benefits of diet-induced weight loss are thought to be compromised by the weight-loss–associated loss of lean body mass, which could increase the risk of sarcopenia (low muscle mass and impaired muscle function). The objective of this review is to provide an overview of what is known about weight-loss–induced muscle loss and its implications for overall physical function (e.g., ability to lift items, walk, and climb stairs). The currently available data in the literature show the following: 1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity. PMID:28507015

Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

PubMed

McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

2014-08-15

To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

Knowledge, perceptions and preferences of elderly regarding protein-enriched functional food.

PubMed

van der Zanden, Lotte D T; van Kleef, Ellen; de Wijk, René A; van Trijp, Hans C M

2014-09-01

Promoting protein consumption in the elderly population may contribute to improving the quality of their later years in life. Our study aimed to explore knowledge, perceptions and preferences of elderly consumers regarding protein-enriched food. We conducted three focus groups with independently living (ID) elderly (N = 24, Mage = 67 years) and three with elderly living in a residential home (RH) (N = 18, Mage = 83 years). Both the ID and RH elderly were predominantly sceptical about functional food in general. Confusion, distrust and a perceived lack of personal relevance were main perceived barriers to purchasing and consuming these products, although a majority of the participants did report occasionally consuming at least one type of functional food. For the ID elderly, medical advice was an important facilitator that could overcome barriers to purchasing and consuming protein-enriched food, indicating the importance of personal relevance for this group. For the RH elderly, in contrast, sensory appeal of protein-enriched foods was a facilitator. Carrier preferences were similar for the two groups; the elderly preferred protein-enriched foods based on healthy products that they consumed frequently. Future studies should explore ways to deal with the confusion and distrust regarding functional food within the heterogeneous population of elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

Joint laxity and the relationship between muscle strength and functional ability in patients with osteoarthritis of the knee.

PubMed

van der Esch, M; Steultjens, M; Knol, D L; Dinant, H; Dekker, J

2006-12-15

To establish the impact of knee joint laxity on the relationship between muscle strength and functional ability in osteoarthritis (OA) of the knee. A cross-sectional study of 86 patients with OA of the knee was conducted. Tests were performed to determine varus-valgus laxity, muscle strength, and functional ability. Laxity was assessed using a device that measures the angular deviation of the knee in the frontal plane. Muscle strength was measured using a computer-driven isokinetic dynamometer. Functional ability was assessed by observation (100-meter walking test) and self report (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]). Regression analyses were performed to assess the impact of joint laxity on the relationship between muscle strength and functional ability. In regression analyses, the interaction between muscle strength and joint laxity contributed to the variance in both walking time (P = 0.002) and WOMAC score (P = 0.080). The slope of the regression lines indicated that the relationship between muscle strength and functional ability (walking time, WOMAC) was stronger in patients with high knee joint laxity. Patients with knee OA and high knee joint laxity show a stronger relationship between muscle strength and functional ability than patients with OA and low knee joint laxity. Patients with OA, high knee joint laxity, and low muscle strength are most at risk of being disabled.

Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space.

PubMed

Payne, Anthony M; Dodd, Stephen L; Leeuwenburgh, Christiaan

2003-12-01

The decline in muscle function is associated with an age-related decrease in muscle mass and an age-related decline in strength. However, decreased strength is not solely due to decreased muscle mass. The age-related decline in muscle-specific force (force/muscle cross-sectional area), a measure of intrinsic muscle function, also contributes to age-related strength decline, and the mechanisms by which this occurs are only partially known. Moreover, changes in the extracellular space could have a profound effect on skeletal muscle function. Life-long calorie restriction in rodents has shown to be a powerful anti-aging intervention. In this study, we examine whether calorie restriction is able to attenuate the loss of muscle function and elevations in extracellular space associated with aging. We hypothesize that calorie restriction attenuates the age-associated decline in specific force and increases in extracellular space. Measurements of in vitro contractile properties of the extensor digitorum longus (type II) and soleus (type I) muscles from 12-mo and 26- to 28-mo-old ad libitum-fed, as well as 27- to 28-mo-old life-long calorie-restricted male Fischer 344 rats, were performed. We found that calorie restriction attenuated the age-associated decline in muscle mass-to-body mass ratio (mg/g) and strength-to-body mass ratio (N/kg) in the extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle (P > 0.05). Importantly, muscle-specific force (N/cm2) in the extensor digitorum longus, but not in the soleus muscle, of the old calorie-restricted rats was equal to that of the young 12-mo-old animals. Moreover, the age-associated increase in extracellular space was reduced in the fast-twitch extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle with calorie restriction. We also found a significant correlation between the extracellular space and the muscle-specific force in the extensor digitorum longus (r = -0.58; P < 0.05) but not in the soleus muscle (r = -0.38; P > 0.05). Hence, this study shows a loss of muscle function with age and suggests that long-term calorie restriction is an effective intervention against the loss of muscle function with age.

Functional recovery of completely denervated muscle: implications for innervation of tissue-engineered muscle.

PubMed

Kang, Sung-Bum; Olson, Jennifer L; Atala, Anthony; Yoo, James J

2012-09-01

Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and to restore muscle function. To achieve functional recovery, engineered muscle tissue requires integration of the host nerve. In this study, we investigated whether denervated muscle, which is analogous to tissue-engineered muscle tissue, can be reinnervated and can recover muscle function using an in vivo model of denervation followed by neurotization. The outcomes of this investigation may provide insights on the ability of tissue-engineered muscle to integrate with the host nerve and acquire normal muscle function. Eighty Lewis rats were classified into three groups: a normal control group (n=16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n=32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft into the muscle (n=32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200 were performed at 2, 4, 8, and 12 weeks (n=8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks postsurgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0±38.9 vs. 26.3±13.8 g, p<0.001; WRL, 2.7±2.30 vs. 8.3±5.5 s, p=0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group (p<0.001, one-way analysis of variance), and at 12 weeks postsurgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9±0.0 vs. 1.3±0.7 ms, p=0.164; amplitude, 30.2±7.0 vs. 46.4±26.9 mV, p=0.184). Histologically, regeneration of neuromuscular junctions was seen in the transplantation group. This study indicates that transplanted nerve tissue is able to regenerate neuromuscular junctions within denervated muscle, and thus the muscle can recover partial function. However, the function of the denervated muscle remains in the subnormal range even at 12 weeks after direct nerve transplantation. These results suggest that tissue-engineered muscle, which is similarly denervated, could be innervated and become functional in vivo if it is properly integrated with the host nerve.

Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers.

PubMed

Roche, Stuart M; Gumucio, Jonathan P; Brooks, Susan V; Mendias, Christopher L; Claflin, Dennis R

2015-06-16

Analysis of the contractile properties of chemically skinned, or permeabilized, skeletal muscle fibers offers a powerful means by which to assess muscle function at the level of the single muscle cell. Single muscle fiber studies are useful in both basic science and clinical studies. For basic studies, single muscle fiber contractility measurements allow investigation of fundamental mechanisms of force production, and analysis of muscle function in the context of genetic manipulations. Clinically, single muscle fiber studies provide useful insight into the impact of injury and disease on muscle function, and may be used to guide the understanding of muscular pathologies. In this video article we outline the steps required to prepare and isolate an individual skeletal muscle fiber segment, attach it to force-measuring apparatus, activate it to produce maximum isometric force, and estimate its cross-sectional area for the purpose of normalizing the force produced.

Re-animation of muscle flaps for improved function in dynamic myoplasty.

PubMed

Stremel, R W; Zonnevijlle, E D

2001-01-01

The authors report on a series of experiments designed to produce a skeletal muscle contraction functional for dynamic myoplasties. Conventional stimulation techniques recruit all or most of the muscle fibers simultaneously and with maximal strength. This approach has limitations in free dynamic muscle flap transfers that require the muscle to contract immediately after transfer and before re-innervation. Sequential stimulation of segments of the transferred muscle provides a means of producing non-fatiguing contractions of the muscle in the presence or absence of innervation. The muscles studied were the canine gracilis, and all experiments were acute studies in anesthetized animals. Comparison of conventional and sequential segmental neuromuscular stimulation revealed an increase in muscle fatigue resistance and muscle blood flow with the new approach. This approach offers the opportunity for development of physiologically animated tissue and broadening the abilities of reconstructive surgeons in the repair of functional defects. Copyright 2001 Wiley-Liss, Inc.

Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases

PubMed Central

Ultimo, Simona; Zauli, Giorgio; Martelli, Alberto M.; Vitale, Marco; McCubrey, James A.; Capitani, Silvano; Neri, Luca M.

2018-01-01

Skeletal muscle is a dynamic tissue with remarkable plasticity and its growth and regeneration are highly organized, with the activation of specific transcription factors, proliferative pathways and cytokines. The decline of skeletal muscle tissue with age, is one of the most important causes of functional loss of independence in older adults. Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. Physical activity represents one of the most effective preventive agents for muscle decay in aging. Several studies have underlined the importance of microRNAs (miRNAs) in the control of myogenesis and of skeletal muscle regeneration and function. In this review, we reported an overview and recent advances about the role of miRNAs expressed in the skeletal muscle, miRNAs regulation by exercise in skeletal muscle, the consequences of different physical exercise training modalities in the skeletal muscle miRNA profile, their regulation under pathological conditions and the role of miRNAs in age-related muscle wasting. Specific miRNAs appear to be involved in response to different types of exercise and therefore to play an important role in muscle fiber identity and myofiber gene expression in adults and elder population. Understanding the roles and regulation of skeletal muscle miRNAs during muscle regeneration may result in new therapeutic approaches in aging or diseases with impaired muscle function or re-growth. PMID:29682218

Force recovery and axonal regeneration of the sternomastoid muscle reinnervated with the end-to-end nerve anastomosis

PubMed Central

Sobotka, Stanislaw; Mu, Liancai

2012-01-01

Background End-to-end nerve anastomosis (EEA) is a commonly used nerve repair technique. However, this method generally results in poor functional recovery. This study was designed to determine the correlation of functional recovery to the extent of axonal reinnervation after EEA procedure in a rat model. Materials and Methods Seven adult rats were subjected to the immediate reinnervation of an experimentally paralyzed sternomastoid (SM) muscle. The SM nerve was transected and immediately repaired with EEA. The SM muscle at the opposite side, without nerve transection, served as a control. Three months after EEA nerve repair, the muscle force of the SM muscle was measured and the regenerated axons in the muscle were detected using neurofilament immunohistochemistry. Results Three months after surgery, the reinnervated SM muscle produced limited anatomical and functional recovery (calculated as the percentage of the control). Specifically, the wet weight of the operated SM muscle (a measure of muscle mass recovery) was 78.0% of the control. The maximal tetanic force (a measure of muscle functional recovery) was 56.7% of the control. The area fraction of the neurofilament stained intramuscular axons (a measure of axonal regeneration and muscle reinnervation) was measured to be only 13.4% of the control. A positive correlation was revealed between the extent of muscle reinnervation and maximal muscle force. Conclusions The EEA reinnervated SM muscle in the rat yielded unsatisfactory muscle force recovery as a result of mild to moderate nerve regeneration. Further work is needed to improve the surgical procedure, enhance axonal regeneration, and/or develop novel treatment strategies for better functional recovery. PMID:23207170

Force recovery and axonal regeneration of the sternomastoid muscle reinnervated with the end-to-end nerve anastomosis.

PubMed

Sobotka, Stanislaw; Mu, Liancai

2013-06-15

End-to-end nerve anastomosis (EEA) is a commonly used nerve repair technique. However, this method generally results in poor functional recovery. This study was designed to determine the correlation of functional recovery to the extent of axonal reinnervation after EEA procedure in a rat model. Seven adult rats were subjected to the immediate reinnervation of an experimentally paralyzed sternomastoid (SM) muscle. The SM nerve was transected and immediately repaired with EEA. The SM muscle at the opposite side, without nerve transection, served as a control. Three months after EEA nerve repair, the muscle force of the SM muscle was measured and the regenerated axons in the muscle were detected using neurofilament immunohistochemistry. Three months after surgery, the reinnervated SM muscle produced limited anatomical and functional recovery (calculated as the percentage of the control). Specifically, the wet weight of the operated SM muscle (a measure of muscle mass recovery) was 78.0% of the control. The maximal tetanic force (a measure of muscle functional recovery) was 56.7% of the control. The area fraction of the neurofilament stained intramuscular axons (a measure of axonal regeneration and muscle reinnervation) was measured to be only 13.4% of the control. A positive correlation was revealed between the extent of muscle reinnervation and maximal muscle force. The EEA reinnervated SM muscle in the rat yielded unsatisfactory muscle force recovery as a result of mild to moderate nerve regeneration. Further work is needed to improve the surgical procedure, enhance axonal regeneration, and/or develop novel treatment strategies for better functional recovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function.

PubMed

Jeong, Youngjae; Daghlas, Salah A; Kahveci, Alp S; Salamango, Daniel; Gentry, Bettina A; Brown, Marybeth; Rector, R Scott; Pearsall, R Scott; Phillips, Charlotte L

2018-02-01

Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfecta murine (oim) and +/G610C. Wild-type (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with Tris-buffered saline (vehicle) or sActRIIB-mFc and their hindlimb muscles evaluated for mass, morphology, and contractile function. sActRIIB-mFc-treated WT, +/G610C, and oim/oim mice had increased hindlimb muscle weights and myofiber cross-sectional area compared with vehicle-treated counterparts. sActRIIB-mFc-treated oim/oim mice also exhibited increased contractile function relative to vehicle-treated counterparts. Blocking endogenous ActRIIB was effective at increasing muscle size in mouse models of OI, and increasing contractile function in oim/oim mice. ActRIIB inhibitors may provide a potential mutation-specific therapeutic option for compromised muscle function in OI. Muscle Nerve 57: 294-304, 2018. © 2017 Wiley Periodicals, Inc.

Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish.

PubMed

Housley, Michael P; Njaine, Brian; Ricciardi, Filomena; Stone, Oliver A; Hölper, Soraya; Krüger, Marcus; Kostin, Sawa; Stainier, Didier Y R

2016-06-01

Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy.

Functional β-Adrenoceptors Are Important for Early Muscle Regeneration in Mice through Effects on Myoblast Proliferation and Differentiation

PubMed Central

Church, Jarrod E.; Trieu, Jennifer; Sheorey, Radhika; Chee, Annabel Y. -M.; Naim, Timur; Baum, Dale M.; Ryall, James G.; Gregorevic, Paul; Lynch, Gordon S.

2014-01-01

Muscles can be injured in different ways and the trauma and subsequent loss of function and physical capacity can impact significantly on the lives of patients through physical impairments and compromised quality of life. The relative success of muscle repair after injury will largely determine the extent of functional recovery. Unfortunately, regenerative processes are often slow and incomplete, and so developing novel strategies to enhance muscle regeneration is important. While the capacity to enhance muscle repair by stimulating β2-adrenoceptors (β-ARs) using β2-AR agonists (β2-agonists) has been demonstrated previously, the exact role β-ARs play in regulating the regenerative process remains unclear. To investigate β-AR-mediated signaling in muscle regeneration after myotoxic damage, we examined the regenerative capacity of tibialis anterior and extensor digitorum longus muscles from mice lacking either β1-AR (β1-KO) and/or β2-ARs (β2-KO), testing the hypothesis that muscles from mice lacking the β2-AR would exhibit impaired functional regeneration after damage compared with muscles from β1-KO or β1/β2-AR null (β1/β2-KO) KO mice. At 7 days post-injury, regenerating muscles from β1/β2-KO mice produced less force than those of controls but muscles from β1-KO or β2-KO mice did not exhibit any delay in functional restoration. Compared with controls, β1/β2-KO mice exhibited an enhanced inflammatory response to injury, which delayed early muscle regeneration, but an enhanced myoblast proliferation later during regeneration ensured a similar functional recovery (to controls) by 14 days post-injury. This apparent redundancy in the β-AR signaling pathway was unexpected and may have important implications for manipulating β-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury. PMID:25000590

Skeletal muscle and fetal alcohol spectrum disorder.

PubMed

Myrie, Semone B; Pinder, Mark A

2018-04-01

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

Pulmonary Function, Muscle Strength and Mortality in Old Age

PubMed Central

Buchman, A. S.; Boyle, P. A.; Wilson, R.S.; Gu, Liping; Bienias, Julia L.; Bennett, D. A.

2009-01-01

Numerous reports have linked extremity muscle strength with mortality but the mechanism underlying this association is not known. We used data from 960 older persons without dementia participating in the Rush Memory and Aging Project to test two sequential hypotheses: first, that extremity muscle strength is a surrogate for respiratory muscle strength, and second, that the association of respiratory muscle strength with mortality is mediated by pulmonary function. In a series of proportional hazards models, we first demonstrated that the association of extremity muscle strength with mortality was no longer significant after including a term for respiratory muscle strength, controlling for age, sex, education, and body mass index. Next, the association of respiratory muscle strength with mortality was attenuated by more than 50% and no longer significant after including a term for pulmonary function. The findings were unchanged after controlling for cognitive function, parkinsonian signs, physical frailty, balance, physical activity, possible COPD, use of pulmonary medications, vascular risk factors including smoking, chronic vascular diseases, musculoskeletal joint pain, and history of falls. Overall, these findings suggest that pulmonary function may partially account for the association of muscle strength and mortality. PMID:18755207

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

PubMed Central

Corona, Benjamin T.; Ward, Catherine L.; Baker, Hannah B.; Walters, Thomas J.

2014-01-01

The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following TEMR implantation (BAM+MDCs) was 2.3×-fold greater than that observed following implantation of BAM alone. As such, this finding further underscores the potential benefits of including a cellular component in the tissue engineering strategy for VML injury. PMID:24066899

Health care needs of children with Down syndrome and impact of health system performance on children and their families.

PubMed

Phelps, Randall A; Pinter, Joseph D; Lollar, Donald J; Medlen, Joan Guthrie; Bethell, Christina D

2012-04-01

The functional, financial, and social impact on families of children with Down syndrome (DS) in the United States and the role of the US health care system in ameliorating these impacts have not been well characterized. We sought to describe the demographic characteristics and functional difficulties of these children and to determine whether children with DS, compared with children with "intellectual disability" (ID) generally, and compared with other "children and youth with special health care needs" (CYSHCN), are more or less likely to receive health care that meets quality standards related to care coordination and to have their health care service needs met. This study analyzed data from the 2005-2006 National Survey of Children with Special Health Care Needs (n = 40,723). Children and youth aged 0 to 17 years with special health care need (CYSHCN) who experience DS (n = 395) and/or IDs (n = 4252) were compared with each other and other CYSHCN on a range of functioning, family impact, and health care quality variables using bivariate and multivariate methods. Data were weighted to represent all CYSHCN in the United States. Compared with CYSHCN without DS, children with DS were significantly less likely to receive comprehensive care within a medical home (29.7% vs 47.3%; p < .001). Parents of children with DS were also significantly more likely to cut back or stop work due to their child's health needs (23.5% vs 55.1%; p < .001). Although overall system performance was poorer for children with DS compared with those with ID and no DS after adjustment for family income, prevalence on most aspects of quality of care and family impacts evaluated were similar for these 2 groups. In this study, the families of children with DS, and ID generally, are burdened disproportionately when compared with other CYSHCN, reflecting the combination of impairments intrinsic to DS and ID and impacts of suboptimal medical care coordination and social support.

E2F function in muscle growth is necessary and sufficient for viability in Drosophila

PubMed Central

Zappia, Maria Paula; Frolov, Maxim V.

2016-01-01

The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

Skeletal Muscle Ultrasonography in Nutrition and Functional Outcome Assessment of Critically Ill Children: Experience and Insights From Pediatric Disease and Adult Critical Care Studies [Formula: see text].

PubMed

Ong, Chengsi; Lee, Jan Hau; Leow, Melvin K S; Puthucheary, Zudin A

2017-09-01

Evidence suggests that critically ill children develop muscle wasting, which could affect outcomes. Muscle ultrasound has been used to track muscle wasting and association with outcomes in critically ill adults but not children. This review aims to summarize methodological considerations of muscle ultrasound, structural findings, and possibilities for its application in the assessment of nutrition and functional outcomes in critically ill children. Medline, Embase, and CINAHL databases were searched up until April 2016. Articles describing skeletal muscle ultrasound in children and critically ill adults were analyzed qualitatively for details on techniques and findings. Thickness and cross-sectional area of various upper and lower body muscles have been studied to quantify muscle mass and detect muscle changes. The quadriceps femoris muscle is one of the most commonly measured muscles due to its relation to mobility and is sensitive to changes over time. However, the margin of error for quadriceps thickness is too wide to reliably detect muscle changes in critically ill children. Muscle size and its correlation with strength and function also have not yet been studied in critically ill children. Echogenicity, used to detect compromised muscle structure in neuromuscular disease, may be another property worth studying in critically ill children. Muscle ultrasound may be useful in detecting muscle wasting in critically ill children but has not been shown to be sufficiently reliable in this population. Further study of the reliability and correlation with functional outcomes and nutrition intake is required before muscle ultrasound is routinely employed in critically ill children.

Individual muscle control using an exoskeleton robot for muscle function testing.

PubMed

Ueda, Jun; Ming, Ding; Krishnamoorthy, Vijaya; Shinohara, Minoru; Ogasawara, Tsukasa

2010-08-01

Healthy individuals modulate muscle activation patterns according to their intended movement and external environment. Persons with neurological disorders (e.g., stroke and spinal cord injury), however, have problems in movement control due primarily to their inability to modulate their muscle activation pattern in an appropriate manner. A functionality test at the level of individual muscles that investigates the activity of a muscle of interest on various motor tasks may enable muscle-level force grading. To date there is no extant work that focuses on the application of exoskeleton robots to induce specific muscle activation in a systematic manner. This paper proposes a new method, named "individual muscle-force control" using a wearable robot (an exoskeleton robot, or a power-assisting device) to obtain a wider variety of muscle activity data than standard motor tasks, e.g., pushing a handle by hand. A computational algorithm systematically computes control commands to a wearable robot so that a desired muscle activation pattern for target muscle forces is induced. It also computes an adequate amount and direction of a force that a subject needs to exert against a handle by his/her hand. This individual muscle control method enables users (e.g., therapists) to efficiently conduct neuromuscular function tests on target muscles by arbitrarily inducing muscle activation patterns. This paper presents a basic concept, mathematical formulation, and solution of the individual muscle-force control and its implementation to a muscle control system with an exoskeleton-type robot for upper extremity. Simulation and experimental results in healthy individuals justify the use of an exoskeleton robot for future muscle function testing in terms of the variety of muscle activity data.

[Effects of a benzodiazepine derivative, MS4101, on emotional behaviour of untamed cats].

PubMed

Anezaki, K; Sakurada, S; Ando, R; Kisara, K; Nakahama, H

1976-09-01

Effects of MS4101 on emotional behaviour in untamed cats were studied and compared with those of diazepam. Offensive behaviour, i.e., whine response to a rod presented in front of the snout and blowing air on back hair was markedly observed, and whine, attacking and biting responses to tapping with a rod on the back in these cats were marked. Defensive behaviour, i.e., hissing, crouching body, ear flattening to blowing air on back hair, a rod presented and tapping was markedly observed. From 30 min after MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p., offensive behaviour in untamed cats was depressed. ID50 (50% of inhibition dose) of offensive behaviour for MS4101 and diazepam was 2.40 (1.95 approximately 2.95) mg/kg i.p. and 0.96 (0.69 approximately 1.34) mg/kg i.p., respectively. MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p. decreased the offensive behaviour. ID50 of defensive behaviour for MS4101 and diazepam was 3.00 (2.46 approximately 3.66) mg/kg i.p. and 1.45 (1.14 approximately 1.84) mg/kg i.p., respectively. Both MS4101 and diazepam exhibited muscle relaxant effects. Here, diazepam was more effective than MS4101. ED50 of muscle relaxant activity for MS4101 and diazepam was 4.30 (3.03 approximately 6.11) mg/kg i.p., 7.40 (5.04 approximately 10.66) mg/kg i.p., respectively. A single administration of MS4101 and of diazepam in doses 2 mg/kg i.p. enhanced food intake.

Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry.

PubMed

Luo, Haiming; Hernandez, Reinier; Hong, Hao; Graves, Stephen A; Yang, Yunan; England, Christopher G; Theuer, Charles P; Nickles, Robert J; Cai, Weibo

2015-10-13

Early diagnosis remains a task of upmost importance for reducing cancer morbidity and mortality. Successful development of highly specific companion diagnostics targeting aberrant molecular pathways of cancer is needed for sensitive detection, accurate diagnosis, and opportune therapeutic intervention. Herein, we generated a bispecific immunoconjugate [denoted as Bs-F(ab)2] by linking two antibody Fab fragments, an anti-epidermal growth factor receptor (EGFR) Fab and an anti-CD105 Fab, via bioorthogonal "click" ligation of trans-cyclooctene and tetrazine. PET imaging of mice bearing U87MG (EGFR/CD105(+/+)) tumors with (64)Cu-labeled Bs-F(ab)2 revealed a significantly enhanced tumor uptake [42.9 ± 9.5 percentage injected dose per gram (%ID/g); n = 4] and tumor-to-background ratio (tumor/muscle ratio of 120.2 ± 44.4 at 36 h postinjection; n = 4) compared with each monospecific Fab tracer. Thus, we demonstrated that dual targeting of EGFR and CD105 provides a synergistic improvement on both affinity and specificity of (64)Cu-NOTA-Bs-F(ab)2. (64)Cu-NOTA-Bs-F(ab)2 was able to visualize small U87MG tumor nodules (<5 mm in diameter), owing to high tumor uptake (31.4 ± 10.8%ID/g at 36 h postinjection) and a tumor/muscle ratio of 76.4 ± 52.3, which provided excellent sensitivity for early detection. Finally, we successfully confirmed the feasibility of a ZW800-1-labeled Bs-F(ab)2 for near-infrared fluorescence imaging and image-guided surgical resection of U87MG tumors. More importantly, our rationale can be used in the construction of other disease-targeting bispecific antibody fragments for early detection and diagnosis of small malignant lesions.

Isotopic discrimination of stable isotopes of nitrogen (δ15N) and carbon (δ13C) in a host-specific holocephalan tapeworm.

PubMed

Navarro, J; Albo-Puigserver, M; Coll, M; Saez, R; Forero, M G; Kutcha, R

2014-09-01

During the past decade, parasites have been considered important components of their ecosystems since they can modify food-web structures and functioning. One constraint to the inclusion of parasites in food-web models is the scarcity of available information on their feeding habits and host-parasite relationships. The stable isotope approach is suggested as a useful methodology to determine the trophic position and feeding habits of parasites. However, the isotopic approach is limited by the lack of information on the isotopic discrimination (ID) values of parasites, which is pivotal to avoiding the biased interpretation of isotopic results. In the present study we aimed to provide the first ID values of δ(15)N and δ(13)C between the gyrocotylidean tapeworm Gyrocotyle urna and its definitive host, the holocephalan Chimaera monstrosa. We also test the effect of host body size (body length and body mass) and sex of the host on the ID values. Finally, we illustrate how the trophic relationships of the fish host C. monstrosa and the tapeworm G. urna could vary relative to ID values. Similar to other studies with parasites, the ID values of the parasite-host system were negative for both isotopic values of N (Δδ(15)N = - 3.33 ± 0.63‰) and C (Δδ(13)C = - 1.32 ± 0.65‰), independent of the sex and size of the host. By comparing the specific ID obtained here with ID from other studies, we illustrate the importance of using specific ID in parasite-host systems to avoid potential errors in the interpretation of the results when surrogate values from similar systems or organisms are used.

Assessing theory of mind nonverbally in those with intellectual disability and ASD: the penny hiding game.

PubMed

San José Cáceres, Antonia; Keren, Noa; Booth, Rhonda; Happé, Francesca

2014-10-01

Individuals with autism spectrum disorder (ASD) and low intellectual/language abilities are often omitted from experimental studies because of the challenges of testing these individuals. It is vital to develop appropriate and accessible tasks so that this significant part of the spectrum is not neglected. The theory of mind (ToM) has been extensively assessed in ASD, predominantly in relatively high-functioning individuals with reasonable language skills. This study aims to assess the ToM abilities of a sample of 132 participants with intellectual disability (ID) with and without ASD, matched in verbal mental age (VMA) and chronological age, using a naturalistic and nonverbal deception task: the Penny Hiding Game (PHG). The relationship between performance on the PHG and everyday adaptation was also studied. The PHG proved accessible to most participants, suggesting its suitability for use with individuals with low cognitive skills, attentional problems, and limited language. The ASD + ID group showed significantly more PHG errors, and fewer tricks, than the ID group. PHG performance correlated with Vineland adaptation scores for both groups. VMA was a major predictor of passing the task in both groups, and participants with ASD + ID required, on average, 2 years higher VMA than those with ID only, to achieve the same level of PHG success. VMA moderated the association between PHG performance and real-life social skills for the ASD + ID more than the ID group, suggesting that severely impaired individuals with ASD may rely on verbal ability to overcome their social difficulties, whereas individuals with ID alone may use more intuitive social understanding both in the PHG and everyday situations. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Improved adductor function after canine recurrent laryngeal nerve injury and repair using muscle progenitor cells.

PubMed

Paniello, Randal C; Brookes, Sarah; Bhatt, Neel K; Bijangi-Vishehsaraei, Khadijeh; Zhang, Hongji; Halum, Stacey

2017-12-08

Muscle progenitor cells (MPCs) can be isolated from muscle samples and grown to a critical mass in culture. They have been shown to survive and integrate when implanted into rat laryngeal muscles. In this study, the ability of MPC implants to enhance adductor function of reinnervated thyroarytenoid muscles was tested in a canine model. Animal study. Sternocleidomastoid muscle samples were harvested from three canines. Muscle progenitor cells were isolated and cultured to 10 7 cells over 4 to 5 weeks, then implanted into right thyroarytenoid muscles after ipsilateral recurrent laryngeal nerve transection and repair. The left sides underwent the same nerve injury, but no cells were implanted. Laryngeal adductor force was measured pretreatment and again 6 months later, and the muscles were harvested for histology. Muscle progenitor cells were successfully cultured from all dogs. Laryngeal adductor force measurements averaged 60% of their baseline pretreatment values in nonimplanted controls, 98% after implantation with MPCs, and 128% after implantation with motor endplate-enhanced MPCs. Histology confirmed that the implanted MPCs survived, became integrated into thyroarytenoid muscle fibers, and were in close contact with nerve endings, suggesting functional innervation. Muscle progenitor cells were shown to significantly enhance adductor function in this pilot canine study. Patient-specific MPC implantation could potentially be used to improve laryngeal function in patients with vocal fold paresis/paralysis, atrophy, and other conditions. Further experiments are planned. NA. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Molecular and Cellular Mechanisms of Muscle Aging and Sarcopenia and Effects of Electrical Stimulation in Seniors.

PubMed

Barber, Laura; Scicchitano, Bianca Maria; Musaro, Antonio

2015-08-24

The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers), alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors..

A comprehensive framework for functional diversity patterns of marine chromophytic phytoplankton using rbcL phylogeny

PubMed Central

Samanta, Brajogopal; Bhadury, Punyasloke

2016-01-01

Marine chromophytes are taxonomically diverse group of algae and contribute approximately half of the total oceanic primary production. To understand the global patterns of functional diversity of chromophytic phytoplankton, robust bioinformatics and statistical analyses including deep phylogeny based on 2476 form ID rbcL gene sequences representing seven ecologically significant oceanographic ecoregions were undertaken. In addition, 12 form ID rbcL clone libraries were generated and analyzed (148 sequences) from Sundarbans Biosphere Reserve representing the world’s largest mangrove ecosystem as part of this study. Global phylogenetic analyses recovered 11 major clades of chromophytic phytoplankton in varying proportions with several novel rbcL sequences in each of the seven targeted ecoregions. Majority of OTUs was found to be exclusive to each ecoregion, whereas some were shared by two or more ecoregions based on beta-diversity analysis. Present phylogenetic and bioinformatics analyses provide a strong statistical support for the hypothesis that different oceanographic regimes harbor distinct and coherent groups of chromophytic phytoplankton. It has been also shown as part of this study that varying natural selection pressure on form ID rbcL gene under different environmental conditions could lead to functional differences and overall fitness of chromophytic phytoplankton populations. PMID:26861415

Potential effect of exercise in ameliorating insulin resistance at transcriptome level.

PubMed

Hu, Zhigang; Zhou, Lei; He, Tingting

2017-10-24

Insulin resistance can lead to the pathogenesis of type 2 diabetes and exercise can increase insulin sensitivity. And different exercises may have different influences on the mitigation of insulin resistance. It's still unclear how exercise affects inherited insulin resistance at transcriptome level. The purpose of our study was to analyze the potential effects of exercise in ameliorating insulin resistance at transcriptome level. Herein, we analyzed two skeletal muscle transcriptome profiles, including gene profiles between inherited insulin resistant patients and matched healthy controls, and between trained and sedentary subjects (young and old subjects, respectively). Analysis of differentially expressed genes revealed that 12 genes (SGK1, LOC101929876, MYL5, COL6A3, MLF1, LUM, MSTN, COL1A2, COL3A1, IL32, IRS2 and ID1) associated with insulin resistance were reversed by exercise in young subjects, while six genes (MSTN, CFHR1, PFKFB3, IL32, RGCC and NMRK2) were identified in old subjects, suggesting that those genes play potential roles in insulin resistance response to exercise. In addition, we observed that two insulin resistance-related genes, MSTN and IL32, were identified in muscle cells of both young and old subjects, indicating their important roles in the mechanisms behind the beneficial effects of exercise on humans with inherited insulin resistance. Several pathways were also identified, such as "collagen metabolic process", "focal adhesion" and "negative regulation of myoblast differentiation". Taken together, our findings provide novel markers in insulin resistant patients and exercise, and some valuable information for future functional studies on how exercise ameliorating insulin resistance.

Return to play after thigh muscle injury in elite football players: implementation and validation of the Munich muscle injury classification

PubMed Central

Ekstrand, Jan; Askling, Carl; Magnusson, Henrik; Mithoefer, Kai

2013-01-01

Background Owing to the complexity and heterogeneity of muscle injuries, a generally accepted classification system is still lacking. Aims To prospectively implement and validate a novel muscle injury classification and to evaluate its predictive value for return to professional football. Methods The recently described Munich muscle injury classification was prospectively evaluated in 31 European professional male football teams during the 2011/2012 season. Thigh muscle injury types were recorded by team medical staff and correlated to individual player exposure and resultant time-loss. Results In total, 393 thigh muscle injuries occurred. The muscle classification system was well received with a 100% response rate. Two-thirds of thigh muscle injuries were classified as structural and were associated with longer lay-off times compared to functional muscle disorders (p<0.001). Significant differences were observed between structural injury subgroups (minor partial, moderate partial and complete injuries) with increasing lay-off time associated with more severe structural injury. Median lay-off time of functional disorders was 5–8 days without significant differences between subgroups. There was no significant difference in the absence time between anterior and posterior thigh injuries. Conclusions The Munich muscle classification demonstrates a positive prognostic validity for return to play after thigh muscle injury in professional male football players. Structural injuries are associated with longer average lay-off times than functional muscle disorders. Subclassification of structural injuries correlates with return to play, while subgrouping of functional disorders shows less prognostic relevance. Functional disorders are often underestimated clinically and require further systematic study. PMID:23645834

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PubMed

Guinan, Emer M; Doyle, S L; Bennett, A E; O'Neill, L; Gannon, J; Elliott, J A; O'Sullivan, J; Reynolds, J V; Hussey, J

2018-05-01

Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Electromiography comparison of distal and proximal lower limb muscle activity patterns during external perturbation in subjects with and without functional ankle instability.

PubMed

Kazemi, Khadijeh; Arab, Amir Massoud; Abdollahi, Iraj; López-López, Daniel; Calvo-Lobo, César

2017-10-01

Ankle sprain is one of the most common injuries among athletes and the general population. Most ankle injuries commonly affect the lateral ligament complex. Changes in postural sway and hip abductor muscle strength may be generated after inversion ankle sprain. Therefore, the consequences of ankle injury may affect proximal structures of the lower limb. The aim is to describe and compare the activity patterns of distal and proximal lower limb muscles following external perturbation in individuals with and without functional ankle instability. The sample consisted of 16 women with functional ankle instability and 18 healthy women were recruited to participate in this research. The external perturbation via body jacket using surface electromyography, amplitude and onset of muscle activity of gluteus maximums, gluteus medius, tibialis anterior, and peroneus longus was recorded and analyzed during external perturbation. There were differences between the onset of muscles activity due to perturbation direction in the two groups (healthy and functional ankle instability). In the healthy group, there were statistically significant differences in amplitude of proximal muscle activity with distal muscle activity during front perturbation with eyes open and closed. In the functional ankle instability group; there were statistically significant differences in amplitude of proximal muscle activity with distal muscle activity during perturbation of the front and back with eyes open. There were statistically significant differences in the onset of muscle activity and amplitude of muscle activity, with-in and between groups (P<0.05). Therefore, in the presence of functional ankle instability, activation patterns of the lower limb proximal muscles may be altered. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional classification of skeletal muscle networks. I. Normal physiology

PubMed Central

Wang, Yu; Winters, Jack

2012-01-01

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Benefit of pelvic floor muscle therapy in improving sexual function in women with stress urinary incontinence: a pretest-posttest intervention study.

PubMed

Serati, Maurizio; Braga, Andrea; Di Dedda, Maria Carmela; Sorice, Paola; Peano, Elena; Biroli, Antonella; Torella, Marco; Cromi, Antonella; Uccella, Stefano; Salvatore, Stefano; Ghezzi, Fabio

2015-01-01

Very few data are available on the effect of pelvic floor muscle training on sexual function in incontinent women. The authors used the Female Sexual Function Index to assess the effect of pelvic floor muscle training on female sexual function. Participants included women with stress urinary incontinence, without overactive bladder symptoms, who completed a 3-month pelvic floor muscle training. All patients completed the Female Sexual Function Index and the International Consultation on Incontinence Questionnaire-Short Form at baseline and at the 3-month follow-up. Thirty-four patients completed all of the questionnaires; 64.7% patients were referred with stress urinary incontinence without sexual disorders, while 35.3% complained of stress urinary incontinence and sexual symptoms. The International Consultation on Incontinence Questionnaire-Short Form score significantly decreased after 3 months of pelvic floor muscle training (p =.01). The Female Sexual Function Index score significantly improved after pelvic floor muscle training even in women with sexual disorders (12.5 ± 9.5 vs. 29.7 ± 3.7; p <.001). This study showed that pelvic floor muscle training may improve female sexual function in women with pure stress urinary incontinence.

Safe Gene Therapy for Type 1 Diabetes

DTIC Science & Technology

2011-10-01

together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability...together with FoxP3+eGFP+ T- regulatory cells into prediabetic ID-TEC pups. Diabetes incidence and progression will be monitored. As well, the ability of...10. In addition, we will continue to investigate their potential therapeutic function in halting the progression of islet-autoimmunity in prediabetic

Group Centric Networking: Addressing Information Sharing Requirements at the Tactical Edge

DTIC Science & Technology

2016-04-10

gateways are typically used to translate information from one network to another. The challenge with gateways is to understand what information...should be relayed from one network to another (with different message formats and technologies) and what platform should perform the gateway function such...information centric paradigm in that GCN does not specify what constitutes a group ID. Group IDs can be mapped to named data objects, content identifiers

A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients.

PubMed

Curie, Aurore; Brun, Amandine; Cheylus, Anne; Reboul, Anne; Nazir, Tatjana; Bussy, Gérald; Delange, Karine; Paulignan, Yves; Mercier, Sandra; David, Albert; Marignier, Stéphanie; Merle, Lydie; de Fréminville, Bénédicte; Prieur, Fabienne; Till, Michel; Mortemousque, Isabelle; Toutain, Annick; Bieth, Eric; Touraine, Renaud; Sanlaville, Damien; Chelly, Jamel; Kong, Jian; Ott, Daniel; Kassai, Behrouz; Hadjikhani, Nouchine; Gollub, Randy L; des Portes, Vincent

2016-01-01

Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials. We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients. We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2). Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups. We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.

Participation in recreation and cognitive activities as a predictor of cognitive performance of adults with/without Down syndrome.

PubMed

Lifshitz-Vahav, Hefziba; Shnitzer, Shlomit; Mashal, Nira

2016-09-01

The Cognitive Activity Theory suggests an association between participation in cognitive activities during midlife and cognitive functioning in the short term. We examined the impact of participation in cognitively stimulating activities conveyed during leisure activities on crystallized and fluid tests' performance among adults with intellectual disabilities (ID). Adults (n = 32; chronological age = 25-55) with non-specific ID and with Down syndrome rated the frequency of their participation in leisure activities. Pursuits included more cognitively involving (reading, participating in academic courses) and less cognitively involving (cooking, dancing) activities. Three judges ranked activities according to their cognitive load on a 1 (few cognitive components) to 5 (many cognitive components) points scale. The findings indicate two new scales: cognitively stimulating activities and recreational stimulating activities. The crystallized battery included phonemic fluency, synonyms, idioms, and verbal metaphors. The fluid battery included the Homophone Meaning Generation Test, Metaphoric Triad Test, Novel Metaphors Test, and Trail Making Test. Hierarchal regression with chronological and mental age, recreational, and cognitively stimulating activities indicated that participation in recreational activities contributed significantly to the explained variance of word fluency. Participation in cognitive activities contributed significantly to the explained variance of most of the crystallized and fluid tests. The findings support the Cognitive Activity Theory in populations with ID. The findings also support the Compensation Age Theory: not only endogenous factors (age, etiology, IQ level), but also exogenous factors such as life style determining the cognitive functioning of adults with ID. However, frequency and the cognitive load of the activities influenced their cognitive functioning.

Plakins in striated muscle.

PubMed

Boyer, Justin G; Bernstein, Marija A; Boudreau-Larivière, Céline

2010-03-01

Striated muscle cells contain numerous architectural proteins that contribute to the function of muscle as generators of mechanical force. Among these proteins are crosslinkers belonging to the plakin family, namely plectin, microtubule-actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1 (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular plectin and Bpag1/dystonin, exist as several isoforms. The domain organization of these plakin variants dictates their subcellular location and the proteins with which they interact. Several studies suggest that plakins exert unique functions within various compartments of the muscle cell including the sarcolemma, the sarcomere, both neuromuscular and myotendinous junctions in skeletal muscle, and the intercalated discs in cardiac muscle. Plakins may also regulate the cellular placement and function of specific organelles, notably the nucleus, mitochondria, Golgi apparatus, and sarcoplasmic reticulum. Here we review and summarize our current knowledge of the function of plakins in striated muscle cells.

L-acetylcarnitine enhances functional muscle re-innervation.

PubMed

Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

1991-01-01

The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

Joint proprioception, muscle strength, and functional ability in patients with osteoarthritis of the knee.

PubMed

van der Esch, M; Steultjens, M; Harlaar, J; Knol, D; Lems, W; Dekker, J

2007-06-15

To test the hypotheses that poor knee joint proprioception is related to limitations in functional ability, and poor proprioception aggravates the impact of muscle weakness on limitations in functional ability in osteoarthritis (OA) of the knee. Sixty-three patients with symptomatic OA of the knee were tested. Proprioceptive acuity was assessed by establishing the joint motion detection threshold (JMDT) in the anteroposterior direction. Muscle strength was measured using a computer-driven isokinetic dynamometer. Functional ability was assessed by the 100-meter walking test, the Get Up and Go (GUG) test, and the Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) questionnaire. Correlation analyses were performed to assess the relationship between proprioception, muscle strength, and functional ability. Regression analyses were performed to assess the impact of proprioception on the relationship between muscle strength and functional ability. Poor proprioception (high JMDT) was related to more limitation in functional ability (walking time r = 0.30, P < 0.05; GUG time r = 0.30, P < 0.05; WOMAC-PF r = 0.26, P <0.05). In regression analyses, the interaction between proprioception and muscle strength was significantly related to functional ability (walking time, P < 0.001 and GUG time, P < 0.001) but not to WOMAC-PF score (P = 0.625). In patients with poor proprioception, reduction of muscle strength was associated with more severe deterioration of functional ability than in patients with accurate proprioception. Patients with poor proprioception show more limitation in functional ability, but this relationship is rather weak. In patients with poor proprioception, muscle weakness has a stronger impact on limitations in functional ability than in patients with accurate proprioception.

Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

PubMed

Buehring, B; Siglinsky, E; Krueger, D; Evans, W; Hellerstein, M; Yamada, Y; Binkley, N

2018-03-01

DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p < 0.0001) from one another with DXA total body less head being highest at 37.8 (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat chair rise. Lean mass measures were unrelated to the serum biomarkers measured. These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

Elevated PGC-1α activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS.

PubMed

Da Cruz, Sandrine; Parone, Philippe A; Lopes, Vanda S; Lillo, Concepción; McAlonis-Downes, Melissa; Lee, Sandra K; Vetto, Anne P; Petrosyan, Susanna; Marsala, Martin; Murphy, Anne N; Williams, David S; Spiegelman, Bruce M; Cleveland, Don W

2012-05-02

The transcriptional coactivator PGC-1α induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1α levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1α-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1α activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of balance training by knee joint motions on muscle activity in adult men with functional ankle instability.

PubMed

Nam, Seung-Min; Kim, Won-Bok; Yun, Chang-Kyo

2016-05-01

[Purpose] This study examined the effects of balance training by applying knee joint movements on muscle activity in male adults with functional ankle instability. [Subjects and Methods] 28 adults with functional ankle instability, divided randomly into an experimental group, which performed balance training by applying knee joint movements for 20 minutes and ankle joint exercises for 10 minutes, and a control group, which performed ankle joint exercise for 30 minutes. Exercises were completed three times a week for 8 weeks. Electromyographic values of the tibialis anterior, peroneus longus, peroneus brevis, and the lateral gastrocnemius muscles were obtained to compare and analyze muscle activity before and after the experiments in each group. [Results] The experimental group had significant increases in muscle activity in the tibialis anterior, peroneus longus, and lateral gastrocnemius muscles, while muscle activity in the peroneus brevis increased without significance. The control group had significant increases in muscle activity in the tibialis anterior and peroneus longus, while muscle activity in the peroneus brevis and lateral gastrocnemius muscles increased without significance. [Conclusion] In conclusion, balance training by applying knee joint movements can be recommended as a treatment method for patients with functional ankle instability.

3D Cell Printing of Functional Skeletal Muscle Constructs Using Skeletal Muscle-Derived Bioink.

PubMed

Choi, Yeong-Jin; Kim, Taek Gyoung; Jeong, Jonghyeon; Yi, Hee-Gyeong; Park, Ji Won; Hwang, Woonbong; Cho, Dong-Woo

2016-10-01

Engineered skeletal muscle tissues that mimic the structure and function of native muscle have been considered as an alternative strategy for the treatment of various muscular diseases and injuries. Here, it is demonstrated that 3D cell-printing of decellularized skeletal muscle extracellular matrix (mdECM)-based bioink facilitates the fabrication of functional skeletal muscle constructs. The cellular alignment and the shape of the tissue constructs are controlled by 3D cell-printing technology. mdECM bioink provides the 3D cell-printed muscle constructs with a myogenic environment that supports high viability and contractility as well as myotube formation, differentiation, and maturation. More interestingly, the preservation of agrin is confirmed in the mdECM, and significant increases in the formation of acetylcholine receptor clusters are exhibited in the 3D cell-printed muscle constructs. In conclusion, mdECM bioink and 3D cell-printing technology facilitate the mimicking of both the structural and functional properties of native muscle and hold great promise for producing clinically relevant engineered muscle for the treatment of muscular injuries. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vitamin D and muscle function in the elderly: the elixir of youth?

PubMed

Girgis, Christian M

2014-11-01

Circumstantial evidence suggests that vitamin D deficiency may contribute to age-related changes in skeletal muscle. This review discusses recent clinical trials examining effects of vitamin D on muscle function in the elderly, and poses the important question: can vitamin D reverse muscle ageing? Observational studies report an association between vitamin D and muscle atrophy/weakness in elderly subjects. Interventional studies suggest that frail, elderly subjects may benefit from vitamin D supplementation by displaying reduced falls, improved muscle function and increased muscle fibre size. However, meta-analyses do not report convincing effects of vitamin D in the elderly. This may be because of multiple factors including lack of standardized endpoints for muscle function, variable study design and different doses of vitamin D supplementation amongst these studies. The evidence base is therefore inconsistent. Vitamin D deficiency may exacerbate ageing of skeletal muscle. However, current evidence that vitamin D supplementation reverses age-related muscle dysfunction is equivocal and does not justify stringent vitamin D targets in the elderly. Until these issues are clarified, the safest option is to aim for conservative vitamin D targets that are sufficient for normal calcium homeostasis.

Muscle electrical stimulation improves neurovascular control and exercise tolerance in hospitalised advanced heart failure patients.

PubMed

Groehs, Raphaela V; Antunes-Correa, Ligia M; Nobre, Thais S; Alves, Maria-Janieire Nn; Rondon, Maria Urbana Pb; Barreto, Antônio Carlos Pereira; Negrão, Carlos E

2016-10-01

We investigated the effects of muscle functional electrical stimulation on muscle sympathetic nerve activity and muscle blood flow, and, in addition, exercise tolerance in hospitalised patients for stabilisation of heart failure. Thirty patients hospitalised for treatment of decompensated heart failure, class IV New York Heart Association and ejection fraction ≤ 30% were consecutively randomly assigned into two groups: functional electrical stimulation (n = 15; 54 ± 2 years) and control (n = 15; 49 ± 2 years). Muscle sympathetic nerve activity was directly recorded via microneurography and blood flow by venous occlusion plethysmography. Heart rate and blood pressure were evaluated on a beat-to-beat basis (Finometer), exercise tolerance by 6-minute walk test, quadriceps muscle strength by a dynamometer and quality of life by Minnesota questionnaire. Functional electrical stimulation consisted of stimulating the lower limbs at 10 Hz frequency, 150 ms pulse width and 70 mA intensity for 60 minutes/day for 8-10 consecutive days. The control group underwent electrical stimulation at an intensity of < 20 mA. Baseline characteristics were similar between groups, except age that was higher and C-reactive protein and forearm blood flow that were smaller in the functional electrical stimulation group. Functional electrical stimulation significantly decreased muscle sympathetic nerve activity and increased muscle blood flow and muscle strength. No changes were found in the control group. Walking distance and quality of life increased in both groups. However, these changes were greater in the functional electrical stimulation group. Functional electrical stimulation improves muscle sympathetic nerve activity and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised heart failure patients. These findings suggest that functional electrical stimulation may be useful to hospitalised patients with decompensated chronic heart failure. © The European Society of Cardiology 2016.

[Correlations Between Joint Proprioception, Muscle Strength, and Functional Ability in Patients with Knee Osteoarthritis].

PubMed

Chen, Yoa; Yu, Yong; He, Cheng-qi

2015-11-01

To establish correlations between joint proprioception, muscle flexion and extension peak torque, and functional ability in patients with knee osteoarthritis (OA). Fifty-six patients with symptomatic knee OA were recruited in this study. Both proprioceptive acuity and muscle strength were measured using the isomed-2000 isokinetic dynamometer. Proprioceptive acuity was evaluated by establishing the joint motion detection threshold (JMDT). Muscle strength was evaluated by Max torque (Nm) and Max torque/weight (Nm/ kg). Functional ability was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) questionnaire. Correlational analyses were performed between proprioception, muscle strength, and functional ability. A multiple stepwise regression model was established, with WOMAC-PF as dependent variable and patient age, body mass index (BMI), visual analogue scale (VAS)-score, mean grade for Kellgren-Lawrance of both knees, mean strength for quadriceps and hamstring muscles of both knees, and mean JMDT of both knees as independent variables. Poor proprioception (high JMDT) was negatively correlated with muscle strength (P<0.05). There was no significant correlation between knee proprioception (high JMDT) and joint pain (WOMAC pain score), and between knee proprioception (high JMDT) and joint stiffness (WOMAC stiffness score). Poor proprioception (high JMDT) was correlated with limitation in functional ability (WOMAC physical function score r=0.659, P<0.05). WOMAC score was correlated with poor muscle strength (quadriceps muscle strength r = -0.511, P<0.05, hamstring muscle strength r = -0.408, P<0.05). The multiple stepwise regression model showed that high JMDT C standard partial regression coefficient (B) = 0.385, P<0.50 and high VAS-scale score (B=0.347, P<0.05) were significant predictors of WOMAC-PF score. Patients with poor proprioception is associated with poor muscle strength and limitation in functional ability. Patients with symptomatic OA of knees commonly endure with moderate to considerable dysfunction, which is associated with poor proprioception (high JMDT) and high VAS-scale score.

Intermuscular Fat: A Review of the Consequences and Causes

PubMed Central

Marcus, Robin L.; LaStayo, Paul C.; Ryan, Alice S.

2014-01-01

Muscle's structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed. PMID:24527032

TERENA eScience PKI

NASA Astrophysics Data System (ADS)

Sova, Milan

Several National Research and Education Networks associated in TERENA have joined their efforts to build a shared PKI able to serve potentially millions of users from their constituency. The TCS eScience Personal CA takes advantage of national identity federations to facilitate user identity vetting and enrollment procedures. The system uses identity management systems (IdMS) at participating institutions to perform the functions of registration authorities. The certificate enrollment application acts as a SAML Service Provider relying on information provided by IdMS performing as SAML Identity Providers (IdP). When applying for a personal certificate, users authenticate at their home IdP using credentials they normally use to access local services. The IdP controls the certificate issuance process by releasing SAML attributes specifying the user's eligibility for the service and the information to be included in the certificate such as the user's name and email address. The TCS eScience Personal CA is part of the TERENA Certificate Service that uses a commercial PKI provider. Outsourcing the actual CA machinery to a specialized company results in professional-level services such as CRL and OCSP management. The paper describes the legal, organizational and technical aspects of the TCS eScience PKI.

Enhancing visual search abilities of people with intellectual disabilities.

PubMed

Li-Tsang, Cecilia W P; Wong, Jackson K K

2009-01-01

This study aimed to evaluate the effects of cueing in visual search paradigm for people with and without intellectual disabilities (ID). A total of 36 subjects (18 persons with ID and 18 persons with normal intelligence) were recruited using convenient sampling method. A series of experiments were conducted to compare guided cue strategies using either motion contrast or additional cue to basic search task. Repeated measure ANOVA and post hoc multiple comparison tests were used to compare each cue strategy. Results showed that the use of guided strategies was able to capture focal attention in an autonomic manner in the ID group (Pillai's Trace=5.99, p<0.0001). Both guided cue and guided motion search tasks demonstrated functionally similar effects that confirmed the non-specific character of salience. These findings suggested that the visual search efficiency of people with ID was greatly improved if the target was made salient using cueing effect when the complexity of the display increased (i.e. set size increased). This study could have an important implication for the design of the visual searching format of any computerized programs developed for people with ID in learning new tasks.

Vascular delay and administration of basic fibroblast growth factor augment latissimus dorsi muscle flap perfusion and function.

PubMed

Carroll, S M; Carroll, C M; Stremel, R W; Heilman, S J; Steffen, J M; Tobin, G R; Barker, J H

2000-03-01

Ischemia of the distal latissimus dorsi muscle flap occurs when the entire muscle is acutely elevated. Although this level of ischemia may not be critical if the muscle is to be used as a conventional muscle flap, the ischemia causes decreased distal muscle function if it is used for dynamic muscle flap transfer. This experiment was designed to determine whether or not the administration of exogenous basic fibroblast growth factor (bFGF), combined with a sublethal ischemic insult (i.e., vascular delay), would further augment muscle perfusion and function. Both latissimus dorsi muscles of nine canines were subjected to a bipedicle vascular delay procedure immediately followed by thoracodorsal intraarterial injection of 100 microg of bFGF on one side and by intraarterial injection of vehicle on the other. Ten days later, both latissimus dorsi muscles were raised as thoracodorsally based island flaps, with perfusion determined by laser-Doppler fluximetry. The muscles were wrapped around silicone chambers, simulating cardiomyoplasty, and stimulating electrodes were placed around each thoracodorsal nerve. The muscles were then subjected to an experimental protocol to determine muscle contractile function. At the end of the experiment, latissimus dorsi muscle biopsies were obtained for measurement of bFGF expression. The results demonstrated that the administration of 100 microg of bFGF immediately after the vascular delay procedure increases expression of native bFGF. In the distal and middle muscle segments, it also significantly increased muscle perfusion by approximately 20 percent and fatigue resistance by approximately 300 percent. The administration of growth factors may serve as an important adjuvant to surgical procedures using dynamic muscle flap transfers.

Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

PubMed

Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

2016-04-01

In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential.

PubMed

Black, Maureen M; Quigg, Anna M; Hurley, Kristen M; Pepper, Margery Reese

2011-11-01

This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron-rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants. © 2011 International Life Sciences Institute.

Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in children and adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

2010-01-01

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

Staff attributions towards men with intellectual disability who have a history of sexual offending and challenging behaviour.

PubMed

MacKinlay, L; Langdon, P E

2009-09-01

Staff working within secure services for people with intellectual disabilities (ID) are likely to work with sexual offenders, but very little attention has been paid to how they think about this sexual offending behaviour. Forty-eight staff working within secure services for people with ID were recruited and completed the Attribution Style Questionnaire in relation to the sexual offending behaviour and challenging behaviour of men with mild ID. Attributions towards challenging behaviour and sexual offending were compared and relationships between level of ID and seriousness of the sexual offence were explored. The results indicated that staff attributed sexual offending as more external to the staff group than they did for challenging behaviour. Sexual offending behaviour was also seen as more stable, and less controllable by people with ID than was challenging behaviour. Sexual offending was also attributed as more uncontrollable by the staff group than challenging behaviour. There was a significant negative correlation between general intellectual functioning and several attributional dimensions regarding sexual offending, but not challenging behaviour. Sexual offending that was coded as more serious was attributed as universal and uncontrollable by the staff group. The differences between staff attributions regarding challenging behaviour and sexual offending potentially relate to the decision-making processes involved in deciding whether or not to involve criminal justice agencies when someone with ID commits a sexual offence. Further research within this area is warranted.

Effectiveness of hip muscle strengthening in patellofemoral pain syndrome patients: a systematic review.

PubMed

Santos, Thiago R T; Oliveira, Bárbara A; Ocarino, Juliana M; Holt, Kenneth G; Fonseca, Sérgio T

2015-01-01

Patellofemoral pain syndrome (PFPS) is characterized by anterior knee pain, which may limit the performance of functional activities. The influence of hip joint motion on the development of this syndrome has already been documented in the literature. In this regard, studies have investigated the effectiveness of hip muscle strengthening in patients with PFPS. The aims of this systematic review were (1) to summarize the literature related to the effects of hip muscle strengthening on pain intensity, muscle strength, and function in individuals with PFPS and (2) to evaluate the methodological quality of the selected studies. A search for randomized controlled clinical trials was conducted using the following databases: Google Scholar, MEDLINE, PEDro, LILACS, and SciELO. The selected studies had to distinguish the effects of hip muscle strengthening in a group of patients with PFPS, as compared to non-intervention or other kinds of intervention, and had to investigate the following outcomes: pain, muscle strength, and function. The methodological quality of the selected studies was analyzed by means of the PEDro scale. Seven studies were selected. These studies demonstrated that hip muscle strengthening was effective in reducing pain. However, the studies disagreed regarding the treatments' ability to improve muscle strength. Improvement in functional capabilities after hip muscle strengthening was found in five studies. Hip muscle strengthening is effective in reducing the intensity of pain and improving functional capabilities in patients with PFPS, despite the lack of evidence for its ability to increase muscle strength.

Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury.

PubMed

Garg, Koyal; Corona, Benjamin T; Walters, Thomas J

2014-11-15

Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg(-1)·day(-1) was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish

PubMed Central

Housley, Michael P.; Njaine, Brian; Ricciardi, Filomena; Stone, Oliver A.; Hölper, Soraya; Krüger, Marcus; Kostin, Sawa; Stainier, Didier Y. R.

2016-01-01

Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy. PMID:27294373

Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function.

PubMed

Perice, Leland; Barzilai, Nir; Verghese, Joe; Weiss, Erica F; Holtzer, Roee; Cohen, Pinchas; Milman, Sofiya

2016-10-14

Mutations that reduce somatotropic signaling result in improved lifespan and health-span in model organisms and humans. However, whether reduced circulating insulin-like growth factor-I (IGF-I) level is detrimental to cognitive and muscle function in older adults remains understudied. A cross-sectional analysis was performed in Ashkenazi Jews with exceptional longevity (age ≥95 years). Cognition was assessed using the Mini-Mental State Examination and muscle function with the chair rise test, grip-strength, and gait speed. Muscle mass was estimated using the skeletal muscle index. Serum IGF-I was measured with liquid chromatography mass spectrometry. In gender stratified age-adjusted logistic regression analysis, females with IGF-I levels in the first tertile had lower odds of being cognitively impaired compared to females with IGF-I levels within the upper two tertiles, OR (95% CI) 0.39 (0.19-0.82). The result remained significant after adjustment for multiple parameters. No significant association was identified in males between IGF-I and cognition. No relationship was found between IGF-I tertiles and muscle function and muscle mass in females or males. Lower circulating IGF-I is associated with better cognitive function in females with exceptional longevity, with no detriment to skeletal muscle mass and function.

Muscle Functional Morphology in Paleobiology: The Past, Present, and Future of "Paleomyology".

PubMed

Perry, Jonathan M G; Prufrock, Kristen A

2018-03-01

Our knowledge of muscle anatomy and physiology in vertebrates has increased dramatically over the last two-hundred years. Today, much is understood about how muscles contract and about the functional meaning of muscular variation at multiple scales. Progress in muscle anatomy has profited from the availability of broad comparative samples, advances in microscopy have permitted comparisons at increasingly finer scales, and progress in muscle physiology has profited from many carefully designed and executed experiments. Several avenues of future work are promising. In particular, muscle ontogeny (growth and development) is poorly understood for many vertebrate groups. We consider which types of advances in muscle functional morphology are of use to paleobiologists. These are only a modest subset for muscle anatomy and a very small subset for muscle physiology. The relationship between muscle and bone - spatially and mechanically-is critical to any future advances in "paleomyology". Anat Rec, 301:538-555, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Developing a musculoskeletal model of the primate skull: predicting muscle activations, bite force, and joint reaction forces using multibody dynamics analysis and advanced optimisation methods.

PubMed

Shi, Junfen; Curtis, Neil; Fitton, Laura C; O'Higgins, Paul; Fagan, Michael J

2012-10-07

An accurate, dynamic, functional model of the skull that can be used to predict muscle forces, bite forces, and joint reaction forces would have many uses across a broad range of disciplines. One major issue however with musculoskeletal analyses is that of muscle activation pattern indeterminacy. A very large number of possible muscle force combinations will satisfy a particular functional task. This makes predicting physiological muscle recruitment patterns difficult. Here we describe in detail the process of development of a complex multibody computer model of a primate skull (Macaca fascicularis), that aims to predict muscle recruitment patterns during biting. Using optimisation criteria based on minimisation of muscle stress we predict working to balancing side muscle force ratios, peak bite forces, and joint reaction forces during unilateral biting. Validation of such models is problematic; however we have shown comparable working to balancing muscle activity and TMJ reaction ratios during biting to those observed in vivo and that peak predicted bite forces compare well to published experimental data. To our knowledge the complexity of the musculoskeletal model is greater than any previously reported for a primate. This complexity, when compared to more simple representations provides more nuanced insights into the functioning of masticatory muscles. Thus, we have shown muscle activity to vary throughout individual muscle groups, which enables them to function optimally during specific masticatory tasks. This model will be utilised in future studies into the functioning of the masticatory apparatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

PubMed

Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

2015-10-13

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy

PubMed Central

Whitehead, Nicholas P.; Kim, Min Jeong; Bible, Kenneth L.; Adams, Marvin E.; Froehner, Stanley C.

2015-01-01

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases. PMID:26417069

Access to Medicare-funded annual comprehensive health assessments for rural people with intellectual disability.

PubMed

Burton, Heather; Walters, Lucie

2013-01-01

People with intellectual disability (ID) comprise 2-3% of the Australian population. They mostly rely on their GP for primary health care. In rural areas where there are issues with health workforce shortages, there is a risk that people with ID may not get timely access to primary care or may not be aware of the range of healthcare services available to support them. Internationally, research has shown that regular health assessments are beneficial for people with ID. Annual comprehensive health assessments (ACHAs) have been shown to result in increased detection of medical conditions and could assist in reducing the gap in mortality between people with ID and the broader population. In Australia, people with ID have been eligible to access ACHAs under Medicare since 2007. These provide for a regular review of the person's physical, psychological and social functioning. This study explored the extent to which rural people with ID were accessing these ACHAs, and factors which affected their access to ACHAs. In this qualitative study in-depth interviews were conducted with 18 participants including people with ID, carers/support workers and rural doctors. Interviews were then coded and analysed for themes. Seven themes were identified: (1) healthcare barriers in rural areas; (2) cohesion of rural communities; (3) the way rural doctors practice; (4) lack of knowledge/understanding; (5) venturing into new territory; (6) the role of the practice nurse; and (7) the health communication triangle. Despite the well-known problems of lack of services and distance to specialists in rural Australia, there are compensatory factors which were perceived as improving the wellbeing of people with ID, such as increased social cohesion and community connectedness. More education is needed to ensure that the rationale for ACHAs for people with ID is understood and that doctors feel confident to use them. The number of Medicare reforms implemented in a relatively short period presented change-management challenges for rural practices with rural workforce pressures. The role of the carer/support worker is crucial in the health assessment process and can improve the transfer of information about a client with ID between the disability and health sectors and within the health sector.

Knowledge that people with intellectual disabilities have of their inhaled asthma medications: messages for pharmacists.

PubMed

Davis, Sharon R; Durvasula, Seeta; Merhi, Diana; Young, Paul M; Traini, Daniela; Bosnic Anticevich, Sinthia Z

2016-02-01

Fifteen percent of Australians with intellectual disability (ID) are reported to have asthma. People with ID are at risk of poor health knowledge due to deficits in intellectual and adaptive functioning, but their medication knowledge has largely been ignored in research to date. To explore the level of understanding of asthma medication use of people with ID who self-administer their inhaled medications, in order to inform future educational support. Setting The research was conducted in NSW, Australia, at the participants' homes, the point of health care access, or the offices of relevant support organisations. In this qualitative study face-to-face interviews were conducted with people with ID using a semi-structured interview guide. The interviews were recorded, transcribed and thematically analysed. Main outcome Identification of barriers to asthma medication self-management by people with ID. Seventeen people with ID who self-administer their asthma medications were interviewed. Factors influencing their asthma medication knowledge and use included understanding of their illness and the need for medication; aspects of self-management and autonomy versus dependence. This sample of people with ID had a good understanding of the importance of using their inhaled asthma medications, as well as asthma triggers, and the difference between use of preventer and reliever medications. Both enablers and barriers to asthma medication self-management were identified in the domains of managing attacks, adherence, knowledge of side effects and sources of information on correct use of inhalers. The level of autonomy for medication use varied, with motivation to self-manage asthma influenced by the level of support that was practically available to individual participants. This research investigated aspects of asthma medication self-management of people with ID. Based on the barriers identified, pharmacists should promote use of spacers and written asthma action plans as well as counsel people with ID about how to recognise and minimise side effects of asthma medications. Specific strategies for pharmacists when educating people with ID and their caregivers include active listening to determine understanding of concepts, exercising care with language, and working with the person's known routines to maximise adherence with preventer medications.

Comparative functional anatomy of the epaxial musculature of dogs (Canis familiaris) bred for sprinting vs. fighting.

PubMed

Webster, Emma L; Hudson, Penny E; Channon, Sarah B

2014-09-01

The axial musculoskeletal system of quadrupedal mammals is not currently well understood despite its functional importance in terms of facilitating postural stability and locomotion. Here we examined the detailed architecture of the muscles of the vertebral column of two breeds of dog, the Staffordshire bull terrier (SBT) and the racing greyhound, which have been selectively bred for physical combat and high speed sprint performance, respectively. Dissections of the epaxial musculature of nine racing greyhounds and six SBTs were carried out; muscle mass, length, and fascicle lengths were measured and used to calculate muscle physiological cross-sectional area (PCSA), and to estimate maximum muscle potential for force, work and power production. The longissimus dorsi muscle was found to have a high propensity for force production in both breeds of dog; however, when considered in combination with the iliocostalis lumborum muscle it showed enhanced potential for production of power and facilitating spinal extension during galloping gaits. This was particularly the case in the greyhound, where the m. longissimus dorsi and the m. iliocostalis lumborum were estimated to have the potential to augment hindlimb muscle power by ca. 12%. Breed differences were found within various other muscles of the axial musculoskeletal system, particularly in the cranial cervical muscles and also the deep muscles of the thorax which insert on the ribs. These may also highlight key functional adaptations between the two breeds of dog, which have been selectively bred for particular purposes. Additionally, in both breeds of dog, we illustrate specialisation of muscle function by spinal region, with differences in both mass and PCSA found between muscles at varying levels of the axial musculoskeletal system, and between muscle functional groups. © 2014 Anatomical Society.

Functional differentiation of the human lumbar perivertebral musculature revisited by means of muscle fibre type composition.

PubMed

Hesse, Bettina; Fröber, Rosemarie; Fischer, Martin S; Schilling, Nadja

2013-12-01

Human back muscles have been classified as local stabilizers, global stabilizers and global mobilizers. This concept is supported by the distribution of slow and fast muscle fibres in quadrupedal mammals, but has not been evaluated for humans because detailed information on the fibre type composition of their perivertebral musculature is rare. Moreover, such information is derived from spot samples, which are assumed to be representative for the respective muscle. In accordance with the proposed classification, numerous studies in animals indicate great differences in the fibre distribution within and among the muscles due to fibre type regionalization. The aims of this study were to (1) qualitatively explore the applicability of the proposed functional classification for human back muscles by studying their fibre type composition and (2) evaluate the representativeness of spot sampling techniques. For this, the fibre type distribution of the whole lumbar perivertebral musculature of two male cadavers was investigated three-dimensionally using immunohistochemistry. Despite great local variations (e.g., among fascicles), all muscles were composed of about 50% slow and 50% fast fibres. Thus, contradicting the concepts of lumbar muscle function, no functional differentiation of the muscles was observed in our study of the muscle contractile properties. The great similarity in fibre composition among the muscles equips each muscle equally well for a broad range of tasks and therefore has the potential to allow for great functional versatility of the human back musculature. Spot samples do not prove to be representative for the whole muscle. The great intraspecific variability observed previously in single-spot samples is potentially misleading. Copyright © 2013 Elsevier GmbH. All rights reserved.

Comparative functional anatomy of the epaxial musculature of dogs (Canis familiaris) bred for sprinting vs. fighting

PubMed Central

Webster, Emma L; Hudson, Penny E; Channon, Sarah B

2014-01-01

The axial musculoskeletal system of quadrupedal mammals is not currently well understood despite its functional importance in terms of facilitating postural stability and locomotion. Here we examined the detailed architecture of the muscles of the vertebral column of two breeds of dog, the Staffordshire bull terrier (SBT) and the racing greyhound, which have been selectively bred for physical combat and high speed sprint performance, respectively. Dissections of the epaxial musculature of nine racing greyhounds and six SBTs were carried out; muscle mass, length, and fascicle lengths were measured and used to calculate muscle physiological cross-sectional area (PCSA), and to estimate maximum muscle potential for force, work and power production. The longissimus dorsi muscle was found to have a high propensity for force production in both breeds of dog; however, when considered in combination with the iliocostalis lumborum muscle it showed enhanced potential for production of power and facilitating spinal extension during galloping gaits. This was particularly the case in the greyhound, where the m. longissimus dorsi and the m. iliocostalis lumborum were estimated to have the potential to augment hindlimb muscle power by ca. 12%. Breed differences were found within various other muscles of the axial musculoskeletal system, particularly in the cranial cervical muscles and also the deep muscles of the thorax which insert on the ribs. These may also highlight key functional adaptations between the two breeds of dog, which have been selectively bred for particular purposes. Additionally, in both breeds of dog, we illustrate specialisation of muscle function by spinal region, with differences in both mass and PCSA found between muscles at varying levels of the axial musculoskeletal system, and between muscle functional groups. PMID:24917310

Social support and intellectual disabilities: a comparison between social networks of adults with intellectual disability and those with physical disability.

PubMed

Lippold, T; Burns, J

2009-05-01

Social support has been identified as a major protective factor in preventing mental health problems and also as a major contributor to quality of life. People with intellectual disabilities (ID) have been identified as having limited social support structures. Interventions have been focused on promoting their social presence and integration. However, previous studies have shown that this does not always lead to the formation of social relationships. To date few studies have looked at how having an ID leads to impoverished social networks. This study aimed to do this by contrasting the social relationships of people with physical disabilities (PD) and people with ID. Two groups of participants were recruited; 30 people with mild ID and 17 people with PD. Social and functional support networks were assessed, in addition to life experiences. Between and within group differences were then explored statistically. Adults with ID had more restricted social networks than PD, despite being involved in more activities. Social support for adults with ID was mainly provided by family and carers and few relationships with non-disabled people were identified. In contrast adults with PD had larger social networks than had been reported in the mainstream literature and had a balance of relationships with disabled and non-disabled people. The results suggest that there are additional processes attached to having an ID, which lead to continued impoverished lifestyles. The findings also endorse other work that suggests being physically integrated and engaged in a wide range of activities does not guarantee good social and emotional support.

Kinesiophobia, Pain, Muscle Functions, and Functional Performances among Older Persons with Low Back Pain.

PubMed

Ishak, Nor Azizah; Zahari, Zarina; Justine, Maria

2017-01-01

This study aims (1) to determine the association between kinesiophobia and pain, muscle functions, and functional performances and (2) to determine whether kinesiophobia predicts pain, muscle functions, and functional performance among older persons with low back pain (LBP). This is a correlational study, involving 63 institutionalized older persons (age = 70.98 ± 7.90 years) diagnosed with LBP. Anthropometric characteristics (BMI) and functional performances (lower limb function, balance and mobility, and hand grip strength) were measured. Muscle strength (abdominal and back muscle strength) was assessed using the Baseline® Mechanical Push/Pull Dynamometer, while muscle control (transverse abdominus and multifidus) was measured by using the Pressure Biofeedback Unit. The pain intensity and the level of kinesiophobia were measured using Numerical Rating Scale and Tampa Scale of Kinesiophobia, respectively. Data were analyzed using Pearson's correlation coefficients and multivariate linear regressions. No significant correlations were found between kinesiophobia and pain and muscle functions (all p > 0.05). Kinesiophobia was significantly correlated with mobility and balance ( p = 0.038, r = 0.263). Regressions analysis showed that kinesiophobia was a significant predictor of mobility and balance ( p = 0.038). We can conclude that kinesiophobia predicted mobility and balance in older persons with LBP. Kinesiophobia should be continuously assessed in clinical settings to recognize the obstacles that may affect patient's compliance towards a rehabilitation program in older persons with LBP.

Kinesiophobia, Pain, Muscle Functions, and Functional Performances among Older Persons with Low Back Pain

PubMed Central

2017-01-01

Objectives This study aims (1) to determine the association between kinesiophobia and pain, muscle functions, and functional performances and (2) to determine whether kinesiophobia predicts pain, muscle functions, and functional performance among older persons with low back pain (LBP). Methods This is a correlational study, involving 63 institutionalized older persons (age = 70.98 ± 7.90 years) diagnosed with LBP. Anthropometric characteristics (BMI) and functional performances (lower limb function, balance and mobility, and hand grip strength) were measured. Muscle strength (abdominal and back muscle strength) was assessed using the Baseline® Mechanical Push/Pull Dynamometer, while muscle control (transverse abdominus and multifidus) was measured by using the Pressure Biofeedback Unit. The pain intensity and the level of kinesiophobia were measured using Numerical Rating Scale and Tampa Scale of Kinesiophobia, respectively. Data were analyzed using Pearson's correlation coefficients and multivariate linear regressions. Results No significant correlations were found between kinesiophobia and pain and muscle functions (all p > 0.05). Kinesiophobia was significantly correlated with mobility and balance (p = 0.038, r = 0.263). Regressions analysis showed that kinesiophobia was a significant predictor of mobility and balance (p = 0.038). Conclusion We can conclude that kinesiophobia predicted mobility and balance in older persons with LBP. Kinesiophobia should be continuously assessed in clinical settings to recognize the obstacles that may affect patient's compliance towards a rehabilitation program in older persons with LBP. PMID:28634547

1H, 13C, and 15N resonance assignments for the protein coded by gene locus BB0938 of Bordetella bronchiseptica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossi, Paolo; Ramelot, Theresa A.; Xiao, Rong

2005-11-01

The product of gene locus BB0938 from Bordetella bronchiseptica (Swiss-Prot ID: Q7WNU7-BORBR; NESG target ID: BoR11; Wunderlich et al., 2004; Pfam ID: PF03476) is a 128-residue protein of unknown function. This broadly conserved protein family is found in eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 98% of backbone and 94% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a b topology with a seven-residue helical insert, ??????????. BMRB deposit with accession number 6693. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

1H, 13C, and 15N resonance assignments for Escherichia coli ytfP, a member of the broadly conserved UPF0131 protein domain family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aramini, James M.; Swapna, G.V.T.; Huang, Yuanpeng

2005-11-01

Protein ytfP from Escherichia coli (Swiss-Prot ID: YTFP-ECOLI; NESG target ID: ER111; Wunderlich et al., 2004) is a 113-residue member of the UPF0131 protein family (Pfam ID: PF03674) of unknown function. This domain family is found in organisms from all three kingdoms, archaea, eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 97% of backbone and 91% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a mixed a/b topology,????????. BMRB deposit with Accession No. 6448. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

The Promotion of a Functional Fibrosis in Skeletal Muscle with Volumetric Muscle Loss Injury Following the Transplantation of Muscle-ECM

DTIC Science & Technology

2013-02-04

i.e., volumetric muscle loss; VML). The explicit goal is to restore functional capacity to the injured tissue by promoting generation of muscle fibers ...3,23,25,27,28]. As a result, trans- plantation of a variety of ECMs in preclinical animal models has resulted in modest levels of muscle fiber generation at...the site of the defect during the initial months post-injury [20,28e30]. However, an apparent enhanced rate of muscle fiber generation at

Characteristics of locomotion, muscle strength, and muscle tissue in regenerating rat skeletal muscles.

PubMed

Iwata, Akira; Fuchioka, Satoshi; Hiraoka, Koichi; Masuhara, Mitsuhiko; Kami, Katsuya

2010-05-01

Although numerous studies have aimed to elucidate the mechanisms used to repair the structure and function of injured skeletal muscles, it remains unclear how and when movement recovers following damage. We performed a temporal analysis to characterize the changes in movement, muscle function, and muscle structure after muscle injury induced by the drop-mass technique. At each time-point, movement recovery was determined by ankle kinematic analysis of locomotion, and functional recovery was represented by isometric force. As a histological analysis, the cross-sectional area of myotubes was measured to examine structural regeneration. The dorsiflexion angle of the ankle, as assessed by kinematic analysis of locomotion, increased after injury and then returned to control levels by day 14 post-injury. The isometric force returned to normal levels by day 21 post-injury. However, the size of the myotubes did not reach normal levels, even at day 21 post-injury. These results indicate that recovery of locomotion occurs prior to recovery of isometric force and that functional recovery occurs earlier than structural regeneration. Thus, it is suggested that recovery of the movement and function of injured skeletal muscles might be insufficient as markers for estimating the degree of neuromuscular system reconstitution.

The effect of the inspiratory muscle training on functional ability in stroke patients.

PubMed

Jung, Nam-Jin; Na, Sang-Su; Kim, Seung-Kyu; Hwangbo, Gak

2017-11-01

[Purpose] This study was to find out an inspiratory muscle training (IMT) program therapeutic effects on stroke patients' functional ability. [Subjects and Methods] Twenty stroke patients were assigned to one of two groups: inspiratory muscle training (n=10), and control (n=10), randomization. The inspiratory muscle training participants undertook an exercise program for 30 minute per times, 5 times a week for 6 weeks. The investigator measured the patients' trunk impairment scale (TIS) and 6 minute walking test (6MW) for functional ability before and after IMT. [Results] The TIS appeared some significant differences in both groups before and after the training. The 6MW test showed some significant differences in the inspiratory muscle training group, but didn't show any significant difference in the control group. And the differences in both groups after depending the inspiratory muscle training were significantly found in the tests of TIS and 6MW test [Conclusion] The results showed that the inspiratory muscle training in stroke patients are correlated with the trunk stability and locomotion ability, suggesting that physical therapist must take into consideration the inspiratory muscle training, as well as functional training to improve physical function in stroke patients.

The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report.

PubMed

Correa-de-Araujo, Rosaly; Harris-Love, Michael O; Miljkovic, Iva; Fragala, Maren S; Anthony, Brian W; Manini, Todd M

2017-01-01

A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and providing recommendations to address critical clinical and technology research gaps within the field.

Prevalence of older people with intellectual disability in Sweden: a spatial epidemiological analysis.

PubMed

Ng, N; Sandberg, M; Ahlström, G

2015-12-01

The expected increase in longevity of individuals with intellectual disabilities (ID) in many countries of the world is a direct result of medical and social advances, which have also extended the longevity of the general population. It is important to assess the need for social services for people with ID across different administrative levels to ensure sufficient resources are allocated to where they are most needed. This study estimates the annual prevalence of older people with ID from 2004 to 2012 and in different counties and municipalities in Sweden, by sex and age group; identifies proxy indicators related to the care of older people with ID in different counties in 2012 in Sweden and analyses the spatial distribution and clustering of municipalities with a high prevalence of older people with ID. Individuals with ID were identified through the national register based on the Swedish Act concerning Support and Service for Persons with Certain Functional Impairments (the LSS act) and the national death register. This study focuses on older individuals aged 55+ during the period of 2004-2012. The estimated prevalence was calculated at the county and municipality level and plotted on a municipality-level map. Moran's I statistics was used to identify any spatial clustering of municipalities with a large number of individuals with ID. The prevalence of ID among older individuals aged 55+ in Sweden increased from 2004 to 2012. The prevalence was consistently higher among men, and the gender gap increased slightly in recent years. Age-specific prevalence estimates showed ID to be higher in younger age groups, and the gender gap decreased in older age groups. The prevalence was higher in northern counties in Sweden (over 500 individuals per 100 000 population aged 55+). Higher prevalence areas were clustered in northern municipalities, whereas municipalities with high prevalence of older individuals with ID in the middle and southern regions of Sweden demonstrated a more widespread distribution. The existence of clusters of counties with a high prevalence of older individuals with ID necessitates further assessment of how resources have been allocated to different counties and municipalities in Sweden. Investigations of the quality of social services provided to individuals with ID across different counties in Sweden are warranted. It is important to ensure that high quality supports are being provided to older individuals with ID in order to grant them the same right to healthy ageing as their counterparts living without ID throughout their life course. © 2015 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Perceptions of emotion expression and sibling-parent emotion communication in Latino and non-Latino white siblings of children with intellectual disabilities.

PubMed

Long, Kristin A; Lobato, Debra; Kao, Barbara; Plante, Wendy; Grullón, Edicta; Cheas, Lydia; Houck, Christopher; Seifer, Ronald

2013-06-01

Examine general emotion expression and sibling-parent emotion communication among Latino and non-Latino white (NLW) siblings of children with intellectual disabilities (ID) and matched comparisons. 200 siblings (ages 8-15 years) completed the newly developed Sibling-Parent Emotion Communication Scale and existing measures of general emotion expression and psychosocial functioning. Preliminary analyses evaluated scale psychometrics across ethnicity. Structure and internal consistency of the emotion expression and communication measures differed by respondent ethnicity. Latino siblings endorsed more general emotion expression problems and marginally lower sibling-parent emotion communication than NLW siblings. Siblings of children with ID reported marginally more general emotion expression problems than comparisons. Emotion expression problems and lower sibling-parent emotion communication predicted more internalizing and somatic symptoms and poorer personal adjustment, regardless of ID status. Siblings of children with ID endorsed poorer personal adjustment. Cultural differences in emotion expression and communication may increase Latino siblings' risk for emotional adjustment difficulties.

Evaluating Swallowing Muscles Essential for Hyolaryngeal Elevation by Using Muscle Functional Magnetic Resonance Imaging

PubMed Central

Pearson, William G.; Hindson, David F.; Langmore, Susan E.; Zumwalt, Ann C.

2012-01-01

Summary Elevation of the larynx is critical to swallowing function, an observation supported by the fact that radiation therapy-induced dysphagia is associated with reduced laryngeal elevation. We investigated muscles underlying hyolaryngeal elevation by using muscle functional MRI. We acquired scans from 11 healthy subjects to determine whole-muscle T2 signal profiles pre-swallowing, post-swallowing, and after performing swallowing exercises. Results demonstrate muscles essential to laryngeal elevation and exercises that target them. Purpose Reduced hyolaryngeal elevation, a critical event in swallowing, is associated with radiation therapy. Two muscle groups that suspend the hyoid, larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity modulated radiation therapy guidelines designed to preserve structures important to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study used muscle functional magnetic resonance imaging (mfMRI) in normal healthy adults to determine whether both muscle groups are active in swallowing and to test therapeutic exercises thought to be specific to hyolaryngeal elevation. Methods and Materials mfMRI data were acquired from 11 healthy subjects before and after normal swallowing and after swallowing exercise regimens (the Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles were used to evaluate the physiologic response of each muscle to each condition. Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles were used to determine which muscles underlie swallowing and swallowing exercises. Results Post-swallowing effect size changes (where a d value of >0.20 indicates significant activity during swallowing) for the T2 signal profile of the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80 for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide swallowing exercises showed significant effect size changes for all muscles tested, except for the thyrohyoid. Conclusions Muscles of both the suprahyoid and the longitudinal pharyngeal muscle groups are active in swallowing, and both swallowing exercises effectively target muscles elevating the hyolaryngeal complex. mfMRI is useful in testing swallowing muscle function. PMID:22995662

Regulation of Satellite Cell Function in Sarcopenia

PubMed Central

Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

2014-01-01

The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function. PMID:25295003

Effects of inspiratory muscle training on balance ability and abdominal muscle thickness in chronic stroke patients

PubMed Central

Oh, Dongha; Kim, Gayeong; Lee, Wanhee; Shin, Mary Myong Sook

2016-01-01

[Purpose] This study evaluated the effects of inspiratory muscle training on pulmonary function, deep abdominal muscle thickness, and balance ability in stroke patients. [Subjects] Twenty-three stroke patients were randomly allocated to an experimental (n = 11) or control group (n = 12). [Methods] The experimental group received inspiratory muscle training-based abdominal muscle strengthening with conventional physical therapy; the control group received standard abdominal muscle strengthening with conventional physical therapy. Treatment was conducted 20 minutes per day, 3 times per week for 6 weeks. Pulmonary function testing was performed using an electronic spirometer. Deep abdominal muscle thickness was measured by ultrasonography. Balance was measured using the Berg balance scale. [Results] Forced vital capacity, forced expiratory volume in 1 second, deep abdominal muscle thickness, and Berg balance scale scores were significantly improved in the experimental group than in the control group. [Conclusion] Abdominal muscle strengthening accompanied by inspiratory muscle training is recommended to improve pulmonary function in stroke patients, and may also be used as a practical adjunct to conventional physical therapy. PMID:26957739

ACE and ACTN3 genotypes in older women: muscular phenotypes.

PubMed

Lima, R M; Leite, T K M; Pereira, R W; Rabelo, H T; Roth, S M; Oliveira, R J

2011-01-01

This study examined the association between ACE I/D and ACTN3 R577X polymorphisms and muscle-related phenotypes and their adaptation to resistance training in older women. Volunteers (n=246;age=66.7 ± 5.5 years) underwent quadriceps strength assessment using isokinetics and fat-free mass by dual energy X-ray absorptiometry. 79 volunteers performed 24 weeks of resistance training and 75 were studied as controls. Genotypes were identified by standard procedures. No associations were observed for muscle strength for either gene, but volunteers carrying the D/D genotype presented higher appendicular fat-free mass compared to the I-allele carriers (6.3 ± 0.1 vs. 6.1 ± 0.1 kg/m (2)). The X-allele carriers presented higher relative fat-free mass when compared to homozygous R/R (16.3 ± 0.1 vs. 15.9 ± 0.1 kg/m (2)). All fat-free mass variables were significantly greater for carriers of both X/X and D/D genotypes. In response to RT, only the I-allele carriers significantly increased fat-free mass and a significant training × genotype interaction was noted. These findings do not support a pivotal role for the studied polymorphisms in determining muscle strength in older women, but suggest a modest role in fat-free mass determination. Of note, the results provide a novel insight that these genetic variations may interact to determine muscle mass in older women. © Georg Thieme Verlag KG Stuttgart · New York.

Multi-slice MRI reveals heterogeneity in disease distribution along the length of muscle in Duchenne muscular dystrophy.

PubMed

Chrzanowski, Stephen M; Baligand, Celine; Willcocks, Rebecca J; Deol, Jasjit; Schmalfuss, Ilona; Lott, Donovan J; Daniels, Michael J; Senesac, Claudia; Walter, Glenn A; Vandenborne, Krista

2017-09-01

Duchenne muscular dystrophy (DMD) causes progressive pathologic changes to muscle secondary to a cascade of inflammation, lipid deposition, and fibrosis. Clinically, this manifests as progressive weakness, functional loss, and premature mortality. Though insult to whole muscle groups is well established, less is known about the relationship between intramuscular pathology and function. Differences of intramuscular heterogeneity across muscle length were assessed using an ordinal MRI grading scale in lower leg muscles of boys with DMD and correlated to patient's functional status. Cross sectional T 1 weighted MRI images with fat suppression were obtained from ambulatory boys with DMD. Six muscles (tibialis anterior, extensor digitorum longus, peroneus, soleus, medial and lateral gastrocnemii) were graded using an ordinal grading scale over 5 slice sections along the lower leg length. The scores from each slice were combined and results were compared to global motor function and age. Statistically greater differences of involvement were observed at the proximal ends of muscle compared to the midbellies. Multi-slice assessment correlated significantly to age and the Vignos functional scale, whereas single-slice assessment correlated to the Vignos functional scale only. Lastly, differential disease involvement of whole muscle groups and intramuscular heterogeneity were observed amongst similar age subjects. A multi-slice ordinal MRI grading scale revealed that muscles are not uniformly affected, with more advanced disease visible near the tendons in a primarily ambulatory population with DMD. A geographically comprehensive evaluation of the heterogeneously affected muscle in boys with DMD may more accurately assess disease involvement.

Aerobic exercise and respiratory muscle strength in patients with cystic fibrosis.

PubMed

Dassios, Theodore; Katelari, Anna; Doudounakis, Stavros; Dimitriou, Gabriel

2013-05-01

The beneficial role of exercise in maintaining health in patients with cystic fibrosis (CF) is well described. Few data exist on the effect of exercise on respiratory muscle function in patients with CF. Our objective was to compare respiratory muscle function indices in CF patients that regularly exercise with those CF patients that do not. This cross-sectional study assessed nutrition, pulmonary function and respiratory muscle function in 37 CF patients that undertook regular aerobic exercise and in a control group matched for age and gender which consisted of 44 CF patients that did not undertake regular exercise. Respiratory muscle function in CF was assessed by maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax) and pressure-time index of the respiratory muscles (PTImus). Median Pimax and Pemax were significantly higher in the exercise group compared to the control group (92 vs. 63 cm H2O and 94 vs. 64 cm H2O respectively). PTImus was significantly lower in the exercise group compared to the control group (0.089 vs. 0.121). Upper arm muscle area (UAMA) and mid-arm muscle circumference were significantly increased in the exercise group compared to the control group (2608 vs. 2178 mm2 and 23 vs. 21 cm respectively). UAMA was significantly related to Pimax in the exercising group. These results suggest that CF patients that undertake regular aerobic exercise maintain higher indices of respiratory muscle strength and lower PTImus values, while increased UAMA values in exercising patients highlight the importance of muscular competence in respiratory muscle function in this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice.

PubMed

Murphy, Kate T; Cobani, Vera; Ryall, James G; Ibebunjo, Chikwendu; Lynch, Gordon S

2011-04-01

Counteracting the atrophy of skeletal muscle associated with disuse has significant implications for minimizing the wasting and weakness in plaster casting, joint immobilization, and other forms of limb unloading, with relevance to orthopedics, sports medicine, and plastic and reconstructive surgery. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the loss of muscle mass and functional capacity in mice during 14 or 21 days of unilateral hindlimb casting. Twelve-week-old C57BL/10 mice were subjected to unilateral hindlimb plaster casting or served as controls. Mice received subcutaneous injections of saline or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n = 6-9) on days 0 and 7 and were tested for muscle function on day 14, or were treated on days 0, 7, and 14 and tested for muscle function on day 21. Hindlimb casting reduced muscle mass, fiber size, and function of isolated soleus and extensor digitorum longus (EDL) muscles (P < 0.05). PF-354 attenuated the loss of muscle mass, fiber size, and function with greater effects after 14 days than after 21 days of casting, when wasting and weakness had plateaued (P < 0.05). Antibody-directed myostatin inhibition therefore attenuated the atrophy and loss of functional capacity in muscles from mice subjected to unilateral hindlimb casting with reductions in muscle size and strength being most apparent during the first 14 days of disuse. These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for disuse atrophy especially within the first 2 wk of disuse.

GRASP1 regulates synaptic plasticity and learning through endosomal recycling of AMPA receptors

PubMed Central

Chiu, Shu-Ling; Diering, Graham Hugh; Ye, Bing; Takamiya, Kogo; Chen, Chih-Ming; Jiang, Yuwu; Niranjan, Tejasvi; Schwartz, Charles E.; Wang, Tao; Huganir, Richard L.

2017-01-01

Summary Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity. Wild-type GRASP1, but not ID mutants, rescues spine loss in hippocampal CA1 neurons of Grasp1 knockout mice. Together, these results demonstrate a requirement for normal recycling endosome function in AMPAR-dependent synaptic function and neuronal connectivity in vivo, and suggest a potential role for GRASP1 in the pathophysiology of human cognitive disorders. PMID:28285821

Efficacy of a multi-component exercise programme and nutritional supplementation on musculoskeletal health in men treated with androgen deprivation therapy for prostate cancer (IMPACT): study protocol of a randomised controlled trial.

PubMed

Owen, Patrick J; Daly, Robin M; Livingston, Patricia M; Mundell, Niamh L; Dalla Via, Jack; Millar, Jeremy L; Fraser, Steve F

2017-10-03

Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function. This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function. This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer. Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

Epidemiological investigation of muscle-strengthening activities and cognitive function among older adults.

PubMed

Loprinzi, Paul D

2016-06-01

Limited research has examined the association of muscle-strengthening activities and executive cognitive function among older adults, which was this study's purpose. Data from the 1999-2002 NHANES were employed (N = 2157; 60-85 years). Muscle-strengthening activities were assessed via self-report, with cognitive function assessed using the digit symbol substitution test. After adjusting for age, age-squared, gender, race-ethnicity, poverty level, body mass index, C-reactive protein, smoking, comorbid illness and physical activity, muscle-strengthening activities were significantly associated with cognitive function (βadjusted = 3.4; 95% CI: 1.7-5.1; P < 0.001). Compared to those not engaging in aerobic exercise and not meeting muscle-strengthening activity guidelines, those doing 1 (βadjusted = 3.7; 95% CI: 1.9-5.4; P < 0.001) and both (βadjusted = 6.6; 95% CI: 4.8-8.3; P < 0.001) of these behaviors had a significantly higher executive cognitive function score. In conclusion, muscle-strengthening activities are associated with executive cognitive function among older U.S. adults, underscoring the importance of promoting both aerobic exercise and muscle-strengthening activities to older adults. © The Author(s) 2016.

Overexpression of an Isoprenyl Diphosphate Synthase in Spruce Leads to Unexpected Terpene Diversion Products That Function in Plant Defense1[W][OPEN

PubMed Central

Nagel, Raimund; Berasategui, Aileen; Paetz, Christian; Gershenzon, Jonathan; Schmidt, Axel

2014-01-01

Spruce (Picea spp.) and other conifers employ terpenoid-based oleoresin as part of their defense against herbivores and pathogens. The short-chain isoprenyl diphosphate synthases (IDS) are situated at critical branch points in terpene biosynthesis, producing the precursors of the different terpenoid classes. To determine the role of IDS and to create altered terpene phenotypes for assessing the defensive role of terpenoids, we overexpressed a bifunctional spruce IDS, a geranyl diphosphate and geranylgeranyl diphosphate synthase in white spruce (Picea glauca) saplings. While transcript level (350-fold), enzyme activity level (7-fold), and in planta geranyl diphosphate and geranylgeranyl diphosphate levels (4- to 8-fold) were significantly increased in the needles of transgenic plants, there was no increase in the major monoterpenes and diterpene acids of the resin and no change in primary isoprenoids, such as sterols, chlorophylls, and carotenoids. Instead, large amounts of geranylgeranyl fatty acid esters, known from various gymnosperm and angiosperm plant species, accumulated in needles and were shown to act defensively in reducing the performance of larvae of the nun moth (Lymantria monacha), a conifer pest in Eurasia. These results show the impact of overexpression of an IDS and the defensive role of an unexpected accumulation product of terpenoid biosynthesis with the potential for a broader function in plant protection. PMID:24346420

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function.

PubMed

Wang, Yonggang; Zhang, Zhiguo; Guo, Weiying; Sun, Weixia; Miao, Xiao; Wu, Hao; Cong, Xianling; Wintergerst, Kupper A; Kong, Xiangbo; Cai, Lu

2014-07-01

Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death. Copyright © 2014 the American Physiological Society.

Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

NASA Astrophysics Data System (ADS)

Umat, Gazlia; Rambely, Azmin Sham

2014-06-01

Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

38 CFR 4.75 - General considerations for evaluating visual impairment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

38 CFR 4.75 - General considerations for evaluating visual impairment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

38 CFR 4.75 - General considerations for evaluating visual impairment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... refraction), visual field, and muscle function. (b) Examination for visual impairment. The examination must.... Examinations of visual fields or muscle function will be conducted only when there is a medical indication of disease or injury that may be associated with visual field defect or impaired muscle function. Unless...

The impact of obesity on skeletal muscle strength and structure through adolescence to old age.

PubMed

Tomlinson, D J; Erskine, R M; Morse, C I; Winwood, K; Onambélé-Pearson, Gladys

2016-06-01

Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance limitations. The consensus is that obese individuals, regardless of age, have a greater absolute maximum muscle strength compared to non-obese persons, suggesting that increased adiposity acts as a chronic overload stimulus on the antigravity muscles (e.g., quadriceps and calf), thus increasing muscle size and strength. However, when maximum muscular strength is normalised to body mass, obese individuals appear weaker. This relative weakness may be caused by reduced mobility, neural adaptations and changes in muscle morphology. Discrepancies in the literature remain for maximal strength normalised to muscle mass (muscle quality) and can potentially be explained through accounting for the measurement protocol contributing to muscle strength capacity that need to be explored in more depth such as antagonist muscle co-activation, muscle architecture, a criterion valid measurement of muscle size and an accurate measurement of physical activity levels. Current evidence demonstrating the effect of obesity on muscle quality is limited. These factors not being recorded in some of the existing literature suggest a potential underestimation of muscle force either in terms of absolute force production or relative to muscle mass; thus the true effect of obesity upon skeletal muscle size, structure and function, including any interactions with ageing effects, remains to be elucidated.

Force-independent distribution of correlated neural inputs to hand muscles during three-digit grasping.

PubMed

Poston, Brach; Danna-Dos Santos, Alessander; Jesunathadas, Mark; Hamm, Thomas M; Santello, Marco

2010-08-01

The ability to modulate digit forces during grasping relies on the coordination of multiple hand muscles. Because many muscles innervate each digit, the CNS can potentially choose from a large number of muscle coordination patterns to generate a given digit force. Studies of single-digit force production tasks have revealed that the electromyographic (EMG) activity scales uniformly across all muscles as a function of digit force. However, the extent to which this finding applies to the coordination of forces across multiple digits is unknown. We addressed this question by asking subjects (n = 8) to exert isometric forces using a three-digit grip (thumb, index, and middle fingers) that allowed for the quantification of hand muscle coordination within and across digits as a function of grasp force (5, 20, 40, 60, and 80% maximal voluntary force). We recorded EMG from 12 muscles (6 extrinsic and 6 intrinsic) of the three digits. Hand muscle coordination patterns were quantified in the amplitude and frequency domains (EMG-EMG coherence). EMG amplitude scaled uniformly across all hand muscles as a function of grasp force (muscle x force interaction: P = 0.997; cosines of angle between muscle activation pattern vector pairs: 0.897-0.997). Similarly, EMG-EMG coherence was not significantly affected by force (P = 0.324). However, coherence was stronger across extrinsic than that across intrinsic muscle pairs (P = 0.0039). These findings indicate that the distribution of neural drive to multiple hand muscles is force independent and may reflect the anatomical properties or functional roles of hand muscle groups.

Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N.

1983-01-01

The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

PubMed

Hotta, Kazuki; Behnke, Bradley J; Arjmandi, Bahram; Ghosh, Payal; Chen, Bei; Brooks, Rachael; Maraj, Joshua J; Elam, Marcus L; Maher, Patrick; Kurien, Daniel; Churchill, Alexandra; Sepulveda, Jaime L; Kabolowsky, Max B; Christou, Demetra D; Muller-Delp, Judy M

2018-05-15

In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day -1 , 5 days week -1 , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Muscle glycogen and cell function--Location, location, location.

PubMed

Ørtenblad, N; Nielsen, J

2015-12-01

The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status, and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state of the muscle fiber to energy utilization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pilates Method for Lung Function and Functional Capacity in Obese Adults.

PubMed

Niehues, Janaina Rocha; Gonzáles, Inês; Lemos, Robson Rodrigues; Haas, Patrícia

2015-01-01

Obesity is defined as the condition in which the body mass index (BMI) is ≥ 30 kg/m2 and is responsible for decreased quality of life and functional limitations. The harmful effects on ventilatory function include reduced lung capacity and volume; diaphragmatic muscle weakness; decreased lung compliance and stiffness; and weakness of the abdominal muscles, among others. Pilates is a method of resistance training that works with low-impact muscle exercises and is based on isometric exercises. The current article is a review of the literature that aims to investigate the hypothesis that the Pilates method, as a complementary method of training, might be beneficial to pulmonary function and functional capacity in obese adults. The intent of the review was to evaluate the use of Pilates as an innovative intervention in the respiratory dysfunctions of obese adults. In studies with other populations, it has been observed that Pilates can be effective in improving chest capacity and expansion and lung volume. That finding is due to the fact that Pilates works through the center of force, made ​​up of the abdominal muscles and gluteus muscles lumbar, which are responsible for the stabilization of the static and dynamic body that is associated with breath control. It has been observed that different Pilates exercises increase the activation and recruitment of the abdominal muscles. Those muscles are important in respiration, both in expiration and inspiration, through the facilitation of diaphragmatic action. In that way, strengthening the abdominal muscles can help improve respiratory function, leading to improvements in lung volume and capacity. The results found in the current literature review support the authors' observations that Pilates promotes the strengthening of the abdominal muscles and that improvements in diaphragmatic function may result in positive outcomes in respiratory function, thereby improving functional capacity. However, the authors did not find specific studies with obese people, justifying the need for future studies.

The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis.

PubMed

Krishnasamy, Priathashini; Hall, Michelle; Robbins, Sarah R

2018-05-01

The role of skeletal muscle in the pathophysiology of knee OA is poorly understood. To date, the majority of literature has focused on the association of muscle strength with OA symptoms, disease onset and progression. However, deficits or improvements in skeletal muscle strength do not fully explain the mechanisms behind outcome measures in knee OA, such as pain, function and structural disease. This review aims to summarize components of skeletal muscle, providing a holistic view of skeletal muscle mechanisms that includes muscle function, quality and composition and their interactions. Similarly, the role of skeletal muscle in the management of knee OA will be discussed.

Muscle enzyme release does not predict muscle function impairment after triathlon.

PubMed

Margaritis, I; Tessier, F; Verdera, F; Bermon, S; Marconnet, P

1999-06-01

We sought to determine the effects of a long distance triathlon (4 km swim, 120 km bike-ride, and 30 km run) on the four-day kinetics of the biochemical markers of muscle damage, and whether they were quantitatively linked with muscle function impairment and soreness. Data were collected from 2 days before until 4 days after the completion of the race. Twelve triathletes performed the triathlon and five did not. Maximal voluntary contraction (MVC), muscle soreness (DOMS) and total serum CK, CK-MB, LDH, AST and ALT activities were assessed. Significant changes after triathlon completion were found for all muscle damage indirect markers over time (p < 0.0001). MVC of the knee extensor and flexor muscles decreased over time (p < 0.05). There is disparity in the time point at which peak values where reached for DOMS, MVC and enzyme leakage. There is no correlation between serum enzyme leakage, DOMS and MVC impairment which occur after triathlon. Long distance triathlon race caused muscle damage, but extent, as well as muscle recovery cannot be evaluated by the magnitude of changes in serum enzyme activities. Muscle enzyme release cannot be used to predict the magnitude of the muscle function impairment caused by muscle damage.

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration.

PubMed

Urciuolo, Anna; Urbani, Luca; Perin, Silvia; Maghsoudlou, Panagiotis; Scottoni, Federico; Gjinovci, Asllan; Collins-Hooper, Henry; Loukogeorgakis, Stavros; Tyraskis, Athanasios; Torelli, Silvia; Germinario, Elena; Fallas, Mario Enrique Alvarez; Julia-Vilella, Carla; Eaton, Simon; Blaauw, Bert; Patel, Ketan; De Coppi, Paolo

2018-05-30

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis.

Biological organization of the extraocular muscles.

PubMed

Spencer, Robert F; Porter, John D

2006-01-01

Extraocular muscle is fundamentally distinct from other skeletal muscles. Here, we review the biological organization of the extraocular muscles with the intent of understanding this novel muscle group in the context of oculomotor system function. The specific objectives of this review are threefold. The first objective is to understand the anatomic arrangement of the extraocular muscles and their compartmental or layered organization in the context of a new concept of orbital mechanics, the active pulley hypothesis. The second objective is to present an integrated view of the morphologic, cellular, and molecular differences between extraocular and the more traditional skeletal muscles. The third objective is to relate recent data from functional and molecular biology studies to the established extraocular muscle fiber types. Developmental mechanisms that may be responsible for the divergence of the eye muscles from a skeletal muscle prototype also are considered. Taken together, a multidisciplinary understanding of extraocular muscle biology in health and disease provides insights into oculomotor system function and malfunction. Moreover, because the eye muscles are selectively involved or spared in a variety of neuromuscular diseases, knowledge of their biology may improve current pathogenic models of and treatments for devastating systemic diseases.

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

Lumbar muscle structure and function in chronic versus recurrent low back pain: a cross-sectional study.

PubMed

Goubert, Dorien; De Pauw, Robby; Meeus, Mira; Willems, Tine; Cagnie, Barbara; Schouppe, Stijn; Van Oosterwijck, Jessica; Dhondt, Evy; Danneels, Lieven

2017-09-01

Heterogeneity exists within the low back pain (LBP) population. Some patients recover after every pain episode, whereas others suffer daily from LBP complaints. Until now, studies rarely make a distinction between recurrent low back pain (RLBP) and chronic low back pain (CLBP), although both are characterized by a different clinical picture. Clinical experiences also indicate that heterogeneity exists within the CLBP population. Muscle degeneration, like atrophy, fat infiltration, alterations in muscle fiber type, and altered muscle activity, compromises proper biomechanics and motion of the spinal units in LBP patients. The amount of alterations in muscle structure and muscle function of the paraspinal muscles might be related to the recurrence or chronicity of LBP. The aim of this experimental study is to evaluate differences in muscle structure (cross-sectional area and lean muscle fat index) and muscle activity of the multifidus (MF) and erector spinae (ES) during trunk extension, in patients with RLBP, non-continuous CLBP, and continuous CLBP. This cross-sectional study took place in the university hospital of Ghent, Belgium. Muscle structure characteristics and muscle activity were assessed by magnetic resonance imaging (MRI). Fifty-five adults with non-specific LBP (24 RLBP in remission, 15 non-continuous CLBP, 16 continuous CLBP) participated in this study. Total cross-sectional area, muscle cross-sectional area, fat cross-sectional area, lean muscle fat index, T2-rest and T2-shift were assessed. A T1-weighted Dixon MRI scan was used to evaluate spinal muscle cross-sectional area and fat infiltration in the lumbar MF and ES. Muscle functional MRI was used to evaluate the muscle activity of the lumbar MF and ES during a lumbar extension exercise. Before and after the exercise, a pain assessment was performed. This study was supported by grants from the Special Research Fund of Ghent University (DEF12/AOP/022) without potential conflict of interest-associated biases in the text of the paper. Fat cross-sectional area and lean muscle fat index were significantly higher in MF and ES in continuous CLBP compared with non-continuous CLBP and RLBP (p<.05). No differencesbetween groups were found for total cross-sectional area and muscle cross-sectional area in MF or ES (p>.05). Also, no significant differences between groups for T2-rest were established. T2-shift, however, was significantly lower in MF and ES in RLBP compared with, respectively, non-continuous CLBP and continuous CLBP (p<.05). These results indicate a higher amount of fat infiltration in the lumbar muscles, in the absence of clear atrophy, in continuous CLBP compared with RLBP. A lower metabolic activity of the lumbar muscles was seen in RLBP replicating a relative lower intensity in contractions performed by the lumbar muscles in RLBP compared with non-continuous and continuous CLBP. In conclusion, RLBP differs from continuous CLBP for both muscle structure and muscle function, whereas non-continuous CLBP seems comparable with RLBP for lumbar muscle structure and with continuous CLBP for lumbar muscle function. These results underline the differences in muscle structure and muscle function between different LBP populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness of hip muscle strengthening in patellofemoral pain syndrome patients: a systematic review

PubMed Central

Santos, Thiago R. T.; Oliveira, Bárbara A.; Ocarino, Juliana M.; Holt, Kenneth G.; Fonseca, Sérgio T.

2015-01-01

Introduction: Patellofemoral pain syndrome (PFPS) is characterized by anterior knee pain, which may limit the performance of functional activities. The influence of hip joint motion on the development of this syndrome has already been documented in the literature. In this regard, studies have investigated the effectiveness of hip muscle strengthening in patients with PFPS. Objectives: The aims of this systematic review were (1) to summarize the literature related to the effects of hip muscle strengthening on pain intensity, muscle strength, and function in individuals with PFPS and (2) to evaluate the methodological quality of the selected studies. Method: A search for randomized controlled clinical trials was conducted using the following databases: Google Scholar, MEDLINE, PEDro, LILACS, and SciELO. The selected studies had to distinguish the effects of hip muscle strengthening in a group of patients with PFPS, as compared to non-intervention or other kinds of intervention, and had to investigate the following outcomes: pain, muscle strength, and function. The methodological quality of the selected studies was analyzed by means of the PEDro scale. Results: Seven studies were selected. These studies demonstrated that hip muscle strengthening was effective in reducing pain. However, the studies disagreed regarding the treatments' ability to improve muscle strength. Improvement in functional capabilities after hip muscle strengthening was found in five studies. Conclusion: Hip muscle strengthening is effective in reducing the intensity of pain and improving functional capabilities in patients with PFPS, despite the lack of evidence for its ability to increase muscle strength. PMID:26039034

Exploring novel objective functions for simulating muscle coactivation in the neck.

PubMed

Mortensen, J; Trkov, M; Merryweather, A

2018-04-11

Musculoskeletal modeling allows for analysis of individual muscles in various situations. However, current techniques to realistically simulate muscle response when significant amounts of intentional coactivation is required are inadequate. This would include stiffening the neck or spine through muscle coactivation in preparation for perturbations or impacts. Muscle coactivation has been modeled previously in the neck and spine using optimization techniques that seek to maximize the joint stiffness by maximizing total muscle activation or muscle force. These approaches have not sought to replicate human response, but rather to explore the possible effects of active muscle. Coactivation remains a challenging feature to include in musculoskeletal models, and may be improved by extracting optimization objective functions from experimental data. However, the components of such an objective function must be known before fitting to experimental data. This study explores the effect of components in several objective functions, in order to recommend components to be used for fitting to experimental data. Four novel approaches to modeling coactivation through optimization techniques are presented, two of which produce greater levels of stiffness than previous techniques. Simulations were performed using OpenSim and MATLAB cooperatively. Results show that maximizing the moment generated by a particular muscle appears analogous to maximizing joint stiffness. The approach of optimizing for maximum moment generated by individual muscles may be a good candidate for developing objective functions that accurately simulate muscle coactivation in complex joints. This new approach will be the focus of future studies with human subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle

PubMed Central

Muir, Lindsey A.; Murry, Charles E.

2016-01-01

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a KATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle. PMID:27503462

Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

PubMed

Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

2004-07-15

Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle.

PubMed

Muir, Lindsey A; Murry, Charles E; Chamberlain, Jeffrey S

2016-09-07

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a K ATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle.

Effects of pelvic floor muscle training during pregnancy.

PubMed

de Oliveira, Claudia; Lopes, Marco Antonio Borges; Carla Longo e Pereira, Luciana; Zugaib, Marcelo

2007-08-01

The objective of the present study was to evaluate the effect of pelvic floor muscle training in 46 nulliparous pregnant women. The women were divided into 2 groups: an exercise group and a control group. Functional evaluation of the pelvic floor muscle was performed by digital vaginal palpation using the strength scale described by Ortiz and by a perineometer (with and without biofeedback). The functional evaluation of the pelvic floor muscles showed a significant increase in pelvic floor muscle strength during pregnancy in both groups (P < .001). However, the magnitude of the change was greater in the exercise group than in the control group (47.4% vs. 17.3%, P < .001). The study also showed a significant positive correlation (Spearman's test, r = 0.643; P < .001) between perineometry and digital assessment in the strength of pelvic floor muscles. Pelvic floor muscle training resulted in a significant increase in pelvic floor muscle pressure and strength during pregnancy. A significant positive correlation between functional evaluation of the pelvic floor muscle and perineometry was observed during pregnancy.

Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET.

PubMed

Rygh, Cecilie B; Qin, Shengping; Seo, Jai W; Mahakian, Lisa M; Zhang, Hua; Adamson, Roger; Chen, Jane Q; Borowsky, Alexander D; Cardiff, Robert D; Reed, Rolf K; Curry, Fitz-Roy E; Ferrara, Katherine W

2011-02-01

We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10(-8) and 1.3 × 10(-8) cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability. ©2010 AACR.

Relationship of quadriceps muscle power and optimal shortening velocity with angiotensin-converting enzyme activity in older women.

PubMed

Kostka, Joanna; Sikora, Joanna; Kostka, Tomasz

2017-01-01

The goal of this study was to assess whether angiotensin-converting enzyme (ACE) activity is related to muscle function (strength, power and velocity), as well as to assess if ACE inhibitors (ACEIs) and other angiotensin system blocking medications (ASBMs) influence muscle performance in elderly women. Ninety-five community-dwelling elderly women took part in this study. Anthropometric data, blood ACE activity analysis, maximum power (P max ) and optimal shortening velocity (υ opt ) of the knee extensor muscles, handgrip strength, physical activity (PA) and functional performance were measured. Women taking ACEI were on average almost 2 years older than the women who did not take ACEI. They took more medicines and were also characterized by significantly lower level of ACE, but they did not differ in terms of PA level, results of functional performance and parameters characterizing muscle functions. No correlations of ACE activity with P max and handgrip strength, as well as with PA or functional performance were found. Higher ACE activity was connected with lower υ opt for women who did not take any ASBMs (rho =-0.37; p =0.01). Serum ACE activity was not associated with muscle strength, power and functional performance in both ASBM users and nonusers, but was associated with optimal shortening velocity of quadriceps muscles in older women. Further prospective studies are needed to assess if ACEIs or other ASBMs may slow down the decline in muscle function and performance.

Androgen effects on skeletal muscle: implications for the development and management of frailty

PubMed Central

O’Connell, Matthew DL; Wu, Frederick CW

2014-01-01

Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well–tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies. PMID:24457838

Lower extremity muscle functions during full squats.

PubMed

Robertson, D G E; Wilson, Jean-Marie J; St Pierre, Taunya A

2008-11-01

The purpose of this research was to determine the functions of the gluteus maximus, biceps femoris, semitendinosus, rectus femoris, vastus lateralis, soleus, gastrocnemius, and tibialis anterior muscles about their associated joints during full (deep-knee) squats. Muscle function was determined from joint kinematics, inverse dynamics, electromyography, and muscle length changes. The subjects were six experienced, male weight lifters. Analyses revealed that the prime movers during ascent were the monoarticular gluteus maximus and vasti muscles (as exemplified by vastus lateralis) and to a lesser extent the soleus muscles. The biarticular muscles functioned mainly as stabilizers of the ankle, knee, and hip joints by working eccentrically to control descent or transferring energy among the segments during scent. During the ascent phase, the hip extensor moments of force produced the largest powers followed by the ankle plantar flexors and then the knee extensors. The hip and knee extensors provided the initial bursts of power during ascent with the ankle extensors and especially a second burst from the hip extensors adding power during the latter half of the ascent.

Applications of In Vivo Functional Testing of the Rat Tibialis Anterior for Evaluating Tissue Engineered Skeletal Muscle Repair

PubMed Central

Mintz, Ellen L.; Passipieri, Juliana A.; Lovell, Daniel Y.; Christ, George J.

2016-01-01

Despite the regenerative capacity of skeletal muscle, permanent functional and/or cosmetic deficits (e.g., volumetric muscle loss (VML) resulting from traumatic injury, disease and various congenital, genetic and acquired conditions are quite common. Tissue engineering and regenerative medicine technologies have enormous potential to provide a therapeutic solution. However, utilization of biologically relevant animal models in combination with longitudinal assessments of pertinent functional measures are critical to the development of improved regenerative therapeutics for treatment of VML-like injuries. In that regard, a commercial muscle lever system can be used to measure length, tension, force and velocity parameters in skeletal muscle. We used this system, in conjunction with a high power, bi-phase stimulator, to measure in vivo force production in response to activation of the anterior crural compartment of the rat hindlimb. We have previously used this equipment to assess the functional impact of VML injury on the tibialis anterior (TA) muscle, as well as the extent of functional recovery following treatment of the injured TA muscle with our tissue engineered muscle repair (TEMR) technology. For such studies, the left foot of an anaesthetized rat is securely anchored to a footplate linked to a servomotor, and the common peroneal nerve is stimulated by two percutaneous needle electrodes to elicit muscle contraction and dorsiflexion of the foot. The peroneal nerve stimulation-induced muscle contraction is measured over a range of stimulation frequencies (1-200 Hz), to ensure an eventual plateau in force production that allows for an accurate determination of peak tetanic force. In addition to evaluation of the extent of VML injury as well as the degree of functional recovery following treatment, this methodology can be easily applied to study diverse aspects of muscle physiology and pathophysiology. Such an approach should assist with the more rational development of improved therapeutics for muscle repair and regeneration. PMID:27768064

Applications of In Vivo Functional Testing of the Rat Tibialis Anterior for Evaluating Tissue Engineered Skeletal Muscle Repair.

PubMed

Mintz, Ellen L; Passipieri, Juliana A; Lovell, Daniel Y; Christ, George J

2016-10-07

Despite the regenerative capacity of skeletal muscle, permanent functional and/or cosmetic deficits (e.g., volumetric muscle loss (VML) resulting from traumatic injury, disease and various congenital, genetic and acquired conditions are quite common. Tissue engineering and regenerative medicine technologies have enormous potential to provide a therapeutic solution. However, utilization of biologically relevant animal models in combination with longitudinal assessments of pertinent functional measures are critical to the development of improved regenerative therapeutics for treatment of VML-like injuries. In that regard, a commercial muscle lever system can be used to measure length, tension, force and velocity parameters in skeletal muscle. We used this system, in conjunction with a high power, bi-phase stimulator, to measure in vivo force production in response to activation of the anterior crural compartment of the rat hindlimb. We have previously used this equipment to assess the functional impact of VML injury on the tibialis anterior (TA) muscle, as well as the extent of functional recovery following treatment of the injured TA muscle with our tissue engineered muscle repair (TEMR) technology. For such studies, the left foot of an anaesthetized rat is securely anchored to a footplate linked to a servomotor, and the common peroneal nerve is stimulated by two percutaneous needle electrodes to elicit muscle contraction and dorsiflexion of the foot. The peroneal nerve stimulation-induced muscle contraction is measured over a range of stimulation frequencies (1-200 Hz), to ensure an eventual plateau in force production that allows for an accurate determination of peak tetanic force. In addition to evaluation of the extent of VML injury as well as the degree of functional recovery following treatment, this methodology can be easily applied to study diverse aspects of muscle physiology and pathophysiology. Such an approach should assist with the more rational development of improved therapeutics for muscle repair and regeneration.

Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.

PubMed

Schmidt, Simone; Hafner, Patricia; Klein, Andrea; Rubino-Nacht, Daniela; Gocheva, Vanya; Schroeder, Jonas; Naduvilekoot Devasia, Arjith; Zuesli, Stephanie; Bernert, Guenther; Laugel, Vincent; Bloetzer, Clemens; Steinlin, Maja; Capone, Andrea; Gloor, Monika; Tobler, Patrick; Haas, Tanja; Bieri, Oliver; Zumbrunn, Thomas; Fischer, Dirk; Bonati, Ulrike

2018-01-01

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Respiratory muscle strength is not decreased in patients undergoing cardiac surgery.

PubMed

Urell, Charlotte; Emtner, Margareta; Hedenstrom, Hans; Westerdahl, Elisabeth

2016-03-31

Postoperative pulmonary impairments are significant complications after cardiac surgery. Decreased respiratory muscle strength could be one reason for impaired lung function in the postoperative period. The primary aim of this study was to describe respiratory muscle strength before and two months after cardiac surgery. A secondary aim was to describe possible associations between respiratory muscle strength and lung function. In this prospective observational study 36 adult cardiac surgery patients (67 ± 10 years) were studied. Respiratory muscle strength and lung function were measured before and two months after surgery. Pre- and postoperative respiratory muscle strength was in accordance with predicted values; MIP was 78 ± 24 cmH2O preoperatively and 73 ± 22 cmH2O at two months follow-up (p = 0.19). MEP was 122 ± 33 cmH2O preoperatively and 115 ± 38 cmH2O at two months follow-up (p = 0.18). Preoperative lung function was in accordance with predicted values, but was significantly decreased postoperatively. At two-months follow-up there was a moderate correlation between MIP and FEV1 (r = 0.43, p = 0.009). Respiratory muscle strength was not impaired, either before or two months after cardiac surgery. The reason for postoperative lung function alteration is not yet known. Interventions aimed at restore an optimal postoperative lung function should focus on other interventions then respiratory muscle strength training.

A neuro-mechanical model of a single leg joint highlighting the basic physiological role of fast and slow muscle fibres of an insect muscle system.

PubMed

Toth, Tibor Istvan; Schmidt, Joachim; Büschges, Ansgar; Daun-Gruhn, Silvia

2013-01-01

In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1) positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2) the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3) there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles.

Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery.

PubMed

Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

2016-04-01

Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery.

Postural threat influences vestibular-evoked muscular responses.

PubMed

Lim, Shannon B; Cleworth, Taylor W; Horslen, Brian C; Blouin, Jean-Sébastien; Inglis, J Timothy; Carpenter, Mark G

2017-02-01

Standing balance is significantly influenced by postural threat. While this effect has been well established, the underlying mechanisms of the effect are less understood. The involvement of the vestibular system is under current debate, and recent studies that investigated the effects of height-induced postural threat on vestibular-evoked responses provide conflicting results based on kinetic (Horslen BC, Dakin CJ, Inglis JT, Blouin JS, Carpenter MG. J Physiol 592: 3671-3685, 2014) and kinematic (Osler CJ, Tersteeg MC, Reynolds RF, Loram ID. Eur J Neurosci 38: 3239-3247, 2013) data. We examined the effect of threat of perturbation, a different form of postural threat, on coupling (cross-correlation, coherence, and gain) of the vestibulo-muscular relationship in 25 participants who maintained standing balance. In the "No-Threat" conditions, participants stood quietly on a stable surface. In the "Threat" condition, participants' balance was threatened with unpredictable mediolateral support surface tilts. Quiet standing immediately before the surface tilts was compared to an equivalent time from the No-Threat conditions. Surface EMG was recorded from bilateral trunk, hip, and leg muscles. Hip and leg muscles exhibited significant increases in peak cross-correlation amplitudes, coherence, and gain (1.23-2.66×) in the Threat condition compared with No-Threat conditions, and significant correlations were observed between threat-related changes in physiological arousal and medium-latency peak cross-correlation amplitude in medial gastrocnemius (r = 0.408) muscles. These findings show a clear threat effect on vestibular-evoked responses in muscles in the lower body, with less robust effects of threat on trunk muscles. Combined with previous work, the present results can provide insight into observed changes during balance control in threatening situations. This is the first study to show increases in vestibular-evoked responses of the lower body muscles under conditions of increased threat of postural perturbation. While robust findings were observed in hip and leg muscles, less consistent results were found in muscles of the trunk. The present findings provide further support in the ongoing debate for arguments that vestibular-evoked balance responses are influenced by fear and anxiety and explain previous threat-related changes in balance. Copyright © 2017 the American Physiological Society.

Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

PubMed Central

Brotto, Leticia S.; Bougoin, Sylvain; Nosek, Thomas M.; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome

2011-01-01

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle. PMID:21666285

Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.

PubMed

Thornton, Angela M; Zhao, Xiaoli; Weisleder, Noah; Brotto, Leticia S; Bougoin, Sylvain; Nosek, Thomas M; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome; Brotto, Marco

2011-06-01

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

A comparison of the social competence of children with moderate intellectual disability in inclusive versus segregated school settings.

PubMed

Hardiman, Sharon; Guerin, Suzanne; Fitzsimons, Elaine

2009-01-01

This is the first study to compare the social competence of children with moderate intellectual disability in inclusive versus segregated school settings in the Republic of Ireland. A convenience sample was recruited through two large ID services. The sample comprised 45 children across two groups: Group 1 (n=20; inclusive school) and Group 2 (n=25; segregated school). Parents and teachers completed the Strengths and Difficulties Questionnaire and the Adaptive Behaviour Scale-School: 2nd edition. A series of 2 x 2 ANOVAs were carried out on social competence scores using educational placement type (inclusive vs segregated school) and proxy rater (parent vs teacher) as the independent variables. Key findings indicated that children in inclusive schools did not differ significantly from children in segregated schools on the majority of proxy ratings of social competence. This supports the belief that children with intellectual disabilities can function well in different educational settings. Present findings highlight the importance of utilising the functional model of ID when selecting and designing school placements for children with moderate ID.

Effect of a nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

USDA-ARS?s Scientific Manuscript database

Nicotinic acetylcholine receptors (nAChR) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChR located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The...

The Effects of an 8-Week Stabilization Exercise Program on Lumbar Multifidus Muscle Thickness and Activation as Measured With Ultrasound Imaging in Patients With Low Back Pain: An Exploratory Study.

PubMed

Larivière, Christian; Gagnon, Dany H; Henry, Sharon M; Preuss, Richard; Dumas, Jean-Pierre

2018-05-01

Lumbar stabilization exercise programs (LSEP) produce positive effects on clinical outcomes, but the underlying mechanisms remain relatively unexplored. Psychological and neuromuscular mechanisms can be involved, such as a better activation of the lumbar multifidus, which represents one possibility. To determine the following: (1) the effect of an LSEP on lumbar multifidus muscle thickness and activation, as measured with rehabilitative ultrasound imaging (RUSI), in patients with low back pain (LBP); (2) the correlation between RUSI measures and any change in clinical outcomes following the LSEP; and (3) the reliability of RUSI measures in control subjects over 8 weeks. One-arm clinical trial with healthy subjects as a control group; reliability study. LSEP delivered in a clinical setting; outcomes measured in a laboratory setting. A total of 34 patients with nonacute LBP and 28 healthy control subjects. Outcomes were measured before and after an 8-week LSEP in patients with LBP, and at the same time interval (without treatment, to assess reliability) in control subjects. Pain numeric rating scale, Oswestry Disability Index (function), as well as RUSI measures for the lumbar multifidus (LM) muscles at 3 vertebral levels (L5-S1, L4-5, and L3-4) during rest (static) and dynamic contractions (percent thickness change). Patients did not show systematic changes in RUSI measures relative to controls, even though RUSI impairments were observed at baseline (dynamic measure at L5-S1) and even though patients had significant improvements in pain and disability. Correlational analyses with these clinical outcomes suggested that patients had reduced muscle thickness at baseline that was associated with a greater reduction in disability following LSEP; however, LM activation measured at baseline showed the opposite. Static RUSI measures showed excellent reliability at the L4-5 and L3-4 levels, whereas dynamic measures were not reliable. Patients showed less muscle activation than controls at baseline (L5-S1 level), but the LSEP did not normalize this impairment. The links between RUSI measures and the change in clinical outcomes during LSEP should be further explored. This clinical trial has been recorded in the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (ID: ISRCTN94152969). II. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice.

PubMed

Warren, Gordon L; Moran, Amy L; Hogan, Harry A; Lin, Angela S; Guldberg, Robert E; Lowe, Dawn A

2007-11-01

The study's objective was to investigate how estrogen deficiency and run training affect the tibial bone-soleus muscle functional relationship in mice. Female mice were assigned into one of two surgical conditions, ovariectomy (OVX) or sham ovariectomy (sham), and one of two activity conditions, voluntary wheel running (Run) or sedentary (Sed). To determine whether differences observed between OVX and sham conditions could be attributed to estradiol (E(2)), additional OVX mice were supplemented with E(2). Tibial bones were analyzed for their functional capacities, ultimate load, and stiffness. Soleus muscles were analyzed for their functional capacities, maximal isometric tetanic force (P(o)), and peak eccentric force. The ratios of bone functional capacities to those of muscle were calculated. The bone functional capacities were affected by both surgical condition and activity but more strongly by surgical condition. Ultimate load and stiffness for the sham group were 7-12% greater than those for OVX animals (P = 0.002), whereas only stiffness was greater for Run than for Sed animals (9%; P = 0.015). The muscle functional capacities were affected by both surgical condition and activity; however, in contrast to the bone, the muscle was more affected by activity. P(o) and peak eccentric force were 10-21% greater for Run than for Sed animals (P < or = 0.016), whereas only P(o) was greater in sham than in OVX animals (9%; P = 0.011). The bone-to-muscle ratios of functional capacities were affected by activity but not by surgical condition or E(2) supplementation. Thus a mismatch of bone-muscle function occurred in mice that voluntarily ran on wheels, irrespective of estrogen status.

Greater understanding of normal hip physical function may guide clinicians in providing targeted rehabilitation programmes.

PubMed

Kemp, Joanne L; Schache, Anthony G; Makdissi, Michael; Sims, Kevin J; Crossley, Kay M

2013-07-01

This study investigated tests of hip muscle strength and functional performance. The specific objectives were to: (i) establish intra- and inter-rater reliability; (ii) compare differences between dominant and non-dominant limbs; (iii) compare agonist and antagonist muscle strength ratios; (iv) compare differences between genders; and (v) examine relationships between hip muscle strength, baseline measures and functional performance. Reliability study and cross-sectional analysis of hip strength and functional performance. In healthy adults aged 18-50years, normalised hip muscle peak torque and functional performance were evaluated to: (i) establish intra-rater and inter-rater reliability; (ii) analyse differences between limbs, between antagonistic muscle groups and genders; and (iii) associations between strength and functional performance. Excellent reliability (intra-rater ICC=0.77-0.96; inter-rater ICC=0.82-0.95) was observed. No difference existed between dominant and non-dominant limbs. Differences in strength existed between antagonistic pairs of muscles: hip abduction was greater than adduction (p<0.001) and hip ER was greater than IR (p<0.001). Men had greater ER strength (p=0.006) and hop for distance (p<0.001) than women. Strong associations were observed between measures of hip muscle strength (except hip flexion) and age, height, and functional performance. Deficits in hip muscle strength or functional performance may influence hip pain. In order to provide targeted rehabilitation programmes to address patient-specific impairments, and determine when individuals are ready to return to physical activity, clinicians are increasingly utilising tests of hip strength and functional performance. This study provides a battery of reliable, clinically applicable tests which can be used for these purposes. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Role of microRNAs in the age-related changes in skeletal muscle and diet or exercise interventions to promote healthy aging in humans.

PubMed

McGregor, Robin A; Poppitt, Sally D; Cameron-Smith, David

2014-09-01

Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age. Copyright © 2014 Elsevier B.V. All rights reserved.

Contraction dynamics and function of the muscle-tendon complex depend on the muscle fibre-tendon length ratio: a simulation study.

PubMed

Mörl, Falk; Siebert, Tobias; Häufle, Daniel

2016-02-01

Experimental studies show different muscle-tendon complex (MTC) functions (e.g. motor or spring) depending on the muscle fibre-tendon length ratio. Comparing different MTC of different animals examined experimentally, the extracted MTC functions are biased by, for example, MTC-specific pennation angle and fibre-type distribution or divergent experimental protocols (e.g. influence of temperature or stimulation on MTC force). Thus, a thorough understanding of variation of these inner muscle fibre-tendon length ratios on MTC function is difficult. In this study, we used a hill-type muscle model to simulate MTC. The model consists of a contractile element (CE) simulating muscle fibres, a serial element (SE) as a model for tendon, and a parallel elastic element (PEE) modelling tissue in parallel to the muscle fibres. The simulation examines the impact of length variations of these components on contraction dynamics and MTC function. Ensuring a constant overall length of the MTC by L(MTC) = L(SE) + L(CE), the SE rest length was varied over a broad physiological range from 0.1 to 0.9 MTC length. Five different MTC functions were investigated by simulating typical physiological experiments: the stabilising function with isometric contractions, the motor function with contractions against a weight, the capability of acceleration with contractions against a small inertial mass, the braking function by decelerating a mass, and the spring function with stretch-shortening cycles. The ratio of SE and CE mainly determines the MTC function. MTC with comparably short tendon generates high force and maximal shortening velocity and is able to produce maximal work and power. MTC with long tendon is suitable to store and release a maximum amount of energy. Variation of muscle fibre-tendon ratio yielded two peaks for MTC's force response for short and long SE lengths. Further, maximum work storage capacity of the SE is at long relL(SE,0). Impact of fibre-tendon length ratio on MTC functions will be discussed. Considering a constant set of MTC parameters, quantitative changes in MTC performance (work, stiffness, force, energy storage, dissipation) depending on varying muscle fibre-tendon length ratio were provided, which enables classification and grading of different MTC designs.

The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy.

PubMed

Posner, Andrew D; Soslow, Jonathan H; Burnette, W Bryan; Bian, Aihua; Shintani, Ayumi; Sawyer, Douglas B; Markham, Larry W

2016-01-01

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

Parenting stress and child behaviour problems among parents with intellectual disabilities: the buffering role of resources.

PubMed

Meppelder, M; Hodes, M; Kef, S; Schuengel, C

2015-07-01

Parents with intellectual disabilities (ID) are at risk for high levels of parenting stress. The present study evaluated resources, including parental adaptive functioning, financial resources and access to a support network, as moderators of the association between child behaviour problems and parenting stress. A total of 134 parents with ID and their children (ages 1-7 years) were recruited from 10 Dutch care organisations. Questionnaires were administered to the parents to obtain information on parenting stress in the parent and child domain, financial resources and their support network. Teachers and care workers reported on child behaviour problems and parental adaptive functioning, respectively. Parents experienced more stress with regard to their children than towards their own functioning and situation. Parenting stress was less in parents who were not experiencing financial hardship. Child behaviour problems were associated with high child-related parenting stress, not parent-related parenting stress. Large support networks decreased the association between child behaviour problems and child-related parenting stress. Financial resources did not significantly moderate the association. Parenting stress among parents with ID is focused on problems with the child, especially when little social support is available. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Effects of proprioceptive circuit exercise on knee joint pain and muscle function in patients with knee osteoarthritis.

PubMed

Ju, Sung-Bum; Park, Gi Duck; Kim, Sang-Soo

2015-08-01

[Purpose] This study applied proprioceptive circuit exercise to patients with degenerative knee osteoarthritis and examined its effects on knee joint muscle function and the level of pain. [Subjects] In this study, 14 patients with knee osteoarthritis in two groups, a proprioceptive circuit exercise group (n = 7) and control group (n = 7), were examined. [Methods] IsoMed 2000 (D&R Ferstl GmbH, Hemau, Germany) was used to assess knee joint muscle function, and a Visual Analog Scale was used to measure pain level. [Results] In the proprioceptive circuit exercise group, knee joint muscle function and pain levels improved significantly, whereas in the control group, no significant improvement was observed. [Conclusion] A proprioceptive circuit exercise may be an effective way to strengthen knee joint muscle function and reduce pain in patients with knee osteoarthritis.

Biallelic missense variants in ZBTB11 can cause intellectual disability in human.

PubMed

Fattahi, Zohreh; Sheikh, Taimoor I; Musante, Luciana; Rasheed, Memoona; Taskiran, Ibrahim Ihsan; Harripaul, Ricardo; Hu, Hao; Kazeminasab, Somayeh; Alam, Muhammad Rizwan; Hosseini, Masoumeh; Larti, Farzaneh; Ghaderi, Zhila; Celik, Arzu; Ayub, Muhammad; Ansar, Muhammad; Haddadi, Mohammad; Wienker, Thomas F; Ropers, Hans Hilger; Kahrizi, Kimia; Vincent, John B; Najmabadi, H

2018-06-08

Exploring genes and pathways underlying Intellectual Disability (ID) provides insight into brain development and function, clarifying the complex puzzle of how cognition develops. As part of ongoing systematic studies to identify candidate ID genes, linkage analysis and next generation sequencing revealed ZBTB11, as a novel candidate ID gene. ZBTB11 encodes a less-studied transcription regulator and the two identified missense variants in this study may disrupt canonical Zn2+-binding residues of its C2H2 zinc finger domain, leading to possible altered DNA binding. Using HEK293T cells transfected with wild type and mutant GFP-ZBTB11 constructs, we found the ZBTB11 mutants being excluded from the nucleolus, where the wild-type recombinant protein is predominantly localized. Pathway analysis applied to ChIP-seq data deposited in the ENCODE database supports the localization of ZBTB11 in nucleoli, highlighting associated pathways such as rRNA synthesis, ribosomal assembly, RNA modification, stress sensing and provides a direct link between subcellular ZBTB11 location and its function. Furthermore, considering the report of prominent brain and spinal cord degeneration in a zebrafish Zbtb11 mutant, we investigated ZBTB11-ortholog knockdown in Drosophila melanogaster brain by targeting RNAi using the UAS/Gal4 system. The observed approximate reduction to a third of the mushroom body size - possibly through neuronal reduction or degeneration - may affect neuronal circuits in the brain that are required for adaptive behavior, specifying the role of this gene in nervous system. In conclusion, we report two ID families segregating ZBTB11 biallelic mutations disrupting Zn2+-binding motifs, and provide functional evidence linking ZBTB11 dysfunction to this phenotype.

Free Neurovascular Latissimus Dorsi Muscle Transplantation for Reconstruction of Hip Abductors.

PubMed

Barrera-Ochoa, Sergi; Collado-Delfa, Jose Manuel; Sallent, Andrea; Lluch, Alejandro; Velez, Roberto

2017-09-01

Resection of tumors affecting the hip abductors can cause significant decrease in muscle strength and may lead to abnormal gait and poor function. We present a case report showing full functional recovery after resection of a synovial sarcoma affecting the right gluteus medius and minimus muscles with reconstruction free neurovascular latissimus dorsi muscle transplantation. The latissimus dorsi muscle was harvested following standard technique and fixed to the ilium and the greater trochanter. Receptor vessels were end-to-end anastomosed to the subscapular vessels followed by an end-to-end epineural suture between the superior gluteal nerve and the thoracodorsal nerve. A year after surgery, there is no evidence of recurrent disease; electromyographic analysis shows complete reinnervation of the latissimus dorsi muscle flap, and the patient has achieved full functional recovery. Free functional latisimus dorsi transfer could be considered as a viable reconstruction technique after hip abductors resection in tumor surgery.

A comparison of family financial and employment impacts of fragile X syndrome, autism spectrum disorders, and intellectual disability.

PubMed

Ouyang, Lijing; Grosse, Scott D; Riley, Catharine; Bolen, Julie; Bishop, Ellen; Raspa, Melissa; Bailey, Donald B

2014-07-01

This study compares the family financial and employment impacts of having a child with fragile X syndrome (FXS), autism spectrum disorder (ASD), or intellectual disabilities (ID). Data from a 2011 national survey of families of children with FXS were matched with data from the National Survey of Children with Special Health Care Needs 2009-2010 to form four analytic groups: children with FXS (n=189), children with special health care needs with ASD only (n=185), ID only (n=177), or both ASD and ID (n=178). Comparable percentages of parents of children with FXS (60%) and parents of children with both ASD and ID (52%) reported that their families experienced a financial burden as a result of the condition, both of which were higher than the percentages of parents of children with ASD only (39%) or ID only (29%). Comparable percentages of parents of children with FXS (40%) and parents of children with both ASD and ID (46%) reported quitting employment because of the condition, both of which were higher than the percentages of parents of children with ID only (25%) or ASD only (25%). In multivariate analyses controlling for co-occurring conditions and functional difficulties and stratified by age, adjusted odds ratios for the FXS group aged 12-17 years were significantly elevated for financial burden (2.73, 95% CI 1.29-5.77), quitting employment (2.58, 95% CI 1.18-5.65) and reduced hours of work (4.34, 95% CI 2.08-9.06) relative to children with ASD only. Among children aged 5-11 years, the adjusted odds ratios for the FXS group were elevated but statistically insignificant for financial burden (1.63, 95% CI 0.85-3.14) and reducing hours of work (1.34, 95% CI 0.68-2.63) relative to children with ASD only. Regardless of condition, co-occurring anxiety or seizures, limits in thinking, reasoning, or learning ability, and more irritability were significantly associated with more caregiver financial and employment impacts. Proper management of anxiety or seizures and functional difficulties of children with FXS or other developmental disabilities may be important in alleviating adverse family caregiver impacts. Published by Elsevier Ltd.

The European Community Directive -- An Alternative Environmental Impact Assessment Procedure after Massey?

DTIC Science & Technology

1993-09-30

competitive conditions, thereby directly affecting the functioning of the common market .’l B. Environmental Impact Assessment 1. Background The Preamble to the...of the conmon market ." Treaty of Rome, supra note 120, art. 100. ’"EC Directive, supra note 22, Preamble. 14Id. art. 1.2. 16Id. 51 member states...dairy products. (d) Brewing and malting. (e) Confectionery and syrup manufacture. (f) Installations for the slaughter of animals. 86 0 0 (g

Fiber-type distribution in insect leg muscles parallels similarities and differences in the functional role of insect walking legs.

PubMed

Godlewska-Hammel, Elzbieta; Büschges, Ansgar; Gruhn, Matthias

2017-10-01

Previous studies have demonstrated that myofibrillar ATPase (mATPase) enzyme activity in muscle fibers determines their contraction properties. We analyzed mATPase activities in muscles of the front, middle and hind legs of the orthopteran stick insect (Carausius morosus) to test the hypothesis that differences in muscle fiber types and distributions reflected differences in their behavioral functions. Our data show that all muscles are composed of at least three fiber types, fast, intermediate and slow, and demonstrate that: (1) in the femoral muscles (extensor and flexor tibiae) of all legs, the number of fast fibers decreases from proximal to distal, with a concomitant increase in the number of slow fibers. (2) The swing phase muscles protractor coxae and levator trochanteris, have smaller percentages of slow fibers compared to the antagonist stance muscles retractor coxae and depressor trochanteris. (3) The percentage of slow fibers in the retractor coxae and depressor trochanteris increases significantly from front to hind legs. These results suggest that fiber-type distribution in leg muscles of insects is not identical across leg muscles but tuned towards the specific function of a given muscle in the locomotor system.

Correlating interleukin-12 stimulated interferon-γ production and the absence of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF-κB essential modulator (NEMO).

PubMed

Haverkamp, Margje H; Marciano, Beatriz E; Frucht, David M; Jain, Ashish; van de Vosse, Esther; Holland, Steven M

2014-05-01

Patients with hypomorphic mutations in Nuclear Factor-κB Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA. PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-γ, TNF and IL-1β. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls. PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-γ after stimulation with PHA, but normal amounts of IFN-γ after PHA plus IL-12p70. In contrast, IFN-γ production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1β than controls, whereas the production of these cytokines by patients without EDA was normal. Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA.

Expanding the genetic heterogeneity of intellectual disability.

PubMed

Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

2017-11-01

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family

PubMed Central

Sheereen, Atia; Alaamery, Manal; Bawazeer, Shahad; Al Yafee, Yusra; Massadeh, Salam; Eyaid, Wafaa

2017-01-01

Background Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning. Objectives We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members. Methods Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members. Results A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site. Conclusions These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype–phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. PMID:28143899

Multifunctional and Context-Dependent Control of Vocal Acoustics by Individual Muscles

PubMed Central

Srivastava, Kyle H.; Elemans, Coen P.H.

2015-01-01

The relationship between muscle activity and behavioral output determines how the brain controls and modifies complex skills. In vocal control, ensembles of muscles are used to precisely tune single acoustic parameters such as fundamental frequency and sound amplitude. If individual vocal muscles were dedicated to the control of single parameters, then the brain could control each parameter independently by modulating the appropriate muscle or muscles. Alternatively, if each muscle influenced multiple parameters, a more complex control strategy would be required to selectively modulate a single parameter. Additionally, it is unknown whether the function of single muscles is fixed or varies across different vocal gestures. A fixed relationship would allow the brain to use the same changes in muscle activation to, for example, increase the fundamental frequency of different vocal gestures, whereas a context-dependent scheme would require the brain to calculate different motor modifications in each case. We tested the hypothesis that single muscles control multiple acoustic parameters and that the function of single muscles varies across gestures using three complementary approaches. First, we recorded electromyographic data from vocal muscles in singing Bengalese finches. Second, we electrically perturbed the activity of single muscles during song. Third, we developed an ex vivo technique to analyze the biomechanical and acoustic consequences of single-muscle perturbations. We found that single muscles drive changes in multiple parameters and that the function of single muscles differs across vocal gestures, suggesting that the brain uses a complex, gesture-dependent control scheme to regulate vocal output. PMID:26490859

Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status.

PubMed

Comín-Colet, Josep; Enjuanes, Cristina; González, Gina; Torrens, Ainhoa; Cladellas, Mercè; Meroño, Oona; Ribas, Nuria; Ruiz, Sonia; Gómez, Miquel; Verdú, José Maria; Bruguera, Jordi

2013-10-01

To evaluate the effect of iron deficiency (ID) and/or anaemia on health-related quality of life (HRQoL) in patients with chronic heart failure (CHF). We undertook a post-hoc analysis of a cohort of CHF patients in a single-centre study evaluating cognitive function. At recruitment, patients provided baseline information and completed the Minnesota Living with Heart Failure questionnaire (MLHFQ) for HRQoL (higher scores reflect worse HRQoL). At the same time, blood samples were taken for serological evaluation. ID was defined as serum ferritin levels <100 ng/mL or serum ferritin <800 ng/mL with transferrin saturation <20%. Anaemia was defined as haemoglobin ≤12 g/dL. A total of 552 CHF patients were eligible for inclusion, with an average age of 72 years and 40% in NYHA class III or IV. The MLHFQ overall summary scores were 41.0 ± 24.7 among those with ID, vs. 34.4 ± 26.4 for non-ID patients (P = 0.003), indicating worse HRQoL. When adjusted for other factors associated with HRQoL, ID was significantly associated with worse MLHFQ overall summary (P = 0.008) and physical dimension scores (P = 0.002), whereas anaemia was not (both P > 0.05). Increased levels of soluble transferrin receptor were also associated with impaired HRQoL (P ≤ 0.001). Adjusting for haemoglobin and C-reactive protein, ID was more pronounced in patients with anaemia compared with those without (P < 0.001). In patients with CHF, ID but not anaemia was associated with reduced HRQoL, mostly due to physical factors.

Intramuscular Transplantation and Survival of Freshly Isolated Bone Marrow Cells following Skeletal Muscle Ischemia-reperfusion Injury

DTIC Science & Technology

2013-01-01

2) in a rat I/R model, consis- tent with this time course of functional recovery, evidence of muscle fiber damage and regeneration was still present...Contractile function of the anterior crural muscles was assessed by measuring maximal isometric torque as a function of stimulation frequency (20Y200 Hz...from the direct conver- sion of bone marrowYderived cells to muscle fibers , the paracrine secretory effects of stem cells resident in bone marrow

Functional redundancy and nonredundancy between two Troponin C isoforms in Drosophila adult muscles

PubMed Central

Chechenova, Maria B.; Maes, Sara; Oas, Sandy T.; Nelson, Cloyce; Kiani, Kaveh G.; Bryantsev, Anton L.; Cripps, Richard M.

2017-01-01

We investigated the functional overlap of two muscle Troponin C (TpnC) genes that are expressed in the adult fruit fly, Drosophila melanogaster: TpnC4 is predominantly expressed in the indirect flight muscles (IFMs), whereas TpnC41C is the main isoform in the tergal depressor of the trochanter muscle (TDT; jump muscle). Using CRISPR/Cas9, we created a transgenic line with a homozygous deletion of TpnC41C and compared its phenotype to a line lacking functional TpnC4. We found that the removal of either of these genes leads to expression of the other isoform in both muscle types. The switching between isoforms occurs at the transcriptional level and involves minimal enhancers located upstream of the transcription start points of each gene. Functionally, the two TpnC isoforms were not equal. Although ectopic TpnC4 in TDT muscles was able to maintain jumping ability, TpnC41C in IFMs could not effectively support flying. Simultaneous functional disruption of both TpnC genes resulted in jump-defective and flightless phenotypes of the survivors, as well as abnormal sarcomere organization. These results indicated that TpnC is required for myofibril assembly, and that there is functional specialization among TpnC isoforms in Drosophila. PMID:28077621

Distinct roles for Ste20-like kinase SLK in muscle function and regeneration

PubMed Central

2013-01-01

Background Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood. Methods To gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair. Results High levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro. Conclusions Our results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function. PMID:23815977

Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

PubMed Central

Vermillion, Katie L.; Anderson, Kyle J.; Hampton, Marshall

2015-01-01

Throughout the hibernation season, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism, oxygen consumption, and body temperature, along with prolonged fasting and immobility. These conditions necessitate different functional requirements for the heart, which maintains contractile function throughout hibernation, and the skeletal muscle, which remains largely inactive. The adaptations used to maintain these contractile organs under such variable conditions serves as a natural model to study a variety of medically relevant conditions including heart failure and disuse atrophy. To better understand how two different muscle tissues maintain function throughout the extreme fluctuations of hibernation we performed Illumina HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal muscle across the circannual cycle. This analysis resulted in the identification of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle, respectively. In both heart and skeletal muscle we identified a distinct cold-tolerant mechanism utilizing peroxisomal metabolism to make use of elevated levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an early increase in oxidative capacity necessary for the altered fuel utilization and increased oxygen demand of shivering. Expression of the fetal gene expression profile is used to maintain cardiac tissue, either through increasing myocyte size or proliferation of resident cardiomyocytes, while skeletal muscle function and mass are protected through transcriptional regulation of pathways involved in protein turnover. This study provides insight into how two functionally distinct muscles maintain function under the extreme conditions of mammalian hibernation. PMID:25572546

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy

PubMed Central

Pinniger, Gavin J.; Graves, Jamie A.; Grounds, Miranda D.; Arthur, Peter G.

2016-01-01

Key points Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis.Cysteine precursor antioxidants such as N‐acetyl cysteine (NAC) and l‐2‐oxothiazolidine‐4‐carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine.We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug.These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Abstract Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l‐2‐oxothiazolidine‐4‐carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex vivo muscle strength and function, potentially via anti‐inflammatory and antioxidant effects of taurine. OTC treatment increased taurine synthesis in the liver and taurine content of mdx muscle, improved muscle function and decreased inflammation. However, OTC was less effective than taurine treatment, with OTC also decreasing body and EDL muscle weights, suggesting that OTC had some detrimental effects. These data support continued research into the use of taurine as a therapeutic intervention for DMD, and suggest that increasing dietary taurine is the better strategy for increasing taurine content and decreasing severity of dystropathology. PMID:26659826

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

PubMed

Terrill, Jessica R; Pinniger, Gavin J; Graves, Jamie A; Grounds, Miranda D; Arthur, Peter G

2016-06-01

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress. Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug. These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l-2-oxothiazolidine-4-carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex vivo muscle strength and function, potentially via anti-inflammatory and antioxidant effects of taurine. OTC treatment increased taurine synthesis in the liver and taurine content of mdx muscle, improved muscle function and decreased inflammation. However, OTC was less effective than taurine treatment, with OTC also decreasing body and EDL muscle weights, suggesting that OTC had some detrimental effects. These data support continued research into the use of taurine as a therapeutic intervention for DMD, and suggest that increasing dietary taurine is the better strategy for increasing taurine content and decreasing severity of dystropathology. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Ozone-induced dissociation on a traveling wave high-resolution mass spectrometer for determination of double-bond position in lipids.

PubMed

Vu, Ngoc; Brown, Jeffery; Giles, Kevin; Zhang, Qibin

2017-09-15

The position of C=C within fatty acyl chains affects the biological function of lipids. Ozone-induced dissociation mass spectrometry (OzID-MS) has great potential in determination of lipid double-bond position, but has generally been implemented on low-resolution ion trap mass spectrometers. In addition, most of the OzID-MS experiments carried out so far were focused on the sodiated adducts of lipids; fragmentation of the most commonly observed protonated ions generated in LC/MS-based lipidomics workflow has been less explored. Ozone generated in line from an ozone generator was connected to the trap and transfer gas supply line of a Synapt G2 high-resolution mass spectrometer. Protonated ions of different phosphatidylcholines (PC) were generated by electrospray ionization through direct infusion. Different parameters, including traveling wave height and velocity, trap entrance and DC potential, were adjusted to maximize the OzID efficiency. sn-positional isomers and cis/trans isomers of lipids were compared for their reactivity with ozone. Traveling wave height and velocity were tuned to prolong the encounter time between lipid ions and ozone, and resulted in improved OzID efficiency, as did increasing trapping region DC and entrance potential. Under optimized settings, at least 1000 times enhancement in OzID efficiency was achieved compared to that under default settings for monounsaturated PC standards. Monounsaturated C=C in the sn-2 PC isomer reacted faster with ozone than the sn-1 isomer. Similarly, the C=C in trans PC reacted faster than in cis PC. This is the first implementation of OzID in the trap and transfer region of a traveling wave enabled high-resolution mass spectrometer. The OzID reaction efficiency is significantly improved by slowing down ions in the trap region for their prolonged interaction with ozone. This will facilitate application of high-resolution OzID-MS in lipidomics. Copyright © 2017 John Wiley & Sons, Ltd.

No difference in long-term trunk muscle strength, cross-sectional area, and density in patients with chronic low back pain 7 to 11 years after lumbar fusion versus cognitive intervention and exercises.

PubMed

Froholdt, Anne; Holm, Inger; Keller, Anne; Gunderson, Ragnhild B; Reikeraas, Olav; Brox, Jens I

2011-08-01

Reduced muscle strength and density observed at 1 year after lumbar fusion may deteriorate more in the long term. To compare the long-term effect of lumbar fusion and cognitive intervention and exercises on muscle strength, cross-sectional area, density, and self-rated function in patients with chronic low back pain (CLBP) and disc degeneration. Randomized controlled study with a follow-up examination at 8.5 years (range, 7-11 years). Patients with CLBP and disc degeneration randomized to either instrumented posterolateral fusion of one or both of the two lower lumbar levels or a 3-week cognitive intervention and exercise program were included. Isokinetic muscle strength was measured by a Cybex 6000 (Cybex-Lumex, Inc., Ronkonkoma, NY, USA). All patients had previous experience with the test procedure. The back extension (E) flexion (F) muscles were tested, and the E/F ratios were calculated. Cross-sectional area and density of the back muscles were measured at the L3-L4 segment by computed tomography. Patients rated their function by the General Function Score. Trunk muscle strength, cross-sectional area, density, and self-rated function. Fifty-five patients (90%) were included at long-term follow-up. There were no significant differences in cross-sectional area, density, muscle strength, or self-rated function between the two groups. The cognitive intervention and exercise group increased trunk muscle extension significantly (p<.05), and both groups performed significantly better on trunk muscle flexion tests (p<.01) at long-term follow-up. On average, self-rated function improved by 56%, cross-sectional area was reduced by 8.5%, and muscle density was reduced by 27%. Although this study did not assess the morphology of muscles likely damaged by surgery, trunk muscle strength and cross-sectional area above the surgical levels are not different between those who had lumbar fusion or cognitive intervention and exercises at 7- to 11-year follow-up. Copyright © 2011 Elsevier Inc. All rights reserved.

An entropy-assisted musculoskeletal shoulder model.

PubMed

Xu, Xu; Lin, Jia-Hua; McGorry, Raymond W

2017-04-01

Optimization combined with a musculoskeletal shoulder model has been used to estimate mechanical loading of musculoskeletal elements around the shoulder. Traditionally, the objective function is to minimize the summation of the total activities of the muscles with forces, moments, and stability constraints. Such an objective function, however, tends to neglect the antagonist muscle co-contraction. In this study, an objective function including an entropy term is proposed to address muscle co-contractions. A musculoskeletal shoulder model is developed to apply the proposed objective function. To find the optimal weight for the entropy term, an experiment was conducted. In the experiment, participants generated various 3-D shoulder moments in six shoulder postures. The surface EMG of 8 shoulder muscles was measured and compared with the predicted muscle activities based on the proposed objective function using Bhattacharyya distance and concordance ratio under different weight of the entropy term. The results show that a small weight of the entropy term can improve the predictability of the model in terms of muscle activities. Such a result suggests that the concept of entropy could be helpful for further understanding the mechanism of muscle co-contractions as well as developing a shoulder biomechanical model with greater validity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells.

PubMed

Dong, Hye-Jin; Jang, Gyu-Beom; Lee, Hwa-Yong; Park, Se-Ra; Kim, Ji-Young; Nam, Jeong-Seok; Hong, In-Sun

2016-03-11

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.

Iron deficiency and iron deficiency anaemia in women.

PubMed

Percy, Laura; Mansour, Diana; Fraser, Ian

2017-04-01

Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options. Copyright © 2016. Published by Elsevier Ltd.

Functional morphology of the radialis muscle in shark tails.

PubMed

Flammang, Brooke E

2010-03-01

The functional morphology of intrinsic caudal musculature in sharks has not been studied previously, though the kinematics and function of body musculature have been the focus of a great deal of research. In the tail, ventral to the axial myomeres, there is a thin strip of red muscle with fibers angled dorsoposteriorly, known as the radialis. This research gives the first anatomical description of the radialis muscle in sharks, and addresses the hypothesis that the radialis muscle provides postural stiffening in the tail of live swimming sharks. The radialis muscle fibers insert onto the deepest layers of the stratum compactum, the more superior layers of which are orthogonally arrayed and connect to the epidermis. The two deepest layers of the stratum compactum insert onto the proximal ends of the ceratotrichia of the caudal fin. This anatomical arrangement exists in sharks and is modified in rays, but was not found in skates or chimaeras. Electromyography of the caudal muscles of dogfish swimming steadily at 0.25 and 0.5 body lengths per second (Ls(-1)) exhibited a pattern of anterior to posterior activation of the radialis muscle, followed by activation of red axial muscle in the more anteriorly located ipsilateral myomeres of the caudal peduncle; at 0.75 L s(-1), only the anterior portion of the radialis and white axial muscle of the contralateral peduncular myomeres were active. Activity of the radialis muscle occurred during periods of the greatest drag incurred by the tail during the tail beat and preceded the activity of more anteriorly located axial myomeres. This nonconformity to the typical anterior to posterior wave of muscle activation in fish swimming, in combination with anatomical positioning of the radialis muscles and stratum compactum, suggests that radialis activity may have a postural function to stiffen the fin, and does not function as a typical myotomal muscle.

Natural disease history of mouse models for limb girdle muscular dystrophy types 2D and 2F

PubMed Central

Putker, K.; Tanganyika-de Winter, C. L.; Boertje-van der Meulen, J. W.; van Vliet, L.; Overzier, M.; Plomp, J. J.; Aartsma-Rus, A.; van Putten, M.

2017-01-01

Limb-girdle muscular dystrophy types 2D and 2F (LGMD 2D and 2F) are autosomal recessive disorders caused by mutations in the alpha- and delta sarcoglycan genes, respectively, leading to severe muscle weakness and degeneration. The cause of the disease has been well characterized and a number of animal models are available for pre-clinical studies to test potential therapeutic interventions. To facilitate transition from drug discovery to clinical trials, standardized procedures and natural disease history data were collected for these mouse models. Implementing the TREAD-NMD standardized operating procedures, we here subjected LGMD2D (SGCA-null), LGMD2F (SGCD-null) and wild type (C57BL/6J) mice to five functional tests from the age of 4 to 32 weeks. To assess whether the functional test regime interfered with disease pathology, sedentary groups were taken along. Muscle physiology testing of tibialis anterior muscle was performed at the age of 34 weeks. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Mice successfully accomplished the functional tests, which did not interfere with disease pathology. Muscle function of SGCA- and SGCD-null mice was impaired and declined over time. Interestingly, female SGCD-null mice outperformed males in the two and four limb hanging tests, which proved the most suitable non-invasive tests to assess muscle function. Muscle physiology testing of tibialis anterior muscle revealed lower specific force and higher susceptibility to eccentric-induced damage in LGMD mice. Analyzing muscle histopathology and gene expression, we identified the diaphragm as the most affected muscle in LGMD strains. Cardiac fibrosis was found in SGCD-null mice, being more severe in males than in females. Our study offers a comprehensive natural history dataset which will be useful to design standardized tests and future pre-clinical studies in LGMD2D and 2F mice. PMID:28797108

Chronic Pseudomonas aeruginosa infection and respiratory muscle impairment in cystic fibrosis.

PubMed

Dassios, Theodore G; Katelari, Anna; Doudounakis, Stavros; Dimitriou, Gabriel

2014-03-01

Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. This cross-sectional study assessed PImax, PEmax, PTImus, FEV1, FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. Median PImax was significantly lower in CF subjects with chronic P. aeruginosa infection (PImax = 62 cm H2O), compared to subjects who were never infected (PImax = 86 cm H2O, P = .02), free of infection (PImax = 74 cm H2O, P = .01), or intermittently infected (PImax = 72 cm H2O, P = .02). Median PTImus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTImus = .142), compared to subjects who were free of infection (PTImus = .102, P = .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area = 2,219 mm(2)), compared to subjects who were never infected (2,754 mm(2), P = .03), free of infection (2,678 mm(2), P = .01), or intermittently infected (2,603 mm(2), P = .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTImus (P = .03) independently of sex, upper-arm muscle area, and FEV1. CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

Do muscle mass, muscle density, strength, and physical function similarly influence risk of hospitalization in older adults?

PubMed

Cawthon, Peggy Mannen; Fox, Kathleen M; Gandra, Shravanthi R; Delmonico, Matthew J; Chiou, Chiun-Fang; Anthony, Mary S; Sewall, Ase; Goodpaster, Bret; Satterfield, Suzanne; Cummings, Steven R; Harris, Tamara B

2009-08-01

To examine the association between strength, function, lean mass, muscle density, and risk of hospitalization. Prospective cohort study. Two U.S. clinical centers. Adults aged 70 to 80 (N=3,011) from the Health, Aging and Body Composition Study. Measurements were of grip strength, knee extension strength, lean mass, walking speed, and chair stand pace. Thigh computed tomography scans assessed muscle area and density (a proxy for muscle fat infiltration). Hospitalizations were confirmed by local review of medical records. Negative binomial regression models estimated incident rate ratios (IRRs) of hospitalization for race- and sex-specific quartiles of each muscle and function parameter separately. Multivariate models adjusted for age, body mass index, health status, and coexisting medical conditions. During an average 4.7 years of follow-up, 1,678 (55.7%) participants experienced one or more hospitalizations. Participants in the lowest quartile of muscle density were more likely to be subsequently hospitalized (multivariate IRR=1.47, 95% confidence interval (CI)=1.24-1.73) than those in the highest quartile. Similarly, participants with the weakest grip strength were at greater risk of hospitalization (multivariate IRR=1.52, 95% CI=1.30-1.78, Q1 vs. Q4). Comparable results were seen for knee strength, walking pace, and chair stands pace. Lean mass and muscle area were not associated with risk of hospitalization. Weak strength, poor function, and low muscle density, but not muscle size or lean mass, were associated with greater risk of hospitalization. Interventions to reduce the disease burden associated with sarcopenia should focus on increasing muscle strength and improving physical function rather than simply increasing lean mass.

The relationship between preoperative needle electromyography findings and muscle power restoration after surgery in severe carpal tunnel syndrome patients.

PubMed

Hara, Yuki; Nishiura, Yasumasa; Ochiai, Naoyuki; Murai, Shinji; Yamazaki, Masashi

2017-05-01

Needle electromyography provides essential information about the functional aspects of the muscle. But little attention has been given in the literature to needle electromyography examinations in carpal tunnel syndrome. We examined the relationship between preoperative needle electromyography findings and functional recovery of the abductor pollicis brevis (APB) muscle in severe carpal tunnel syndrome patients. The subjects of this study were 49 patients, 58 hands, who fit the following 5 criteria: (1) idiopathic carpal tunnel syndrome; (2) pre-op MMT grade of the APB muscle was M0 or M1; (3) APB-CMAP (compound muscle action potential) was not evoked in a median nerve conduction study; (4) needle electromyography of the APB muscle had been done; (5) underwent carpal tunnel release only. The patients were divided into two groups according to the results of pre-op needle electromyography: voluntary motor unit potential of the APB muscle was evoked [MUP(+) group]or not [MUP(-) group]. We evaluated APB muscle strength at one year after surgery, and patient satisfaction and functional evaluations (CTSI-FS) at more than one year after. The APB muscle recovery rate to M3 or higher was 100% in the MUP(+) group, and 57% in the MUP(-) group. Patient satisfaction was also high and functional recovery was sufficient in the MUP(+) group. No patients requested a second opponensplasty. Our findings suggest that post-op restoration of thumb function relates to whether or not the MUP ofthe APB muscle is evoked. Single-stage opponensplasty may be unnecessary if the MUP of the APB muscle is; evoked. Needle electromyography is therefore useful in consideration for opponensplasty. Level Ⅲ, case-control study. Copyright © 2017. Published by Elsevier B.V.

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai

Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species.more » The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.« less

Alterations in intrinsic mitochondrial function with aging are fiber type-specific and do not explain differential atrophy between muscles.

PubMed

Picard, Martin; Ritchie, Darmyn; Thomas, Melissa M; Wright, Kathryn J; Hepple, Russell T

2011-12-01

To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2) emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2) emission per O(2) flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Muscle-derived Decellularised Extracellular Matrix Improves Functional Recovery in a Rat Latissimus Dorsi Muscle Defect Model

DTIC Science & Technology

2013-12-01

battlefield wounds, often involving volumetric muscle loss (VML). The physical loss of muscle results in functional deficits and cosmetic ...repair with M-ECM and 3) sham (all procedures except muscle excision). Four and 8 weeks post- surgery , the isometric contractile properties of the LD... Surgery (2013) 66, 1750e1758 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is

Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application.

PubMed

Pevec, Danira; Novinscak, Tomislav; Brcic, Luka; Sipos, Kristijan; Jukic, Ivana; Staresinic, Mario; Mise, Sandro; Brcic, Iva; Kolenc, Danijela; Klicek, Robert; Banic, Tihomir; Sever, Marko; Kocijan, Ana; Berkopic, Lidija; Radic, Bozo; Buljat, Gojko; Anic, Tomislav; Zoricic, Ivan; Bojanic, Ivan; Seiwerth, Sven; Sikiric, Predrag

2010-03-01

The effect of systemic and local peptide treatment effective in muscle contusion and then on counteraction of corticosteroid-induced impairment was tested. The pentadecapeptide BPC 157, given without a carrier, improved the healing of transected quadriceps muscle. It also improved muscle healing in rats with muscle crush injury when applied systemically or locally. Importantly, it counteracted corticosteroid-impairment in tendon to bone healing. Thus BPC 157 is proposed as an effective treatment that can improve muscle healing in spite of corticosteroid treatment. After the gastrocnemius muscle complex had been injured, rats received BPC 157 (intraperitoneally or locally as a cream) and/or 6alpha-methylprednisolone (intraperitoneally) only once (immediately after injury, sacrifice at 2 h) or once daily (final dose 24 hours before sacrifice and/or assessment procedure at days 1, 2, 4, 7, and 14). Muscle healing was evaluated functionally, macroscopically, and histologically. Without therapy, crushed gastrocnemius muscle complex controls showed limited improvement. 6alpha-methylprednisolone markedly aggravated healing. In contrast, BPC 157 induced faster muscle healing and full function restoration and improved muscle healing despite systemic corticosteroid treatment when given intraperitoneally or locally and demonstrated functionally, macroscopically, and histologically at all investigated intervals. BPC 157 completely reversed systemic corticosteroid-impaired muscle healing.

Discrepancies between Skinned Single Muscle Fibres and Whole Thigh Muscle Function Characteristics in Young and Elderly Human Subjects

PubMed Central

2016-01-01

We aimed to analyse the mechanical properties of skinned single muscle fibres derived from the vastus lateralis (VL) muscle in relation to those of the whole intact thigh muscle and to compare any difference between young and older adults. Sixteen young men (29.25 ± 4.65 years), 11 older men (71.45 ± 2.94 years), 11 young women (29.64 ± 4.88 years), and 7 older women (67.29 ± 1.70 years) were recruited. In vivo analyses were performed for mechanical properties such as isokinetic performance, isometric torque, and power. Specific force and maximum shortening velocity (Vo) were measured with single muscle fibres. Sex difference showed greater impact on the functional properties of both the whole muscle (p < 0.01) and single muscle fibres than aging (p < 0.05). Sex difference, rather than aging, yielded more remarkable differences in gross mechanical properties in the single muscle fibre study in which significant differences between young men and young women were found only in the cross-sectional area and Vo (p < 0.05). Age and sex differences reflect the mechanical properties of both single muscle fibres and whole thigh muscle, with the whole muscle yielding more prominent functional properties. PMID:28070513

Functional polymorphisms associated with human muscle size and strength.

PubMed

Thompson, Paul D; Moyna, Niall; Seip, Richard; Price, Thomas; Clarkson, Priscilla; Angelopoulos, Theodore; Gordon, Paul; Pescatello, Linda; Visich, Paul; Zoeller, Robert; Devaney, Joseph M; Gordish, Heather; Bilbie, Stephen; Hoffman, Eric P

2004-07-01

Skeletal muscle is critically important to human performance and health, but little is known of the genetic factors influencing muscle size, strength, and its response to exercise training. The Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength, or FAMuSS, Study is a multicenter, NIH-funded program to examine the influence of gene polymorphisms on skeletal muscle size and strength before and after resistance exercise training. One thousand men and women, age 18 - 40 yr, will train their nondominant arm for 12 wk. Skeletal muscle size (magnetic resonance imaging) and isometric and dynamic strength will be measured before and after training. Individuals whose baseline values or response to training deviate > or = 1.5 SD will be defined as outliers and examined for genetic variants. Initially candidate genes previously associated with muscle performance will be examined, but the study will ultimately attempt to identify genes associated with muscle performance. FAMuSS should help identify genetic factors associated with muscle performance and the response to exercise training. Such insight should contribute to our ability to predict the individual response to exercise training but may also contribute to understanding better muscle physiology, to identifying individuals who are susceptible to muscle loss with environmental challenge, and to developing pharmacologic agents capable of preserving muscle size and function.

Musculoskeletal Model-Guided, Customizable Selection of Shoulder and Elbow Muscles for a C5 SCI Neuroprosthesis

PubMed Central

Hincapie, Juan Gabriel; Blana, Dimitra; Chadwick, Edward K.; Kirsch, Robert F.

2010-01-01

Individuals with C5/C6 spinal cord injury (SCI) have a number of paralyzed muscles in their upper extremities that can be electrically activated in a coordinated manner to restore function. The selection of a practical subset of paralyzed muscles for stimulation depends on the specific condition of the individual, the functions targeted for restoration, and surgical considerations. This paper presents a musculoskeletal model-based approach for optimizing the muscle set used for functional electrical stimulation (FES) of the shoulder and elbow in this population. Experimentally recorded kinematics from able-bodied subjects served as inputs to a musculoskeletal model of the shoulder and elbow, which was modified to reflect the reduced muscle force capacities of an individual with C5 SCI but also the potential of using FES to activate paralyzed muscles. A large number of inverse dynamic simulations mimicking typical activities of daily living were performed that included 1) muscles with retained voluntary control and 2) many different combinations of stimulated paralyzed muscles. These results indicate that a muscle set consisting of the serratus anterior, infraspinatus and triceps would enable the greatest range of relevant movements. This set will become the initial target in a C5 SCI neuroprosthesis to restore shoulder and elbow function. PMID:18586604

Acute effects of inspiratory muscle warm-up on pulmonary function in healthy subjects.

PubMed

Özdal, Mustafa

2016-06-15

The acute effects of inspiratory muscle warm-up on pulmonary functions were examined in 26 healthy male subjects using the pulmonary function test (PFT) in three different trials. The control trial (CON) did not involve inspiratory muscle warm-up, while the placebo (IMWp) and experimental (IMW) trials involved inspiratory muscle warm-up. There were no significant changes between the IMWp and CON trials (p>0.05). All the PFT measurements, including slow vital capacity, inspiratory vital capacity, forced vital capacity, forced expiratory volume in one second, maximal voluntary ventilation, and maximal inspiratory pressure were significantly increased by 3.55%, 12.52%, 5.00%, 2.75%, 2.66%, and 7.03% respectively, in the subjects in the IMW trial than those in the CON trial (p<0.05). These results show that inspiratory muscle warm-up improved the pulmonary functions. The mechanisms responsible for these improvements are probably associated with the concomitant increase in the inspiratory muscle strength, and the cooperation of the upper thorax, neck, and respiratory muscles, and increased level of reactive O2 species in muscle tissue, and potentially improvement of muscle O2 delivery-to-utilization. However, further investigation is required to determine the precise mechanisms responsible from among these candidates. Copyright © 2016 Elsevier B.V. All rights reserved.

[Muscle and function management by the physiotherapist in orthodontic and orthodonto-surgical treatment. Oral myofunctional rehabilitation].

PubMed

Girard, Marion; Leroux, Claire

2015-03-01

Can we hope to dispense with muscle and function management in orthodontic and orthodonto-surgical treatment plans? How can the specialized physiotherapist assist, facilitate and stabilize the work done by the orthodontist and maxillo-facial surgeon and help avoid relapses? Treatment aims to achieve dental alignment and occlusal balance in direct association with balance of the tongue muscles, cutaneous muscles, masticatory and postural muscles and functions in the orofacial region. Restoration of balance between agonist and antagonist muscles is achieved by relaxing contracted muscles and by gradually building up weak muscle tone. If effective and lasting treatment results are to be obtained, active patient participation is mandatory during rehabilitation of oro-maxillo-facial disorders and must encompass the tongue, lips, cheeks, masticatory system, ventilation and general posture as well as management of the parafunctions. These procedures are essential in dentofacial orthopedic treatment of both children and adults. Practical cases will be used to demonstrate the contribution that myofunctional rehabilitation can make. Regarding natural functions, very satisfactory results are obtained provided patients do daily muscle exercises and day-long training in the correct postures and practical drills they have been taught over a period of at least six months and under the supervision of the physiotherapist. © EDP Sciences, SFODF, 2015.

Impact of angiotensin II on skeletal muscle metabolism and function in mice: contribution of IGF-1, Sirtuin-1 and PGC-1α.

PubMed

Kackstein, Katharina; Teren, Andrej; Matsumoto, Yasuharu; Mangner, Norman; Möbius-Winkler, Sven; Linke, Axel; Schuler, Gerhard; Punkt, Karla; Adams, Volker

2013-05-01

Activation of the renin-angiotensin-aldosterone system and increased levels of angiotensin II (Ang-II) occurs in numerous cardiovascular diseases such as chronic heart failure (CHF). Another hallmark in CHF is a reduced exercise tolerance with impaired skeletal muscle function. The aim of this study was to investigate in an animal model the impact of Ang-II on skeletal muscle function and concomitant molecular alterations. Mice were infused with Ang-II for 4 weeks. Subsequently, skeletal muscle function of the soleus muscle was assessed. Expression of selected proteins was quantified by qRT-PCR and Western blot. Infusion of Ang-II resulted in a 33% reduction of contractile force, despite a lack of changes in muscle weight. At the molecular level an increased expression of NAD(P)H oxidase and a reduced expression of Sirt1, PGC-1α and IGF-1 were noticed. No change was evident for the ubiquitin E3-ligases MuRF1 and MafBx and α-sarcomeric actin expression. Cytophotometrical analysis of the soleus muscle revealed a metabolic shift toward a glycolytic profile. This study provides direct evidence of Ang-II-mediated, metabolic deterioration of skeletal muscle function despite preserved muscle mass. One may speculate that the Ang-II-mediated loss of muscle force is due to an activation of NAD(P)H oxidase expression and a subsequent ROS-induced down regulation of IGF-1, PGC-1α and Sirt1. Copyright © 2012 Elsevier GmbH. All rights reserved.

The influence of ACE ID and ACTN3 R577X polymorphisms on lower-extremity function in older women in response to high-speed power training.

PubMed

Pereira, Ana; Costa, Aldo M; Leitão, José C; Monteiro, António M; Izquierdo, Mikel; Silva, António J; Bastos, Estela; Marques, Mário C

2013-12-06

We studied the influence of the ACE I/D and ACTN3 R577X polymorphisms (single or combined) on lower-extremity function in older women in response to high-speed power training. One hundred and thirty-nine healthy older Caucasian women participated in this study (age: 65.5 ± 8.2 years, body mass: 67.0 ± 10.0 kg and height: 1.57 ± 0.06 m). Walking speed (S10) performance and functional capacity assessed by the "get-up and go" (GUG) mobility test were measured at baseline (T1) and after a consecutive 12-week period of high-speed power training (40-75% of one repetition maximum in arm and leg extensor exercises; 3 sets 4-12 reps, and two power exercises for upper and lower extremity). Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR methods. Genotype distributions between groups were compared by Chi-Square test and the gains in physical performance were analyzed by two-way, repeated-measures ANOVA. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes (P > 0.05). ACE I/D and ACTN3 polymorphisms showed a significant interaction genotype-training only in S10 (P = 0.012 and P = 0.044, respectively) and not in the GUG test (P = 0.311 and P = 0.477, respectively). Analyses of the combined effects between genotypes showed no other significant differences in all phenotypes (P < 0.05) at baseline. However, in response to high-speed power training, a significant interaction on walking speed (P = 0.048) was observed between the "power" (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Thus, ACE I/D and ACTN3 R577X polymorphisms are likely candidates in the modulation of exercise-related gait speed phenotype in older women but not a significant influence in mobility traits.

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

PubMed

Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

2016-06-01

The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

An education program about pelvic floor muscles improved women's knowledge but not pelvic floor muscle function, urinary incontinence or sexual function: a randomised trial.

PubMed

de Andrade, Roberta Leopoldino; Bø, Kari; Antonio, Flavia Ignácio; Driusso, Patricia; Mateus-Vasconcelos, Elaine Cristine Lemes; Ramos, Salvador; Julio, Monica Pitanguy; Ferreira, Cristine Homsi Jorge

2018-04-01

Does an educational program with instructions for performing 'the Knack' improve voluntary contraction of the pelvic floor muscles, reduce reports of urinary incontinence, improve sexual function, and promote women's knowledge of the pelvic floor muscles? Randomised, controlled trial with concealed allocation, intention-to-treat analysis and blinded assessors. Ninety-nine women from the local community. The experimental group (n=50) received one lecture per week for 4 weeks, and instructions for performing 'the Knack'. The control group (n=49) received no intervention. The primary outcome was maximum voluntary contraction of the pelvic floor muscles measured using manometry. Secondary outcomes were: ability to contract the pelvic floor muscles measured using vaginal palpation; severity of urinary incontinence measured by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scored from 0 to 21; self-reported sexual function; and knowledge related to the pelvic floor. Outcomes were measured at baseline and after 4 weeks. The intervention did not significantly improve: maximum voluntary contraction (MD 2.7 cmH 2 O higher in the experimental group, 95% CI -0.5 to 5.9); ability to contract the pelvic floor muscles (RR 2.18, 95% CI 0.49 to 9.65); or self-reported severity of urinary incontinence (MD 1 point greater reduction in the experimental group, 95% CI -3 to 1). Sexual function did not significantly differ between groups, but very few of the women engaged in sexual activity during the study period. The educational program did, however, significantly increase women's knowledge related to the location, functions and dysfunctions of the pelvic floor muscles, and treatment options. Education and teaching women to perform 'the Knack' had no significant effect on voluntary contraction of the pelvic floor muscles, urinary incontinence or sexual function, but it promoted women's knowledge about the pelvic floor. Brazilian Registry of Clinical Trials, RBR-95sxqv. [de Andrade RL, Bø K, Antonio FI, Driusso P, Mateus-Vasconcelos ECL, Ramos S, Julio MP, Ferreira CHJ (2018) An education program about pelvic floor muscles improved women's knowledge but not pelvic floor muscle function, urinary incontinence or sexual function: a randomised trial. Journal of Physiotherapy 64: 91-96]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb.

PubMed

Charles, James P; Cappellari, Ornella; Spence, Andrew J; Hutchinson, John R; Wells, Dominic J

2016-01-01

Mice are one of the most commonly used laboratory animals, with an extensive array of disease models in existence, including for many neuromuscular diseases. The hindlimb is of particular interest due to several close muscle analogues/homologues to humans and other species. A detailed anatomical study describing the adult morphology is lacking, however. This study describes in detail the musculoskeletal geometry and skeletal muscle architecture of the mouse hindlimb and pelvis, determining the extent to which the muscles are adapted for their function, as inferred from their architecture. Using I2KI enhanced microCT scanning and digital segmentation, it was possible to identify 39 distinct muscles of the hindlimb and pelvis belonging to nine functional groups. The architecture of each of these muscles was determined through microdissections, revealing strong architectural specialisations between the functional groups. The hip extensors and hip adductors showed significantly stronger adaptations towards high contraction velocities and joint control relative to the distal functional groups, which exhibited larger physiological cross sectional areas and longer tendons, adaptations for high force output and elastic energy savings. These results suggest that a proximo-distal gradient in muscle architecture exists in the mouse hindlimb. Such a gradient has been purported to function in aiding locomotor stability and efficiency. The data presented here will be especially valuable to any research with a focus on the architecture or gross anatomy of the mouse hindlimb and pelvis musculature, but also of use to anyone interested in the functional significance of muscle design in relation to quadrupedal locomotion.

Monitoring respiratory muscles.

PubMed

Nava, S

1998-12-01

The respiratory system consists of two main parts, the lung and the ventilatory pump. The latter consists of the bony structure of the thorax, the central respiratory controllers, the inspiratory and expiratory muscles, and the nerves innervating these muscles. Respiratory muscle fatigue occurs when respiratory muscle endurance is exceeded. Muscle fatigue is defined as a condition in which there is a reduction in the capacity for developing force and/or velocity of a muscle, resulting from muscle activity, and which is reversible by rest. The respiratory muscles are somewhat difficult to assess and the techniques employed are still relatively primitive. The most important methods of respiratory muscles function assessment are: 1) the vital capacity manoeuvre, which depends on maximum inspiratory and expiratory effort by the muscles and may be a useful indicator of respiratory muscle function; 2) radiological screening has been proposed for the detection of diaphragm paralysis. This may be helpful if the paralysis is unilateral, but bilateral paralysis is difficult to detect; and 3) respiratory muscles strength may be assessed with either voluntary or nonvoluntary manoeuvres. The function of the inspiratory muscles is assessed with 3 voluntary dependent manoeuvres. They are the so called Müller manoeuvre (or maximal inspiratory pressure), the sniff test and the combined test. All these three manoeuvres generate a pressure that is a reflection of complex interactions between several muscle groups since the efforts produce different mechanisms of activity of inspiratory and expiratory muscles. Two techniques are presently employed to assess diaphragm function, not being dependent on the patient's motivation: electrical phrenic nerve stimulation and cervical magnetic stimulation. Since it is less painful, magnetic cervical stimulation overcomes some of the difficulties encountered during electrical stimulation. With these two techniques recordings of diaphragmatic force are possible, and at the same time useful information about the conduction time of both phrenic nerves can be obtained.

Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension

PubMed Central

Manders, Emmy; Bonta, Peter I.; Kloek, Jaap J.; Symersky, Petr; Bogaard, Harm-Jan; Hooijman, Pleuni E.; Jasper, Jeff R.; Malik, Fady I.; Stienen, Ger J. M.; Vonk-Noordegraaf, Anton; de Man, Frances S.

2016-01-01

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients. PMID:27190061

Lifting the nebula: novel insights into skeletal muscle contractility.

PubMed

Ottenheijm, Coen A C; Granzier, Henk

2010-10-01

Nebulin is a giant protein and a constituent of the skeletal muscle sarcomere. The name of this protein refers to its unknown (i.e., nebulous) function. However, recent rapid advances reveal that nebulin plays important roles in the regulation of muscle contraction. When these functions of nebulin are compromised, muscle weakness ensues, as is the case in patients with nemaline myopathy.

Vascular delay of the latissimus dorsi muscle: an essential component of cardiomyoplasty.

PubMed

Carroll, S M; Carroll, C M; Stremel, R W; Heilman, S J; Tobin, G R; Barker, J H

1997-04-01

Cardiomyoplasty (CMP) uses the latissimus dorsi muscle (LDM) to assist the heart in cases of cardiac failure. Distal ischemia and necrosis of the LDM is a recognized complication of CMP that can reduce distal muscle function and the mechanical effectiveness of CMP. Canine (n = 9) LDMs were subjected to a 10-day period of vascular delay followed by a simulated CMP. Two weeks after simulated CMP (corresponding to the healing delay between CMP and the onset of LDM stimulation used in the clinical setting), LDM perfusion was measured in the distal, middle, and proximal segments of the muscle, and circumferential (distal and middle squeezing muscle function) and longitudinal (proximal pulling muscle function) force generation and fatigue rates were measured. The results were compared with the contralateral nondelayed simulated CMP. Muscle perfusion was significantly (p < 0.05) greater in the distal and middle segments of vascular-delayed LDMs. Circumferential muscle force generation and fatigue rates were significantly (p < 0.05) improved in the vascular-delayed LDMs. Vascular delay can significantly improve LDM perfusion and function in a model that closely reflects clinical CMP, and the use of vascular delay may improve clinical outcomes in CMP.

Systemic Down-Regulation of Delta-9 Desaturase Promotes Muscle Oxidative Metabolism and Accelerates Muscle Function Recovery following Nerve Injury

PubMed Central

Henriques, Alexandre; Lequeu, Thiebault; Rene, Frederique; Bindler, Françoise; Dirrig-Grosch, Sylvie; Oudart, Hugues; Palamiuc, Lavinia; Metz-Boutigue, Marie-Helene; Dupuis, Luc; Marchioni, Eric; Gonzalez De Aguilar, Jose-Luis; Loeffler, Jean-Philippe

2013-01-01

The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles. PMID:23785402

SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy.

PubMed

Goldstein, Jeffery A; Kelly, Sean M; LoPresti, Peter P; Heydemann, Ahlke; Earley, Judy U; Ferguson, Edwin L; Wolf, Matthew J; McNally, Elizabeth M

2011-03-01

Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy. The dystrophin complex provides stability to the plasma membrane of striated muscle during muscle contraction. Increased SMAD signaling due to activation of the transforming growth factor-β (TGFβ) pathway has been described in muscular dystrophy; however, it is not known whether this canonical TGFβ signaling is pathogenic in the muscle itself. Drosophila deleted for the γ/δ-sarcoglycan gene (Sgcd) develop progressive muscle and heart dysfunction and serve as a model for the human disorder. We used dad-lacZ flies to demonstrate the signature of TGFβ activation in response to exercise-induced injury in Sgcd null flies, finding that those muscle nuclei immediately adjacent to muscle injury demonstrate high-level TGFβ signaling. To determine the pathogenic nature of this signaling, we found that partial reduction of the co-SMAD Medea, homologous to SMAD4, or the r-SMAD, Smox, corrected both heart and muscle dysfunction in Sgcd mutants. Reduction in the r-SMAD, MAD, restored muscle function but interestingly not heart function in Sgcd mutants, consistent with a role for activin but not bone morphogenic protein signaling in cardiac dysfunction. Mammalian sarcoglycan null muscle was also found to exhibit exercise-induced SMAD signaling. These data demonstrate that hyperactivation of SMAD signaling occurs in response to repetitive injury in muscle and heart. Reduction of this pathway is sufficient to restore cardiac and muscle function and is therefore a target for therapeutic reduction.

SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy

PubMed Central

Goldstein, Jeffery A.; Kelly, Sean M.; LoPresti, Peter P.; Heydemann, Ahlke; Earley, Judy U.; Ferguson, Edwin L.; Wolf, Matthew J.; McNally, Elizabeth M.

2011-01-01

Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy. The dystrophin complex provides stability to the plasma membrane of striated muscle during muscle contraction. Increased SMAD signaling due to activation of the transforming growth factor-β (TGFβ) pathway has been described in muscular dystrophy; however, it is not known whether this canonical TGFβ signaling is pathogenic in the muscle itself. Drosophila deleted for the γ/δ-sarcoglycan gene (Sgcd) develop progressive muscle and heart dysfunction and serve as a model for the human disorder. We used dad-lacZ flies to demonstrate the signature of TGFβ activation in response to exercise-induced injury in Sgcd null flies, finding that those muscle nuclei immediately adjacent to muscle injury demonstrate high-level TGFβ signaling. To determine the pathogenic nature of this signaling, we found that partial reduction of the co-SMAD Medea, homologous to SMAD4, or the r-SMAD, Smox, corrected both heart and muscle dysfunction in Sgcd mutants. Reduction in the r-SMAD, MAD, restored muscle function but interestingly not heart function in Sgcd mutants, consistent with a role for activin but not bone morphogenic protein signaling in cardiac dysfunction. Mammalian sarcoglycan null muscle was also found to exhibit exercise-induced SMAD signaling. These data demonstrate that hyperactivation of SMAD signaling occurs in response to repetitive injury in muscle and heart. Reduction of this pathway is sufficient to restore cardiac and muscle function and is therefore a target for therapeutic reduction. PMID:21138941

Muscle anatomy and dynamic muscle function in osteogenesis imperfecta type I.

PubMed

Veilleux, Louis-Nicolas; Lemay, Martin; Pouliot-Laforte, Annie; Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

2014-02-01

Results of previous studies suggested that children and adolescents with osteogenesis imperfecta (OI) type I have a muscle force deficit. However, muscle function has only been assessed by static isometric force tests and not in more natural conditions such as dynamic force and power tests. The purpose of this study was to assess lower extremity dynamic muscle function and muscle anatomy in OI type I. The study was performed in the outpatient department of a pediatric orthopedic hospital. A total of 54 individuals with OI type I (6-21 years; 20 male) and 54 age- and sex-matched controls took part in this study. Calf muscle cross-sectional area and density were measured by peripheral quantitative computed tomography. Lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by jumping mechanography through 5 tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Compared with age- and sex-matched controls, patients with OI type I had smaller muscle size (P = .04) but normal muscle density (P = .21). They also had lower average peak force and lower specific force (peak force/muscle cross-sectional area; all P < .008). Average peak power was lower in patients with OI type I but not significantly so (all P > .054). Children and adolescents with OI type I have, on average, a significant force deficit in the lower limb as measured by dynamic force tests. Nonetheless, these data also show that OI type I is compatible with normal muscle performance in some individuals.

Muscle Satellite Cell Protein Teneurin‐4 Regulates Differentiation During Muscle Regeneration

PubMed Central

Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So‐ichiro; Okano, Hideyuki; Takeda, Shin'ichi

2015-01-01

Abstract Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin‐4 (Ten‐4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten‐4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten‐4‐deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten‐4‐deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten‐4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten‐4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. Stem Cells 2015;33:3017–3027 PMID:26013034

Respiratory Muscle Plasticity

PubMed Central

Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

2014-01-01

Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

Expression and functional characterization of Smyd1a in myofibril organization of skeletal muscles.

PubMed

Gao, Jie; Li, Junling; Li, Bao-Jun; Yagil, Ezra; Zhang, Jianshe; Du, Shao Jun

2014-01-01

Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown. To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos. Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process.

AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

PubMed

Riedl, Isabelle; Osler, Megan E; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A; Chibalin, Alexander V; Zierath, Juleen R

2016-03-15

Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKγ3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. Copyright © 2016 the American Physiological Society.

Ulk1-mediated autophagy plays an essential role in mitochondrial remodeling and functional regeneration of skeletal muscle

PubMed Central

Call, Jarrod A.; Wilson, Rebecca J.; Laker, Rhianna C.; Zhang, Mei; Kundu, Mondira

2017-01-01

Autophagy is a conserved cellular process for degrading aggregate proteins and dysfunctional organelle. It is still debatable if autophagy and mitophagy (a specific process of autophagy of mitochondria) play important roles in myogenic differentiation and functional regeneration of skeletal muscle. We tested the hypothesis that autophagy is critical for functional regeneration of skeletal muscle. We first observed time-dependent increases (3- to 6-fold) of autophagy-related proteins (Atgs), including Ulk1, Beclin1, and LC3, along with reduced p62 expression during C2C12 differentiation, suggesting increased autophagy capacity and flux during myogenic differentiation. We then used cardiotoxin (Ctx) or ischemia-reperfusion (I/R) to induce muscle injury and regeneration and observed increases in Atgs between days 2 and 7 in adult skeletal muscle followed by increased autophagy flux after day 7. Since Ulk1 has been shown to be essential for mitophagy, we asked if Ulk1 is critical for functional regeneration in skeletal muscle. We subjected skeletal muscle-specific Ulk1 knockout mice (MKO) to Ctx or I/R. MKO mice had significantly impaired recovery of muscle strength and mitochondrial protein content post-Ctx or I/R. Imaging analysis showed that MKO mice have significantly attenuated recovery of mitochondrial network at 7 and 14 days post-Ctx. These findings suggest that increased autophagy protein and flux occur during muscle regeneration and Ulk1-mediated mitophagy is critical for recovery for the mitochondrial network and hence functional regeneration. PMID:28356270

AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload

PubMed Central

Riedl, Isabelle; Osler, Megan E.; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A.; Chibalin, Alexander V.

2016-01-01

Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5′-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3225Q and AMPKγ3-knockout (Prkag3−/−) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. PMID:26758685

Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

PubMed Central

Murray, Iain R.; Baily, James E.; Chen, William C.W.; Dar, Ayelet; Gonzalez, Zaniah N.; Jensen, Andrew R.; Petrigliano, Frank A.; Deb, Arjun; Henderson, Neil C.

2017-01-01

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease. PMID:27595928

Evaluation of a PSMA-targeted BNF nanoparticle construct

NASA Astrophysics Data System (ADS)

Behnam Azad, Babak; Banerjee, Sangeeta R.; Pullambhatla, Mrudula; Lacerda, Silvia; Foss, Catherine A.; Wang, Yuchuan; Ivkov, Robert; Pomper, Martin G.

2015-02-01

Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 +/- 0.4 percentage injected dose per gram of tissue (%ID g-1)], with tumor/blood and tumor/muscle ratios of 7.5 +/- 2.4 and 11.6 +/- 1.2 %ID g-1, respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo.Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 +/- 0.4 percentage injected dose per gram of tissue (%ID g-1)], with tumor/blood and tumor/muscle ratios of 7.5 +/- 2.4 and 11.6 +/- 1.2 %ID g-1, respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06069e

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy

PubMed Central

Zaharieva, Irina T.; Thor, Michael G.; Oates, Emily C.; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T.; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D’Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R.; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A.; Morgan, Jennifer E.; Laing, Nigel G.; Vallance, Hilary; Ruben, Peter; Hanna, Michael G.; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope

2016-01-01

Abstract See Cannon (doi: 10.1093/brain/awv400 ) for a scientific commentary on this article. Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Na v 1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero - or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A mutations showed loss-of-function of the mutant Na v 1.4 channels. All, apart from one, of the mutations either caused fully non-functional channels, or resulted in a reduced channel activity. Each of the affected cases carried at least one full loss-of-function mutation. In five out of six families, a second loss-of-function mutation was present on the trans allele. These functional results provide convincing evidence for the pathogenicity of the identified mutations and suggest that different degrees of loss-of-function in mutant Na v 1.4 channels are associated with attenuation of the skeletal muscle action potential amplitude to a level insufficient to support normal muscle function. The results demonstrate that recessive loss-of-function SCN4A mutations should be considered in patients with a congenital myopathy. PMID:26700687

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

PubMed

Zaharieva, Irina T; Thor, Michael G; Oates, Emily C; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D'Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A; Morgan, Jennifer E; Laing, Nigel G; Vallance, Hilary; Ruben, Peter; Hanna, Michael G; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope; Muntoni, Francesco

2016-03-01

Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A mutations showed loss-of-function of the mutant Nav1.4 channels. All, apart from one, of the mutations either caused fully non-functional channels, or resulted in a reduced channel activity. Each of the affected cases carried at least one full loss-of-function mutation. In five out of six families, a second loss-of-function mutation was present on the trans allele. These functional results provide convincing evidence for the pathogenicity of the identified mutations and suggest that different degrees of loss-of-function in mutant Nav1.4 channels are associated with attenuation of the skeletal muscle action potential amplitude to a level insufficient to support normal muscle function. The results demonstrate that recessive loss-of-function SCN4A mutations should be considered in patients with a congenital myopathy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Effects of protein supplements on muscle damage, soreness and recovery of muscle function and physical performance: a systematic review.

PubMed

Pasiakos, Stefan M; Lieberman, Harris R; McLellan, Tom M

2014-05-01

Protein supplements are frequently consumed by athletes and recreationally-active individuals, although the decision to purchase and consume protein supplements is often based on marketing claims rather than evidence-based research. To provide a systematic and comprehensive analysis of literature examining the hypothesis that protein supplements enhance recovery of muscle function and physical performance by attenuating muscle damage and soreness following a previous bout of exercise. English language articles were searched with PubMed and Google Scholar using protein and supplements together with performance, exercise, competition and muscle, alone or in combination as keywords. Inclusion criteria required studies to recruit healthy adults less than 50 years of age and to evaluate the effects of protein supplements alone or in combination with carbohydrate on performance metrics including time-to-exhaustion, time-trial or isometric or isokinetic muscle strength and markers of muscle damage and soreness. Twenty-seven articles were identified of which 18 dealt exclusively with ingestion of protein supplements to reduce muscle damage and soreness and improve recovery of muscle function following exercise, whereas the remaining 9 articles assessed muscle damage as well as performance metrics during single or repeat bouts of exercise. Papers were evaluated based on experimental design and examined for confounders that explain discrepancies between studies such as dietary control, training state of participants, sample size, direct or surrogate measures of muscle damage, and sensitivity of the performance metric. High quality and consistent data demonstrated there is no apparent relationship between recovery of muscle function and ratings of muscle soreness and surrogate markers of muscle damage when protein supplements are consumed prior to, during or after a bout of endurance or resistance exercise. There also appears to be insufficient experimental data demonstrating ingestion of a protein supplement following a bout of exercise attenuates muscle soreness and/or lowers markers of muscle damage. However, beneficial effects such as reduced muscle soreness and markers of muscle damage become more evident when supplemental protein is consumed after daily training sessions. Furthermore, the data suggest potential ergogenic effects associated with protein supplementation are greatest if participants are in negative nitrogen and/or energy balance. Small sample numbers and lack of dietary control limited the effectiveness of several investigations. In addition, studies did not measure the effects of protein supplementation on direct indices of muscle damage such as myofibrillar disruption and various measures of protein signaling indicative of a change in rates of protein synthesis and degradation. As a result, the interpretation of the data was often limited. Overwhelmingly, studies have consistently demonstrated the acute benefits of protein supplementation on post-exercise muscle anabolism, which, in theory, may facilitate the recovery of muscle function and performance. However, to date, when protein supplements are provided, acute changes in post-exercise protein synthesis and anabolic intracellular signaling have not resulted in measureable reductions in muscle damage and enhanced recovery of muscle function. Limitations in study designs together with the large variability in surrogate markers of muscle damage reduced the strength of the evidence-base.

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

PubMed Central

Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

2000-01-01

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle. PMID:10995435

Sex hormones and skeletal muscle weakness.

PubMed

Sipilä, Sarianna; Narici, Marco; Kjaer, Michael; Pöllänen, Eija; Atkinson, Ross A; Hansen, Mette; Kovanen, Vuokko

2013-06-01

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

The central role of muscle stem cells in regenerative failure with aging

PubMed Central

Blau, Helen M; Cosgrove, Benjamin D; Ho, Andrew T V

2016-01-01

Skeletal muscle mass, function, and repair capacity all progressively decline with aging, restricting mobility, voluntary function, and quality of life. Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues. In adult tissues, MuSCs are retained in a quiescent state until they are primed to regenerate damaged muscle through cycles of self-renewal divisions. With aging, muscle tissue homeostasis is progressively disrupted and the ability of MuSCs to repair injured muscle markedly declines. Until recently, this decline has been largely attributed to extrinsic age-related alterations in the microenvironment to which MuSCs are exposed. However, as highlighted in this Perspective, recent reports show that MuSCs also progressively undergo cell-intrinsic alterations that profoundly affect stem cell regenerative function with aging. A more comprehensive understanding of the interplay of stem cell–intrinsic and extrinsic factors will set the stage for improving cell therapies capable of restoring tissue homeostasis and enhancing muscle repair in the aged. PMID:26248268

Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic mice and patients with Duchenne muscular dystrophy.

PubMed

Church, Jarrod E; Trieu, Jennifer; Chee, Annabel; Naim, Timur; Gehrig, Stefan M; Lamon, Séverine; Angelini, Corrado; Russell, Aaron P; Lynch, Gordon S

2014-04-01

New Findings What is the central question of this study? The Notch signalling pathway plays an important role in muscle regeneration, and activation of the pathway has been shown to enhance muscle regeneration in aged mice. It is unknown whether Notch activation will have a similarly beneficial effect on muscle regeneration in the context of Duchenne muscular dystrophy (DMD). What is the main finding and its importance? Although expression of Notch signalling components is altered in both mouse models of DMD and in human DMD patients, activation of the Notch signalling pathway does not confer any functional benefit on muscles from dystrophic mice, suggesting that other signalling pathways may be more fruitful targets for manipulation in treating DMD. Abstract In Duchenne muscular dystrophy (DMD), muscle damage and impaired regeneration lead to progressive muscle wasting, weakness and premature death. The Notch signalling pathway represents a central regulator of gene expression and is critical for cellular proliferation, differentiation and apoptotic signalling during all stages of embryonic muscle development. Notch activation improves muscle regeneration in aged mice, but its potential to restore regeneration and function in muscular dystrophy is unknown. We performed a comprehensive examination of several genes involved in Notch signalling in muscles from dystrophin-deficient mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx mice were observed, with other targets being inconsistent across species. Activation and inhibition of Notch signalling, followed by measures of muscle regeneration and function, were performed in the mouse models of DMD. Notch activation had no effect on functional regeneration in C57BL/10, mdx or dko mice. Notch inhibition significantly depressed the frequency-force relationship in regenerating muscles of C57BL/10 and mdx mice after injury, indicating reduced force at each stimulation frequency, but enhanced the frequency-force relationship in muscles from dko mice. We conclude that while Notch inhibition produces slight functional defects in dystrophic muscle, Notch activation does not significantly improve muscle regeneration in murine models of muscular dystrophy. Furthermore, the inconsistent expression of Notch targets between murine models and DMD patients suggests caution when making interspecies comparisons.

Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

PubMed

Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

2014-09-01

Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (p<0.05). Aging also reduced LDH-A mRNA abundance, however there was no age effect on LDH-B mRNA abundance. In 5-month muscle, both ND and OV decreased LDH-A and LDH-B activity. However, there was no synergistic or additive effect. In 5-month muscle, ND and OV decreased LDH-A mRNA expression with no change in LDH-B expression. In 25-month muscle, ND and OV increased LDH-A and LDH-B activity. LDH-A mRNA expression was not altered by ND or OV in aged muscle. However, there was a main effect of OV to decrease LDH-B mRNA expression. There was also an age-induced LDH isoform shift. ND and OV treatment increased the "fast" LDH isoforms in aged muscle, whereas ND and OV increased the "slow" isoforms in young muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Unmet Health Services Needs Among US Children with Developmental Disabilities: Associations with Family Impact and Child Functioning.

PubMed

Lindly, Olivia J; Chavez, Alison E; Zuckerman, Katharine E

To determine associations of unmet needs for child or family health services with (1) adverse family financial and employment impacts and (2) child behavioral functioning problems among US children with autism spectrum disorder (ASD), developmental delay (DD), and/or intellectual disability (ID). This was a secondary analysis of parent-reported data from the 2009 to 2010 National Survey of Children with Special Health Care Needs linked to the 2011 Survey of Pathways to Diagnosis and Services. The study sample (n = 3,518) represented an estimated 1,803,112 US children aged 6 to 17 years with current ASD, DD, and/or ID (developmental disabilities). Dependent variables included adverse family financial and employment impacts, as well as child behavioral functioning problems. The independent variables of interest were unmet need for (1) child health services and (2) family health services. Multivariable logistic regression models were fit to examine associations. Unmet need for child and family health services, adverse family financial and employment impacts, and child behavioral functioning problems were prevalent among US children with developmental disabilities. Unmet needs were associated with an increased likelihood of adverse family employment and financial impacts. Unmet needs were associated with an increased likelihood of child behavioral functioning problems the following year; however, this association was not statistically significant. Unmet needs are associated with adverse impacts for children with developmental disabilities and their families. Increased access to and coordination of needed health services following ASD, DD, and/or ID diagnosis may improve outcomes for children with developmental disabilities and their families.

Five clinical tests to assess balance following ball exercises and treadmill training in adult persons with intellectual disability.

PubMed

Carmeli, Eli; Bar-Chad, Shmuel; Lotan, Meir; Merrick, Joav; Coleman, Raymond

2003-08-01

Incidence rates of falling increase progressively with aging. Preventing or delaying the onset of functional decline is a crucial important goal, because more individuals with intellectual disability (ID) are living well into their sixth and seventh decades. The question of whether walking and ball exercises can effect balance performance has never been reported. This pilot study was conducted to determine the effects of therapeutic training on improving balance capabilities in adults with mild ID. The study included 13 women and 4 men, aged 50-67 years (mean age 56.5 years) residing in a residential care center. Five clinical tests were used to determine the "real" picture of the locomotor function and balance before and after the training protocol. Baseline values were determined using 2 control groups of age-matched adults with and without ID. The tests included modified get-up-and-go, full turn, forward reach, sit-to-stand, and one-legged standing. Therapeutic training for 6 months included dynamic ball exercises and treadmill walking with a 2-3% positive inclination. Participants in the program showed little to no improvement in terms of their static and dynamic balance compared to their initial values. Thus, only 2 of the tests showed statistical significance. Lack of improvement was noted in both postural and balance control in adults with mild ID as a result of 6 months of intervention by means of ball exercise and treadmill training.

Correlation between thoracolumbar curvatures and respiratory function in older adults.

PubMed

Rahman, Nor Najwatul Akmal Ab; Singh, Devinder Kaur Ajit; Lee, Raymond

2017-01-01

Aging is associated with alterations in thoracolumbar curvatures and respiratory function. Research information regarding the correlation between thoracolumbar curvatures and a comprehensive examination of respiratory function parameters in older adults is limited. The aim of the present study was to examine the correlation between thoracolumbar curvatures and respiratory function in community-dwelling older adults. Thoracolumbar curvatures (thoracic and lumbar) were measured using a motion tracker. Respiratory function parameters such as lung function, respiratory rate, respiratory muscle strength and respiratory muscle thickness (diaphragm and intercostal) were measured using a spirometer, triaxial accelerometer, respiratory pressure meter and ultrasound imaging, respectively. Sixty-eight community-dwelling older males and females from Kuala Lumpur, Malaysia, with mean (standard deviation) age of 66.63 (5.16) years participated in this cross-sectional study. The results showed that mean (standard deviation) thoracic curvature angle and lumbar curvature angles were -46.30° (14.66°) and 14.10° (10.58°), respectively. There was a significant negative correlation between thoracic curvature angle and lung function (forced expiratory volume in 1 second: r =-0.23, P <0.05; forced vital capacity: r =-0.32, P <0.05), quiet expiration intercostal thickness ( r =-0.22, P <0.05) and deep expiration diaphragm muscle thickness ( r =-0.21, P <0.05). The lumbar curvature angle had a significant negative correlation with respiratory muscle strength ( r =-0.29, P <0.05) and diaphragm muscle thickness at deep inspiration ( r =-0.22, P <0.05). However, respiratory rate was correlated neither with thoracic nor with lumbar curvatures. The findings of this study suggest that increase in both thoracic and lumbar curvatures is correlated with decrease in respiratory muscle strength, respiratory muscle thickness and some parameters of lung function. Clinically, both thoracic and lumbar curvatures, respiratory muscles and lung function should be taken into consideration in the holistic management of respiratory function among older adults.

Skeletal muscle contraction in protecting joints and bones by absorbing mechanical impacts

NASA Astrophysics Data System (ADS)

Rudenko, O. V.; Tsyuryupa, S.; Sarvazyan, A.

2016-09-01

We have previously hypothesized that the dissipation of mechanical energy of external impact is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In this paper, a mathematical justification of this hypothesis is presented. First, a simple mechanical model, in which the muscle is considered as a simple Hookean spring, is considered. This analysis serves as an introduction to the consideration of a biomechanical model taking into account the molecular mechanism of muscle contraction, kinetics of myosin bridges, sarcomere dynamics, and tension of muscle fibers. It is shown that a muscle behaves like a nonlinear and adaptive spring tempering the force of impact and increasing the duration of the collision. The temporal profiles of muscle reaction to the impact as functions of the levels of muscle contraction, durations of the impact front, and the time constants of myosin bridges closing, are obtained. The absorption of mechanical shock energy is achieved due to the increased viscoelasticity of the contracting skeletal muscle. Controlling the contraction level allows for the optimization of the stiffness and viscosity of the muscle necessary for the protection of the joints and bones.

Exercise and nutritional interventions for improving aging muscle health.

PubMed

Forbes, Scott C; Little, Jonathan P; Candow, Darren G

2012-08-01

Skeletal muscle mass declines with age (i.e., sarcopenia) resulting in muscle weakness and functional limitations. Sarcopenia has been associated with physiological changes in muscle morphology, protein and hormonal kinetics, insulin resistance, inflammation, and oxidative stress. The purpose of this review is to highlight how exercise and nutritional intervention strategies may benefit aging muscle. It is well known that resistance exercise training increases muscle strength and size and evidence also suggests that resistance training can increase mitochondrial content and decrease oxidative stress in older adults. Recent findings suggest that fast-velocity resistance exercise may be an effective intervention for older adults to enhance muscle power and functional capacity. Aerobic exercise training may also benefit aging skeletal muscle by enhancing mitochondrial bioenergetics, improving insulin sensitivity, and/or decreasing oxidative stress. In addition to exercise, creatine monohydrate, milk-based proteins, and essential fatty acids all have biological effects which could enhance some of the physiological adaptations from exercise training in older adults. Additional research is needed to determine whether skeletal muscle adaptations to increased activity in older adults are further enhanced with effective nutritional interventions and whether this is due to enhanced muscle protein synthesis, improved mitochondrial function, and/or a reduced inflammatory response.

Equilibrium-point control of human elbow-joint movement under isometric environment by using multichannel functional electrical stimulation

PubMed Central

Matsui, Kazuhiro; Hishii, Yasuo; Maegaki, Kazuya; Yamashita, Yuto; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio

2014-01-01

Functional electrical stimulation (FES) is considered an effective technique for aiding quadriplegic persons. However, the human musculoskeletal system has highly non-linearity and redundancy. It is thus difficult to stably and accurately control limbs using FES. In this paper, we propose a simple FES method that is consistent with the motion-control mechanism observed in humans. We focus on joint motion by a pair of agonist-antagonist muscles of the musculoskeletal system, and define the “electrical agonist-antagonist muscle ratio (EAA ratio)” and “electrical agonist-antagonist muscle activity (EAA activity)” in light of the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, respectively, to extract the equilibrium point and joint stiffness from electromyography (EMG) signals. These notions, the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, are based on the hypothesis that the equilibrium point and stiffness of the agonist-antagonist motion system are controlled by the central nervous system. We derived the transfer function between the input EAA ratio and force output of the end-point. We performed some experiments in an isometric environment using six subjects. This transfer-function model is expressed as a cascade-coupled dead time element and a second-order system. High-speed, high-precision, smooth control of the hand force were achieved through the agonist-antagonist muscle stimulation pattern determined by this transfer function model. PMID:24987326

Equilibrium-point control of human elbow-joint movement under isometric environment by using multichannel functional electrical stimulation.

PubMed

Matsui, Kazuhiro; Hishii, Yasuo; Maegaki, Kazuya; Yamashita, Yuto; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio

2014-01-01

Functional electrical stimulation (FES) is considered an effective technique for aiding quadriplegic persons. However, the human musculoskeletal system has highly non-linearity and redundancy. It is thus difficult to stably and accurately control limbs using FES. In this paper, we propose a simple FES method that is consistent with the motion-control mechanism observed in humans. We focus on joint motion by a pair of agonist-antagonist muscles of the musculoskeletal system, and define the "electrical agonist-antagonist muscle ratio (EAA ratio)" and "electrical agonist-antagonist muscle activity (EAA activity)" in light of the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, respectively, to extract the equilibrium point and joint stiffness from electromyography (EMG) signals. These notions, the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, are based on the hypothesis that the equilibrium point and stiffness of the agonist-antagonist motion system are controlled by the central nervous system. We derived the transfer function between the input EAA ratio and force output of the end-point. We performed some experiments in an isometric environment using six subjects. This transfer-function model is expressed as a cascade-coupled dead time element and a second-order system. High-speed, high-precision, smooth control of the hand force were achieved through the agonist-antagonist muscle stimulation pattern determined by this transfer function model.

Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis.

PubMed

Romero-Suarez, Sandra; Shen, Jinhua; Brotto, Leticia; Hall, Todd; Mo, Chenglin; Valdivia, Héctor H; Andresen, Jon; Wacker, Michael; Nosek, Thomas M; Qu, Cheng-Kui; Brotto, Marco

2010-08-01

We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca2+ homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia.

Functional adaptation between yeast actin and its cognate myosin motors.

PubMed

Stark, Benjamin C; Wen, Kuo-Kuang; Allingham, John S; Rubenstein, Peter A; Lord, Matthew

2011-09-02

We employed budding yeast and skeletal muscle actin to examine the contribution of the actin isoform to myosin motor function. While yeast and muscle actin are highly homologous, they exhibit different charge density at their N termini (a proposed myosin-binding interface). Muscle myosin-II actin-activated ATPase activity is significantly higher with muscle versus yeast actin. Whether this reflects inefficiency in the ability of yeast actin to activate myosin is not known. Here we optimized the isolation of two yeast myosins to assess actin function in a homogenous system. Yeast myosin-II (Myo1p) and myosin-V (Myo2p) accommodate the reduced N-terminal charge density of yeast actin, showing greater activity with yeast over muscle actin. Increasing the number of negative charges at the N terminus of yeast actin from two to four (as in muscle) had little effect on yeast myosin activity, while other substitutions of charged residues at the myosin interface of yeast actin reduced activity. Thus, yeast actin functions most effectively with its native myosins, which in part relies on associations mediated by its outer domain. Compared with yeast myosin-II and myosin-V, muscle myosin-II activity was very sensitive to salt. Collectively, our findings suggest differing degrees of reliance on electrostatic interactions during weak actomyosin binding in yeast versus muscle. Our study also highlights the importance of native actin isoforms when considering the function of myosins.

An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury.

PubMed

Aurora, Amit; Roe, Janet L; Corona, Benjamin T; Walters, Thomas J

2015-10-01

Extracellular matrix (ECM) derived scaffolds continue to be investigated for the treatment of volumetric muscle loss (VML) injuries. Clinically, ECM scaffolds have been used for lower extremity VML repair; in particular, MatriStem™, a porcine urinary bladder matrix (UBM), has shown improved functional outcomes and vascularization, but limited myogenesis. However, efficacy of the scaffold for the repair of traumatic muscle injuries has not been examined systematically. In this study, we demonstrate that the porcine UBM scaffold when used to repair a rodent gastrocnemius musculotendinous junction (MTJ) and tibialis anterior (TA) VML injury does not support muscle tissue regeneration. In the MTJ model, the scaffold was completely resorbed without tissue remodeling, suggesting that the scaffold may not be suitable for the clinical repair of muscle-tendon injuries. In the TA VML injury, the scaffold remodeled into a fibrotic tissue and showed functional improvement, but not due to muscle fiber regeneration. The inclusion of physical rehabilitation also did not improve functional response or tissue remodeling. We conclude that the porcine UBM scaffold when used to treat VML injuries may hasten the functional recovery through the mechanism of scaffold mediated functional fibrosis. Thus for appreciable muscle regeneration, repair strategies that incorporate myogenic cells, vasculogenic accelerant and a myoconductive scaffold need to be developed. Published by Elsevier Ltd.

Effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy

PubMed Central

Choi, Jong-Bae

2016-01-01

[Purpose] The aim of this study was to investigate the effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy. [Subjects and Methods] Nine subjects received the electrical stimulation and traditional dysphagia therapy. Electrical stimulation was applied to stimulate each subject’s facial muscles 30 minutes a day, 5 days a week, for 4 weeks. [Results] Subjects showed significant improvement in cheek and lip strength and oral function after the intervention. [Conclusion] This study demonstrates that electrical stimulation improves facial muscle strength and oral function in stroke patients with dysphagia. PMID:27799689

Effects of Elastic Resistance Exercise on Muscle Strength and Functional Performance in Healthy Adults: A Systematic Review and Meta-Analysis.

PubMed

de Oliveira, Poliana Alves; Blasczyk, Juscelino Castro; Souza Junior, Gerson; Lagoa, Karina Ferreira; Soares, Milene; de Oliveira, Ricardo Jacó; Filho, Paulo José Barbosa Gutierres; Carregaro, Rodrigo Luiz; Martins, Wagner Rodrigues

2017-04-01

Elastic Resistance Exercise (ERE) has already demonstrated its effectiveness in older adults and, when combined with the resistance generated by fixed loads, in adults. This review summarizes the effectiveness of ERE performed as isolated method on muscle strength and functional performance in healthy adults. A database search was performed (MEDLine, Cochrane Library, PEDro and Web of Knowledge) to identify controlled clinical trials in English language. The mean difference (MD) with 95% confidence intervals (CIs) and overall effect size were calculated for all comparisons. The PEDro scale was used assess the methodological quality. From the 93 articles identified by the search strategy, 5 met the inclusion criteria, in which 3 presented high quality (PEDro > 6). Meta-analyses demonstrated that the effects of ERE were superior when compared with passive control on functional performance and muscle strength. When compared with active controls, the effect of ERE was inferior on function performance and with similar effect on muscle strength. ERE are effective to improve functional performance and muscle strength when compared with no intervention, in healthy adults. ERE are not superior to other methods of resistance training to improve functional performance and muscle strength in health adults.

Are Non-Intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

ERIC Educational Resources Information Center

Ratto, Allison B.; Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-01-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black…

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function*

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2014-01-01

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile508, Asn509, and Asp511) in communicating with converter domain residue Arg759. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle. PMID:24627474

FAST CP: protocol of a randomised controlled trial of the efficacy of a 12-week combined Functional Anaerobic and Strength Training programme on muscle properties and mechanical gait deficiencies in adolescents and young adults with spastic-type cerebral palsy

PubMed Central

Gillett, Jarred G; Lichtwark, Glen A; Boyd, Roslyn N; Barber, Lee A

2015-01-01

Introduction Individuals with cerebral palsy (CP) have muscles that are smaller, weaker and more resistant to stretch compared to typically developing people. Progressive resistance training leads to increases in muscle size and strength. In CP, the benefits of resistance training alone may not transfer to improve other activities such as walking; however, the transfer of strength improvements to improved mobility may be enhanced by performing training that involves specific functional tasks or motor skills. This study aims to determine the efficacy of combined functional anaerobic and strength training in (1) influencing muscle strength, structure and function and (2) to determine if any changes in muscle strength and structure following training impact on walking ability and gross motor functional capacity and performance in the short (following 3 months of training) and medium terms (a further 3 months post-training). Methods and analysis 40 adolescents and young adults with CP will be recruited to undertake a 12-week training programme. The training programme will consist of 3×75 min sessions per week, made up of 5 lower limb resistance exercises and 2–3 functional anaerobic exercises per session. The calf muscles will be specifically targeted, as they are the most commonly impacted muscles in CP and are a key muscle group involved in walking. If, as we believe, muscle properties change following combined strength and functional training, there may be long-term benefits of this type of training in slowing the deterioration of muscle function in people with spastic-type CP. Ethics and dissemination Ethical approval has been obtained from the ethics committees at The University of Queensland (2014000066) and Children's Health Queensland (HREC/15/QRCH/30). The findings will be disseminated by publications in peer-reviewed journals, conferences and local research organisations’ media. Trial registration number Australian and New Zealand Clinical Trials Registry (ACTRN12614001217695). PMID:26116614

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2008-04-08

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2010-10-05

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Iron status of military personnel deployed to Afghanistan.

PubMed

Wilson, Candy; McClung, James P; Karl, J Philip; Brothers, Michael D

2011-12-01

Iron is a micronutrient necessary for energy metabolism and for oxygen transport and delivery. Depletion of iron stores (iron deficiency [ID]) may lead to iron deficiency anemia (IDA), which affects mood, cognitive function, and physical performance. Previous studies indicated that iron status may decline during military training. This study assessed the iron status and prevalence of ID and IDA in military personnel deployed to Bagram Air Base, Afghanistan (1492 m). Within the pool of 294 participants (149 male and 145 female), 2 males (1%) and 8 females (6%) presented with ID. Although IDA was not observed in males, 3 females (2%) met the criteria for IDA. Female sex (p = 0.05) and self-reported history of anemia (p < 0.05) were associated with diminished iron status. Amenorrhea was associated with higher ferritin (p < 0.05) and hemoglobin (p < 0.05) levels. Although ID and IDA did not affect a large portion of the deployed population assessed in this study, findings suggest that risk factors including female sex, history of anemia, and regular menstruation should be considered in the assessment of iron status in military personnel.

Perceptions of Emotion Expression and Sibling–Parent Emotion Communication in Latino and Non-Latino White Siblings of Children With Intellectual Disabilities

PubMed Central

Lobato, Debra; Kao, Barbara; Plante, Wendy; Grullón, Edicta; Cheas, Lydia; Houck, Christopher; Seifer, Ronald

2013-01-01

Objective Examine general emotion expression and sibling–parent emotion communication among Latino and non-Latino white (NLW) siblings of children with intellectual disabilities (ID) and matched comparisons. Methods 200 siblings (ages 8–15 years) completed the newly developed Sibling–Parent Emotion Communication Scale and existing measures of general emotion expression and psychosocial functioning. Preliminary analyses evaluated scale psychometrics across ethnicity. Results Structure and internal consistency of the emotion expression and communication measures differed by respondent ethnicity. Latino siblings endorsed more general emotion expression problems and marginally lower sibling–parent emotion communication than NLW siblings. Siblings of children with ID reported marginally more general emotion expression problems than comparisons. Emotion expression problems and lower sibling–parent emotion communication predicted more internalizing and somatic symptoms and poorer personal adjustment, regardless of ID status. Siblings of children with ID endorsed poorer personal adjustment. Conclusion Cultural differences in emotion expression and communication may increase Latino siblings’ risk for emotional adjustment difficulties. PMID:23459309

Noninvasive analysis of human neck muscle function

NASA Technical Reports Server (NTRS)

Conley, M. S.; Meyer, R. A.; Bloomberg, J. J.; Feeback, D. L.; Dudley, G. A.

1995-01-01

STUDY DESIGN. Muscle use evoked by exercise was determined by quantifying shifts in signal relaxation times of T2-weighted magnetic resonance images. Images were collected at rest and after exercise at each of two intensities (moderate and intense) for each of four head movements: 1) extension, 2) flexion, 3) rotation, and 4) lateral flexion. OBJECTIVE. This study examined the intensity and pattern of neck muscle use evoked by various movements of the head. The results will help elucidate the pathophysiology, and thus methods for treating disorders of the cervical musculoskeletal system. SUMMARY OF BACKGROUND DATA. Exercise-induced contrast shifts in T2 has been shown to indicate muscle use during the activity. The noninvasive nature of magnetic resonance imaging appears to make it an ideal approach for studying the function of the complex neuromuscular system of the neck. METHODS. The extent of T2 increase was examined to gauge how intensely nine different neck muscles or muscle pairs were used in seven subjects. The absolute and relative cross-sectional area of muscle showing a shift in signal relaxation was assessed to infer the pattern of use among and within individual neck muscles or muscle pairs. RESULTS. Signal relaxation increased with exercise intensity for each head movement. The absolute and relative cross-sectional area of muscle showing a shift in signal relaxation also increased with exercise load. Neck muscles or muscle pairs extensively used to perform each head movement were: extension--semispinalis capitis and cervicis and splenius capitis; flexion--sternocleidomastoid and longus capitis and colli; rotation--splenius capitis, levator scapulae, scalenus, semispinalis capitis ipsilateral to the rotation, and sternocleidomastoid contralateral; and lateral flexion--sternocleidomastoid CONCLUSION. The results of this study, in part, agree with the purported functions of neck muscles derived from anatomic location. This also was true for the few selected muscles that have been examined in human electromyographic studies. Neck muscle function and morphology can be studied at a detailed level using exercise-induced shifts in magnetic resonance images.

Effects of aging on mitochondrial function in skeletal muscle of American Quarter Horses

PubMed Central

Li, Chengcheng; White, Sarah H.; Warren, Lori K.

2016-01-01

Skeletal muscle function, aerobic capacity, and mitochondrial (Mt) function have been found to decline with age in humans and rodents. However, not much is known about age-related changes in Mt function in equine skeletal muscle. Here, we compared fiber-type composition and Mt function in gluteus medius and triceps brachii muscle between young (age 1.8 ± 0.1 yr, n = 24) and aged (age 17-25 yr, n = 10) American Quarter Horses. The percentage of myosin heavy chain (MHC) IIX was lower in aged compared with young muscles (gluteus, P = 0.092; triceps, P = 0.012), while the percentages of MHC I (gluteus; P < 0.001) and MHC IIA (triceps; P = 0.023) were increased. Mass-specific Mt density, indicated by citrate synthase activity, was unaffected by age in gluteus, but decreased in aged triceps (P = 0.023). Cytochrome-c oxidase (COX) activity per milligram tissue and per Mt unit decreased with age in gluteus (P < 0.001 for both) and triceps (P < 0.001 and P = 0.003, respectively). Activity of 3-hydroxyacyl-CoA dehydrogenase per milligram tissue was unaffected by age, but increased per Mt unit in aged gluteus and triceps (P = 0.023 and P < 0.001, respectively). Mt respiration of permeabilized muscle fibers per milligram tissue was unaffected by age in both muscles. Main effects of age appeared when respiration was normalized to Mt content, with increases in LEAK, oxidative phosphorylation capacity, and electron transport system capacity (P = 0.038, P = 0.045, and P = 0.007, respectively), independent of muscle. In conclusion, equine skeletal muscle aging was accompanied by a shift in fiber-type composition, decrease in Mt density and COX activity, but preserved Mt respiratory function. PMID:27283918

Pulmonary Function, Muscle Strength, and Incident Mobility Disability in Elders

PubMed Central

Buchman, Aron S.; Boyle, Patricia A.; Leurgans, Sue E.; Evans, Denis A.; Bennett, David A.

2009-01-01

Muscle strength, including leg strength and respiratory muscle strength, are relatively independently associated with mobility disability in elders. However, the factors linking muscle strength with mobility disability are unknown. To test the hypothesis that pulmonary function mediates the association of muscle strength with the development of mobility disability in elders, we used data from a longitudinal cohort study of 844 ambulatory elders without dementia participating in the Rush Memory and Aging Project with a mean follow-up of 4.0 years (SD = 1.39). A composite measure of pulmonary function was based on spirometric measures of forced vital capacity, forced expiratory volume, and peak expiratory flow. Respiratory muscle strength was based on maximal inspiratory pressure and expiratory pressure and leg strength based on hand-held dynamometry. Mobility disability was defined as a gait speed less than or equal to 0.55 m/s based on annual assessment of timed walk. Secondary analyses considered time to loss of the ability to ambulate. In separate proportional hazards models which controlled for age, sex, and education, composite measures of pulmonary function, respiratory muscle strength, and leg strength were each associated with incident mobility disability (all P values < 0.001). Further, all three were related to the development of incident mobility disability when considered together in a single model (pulmonary function: hazard ratio [HR], 0.721; 95% confidence interval [CI], 0.577, 0.902; respiratory muscle strength: HR, 0.732; 95% CI, 0.593, 0.905; leg strength: HR, 0.791; 95% CI, 0.640, 0.976). Secondary analyses examining incident loss of the ability to ambulate revealed similar findings. Overall, these findings suggest that lower levels of pulmonary function and muscle strength are relatively independently associated with the development of mobility disability in the elderly. PMID:19934353

The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.

PubMed

Carson, James A; Hardee, Justin P; VanderVeen, Brandon N

2016-06-01

While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.