The relationship between lower limb muscle volume and body mass in ambulant individuals with bilateral cerebral palsy.

BACKGROUND: Individuals with cerebral palsy have smaller muscle volumes normalised to body mass than their typically developing peers. The aim of this study is to investigate the relationship between lower limb muscle volume and body mass in young people with bilateral cerebral palsy and their typically developing peers. METHODS: Twenty-five participants with bilateral cerebral palsy (aged 14.7±3.0 years, GMFCS level I-III) and 25 of their typically developing peers (aged 16.8±3.3 years) took part in this study. None of the participants had undergone orthopaedic surgery, botulinum toxin injections, or serial casting in the previous year. All participants underwent magnetic resonance imaging of both lower limbs. Nine major muscles of each lower limb were individually manually segmented and the muscle volumes calculated. RESULTS: Body mass and total lower limb muscle volume were significantly linearly related in both the cerebral palsy (R2 = 0.75, p<0.001) and typically developing (R2 = 0.77, p<0.001) groups. The slope of the relationship between muscle volume and body mass was significantly shallower in the cerebral palsy group compared to the typically developing group (p=0.007). CONCLUSIONS: This cross-sectional study suggests that the increase in size of lower limb muscles relative to body mass is reduced in adolescents and young adults with cerebral palsy. Longitudinal studies are required to further investigate altered muscle growth trajectories in this group and their impact on long-term mobility.

Intramuscular fat in ambulant young adults with bilateral spastic cerebral palsy.

BACKGROUND: It is known that individuals with bilateral spastic cerebral palsy (BSCP) have small and weak muscles. However, no studies to date have investigated intramuscular fat infiltration in this group. The objective of this study is to determine whether adults with BSCP have greater adiposity in and around their skeletal muscles than their typically developing (TD) peers as this may have significant functional and cardio-metabolic implications for this patient group. METHODS: 10 young adults with BSCP (7 male, mean age 22.5 years, Gross Motor Function Classification System (GMFCS) levels I-III), and 10 TD young adults (6 male, mean age 22.8 years) took part in this study. 11 cm sections of the left leg of all subjects were imaged using multi-echo gradient echo chemical shift imaging (mDixon). Percentage intermuscular fat (IMAT), intramuscular fat (IntraMF) and a subcutaneous fat to muscle volume ratio (SF/M) were calculated. RESULTS: IntraMF was higher with BSCP for all muscles (p = 0.001-0.013) and was significantly different between GMFCS levels (p < 0.001), with GMFCS level III having the highest IntraMF content. IMAT was also higher with BSCP p < 0.001). No significant difference was observed in SF/M between groups. CONCLUSION: Young adults with BSCP have increased intermuscular and intramuscular fat compared to their TD peers. The relationship between these findings and potential cardio-metabolic and functional sequelae are yet to be investigated.

miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components.

In animals, microRNAs (miRNAs) generally repress gene expression by binding to sites in the 3'-untranslated region (UTR) of target mRNAs. miRNAs have also been reported to repress or activate gene expression by binding to 5'-UTR sites, but the extent of such regulation and the factors that govern these different responses are unknown. Liver-specific miR-122 binds to sites in the 5'-UTR of hepatitis C virus (HCV) RNA and positively regulates the viral life cycle, in part by stimulating HCV translation. Here, we characterize the features that allow miR-122 to activate translation via the HCV 5'-UTR. We find that this regulation is a highly specialized process that requires uncapped RNA, the HCV internal ribosome entry site (IRES) and the 3' region of miR-122. Translation activation does not involve a previously proposed structural transition in the HCV IRES and is mediated by Argonaute proteins. This study provides an important insight into the requirements for the miR-122-HCV interaction, and the broader consequences of miRNAs binding to 5'-UTR sites.

Regulation and biological function of the liver-specific miR-122.

miRNAs (microRNAs) are important regulators of gene expression. In higher eukaryotes, the tightly controlled expression of different miRNAs, each of which regulates multiple target mRNAs, is crucial for the maintenance of tissue type and the control of differentiation. miR-122 is a highly liver-specific miRNA that is important in hepatitis C virus infection, cholesterol metabolism and hepatocellular carcinoma. In the present review, we discuss the effects of miR-122 on liver physiology and pathology. Recent evidence of pathways involved in the regulation of miR-122 expression is also considered.

Lower limb muscle volumes in bilateral spastic cerebral palsy.

AIM: Muscle weakness is a feature of individuals with spastic cerebral palsy (SCP) but there are few reports in the literature of muscle volume in this group. This study compares muscle volumes in adolescents and young adults with SCP with those of their typically developing (TD) peers. DESIGN: Measurements of the volumes of nine major lower limb muscles in 19 independently ambulant subjects with SCP (mean age 14.2 years (sd 2.7), 11 male, GMFCS I (n=5); GMFCS II (n=14)), 19 TD subjects (mean age 16.5 years (sd 3.0), 11 male) were made using magnetic resonance imaging. RESULTS: Lower limb muscles were smaller in the SCP group (p≤0.023 in all muscles) than the TD group with the exception of the vastii (lateralis+intermedius; p=0.868) and gluteus maximus (p=0.056). Average muscle volume deficit was 27.9%. Muscle volume deficits were significantly greater for distal muscles than proximal muscles (p<0.001). CONCLUSIONS: Reduced muscle size in adolescence and the natural history of sarcopenia in adulthood may contribute to the early loss of mobility of adults with SCP.

Bone strength is related to muscle volume in ambulant individuals with bilateral spastic cerebral palsy.

OBJECTIVE: The aim of this study is to investigate how bone strength in the distal femur and proximal tibia are related to local muscle volume in ambulant individuals with bilateral spastic cerebral palsy (CP). METHODS: Twenty-seven participants with CP (mean age: 14.6±2.9years; Gross Motor Function Classification System (GMFCS) levels I-III) and twenty-two typically developing (TD) peers (mean age: 16.7±3.3years) took part in this study. Periosteal and medullary diameter in the distal femur and cortical bone cross-sectional area (CSA) and thickness (CT) in the distal femur and proximal tibia were measured along with nine lower limb muscle volumes using MRI. Additionally, the polar section modulus (Zp) and buckling ratio (BR) were calculated to estimate bone bending strength and compressional bone stability respectively in the distal femur. The relationships of all measured parameters with muscle volume, height, age, body mass, gender, and subject group were investigated using a generalized linear model (GZLM). RESULTS: In the distal femur, Zp was significantly positively related to thigh muscle volume (p=0.007), and height (p=0.026) but not significantly related to subject group (p=0.076) or body mass (p=0.098). BR was not significantly different between groups and was not related to any of the variables tested. Cortical bone CSA was significantly lower in the CP group at both the distal femur (p=0.002) and proximal tibia (p=0.009). It was also positively associated with thigh muscle volume (p<0.001) at the distal femur, and with subject height (p=0.005) at the proximal tibia. CONCLUSIONS: Bending and compressional strength of the femur, estimated from Zp and cortical bone CSA respectively, is associated with reduced thigh muscle volume. Increasing muscle volume by strength training may have a positive effect on bone mechanics in individuals with CP.

The role of microRNAs in viral infection.

MicroRNAs (miRNAs) are small non-coding RNA molecules that have emerged in recent years as central regulators of eukaryotic gene expression. In mammalian systems, miRNAs are associated with numerous pathological and physiological pathways. miRNAs are important in many viral infections, with different viral families expressing their own miRNAs, manipulating host miRNA expression, or showing direct or indirect regulation by host or viral miRNAs. In this chapter we will examine the current evidence for interplay between the miRNA pathway and viral infections in mammals.