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Correlation plot between functional and muscle morphological measurements and boxplots of areal percentages for different fiber types

Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle.

Background and aim: Transient elastography can detect liver fibrosis by estimation of liver stiffness. Results may be falsely high when blood flow to the liver is increased, such as during late stages of pregnancy. The aim of the present study was to longitudinally evaluate transient elastography in healthy pregnant women. Methods: We recruited 24 healthy women with normal singleton pregnancies in a longitudinal cohort study. All women underwent transient elastography at gestational week 18–20, week 26–28 and week 36–38, as well as after a minimum of 8 weeks postpartum. Results: Mean age at baseline was 30.6 years ± 4.1, and mean BMI was 22.3 kg/m2±1.9. 14 women (58%) were nulliparous. The pregnancy outcomes were normal, with no cases of preeclampsia or gestational diabetes. Mean gestational length was 284 days ± 7. Mean liver stiffness increased from 3.8 kPa during the second trimester to 5.9 kPa during the third trimester (p = .002). At the third trimester, 2 women (8%) had an elastography measurement of >7.9 kPa. Postpartum, liver stiffness decreased to early second trimester levels (5.9 to 3.8 kPa, p = .002), and no woman had liver stiffness values above 7.9 kPa. Likewise, the mean Controlled Attenuation Parameter (CAP) increased from 186 dB/m in the second trimester to 215 dB/m in the third trimester (p = .01) and reversed postpartum (215 to 193 dB/m, p = .03). Conclusion: Liver stiffness and CAP increase reversibly during normal pregnancies, and slightly elevated levels in the third trimester can be considered a normal finding. Lay summary An ultrasound-based method called transient elastography can be used to measure fat content and estimate fibrosis in the liver. In this study, we examined healthy women three times during their pregnancy and once after labor to evaluate the effects of a normal pregnancy on a healthy liver. The ultrasound-estimation of fibrosis and fat content increased during pregnancy and reversed afterwards, without any other signs of disease in the liver.

Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function. Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography. Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 +/- 23 vs. 25 +/- 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 +/- 8 vs. 2 +/- 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 +/- 8 vs. 3 +/- 3%, P = .05). Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI

Altered fucosylation of glycoproteins is associated with development of hepatocellular carcinoma (HCC). Lectins have been commonly used to assay changes in fucosylation of plasma glycoproteins. In the present study a recombinantly engineered form of the fucose binding lectin Aleuria aurantia (AAL) consisting of a single binding site for fucose (S2), was used to construct a reverse lectin ELISA method. Microtiter plates coated with the S2 lectin were used to capture glycoproteins from plasma samples followed by antibody detection of S2-bound fucosylated α1-acid glycoprotein (S2-bound AGP). The method was used to compare the level of S2-bound AGP in serum samples from a small cohort of patients with hepatitis, cirrhosis or HCC. Using the reverse S2 lectin ELISA it was shown that the levels of S2-bound AGP was significantly higher in HCC patients compared to non-cancer patients and that there was also a significant elevation of S2-bound AGP in HCC patients compared to cirrhosis patients. There was no correlation between the level of S2-bound AGP and total AGP concentration. The performance of S2-bound AGP in differentiating HCC from cirrhosis samples or hepatitis samples were compared to other markers. A combination of S2-bound AGP, α-fetoprotein and AGP concentration showed performances giving area under receiver operating curves of 0.87 and 0.95 respectively.

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 120 kb)

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 120 kb)