Surgical Repositioning of the Premaxilla: Incidence, Indications and Growth Study About a 189 Bilateral Cleft Lip ± Palate Population.

OBJECTIVE: We aimed to evaluate the rate of patient requiring Surgical Repositioning of the Premaxilla in a population carrying BCL ± P, retrieve age and operative indication. Our secondary objective was to present further facial growth characteristics. SETTINGS: This was a retrospective, single-center cohort study conducted in Nantes University Hospital, Oral and Maxillofacial Surgery department, tertiary cleft center. PATIENTS: Patients with BCL ± P born between 1980 and 2019 treated at Nantes University Hospital were included. MAIN OUTCOME MEASURE: Our primary outcome measure was the rate of patient requiring SRP. RESULTS: Over the whole period, 189 patients with BCL ± P were identified. Three patients (1,58%) underwent SRP. Patients who underwent SRP all had BCLP. SRP was performed during their primary dentition period. The indication for surgical repositioning was always premaxilla vertical overgrowth with an overbite over 10 mm. Facial growth features in the three patients were mostly comparable with a population carrying BCLP who had no premaxillary surgery. CONCLUSION: Our results showed a low incidence of SRP. No SRP was necessary during early infancy (ie, before lip repair) or during adulthood. Surgical repositioning of the premaxilla is beneficial for patient with orthodontically uncorrectable vertical premaxillary excess, even more since facial development compared with other patients with BCLP appears comparable.

Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

BACKGROUND: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. METHODS: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). RESULTS: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]. CONCLUSIONS: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.

COPD is deleterious for pericytes: implications during training-induced angiogenesis in skeletal muscle.

Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%V̇o2: COPD-RI) or absolute (mL·min-1·kg-1: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2+ pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (V̇o2VT) than both patients with COPD-RI and patients with COPD-AI (Group × Time: P = 0.004). Despite a preserved increase in the C/F ratio, NG2+ pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time: P = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology (P < 0.001) and drastically reduced MSC differentiation into pericytes (P < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.NEW & NOTEWORTHY This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.

Effects of a human microenvironment on the differentiation of human myoblasts.

Myogenic differentiation mechanisms are generally assessed using a murine cell line placed in low concentrations of an animal-derived serum. To more closely approximate in vivo pathophysiological conditions, recent studies have combined the use of human muscle cells with human serum. Nevertheless, the in vitro studies of the effects of a human microenvironment on the differentiation process of human myoblasts require the identification of the culture conditions that would provide an optimal and reproducible differentiation process of human muscle cells. We assessed the differentiation variability resulting from the use of human myoblasts and serums from healthy subjects by measuring the myotube diameter, fusion index and surface covered by myotubes. We showed the preserved cell-dependent variability of the differentiation response of myoblasts cultured in human serums compared to FBS. We found that using a pool of serums reduced the serum-dependent variability of the myogenic response compared to individual serums. We validated our methodology by showing the atrophying effect of pooled serums from COPD patients on healthy human myotubes. By replacing animal-derived tissues with human myoblasts and serums, and by validating the sensitivity of cultured human muscle cells to a pathological microenvironment, this human cell culture model offers a valuable tool for studying the role of the microenvironment in chronic disease.

Impaired training-induced angiogenesis process with loss of pericyte-endothelium interactions is associated with an abnormal capillary remodelling in the skeletal muscle of COPD patients.

Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = - 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients. TRIAL REGISTRATION: NCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

Interactive whiteboard use in clinical reasoning sessions to teach diagnostic test ordering and interpretation to undergraduate medical students.

BACKGROUND: Over-testing of patients is a significant problem in clinical medicine that can be tackled by education. Clinical reasoning learning (CRL) is a potentially relevant method for teaching test ordering and interpretation. The feasibility might be improved by using an interactive whiteboard (IWB) during the CRL sessions to enhance student perceptions and behaviours around diagnostic tests. Overall, IWB/CRL could improve their skills. METHODS: Third-year undergraduate medical students enrolled in a vertically integrated curriculum were randomized into two groups before clinical placement in either a respiratory disease or respiratory physiology unit: IWB-based CRL plus clinical mentoring (IWB/CRL + CM: n = 40) or clinical mentoring only (CM-only: n = 40). Feasibility and learning outcomes were assessed. In addition, feedback via questionnaire of the IWB students and their classmates (n = 233) was compared. RESULTS: Analyses of the IWB/CRL sessions (n = 40, 27 paperboards) revealed that they met validated learning objectives. Students perceived IWB as useful and easy to use. After the IWB/CRL + CM sessions, students mentioned more hypothesis-based indications in a test ordering file (p <  0.001) and looked for more nonclinical signs directly on raw data tests (p <  0.01) compared with students in the CM-only group. Last, among students who attended pre- and post-assessments (n = 23), the number of diagnostic tests ordered did not change in the IWB/CRL + CM group (+ 7%; p = N.S), whereas it increased among CM-only students (+ 30%; p <  0.001). Test interpretability increased significantly in the IWB/CRL + CM group (from 4.7 to 37.2%; p <  0.01) but not significantly in the CM-only group (from 2.4 to 9.8%; p = 0.36). CONCLUSIONS: Integrating IWB into CRL sessions is feasible to teach test ordering and interpretation to undergraduate students. Moreover, student feedback and prospective assessment suggested a positive impact of IWB/CRL sessions on students' learning.

Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease.

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3-methyladenine (3-MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.

Retinoic acid maintains human skeletal muscle progenitor cells in an immature state.

Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3. These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors.

Maxillofacial features and systemic malformations in expanded spectrum Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare, multisystemic congenital disease with estimated frequency of 1/26370 births in Europe. Most cases are sporadic and caused by unilateral abnormal morphogenesis of the first and second pharyngeal arches. The aim of this study is to define the types and frequency of maxillofacial and systemic malformations in HFM patients. This is a case series study of patients with HFM evaluated at a single institution. Data were acquired through history, physical examination, photographs, diagnostic radiology, and laboratory and analyzed by the FileMakerPro database on 95 patients (54F; 41M) of which 89 met the inclusion criteria. Mandibular hypoplasia was observed in 86 patients with right-side preponderance (50). One patient had bilateral mandibular hypoplasia. Seventy-four had external ear anomalies (anotia or microtia). Eleven had bilateral malformed ears. Hearing impairment, associated with stenosis or atresia of the external ear canal, was found in 69 patients (eight with bilateral canal defects). Ocular anomalies were seen in 41 (23 with dermoid cysts) and 39 had orbital malformations. Facial nerve paralysis was observed in 38 patients. Cleft lip/palate (10), preauricular tags (55), and macrostomia (41) were also described. A total of 73/86 had systemic malformations, mainly vertebral (40), genitourinary (25), and cardiovascular (28). Sixteen had cerebral anomalies (four with intellectual disability). All patients suspected of HFM should undergo a complete systematic clinical and imaging investigation to define the full scope of anomalies. Since the disease is rare and complex, affected patients should be monitored by specialized multidisciplinary team centers.

Standardized Method to Measure Muscle Force at the Bedside in Hemodialysis Patients.

OBJECTIVES: In hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients. DESIGN: Repeated-measures cross-sectional study. SETTING: Clinical and academic hospital. PARTICIPANTS: Fifty-three healthy adult subjects (23 males, 36.5 + 12.5 y.o.) and 21 hemodialysis patients (14 males, 72.4 + 13.3 y.o., dialysis vintage 30 + 75.1 months). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: MVF measurements were assessed with belt-stabilized HHD and dynamometer chair, by two independent investigators. The agreement between the two devices would be quantified using the Bland-Altman 95% limits of agreement (LOA) method and the Spearman correlation. RESULTS: For healthy subjects and hemodialysis patients, Spearman coefficients between belt-stabilized HHD and dynamometer chair were 0.63 and 0.75, respectively (P < .05). In hemodialysis group, reliability was excellent for both the intratester and intertester reliability R2 = 0.85 (P < .01) and R2 = 0.90 (P < .01), respectively. In all individuals, the mean difference between the dynamometer chair and the belt-stabilized HHD was -13.07 ± 21.77 N.m. (P < .001). The LOA for the upper and the lower was 29.59 and -55.73 N.m., respectively. CONCLUSION: In healthy subjects and in hemodialysis patients, the belt-stabilized HHD dynamometer appears as a valid and reliable method to measure in clinical practice isometric MVF of quadriceps in hemodialysis patients. Therefore, the belt-stabilized HHD appears as a suitable and a relevant diagnostic tool for the identification of muscle dysfunction in hemodialysis patients.

Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients.

The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.

Optic neuropathy, cardiomyopathy, cognitive disability in patients with a homozygous mutation in the nuclear MTO1 and a mitochondrial MT-TF variant.

We report on clinical, genetic and metabolic investigations in a family with optic neuropathy, non-progressive cardiomyopathy and cognitive disability. Ophthalmic investigations (slit lamp examination, funduscopy, OCT scan of the optic nerve, ERG and VEP) disclosed mild or no decreased visual acuity, but pale optic disc, loss of temporal optic fibers and decreased VEPs. Mitochondrial DNA and exome sequencing revealed a novel homozygous mutation in the nuclear MTO1 gene and the homoplasmic m.593T>G mutation in the mitochondrial MT-TF gene. Muscle biopsy analyses revealed decreased oxygraphic Vmax values for complexes I+III+IV, and severely decreased activities of the respiratory chain complexes (RCC) I, III and IV, while muscle histopathology was normal. Fibroblast analysis revealed decreased complex I and IV activity and assembly, while cybrid analysis revealed a partial complex I deficiency with normal assembly of the RCC. Thus, in patients with a moderate clinical presentation due to MTO1 mutations, the presence of an optic atrophy should be considered. The association with the mitochondrial mutation m.593T>G could act synergistically to worsen the complex I deficiency and modulate the MTO1-related disease.

Comparison of two methods to report potentially avoidable hospitalizations in France in 2012: a cross-sectional study.

BACKGROUND: Potentially avoidable hospitalizations represent an indirect measure of access to effective primary care. However many approaches have been proposed to measure them and results may differ considerably. This work aimed at examining the agreement between the Weissman and Ansari approaches in order to measure potentially avoidable hospitalizations in France. METHODS: Based on the 2012 French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information), potentially avoidable hospitalizations were measured using two approaches proposed by Weissman et al. and by Ansari et al. Age- and sex-standardised rates were calculated in each department. The two approaches were compared for diagnosis groups, type of stay, severity, age, sex, and length of stay. RESULTS: The number and age-standardised rate of potentially avoidable hospitalizations estimated by the Weissman et al. and Ansari et al. approaches were 742,474 (13.3 cases per 1,000 inhabitants) and 510,206 (9.0 cases per 1,000 inhabitants), respectively. There are significant differences by conditions groups, age, length of stay, severity level, and proportion of medical stays between the Weissman and Ansari methods. CONCLUSIONS: Regarding potentially avoidable hospitalizations in France in 2012, the agreement between the Weissman and Ansari approaches is poor. The method used to measure potentially avoidable hospitalizations is critical, and might influence the assessment of accessibility and performance of primary care.

MASK-rhinitis, a single tool for integrated care pathways in allergic rhinitis.

Allergic rhinitis (AR) is among the most common diseases globally. MASK-rhinitis is a simple ICT tool to implement care pathways for allergic rhinitis from patients to health care providers using a common language and a clinical decision support system. This is based on the assessment of the control of allergic rhinitis by a visual analogue scale on and App and a tablet. MASK-rhinitis will allow (i) the patients to screen for allergic disease, (ii) the pharmacists, to guide them in the prescription of OTC medications and direct the uncontrolled patients to physicians, (iii) the primary care physician, to prescribe appropriate treatment and to follow-up with the patient according to the physician's instructions (CDSS) and assessment of control and (vi) the specialist and outpatient clinics in allergology, if there is failure to gain control by the primary physician. MASK-rhinitis will be important for establishing care pathways across the life cycle, stratify patients with severe uncontrolled rhinitis and to perform clinical trials.

Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival.

Protection of satellite cells from cytotoxic damages is crucial to ensure efficient adult skeletal muscle regeneration and to improve therapeutic efficacy of cell transplantation in degenerative skeletal muscle diseases. It is therefore important to identify and characterize molecules and their target genes that control the viability of muscle stem cells. Recently, we demonstrated that high aldehyde dehydrogenase activity is associated with increased viability of human myoblasts. In addition to its detoxifying activity, aldehyde dehydrogenase can also catalyze the irreversible oxidation of vitamin A to retinoic acid; therefore, we examined whether retinoic acid is important for myoblast viability. We showed that when exposed to oxidative stress induced by hydrogen peroxide, adherent human myoblasts entered apoptosis and lost their capacity for adhesion. Pre-treatment with retinoic acid reduced the cytotoxic damage ex vivo and enhanced myoblast survival in transplantation assays. The effects of retinoic acid were maintained in dystrophic myoblasts derived from facioscapulohumeral patients. RT-qPCR analysis of antioxidant gene expression revealed glutathione peroxidase 3 (Gpx3), a gene encoding an antioxidant enzyme, as a potential retinoic acid target gene in human myoblasts. Knockdown of Gpx3 using short interfering RNA induced elevation in reactive oxygen species and cell death. The anti-cytotoxic effects of retinoic acid were impaired in GPx3-inactivated myoblasts, which indicates that GPx3 regulates the antioxidative effects of retinoic acid. Therefore, retinoid status and GPx3 levels may have important implications for the viability of human muscle stem cells.

Relationship between CT air trapping criteria and lung function in small airway impairment quantification.

BACKGROUND: Small airways are regarded as the elective anatomic site of obstruction in most chronic airway diseases. Expiratory computed tomography (CT) is increasingly used to assess obstruction at this level but there is no consensus regarding the best quantification method. We aimed to evaluate software-assisted CT quantification of air trapping for assessing small airway obstruction and determine which CT criteria better predict small airway obstruction on single breath nitrogen test (SBNT). METHODS: Eighty-nine healthy volunteers age from 60 to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day. Air trapping was estimated using dedicated software measuring on inspiratory and expiratory CT low attenuation area (LAA) lung proportion and mean lung density (MLD). CT indexes were compared to SBNT results using the Spearman correlation coefficient and hierarchical dendrogram analysis. In addition, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal CT air-trapping criterion. RESULTS: 43 of 89 subjects (48,3%) had dN2 value above the threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to inspiratory MLD ratio (r = 0.40) and LAA for the range -850 -1024 HU (r = 0.29) and for the range -850 -910 HU (r = 0.37) were positively correlated with SBNT results. E/I MLD was the most suitable criterion for its expression. Expiratory to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small airway obstruction assessment. CONCLUSION: Among all CT criteria, all correlating with small airway obstruction on SBNT, E/I MLD was the most suitable criterion for its expression in asymptomatic subjects with mild small airway obstruction TRIAL REGISTRATION: Registered at Clinicaltrials.gov, identifier: NCT01230879.

Application of bilateral condylectomy as an alternative surgical treatment for Class III malocclusion with posterior vertical excess, a technical note.

The Posterior vertical excess (PVE) associates a symmetric ramus and condyle elongation to an Angle Class III malocclusion. This dento-skeletal discrepancy can be isolated or associated to a condyle hyperplasia or a transverse overgrowth of the mandible due to macroglossia. We present the technique and the postoperative results of bilateral condylectomy applied for the surgical correction of PVE. Bilateral condylectomy represents an alternative to the bimaxillary surgery and adds to the therapeutic arsenal for the correction of Angle Class III malocclusion.

Which sub-compartments of fat mass and fat-free mass are related to blood viscosity factors?

The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (r = 0.562) and its two components muscle mass (r = 0.516) and non-muscular fat-free mass (r = 0.452), and also trunk fat mass (r = 0.383) and waist-to hip ratio (r = 0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.

Muscle strength, quantity and quality and muscle fat quantity and their association with oxidative stress in patients with facioscapulohumeral muscular dystrophy: Effect of antioxidant supplementation.

The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.

DUX4 expression in FSHD muscle cells: how could such a rare protein cause a myopathy?

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent hereditary muscle disorders. It is linked to contractions of the D4Z4 repeat array in 4q35. We have characterized the double homeobox 4 (DUX4) gene in D4Z4 and its mRNA transcribed from the distal D4Z4 unit to a polyadenylation signal in the flanking pLAM region. It encodes a transcription factor expressed in FSHD but not healthy muscle cells which initiates a gene deregulation cascade causing differentiation defects, muscle atrophy and oxidative stress. PITX1 was the first identified DUX4 target and encodes a transcription factor involved in muscle atrophy. DUX4 was found expressed in only 1/1000 FSHD myoblasts. We have now shown it was induced upon differentiation and detected in about 1/200 myotube nuclei. The DUX4 and PITX1 proteins presented staining gradients in consecutive myonuclei which suggested a diffusion as known for other muscle nuclear proteins. Both protein half-lifes were regulated by the ubiquitin-proteasome pathway. In addition, we could immunodetect the DUX4 protein in FSHD muscle extracts. As a model, we propose the DUX4 gene is stochastically activated in a small number of FSHD myonuclei. The resulting mRNAs are translated in the cytoplasm around an activated nucleus and the DUX4 proteins diffuse to adjacent nuclei where they activate target genes such as PITX1. The PITX1 protein can further diffuse to additional myonuclei and expand the transcriptional deregulation cascade initiated by DUX4. Together the diffusion and the deregulation cascade would explain how a rare protein could cause the muscle defects observed in FSHD.