Maxillary Sinus Lift with Beta-Tricalcium Phosphate (β-TCP) in Edentulous Patients: A Nanotomographic and Raman Study

Sinus lift elevation restores bone mass at the maxilla in edentulate patients before the placement of dental implants. It consists of opening the lateral side of the sinus and grafting beta-tricalcium phosphate granules (β-TCP) under the olfactory membrane. Bone biopsies were obtained in five patients after 60 weeks. They were embedded undecalcified in poly(methyl methacrylate) (pMMA); blocks were analyzed by nanocomputed tomography (nanoCT); specific areas were studied by Raman microspectroscopy. Remnants of β-TCP were osseointegrated and covered with mineralized bone; osteoid tissue was also filling the inner porosity. Macrophages having engulfed numerous β-TCP grains were observed in marrow spaces. β-TCP was identified by nanoCT as osseointegrated particles and as granules in the cytoplasm of macrophages. Raman microspectroscopy permitted to compare the spectra of β-TCP and bone in different areas. The ratio of the ~820 cm(-1) band of pMMA (-CH2 groups) on the ν1 phosphate band at 960 cm(-1) reflected tissue hydration because water was substituted by MMA during histological processing. In bone, the ratio of the ~960 cm(-1) phosphate to the amide 1 band and the ratio ν2 phosphate band by the 1240-1250 amide III band reflect the mineralization degree. Specific bands of β-TCP were found in osseointegrated β-TCP granules and in the grains phagocytized by the macrophages. The hydration degree was maximal for β-TCP phagocytized by macrophages. Raman microspectroscopy associated with nanoCT is a powerful tool in the analysis of the biomaterial degradation and osseointegration

Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion in the huntingtin (htt) gene. We found that peroxisome proliferator-activated receptor delta (PPARδ) interacts with htt and that mutant htt represses PPARδ-mediated transactivation. Increased PPARδ transactivation ameliorated mitochondrial dysfunction and improved cell survival of HD neurons. Expression of dominant-negative PPARδ in CNS was sufficient to induce motor dysfunction, neurodegeneration, mitochondrial abnormalities, and transcriptional alterations that recapitulated HD-like phenotypes. Expression of dominant-negative PPARδ specifically in the striatum of medium spiny neurons in mice yielded HD-like motor phenotypes, accompanied by striatal neuron loss. In mouse models of HD, pharmacologic activation of PPAR δ, using the agonist KD3010, improved motor function, reduced neurodegeneration, and increased survival. PPAR δ activation also reduced htt-induced neurotoxicity in vitro and in medium spiny-like neurons generated from human HD stem cells, indicating that PPAR δ activation may be beneficial in individuals with HD and related disorders

Late effects of cycle competition on arterial stiffness. A preliminary study.

International audienceAIM: The purpose of this study was to examine the effects of a cycle competition on the large arteries stiffness, 24-hours after the end of the effort. METHODS: Two males elite cyclists were studied before and after performing a stage-race. Their heart rate (HR) was measured continuously during the two competition days. The impact of the competition on their vascular system was determined using the measure of pulse wave velocity (PWV), an index of regional arterial stiffness. HR and blood pressure were also measured before and 24-hours postexercise. RESULTS: During the race, mean cyclists HR were relatively similar. Changes in PWV and HR were found after competition: these measures increased for the offensive subject and decreased for the other. CONCLUSIONS: Despite their involvement in the same cycling competition, we suggest that the long-term effects induced by effort on arterial stiffness were inverted according to the subject's comportment during the race. This study should be completed by others measures in order to precise our results and to precise the possible link between arteries stiffness and the recovery kinetic process, both depending on the cardiovascular autonomic nervous system control

Degree of Coordination between Breathing and Rhythmic Arm Movements During Hand Rim Wheelchair Propulsion

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Hepatocellular type II fibrinogen inclusions in a patient with severe COVID-19 and hepatitis.

Many centres have noticed a high number of venous thromboembolism (VTE) events among critically ill inpatients with COVID-19 pneumonia. The aims of this study were (1) to summarise the reported risk of VTE associated with COVID-19 infections and (2) to summarise guidance documents on thromboprophylaxis in COVID-19 patients, in a systematic review

Colloidal optical waveguides with integrated local light sources built by capillary force assembly

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Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis

Hypofibrinogenemia is a rare inherited disorder characterized by low levels of circulating fibrinogen, caused by mutations within 1 of the 3 fibrinogen genes. We report here the case of a 61-year-old man with chronic liver function test alterations. Liver biopsy examination revealed chronic hepatitis complicated by cirrhosis and weakly eosinophilic globular cytoplasmic inclusions within the hepatocytes, faintly stained with PAS-diastase. On immunohistochemistry, the inclusions reacted strongly with human antifibrinogen antibodies. Coagulation investigations of the propositus and his 2 sons showed low functional and antigenic fibrinogen concentrations that were indicative of hypofibrinogenemia. A liver biopsy performed on the 28-year-old son demonstrated the same globular cytoplasmic inclusions, albeit without associated chronic liver disease. PCR amplification followed by sequencing showed that all 3 were heterozygous for a CGG>TGG mutation at codon 375 of the fibrinogen gamma-chain gene (FGG), corresponding to an Arg>Trp substitution. This is the first in an adult male and the second published case with a discernible hepatic fibrinogen endoplasmic reticulum storage disease due to an FGG Arg375Trp (fibrinogen Aguadilla) mutation. Our results suggest that familial hypofibrinogenemia should be considered in the differential diagnosis of a progressive liver disease associated to hepatocellular intracytoplasmic globular inclusions