Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect

The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1)

The influence of age and osteoporosis on bone marrow stem cells from rats

OBJECTIVES: This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. METHODS: Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. RESULTS: CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). CONCLUSION: Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats

A mutual reference shape based on information theory

International audienceIn this paper, we propose to consider the estimation of a refer-ence shape from a set of different segmentation results using both active contours and information theory. The reference shape is defined as the minimum of a criterion that benefits from both the mutual information and the joint entropy of the input segmentations and called a mutual shape. This energy criterion is here justified using similarities between informa-tion theory quantities and area measures, and presented in a continuous variational framework. This framework brings out some interesting evaluation measures such as the speci-ficity and sensitivity. In order to solve this shape optimization problem, shape derivatives are computed for each term of the criterion and interpreted as an evolution equation of an active contour. Some synthetical examples allow us to cast the light on the difference between our mutual shape and an average shape. Our framework has been considered for the estimation of a mutual shape for the evaluation of cardiac segmentation methods in MRI

Piston core record of Late Paleogene (31 Ma) to recent seafloor hydrothermal activity in the Southwest Pacific Basin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94790/1/palo1386.pd

Segmentation and kinematics of the North America-Caribbean plate boundary offshore Hispaniola

We explored the submarine portions of the Enriquillo–Plantain Garden Fault zone (EPGFZ) and the Septentrional–Oriente Fault zone (SOFZ) along the Northern Caribbean plate boundary using high-resolution multibeam echo-sounding and shallow seismic reflection. The bathymetric data shed light on poorly documented or previously unknown submarine fault zones running over 200 km between Haiti and Jamaica (EPGFZ) and 300 km between the Dominican Republic and Cuba (SOFZ). The primary plate-boundary structures are a series of strike-slip fault segments associated with pressure ridges, restraining bends, step overs and dogleg offsets indicating very active tectonics. Several distinct segments 50–100 km long cut across pre-existing structures inherited from former tectonic regimes or bypass recent morphologies formed under the current strike-slip regime. Along the most recent trace of the SOFZ, we measured a strike-slip offset of 16.5 km, which indicates steady activity for the past ~1.8 Ma if its current GPS-derived motion of 9.8 ± 2 mm a−1 has remained stable during the entire Quaternary.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Gravity-driven instabilities: interplay between state-and-velocity dependent frictional sliding and stress corrosion damage cracking

We model the progressive maturation of a heterogeneous mass towards a gravity-driven instability, characterized by the competition between frictional sliding and tension cracking, using array of slider blocks on an inclined basal surface, which interact via elastic-brittle springs. A realistic state- and rate-dependent friction law describes the block-surface interaction. The inner material damage occurs via stress corrosion. Three regimes, controlling the mass instability and its precursory behavior, are classified as a function of the ratio $T_c/T_f$ of two characteristic time scales associated with internal damage/creep and with frictional sliding. For $T_c/T_f \gg 1$, the whole mass undergoes a series of internal stick and slip events, associated with an initial slow average downward motion of the whole mass, and progressively accelerates until a global coherent runaway is observed. For $T_c/T_f \ll 1$, creep/damage occurs sufficiently fast compared with nucleation of sliding, causing bonds to break, and the bottom part of the mass undergoes a fragmentation process with the creation of a heterogeneous population of sliding blocks. For the intermediate regime $T_c/T_f \sim 1$, a macroscopic crack nucleates and propagates along the location of the largest curvature associated with the change of slope from the stable frictional state in the upper part to the unstable frictional sliding state in the lower part. The other important parameter is the Young modulus $Y$ which controls the correlation length of displacements in the system.Comment: 40 pages, 13 figure

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research