Deletion of the ghrelin receptor GHSR corrects the trabecular, but not the cortical bone changes in the femoral head of ob/ob mice

Background: There exists an intriguing and complex relationship between fat and bone cells with respect to aging and osteoporosis, which is mediated in part by leptin. Genetically obese mice (ob/ob), that lack leptin, have aheterogeneous bone phenotype, with differential effects on cortical and trabecular compartments. Besides its role in bone metabolism, leptin is most well known for its anorexigenic properties. Opposed in action to leptin is ghrelin, a potent orexigenic peptide hormone derived from the stomach. Ghrelin and leptin also act as each other’s antagonists in gonadal and immune system function.Objective: To determine if ghrelin opposes leptin action on bone metabolism.Methods: Characterization of femoral micro-architecture in 6 months old male wild type, ob/ob, ghrelin receptor knockout (Ghsr -/-), and ob/ob.Ghsr-/- mice using micro-computed tomography.Results: Deletion of Ghsr alone did not significantly alter bone micro-architecture in wild type mice. Deletion of leptin reduced cortical volume and thickness in the femoral head of wild type mice, while it increased endocortical volume. Tissue volume remained unaffected. Conversely, deletion of leptin increased trabecular bone volume, trabecular number and connectivity in wild type mice. Additional deletion of Ghsr in ob/ob mice restored the changes to wild type levels in trabecular bone, but not in cortical bone (all not significant).Conclusion: We found that leptin deficiency has a negative effect on cortical and a positive effect on trabecular bone micro-architecture, confirming the heterogeneous skeletal effects observed by others in ob/ob mice. Knocking out ghrelin signaling compensates for the effect of leptin deficiency on trabecular bone. These observations demonstrate the positive activity of ghrelin signaling in bone, and suggest that ghrelin and leptin have opposing actions on bone metabolism

Bodemvocht uit satellietdata: wat kan de Nederlandse waterbeheerder ermee?

Het onderzoeksproject ‘Optimizing Water Availability with Sentinel-1 Satellites’ heeft als doel te onderzoeken hoe satellietdata gebruikt kan worden in het Nederlandse waterbeheer. Het onderzoek laat zien dat de satelliet Sentinel-1 buiten het groeiseizoen om al een vrij goed beeld geeft van het bodemvochtgehalte. Hiermee kan bijvoorbeeld de berijdbaarheid van landbouwpercelen in kaart gebracht kan worden. Ook is met Deltares en HKV een data-assimilatietool ontwikkeld die ingezet kan worden om simulaties met het Landelijk Hydrologisch Model te verbeteren

Prognosis and institutionalization of frail community-dwelling older patients following a proximal femoral fracture:a multicenter retrospective cohort study

SUMMARY: Hip fractures are a serious public health issue with major consequences, especially for frail community dwellers. This study found a poor prognosis at 6 months post-trauma with regard to life expectancy and rehabilitation to pre-fracture independency levels. It should be realized that recovery to pre-trauma functioning is not a certainty for frail community-dwelling patients. INTRODUCTION: Proximal femoral fractures are a serious public health issue in the older patient. Although a significant rise in frail community-dwelling elderly is expected because of progressive aging, a clear overview of the outcomes in these patients sustaining a proximal femoral fracture is lacking. This study assessed the prognosis of frail community-dwelling patients who sustained a proximal femoral fracture. METHODS: A multicenter retrospective cohort study was performed on frail community-dwelling patients with a proximal femoral fracture who aged over 70 years. Patients were considered frail if they were classified as American Society of Anesthesiologists score ≥ 4 and/or a BMI < 18.5 kg/m(2) and/or Functional Ambulation Category ≤ 2 pre-trauma. The primary outcome was 6-month mortality. Secondary outcomes were adverse events, health care consumption, rate of institutionalization, and functional recovery. RESULTS: A total of 140 out of 2045 patients matched the inclusion criteria with a median age of 85 (P(25)–P(75) 80–89) years. The 6-month mortality was 58 out of 140 patients (41%). A total of 102 (73%) patients experienced adverse events. At 6 months post-trauma, 29 out of 120 (24%) were readmitted to the hospital. Out of the 82 surviving patients after 6 months, 41 (50%) were unable the return to their home, and only 32 (39%) were able to achieve outdoor ambulation. CONCLUSION: Frail community-dwelling older patients with a proximal femoral fracture have a high risk of death, adverse events, and institutionalization and often do not reobtain their pre-trauma level of independence. Foremost, the results can be used for realistic expectation management

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Constraints on Gamma-ray Emission from the Galactic Plane at 300 TeV

We describe a new search for diffuse ultrahigh energy gamma-ray emission associated with molecular clouds in the galactic disk. The Chicago Air Shower Array (CASA), operating in coincidence with the Michigan muon array (MIA), has recorded over 2.2 x 10^{9} air showers from April 4, 1990 to October 7, 1995. We search for gamma rays based upon the muon content of air showers arriving from the direction of the galactic plane. We find no significant evidence for diffuse gamma-ray emission, and we set an upper limit on the ratio of gamma rays to normal hadronic cosmic rays at less than 2.4 x 10^{-5} at 310 TeV (90% confidence limit) from the galactic plane region: (50 degrees < l < 200 degrees); -5 degrees < b < 5 degrees). This limit places a strong constraint on models for emission from molecular clouds in the galaxy. We rule out significant spectral hardening in the outer galaxy, and conclude that emission from the plane at these energies is likely to be dominated by the decay of neutral pions resulting from cosmic rays interactions with passive target gas molecules.Comment: Astrophysical Journal, submitted, 11 pages, AASTeX Latex, 3 Postscript figure