Search results for "Fragility"
showing 10 items of 75 documents
Very Long Term Stabilization of a 2D Magnet down to the Monolayer for Device Integration
2020
2D materials have recently demonstrated a strong potential for spintronic applications. This has been further reinforced by the discovery of ferromagnetic 2D layers. Nevertheless, the fragility of ...
Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility
2018
International audience; Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut dev…
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
2021
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…
Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects o…
2022
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds…
Osteoporosi e diabete mellito. [Osteoporosis and diabetes]
2004
Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic …
Novel formulations of oral bisphosphonates in the treatment of osteoporosis
2022
AbstractOral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still mainta…
Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity.
1999
Antioxidant activity of melatonin in human erythrocytes, exposed to oxidative stress by cumene hydroperoxide (cumOOH), was investigated. CumOOH at 300 microM progressively oxidized a 1% suspension of red blood cells (RBCs), leading to 100% hemolysis in 180 min. Malondialdehyde and protein carbonyls in the membrane showed a progressive increase, as a result of the oxidative damage to membrane lipids and proteins, reaching peak values after 30 and 40 min, respectively. The membrane antioxidant vitamin E and the cytosolic reduced glutathione (GSH) were totally depleted in 20 min. As a consequence of the irreversible oxidative damage to hemoglobin (Hb), hemin accumulated into the RBC membrane d…
Stochastic Vulnerability Assessment of Masonry Structures: Concepts, Modeling and Restoration Aspects
2019
A methodology aiming to predict the vulnerability of masonry structures under seismic action is presented herein. Masonry structures, among which many are cultural heritage assets, present high vulnerability under earthquake. Reliable simulations of their response to seismic stresses are exceedingly difficult because of the complexity of the structural system and the anisotropic and brittle behavior of the masonry materials. Furthermore, the majority of the parameters involved in the problem such as the masonry material mechanical characteristics and earthquake loading characteristics have a stochastic-probabilistic nature. Within this framework, a detailed analytical methodological approac…
IS THERE A RELATIONSHIP BETWEEN MILD-MODERATE BACK PAIN AND FRAGILITY FRACTURES? ORIGINAL INVESTIGATION
2020
Introduction: Fragility fractures are the cause of 43 thousand deaths: 50% are caused by femur fractures, 28% by vertebral fractures and 22% by various fractures in women, in men the percentages are 47%, 39% and 14% respectively. Vertebral fractures are the most common, 30-50% women over age 50 will experience one of them. Worldwide, is estimated that a new vertebral fracture occurs every 22 seconds. Additionally, vertebral fractures strongly predict the risk of both further fractures and re-fractures, in any skeletal segment. Vertebral fractures are often asymptomatic. Early diagnosis of these is extremely important. The aim of the study is to show, within a population of women over-50 in …