Structuration of natural muds in a rheological point of view.

This paper discusses the filling of estuary problem which can be defined as the accumulation of fine materials that causes the invasion of muds all over the estuary and that has a direct effect on the fauna and flora in the river, fishing, swimming and the beauty of the landscapes. All this consequences have social, environmental and economic impact. In the context of the study of this phenomena, analysis of the structuration mechanisms of sedimentary materials in estuaries is carried out in order to better understand the fillings estuarine areas and specially to consider sustainable solutions of “cleansing” of these areas. The Rance estuary is particularly targeted by the study. The aim is to provide answers on the rheological behavior of natural vessels by distinguishing the most significant scales to detect structural factors influencing the rheological parameters

Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine. RESULTS: We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years. CONCLUSIONS: Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD

A hot spot of olive biodiversity in the Tunisian oasis of degache

Tunisia is one of the world's largest producers of olive oil, and it preserves pools of olive genetic diversity that are still unexplored. A recent prospection and collection program of the National Gene Bank of Tunisia (NGBT) focused on the vast oasis of Degache, in the south west part of Tunisia, where 47 samples were collected and genetically characterized through simple sequence repeat (SSR) markers. Identification and authentication of genotypes were obtained through comparison with reference cultivars belonging to the Olive National Collection of Tunisia (IOC) and with cultivars from Algeria, Italia, Syria and Lebanon. Degache olive genotypes showed large genetic variability, a significant diversity from the reference germplasm, and a clear differentiation from modern varieties. The population structure analysis identified four gene pools characterizing genotypes from different area of origin. Two gene pools appear to be more represented in germplasm from southern Tunisia, where environmental conditions at critical plant development phases, are harsher. This suggests that this germplasm might present traits of adaptation useful for breeding to improve resilience to abiotic stresses. Our results will support ex situ and in situ conservation activities of Tunisian olive germplasm pursued by the National Gene Bank of Tunisia

Differentially loaded radiostereometric analysis (DLRSA) in torsion adds essential information in diaphyseal bone healing: the example of a tibial osteotomy

BACKGROUND: Clinical assessment and conventional imaging, which are currently used to monitor fracture healing, do not provide information on the mechanical properties of the healing construct. This limits their use in patient management decisions. Differentially loaded radiostereometric analysis (DLRSA) is a technique developed to assess the mechanical properties of healing fractures in vivo. DLRSA measures the relative micromotion of tantalum beads inserted into bone fracture fragments in response to load across the fracture site. To date, these loads have been applied axially, although in fractures fixed with devices which are highly resistant to axial loads, such as locked intramedullary nails, torsional testing may be more sensitive to healing. The aim of this study was to establish a method to investigate DLRSA using torsional loading for clinical application. METHODS: A device was designed and built to apply torsional loads to the tibia. The test case was an oblique plain corrective osteotomy of a tibial diaphysis stabilized with an intramedullary nail and with tantalum beads inserted into the two adjacent bone segments. Post surgical examinations were made at 2 weeks, 2, 4, and 6 months as well as 1 and 2 years. Healing was monitored with the use of plain film radiographs, computed tomography (CT) and DLRSA. Axial loads of 30kg and an external torsion of 5Nm were applied during DLRSA examinations and the resultant displacement and stiffness were calculated. RESULTS: Torsional DLRSA demonstrated progressive changes in angular displacements and torsional stiffness consistent with the fracture healing observed by CT. By contrast, axial DLRSA was not informative and was more reflective of the stability of the fixation than healing bone. CONCLUSION: The addition of torsional assessments to DLRSA provides an important investigative option in assessing the biomechanical properties of bone healing in vivo.M.J. Chehade, I.A. Vakaci, S.A. Callary, D.M. Findlay and L.B. Solomo

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly

We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debr,-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A > G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. Conclusion: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period.Peer reviewe

A global perspective on the challenges and opportunities in learning about rheumatic and musculoskeletal diseases in undergraduate medical education : White paper by the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD).

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local settin

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimer\u2019s disease and type II diabetes, identified a tripyridylamide, ADH-6, that abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53\u2019s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment effectively shrinks xenografts harboring mutant p53, while exhibiting no toxicity to healthy tissue, thereby substantially prolonging survival. This study demonstrates the successful application of a bona fide small-molecule amyloid inhibitor as a potent\ua0anticancer agent

Systematic Review of Outcome Measures Used in Observational Studies of Adults with Eosinophilic Esophagitis.

BACKGROUND Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients. METHODS We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects. RESULTS We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE. CONCLUSIONS Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE

Should we provide outreach rehabilitation to very old people living in Nursing Care Facilities after a hip fracture? A randomised controlled trial

Objective: to determine whether a 4-week postoperative rehabilitation program delivered in Nursing Care Facilities (NCFs) would improve quality of life and mobility compared with receiving usual care. Design: parallel randomised controlled trial with integrated health economic study. Setting: NCFs, in Adelaide South Australia. Subjects: people aged 70 years and older who were recovering from hip fracture surgery and were walking prior to hip fracture. Measurements: primary outcomes: mobility (Nursing Home Life-Space Diameter (NHLSD)) and quality of life (DEMQOL) at 4 weeks and 12 months. Results: participants were randomised to treatment (n = 121) or control (n = 119) groups. At 4 weeks, the treatment group had better mobility (NHLSD mean difference -1.9; 95% CI: -3.3, -0.57; P = 0.0055) and were more likely to be alive (log rank test P = 0.048) but there were no differences in quality of life. At 12 months, the treatment group had better quality of life (DEMQOL sum score mean difference = -7.4; 95% CI: -12.5 to -2.3; P = 0.0051), but there were no other differences between treatment and control groups. Quality adjusted life years (QALYs) gained over 12 months were 0.0063 higher per participant (95% CI: -0.0547 to 0.0686). The resulting incremental cost effectiveness ratios (ICERs) were $5,545 Australian dollars per unit increase in the NHLSD (95$244 to $15,159) and$328,685 per QALY gained (95% CI: $82,654 to$75,007,056). Conclusions: the benefits did not persist once the rehabilitation program ended but quality of life at 12 months in survivors was slightly higher. The case for funding outreach home rehabilitation in NCFs is weak from a traditional health economic perspective.Maria Crotty, Maggie Killington, Enwu Liu, Ian D. Cameron, Susan Kurrle, Billingsley Kaambwa, Owen Davies, Michelle Miller, Mellick Chehade, Julie Ratcliff

Modeling the climate impact of Southern Hemisphere ozone depletion:the importance of the ozone dataset

The ozone hole is an important driver of recent Southern Hemisphere (SH) climate change, and capturing these changes is a goal of climate modeling. Most climate models are driven by off-line ozone data sets. Previous studies have shown that there is a substantial range in estimates of SH ozone depletion, but the implications of this range have not been examined systematically. We use a climate model to evaluate the difference between using the ozone forcing (Stratospheric Processes and their Role in Climate (SPARC)) used by many Intergovernmental Panel on Climate Change Fifth Assessment Report (Coupled Model Intercomparison Project) models and one at the upper end of the observed depletion estimates (Binary Database of Profiles (BDBP)). In the stratosphere, we find that austral spring/summer polar cap cooling, geopotential height decreases, and zonal wind increases in the BDBP simulations are all doubled compared to the SPARC simulations, while tropospheric responses are 20–100% larger. These results are important for studies attempting to diagnose the climate fingerprints of ozone depletion