High prevalence of radiological vertebral fractures in adult patients with Ehlers-Danlos syndrome

Previous studies have reported an increased prevalence of osteoporosis in Ehlers–Danlos syndrome (EDS), but these were limited by a small number of patients and lack of information on fragility fractures. In this cross-sectional study, we evaluated the prevalence of radiological vertebral fractures (by quantitative morphometry) and bone mineral density (BMD, at lumbar spine, total hip and femoral neck by dual-energy X-ray absorptiometry) in 52 consecutive patients with EDS (10 males, 42 females; median age 41 years, range: 21–71; 12 with EDS classic type, 37 with EDS hypermobility type, 1 with classic vascular-like EDS, and 2 without specific classification) and 197 control subjects (163 females and 34 males; median age 49 years, range: 26–83) attending an outpatient bone clinic. EDS patients were also evaluated for back pain by numeric pain rating scale (NRS-11).Vertebral fractures were significantly more prevalent in EDS as compared to the control subjects (38.5% vs. 5.1%; p < 0.001) without significant differences in BMD at either skeletal sites. In EDS patients, the prevalence of vertebral fractures was not significantly (p = 0.72) different between classic and hypermobility types. BMD was not significantly different between fractured and non-fractured EDS patients either at lumbar spine (p = 0.14), total hip (p = 0.08), or femoral neck (p = 0.21). Severe back pain (≥ 7 NRS) was more frequent in EDS patients with vertebral fractures as compared to those without fractures (60% vs. 28%; p = 0.04). In conclusion, this is the first study showing high prevalence of vertebral fractures in a relatively large population of EDS patients. Vertebral fractures were associated with more severe back pain suggesting a potential involvement of skeletal fragility in determining poor quality of life. The lack of correlation between vertebral fractures and BMD is consistent with the hypothesis that bone quality may be impaired in EDS

Clinical and molecular characterization of 40 patients with classic Ehlers--Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS

Enzymatic pre-treatment of fruit pomace for fibre hydrolysis and antioxidants release

Processing of grapes and other fruits in the wine and fruit juice industry generates huge amounts of solid residues (pomace) which, if not properly disposed of, can represent an environmental concern due to their high organic load. To avoid landfill and incineration, different alternative uses are available and commonly applied. Among these, the most common are for feeding, composting and biogas production which are, anyway, not proper valorisation strategies. On the other hand, fruit pomaces are by-products still rich in bioactive components, such as dietary fibre and phenolic/antioxidant compounds. Considering the positive health potentials of such components, together with their potential technological role (as texturing and antioxidant ingredients), fruit pomaces may then be simply dried and milled to get functional food ingredients. It is known however, that incorporation of high levels of raw fibres into food products often causes unpleasant textures and colours. Furthermore, phenolic compounds only partially occur in fruit pomace as free compounds, while they are bound to cell wall (fibre) fractions. Enzymatic hydrolysis processes could be applied as a pre-drying treatment of fruit pomace to improve the functional properties of the final powders in terms of fibre composition and antioxidants release. In this study different fruit skins separated from different pomaces (grape, apple and blackcurrant) were submitted to an enzymatic treatment before drying. Two different commercial pectinase preparations were used: One already used in the apple juice processing for the treatment of apple and blackcurrant skins, the other currently used in the winemaking process for the treatment of grape skins. Untreated and treated dried skins were analysed for structural carbohydrates, soluble and insoluble dietary fibre, free glucose and xylose, water holding capacity, water solubility and total phenolics and antioxidants release. The results were highly variable depending on the fruit type, probably due to a different cell wall composition which requires targeted enzyme selection. In general, the enzyme treatment led to an increase in water solubility, water and oil holding capacity and free monosaccharides. Release of antioxidant compounds was observed only for apple peels

An integrative review of the factors influencing older nurses’ timing of retirement

Aims: To summarise the international empirical literature to provide a comprehensive understanding of older nurses’ decision making surrounding the timing of their retirement. Background: The global nursing shortage is increasing. Amongst some countries it has become an economic imperative to consider raising the state pension age and to extend working lives. Design: An integrative literature review using an integrated design. Data sources: MEDLINE, CINAHL and Business Source Premier databases were searched for studies between January 2007 ‐ October 2019. Review Methods: Quality appraisal of the studies were conducted. Findings were summarised, grouped into categories and themes extracted. Two models were developed for data representation. Results: 132 studies were identified by the search strategy. Of these, 27 articles were included for appraisal and synthesis. 16 papers were quantitative, seven qualitative and four mixed methods. The research took place in 13 different geographical locations. Most studies were of a questionnaire design, followed by interviews and focus groups. The total participant sample was 35,460. Through a synthesis of the studies, four themes were identified: Health, Well‐being and Family factors; Employer factors; Professional factors; Financial factors. Conclusion: This review revealed the heterogeneity of studies on this subject and confirmed previous findings but also established a ranking of criteria that influences nurses’ decision making: age, followed by personal and organisational factors. Four extracted themes of push and pull factors map onto these factors. No ‘one‐size‐fits‐all’ strategy exists to ensure the extension of older nurses’ working lives. Organisations need to foster an environment where older nurses feel respected and heard and where personal and professional needs are addressed

A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

PurposeIn 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date.MethodsWe report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data.ResultsBased on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals.ConclusionOur data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS

The isotopic (δ18O, δ2H, δ13C, δ15N, δ34S, 87Sr/86Sr, δ11B) composition of Adige river water records natural and anthropogenic processes

The water composition of the river Adige displays a Ca–HCO3 hydrochemical facies, mainly due to rock weathering. Nitrate is the only component that has increased in relation to growing anthropogenic inputs. The aim of this paper was to identify the origin of the dissolved components in this river and to establish the relationship between these components and critical zone processes within an evolving framework where climatic and human impacts are influencing the riverine system. In particular, emphasis is given to a wide spectrum of isotope data (δ18O, δ2H, δ13C, δ15N, δ34S, 87Sr/86Sr, δ11B), which is considered useful for determining water origin as well as natural and anthropogenic impacts on riverine geochemistry. Together with oxygen and hydrogen isotopes, which are strictly related to the climatic conditions (precipitation, temperature, humidity), the carbon, sulphur, strontium and boron signatures can describe the magnitude of rock weathering, which is in turn linked to the climatic parameters. δ13CDIC varies regularly along the riverine profile between −4.5‰ and −9.5‰, and δ34SSO4 varies regularly between +4.4‰ and +11.4‰. On the other hand, δ15NNO3 shows a more scattered distribution between +3.9‰ and +10.5‰, with sharp variations along the riverine profile. 87Sr/86Sr varies between 0.72797 in the upper part of the catchment and 0.71068 in the lower part. δ11B also shows a rough trend, with values approaching 7.6‰ in the upper part and 8.5‰ in the lower part. In our view, the comparatively low δ34S, δ11B, and high 87Sr/86Sr values, could be a proxy for increasing silicate weathering, which is a process that is sensitive to increases in temperature

A new method for free testosterone assay: clinical evaluation.

The Authors propose a new direct method for the determination of free Testosterone (F. Te). Our study was made following this method: 1) on a control group composed of 12 healthy men and 21 healthy women, and 2) on a group of 29 patients suffering from Polycystic Ovary Syndrome (PCOS) with clinical signs of hyperandrogenism. This pathological group presented acne and hirsutism in 95% of the cases. The Authors demonstrate how the determination of F

A new method for free testosterone assay: clinical evaluation.

The Authors propose a new direct method for the determination of free Testosterone (F.Te). Our study was made following this method: 1) on a control group composed of 12 healthy men and 21 healthy women, and 2) on a group of 29 patients suffering from Polycystic Ovary Syndrome (PCOS) with clinical signs of hyperandrogenism. This pathological group presented acne and hirsutism in 95% of the cases. The Authors demonstrate how the determination of F.Te permits a 93.1% correct endocrinological diagnosis of hyperandrogenism