Defective WNT signaling may protect from articular cartilage deterioration - a quantitative MRI study on subjects with a heterozygous WNT1 mutation

Objective: WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Design: Cohort comprised mutation-positive (N = 13; age 17-76 years) and mutation-negative (N = 13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1 rho relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. Results: All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1r relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Conclusions: Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

PLS3Mutations Cause Severe Age and Sex-Related Spinal Pathology

Objective:Mutations in the X-chromosomalPLS3-gene, encoding Plastin 3, lead to severe early-onset osteoporosis, suggesting a major role for PLS3 in bone metabolism. However, the consequences of abnormal PLS3 function in bone and other tissues remain incompletely characterized. This study evaluated spinal consequences of aberrant PLS3 function in patients withPLS3mutations. Design:A cross-sectional cohort study with spinal magnetic resonance imaging of 15PLS3mutation-positive (age range 9-77 years) and 13 mutation-negative (9-70 years) subjects. Images were reviewed for spinal alignment, vertebral heights and morphology, intervertebral disc changes and possible endplate deterioration. Results:Vertebral changes were significantly more prevalent in the mutation-positive subjects compared with the mutation-negative subjects; they were most abundant in upper thoracic spine, and in all age groups and both sexes, although more prominent in males. Difference in anterior vertebral height reduction was most significant in T5 and T6 (p= 0.046 andp= 0.041, respectively). Mid-vertebral height reduction was most significant in T3 and T5 (p= 0.037 andp= 0.005, respectively), and, for male mutation-positive subjects only, in T4 and T6-10 (p= 0.005-0.030 for each vertebra). Most of the abnormal vertebrae were biconcave in shape but thoracic kyphosis or lumbar lordosis were unchanged. Vertebral endplates were well-preserved in the mutation-positive subjects with even fewer Schmorl nodes than the mutation-negative subjects (10 vs. 16). Conclusions:Compromised PLS3 function introduces severe and progressive changes to spinal structures that are present already in childhood, in both sexes and most abundant in upper thoracic spine. Cartilaginous structures are well-preserved.Peer reviewe

Defective WNT signaling associates with bone marrow fibrosis-a cross-sectional cohort study in a family with WNT1 osteoporosis

This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology. We aimed to explore bone marrow findings in a large family with early-onset osteoporosis due to a heterozygous WNT1 mutation. We analyzed peripheral blood samples, and bone marrow aspirates and biopsies from 10 subjects with WNT1 mutation p.C218G. One subject was previously diagnosed with idiopathic myelofibrosis and others had no previously diagnosed hematologic disorders. The findings were correlated with the skeletal phenotype, as evaluated by number of peripheral and spinal fractures and bone mineral density. Peripheral blood samples showed no abnormalities in cell counts, morphology or distributions but mild increase in platelet count. Bone marrow aspirates (from 8/10 subjects) showed mild decrease in bone marrow iron storages in 6 and variation in cell distributions in 5 subjects. Bone marrow biopsies (from 6/10 subjects) showed increased bone marrow reticulin (grade MF-2 in the myelofibrosis subject and grade MF-1 in 4 others), and an increase in overall, and a shift towards early-phase, granulopoiesis. The bone marrow findings did not associate with the severity of skeletal phenotype. Defective WNT signaling associates with a mild increase in bone marrow reticulin and may predispose to myelofibrosis, while overall hematopoiesis and peripheral blood values are unaltered in individuals with a WNT1 mutation. In this family with WNT1 osteoporosis, bone marrow findings were not related to the severity of osteoporosis.Peer reviewe

Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling

Context: WNT signaling is fundamental to bone health, and its aberrant activation leads to skeletal pathologies. The heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset and progressive osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone turnover markers are normal in mutation-positive patients. Objective: This study sought to explore the circulating microRNA (miRNA) pattern in patients with impaired WNT signaling. Design and Setting: A cross-sectional cohort study at a university hospital. Participants: Altogether, 12 mutation-positive (MP) subjects (median age, 39 years; range, 11 to 76 years) and 12 mutation-negative (MN) subjects (35 years; range, 9 to 59 years) from two Finnish families with WNT1 osteoporosis due to the heterozygous p.C218G WNT1 mutation. Methods and Main Outcome Measure: Serum samples were screened for 192 miRNAs using quantitative polymerase chain reaction. Findings were compared between WNT1 MP and MN subjects. Results: The pattern of circulating miRNAs was significantly different in the MP subjects compared with the MN subjects, with two upregulated (miR-18a-3p and miR-223-3p) and six downregulated miRNAs (miR-22-3p, miR-31-5p, miR-34a-5p, miR-143-5p, miR-423-5p, and miR-423-3p). Three of these (miR-22-3p, miR-34a-5p, and miR-31-5p) are known inhibitors of WNT signaling: miR-22-3p and miR-34a-5p target WNT1 messenger RNA, and miR-31-5p is predicted to bind to WNT1 3'UTR. Conclusions: The circulating miRNA pattern reflects WNT1 mutation status. The findings suggest that the WNT1 mutation disrupts feedback regulation between these miRNAs and WNT1, providing insights into the pathogenesis of WNT-related bone disorders. These miRNAs may have potential in the diagnosis and treatment of osteoporosis.Peer reviewe

The Cinderella moment:Exploring consumers’ motivations to engage with renting as collaborative luxury consumption mode

Past literature argued that the purchase of luxury goods is driven by people’s motivation to conform or fit into our economic and social system. In this study, the authors focus on a new aspect of consumption, i.e. renting instead of purchasing luxury goods, backed by the emerging opportunities of sharing economy platforms. Drawing upon the analysis of spontaneous consumers’ online communications (in the form of tweets), this research aims to investigate the motivations to engage with luxury garment renting within a collaborative consumption context. To this end, a series of automatic content analyses, via two studies, were conducted using the tweets posted with respect to the Run the Runway collaborative consumption platform. Results demonstrate consumers’ increased willingness to show their social status through renting rather than owning luxurious apparel based on five main motivators (need to wear new clothes for a special event, inspirations created by the products/brands, possibility to explore a new way of consuming luxury goods, need to make more sustainable choices, and to increase the life cycle of each luxury product). The implications of these findings are discussed, while they pave the way for future research in collaborative consumption of luxury retailing

Incidence and familial risk of premature ovarian insufficiency in the Finnish female population

STUDY QUESTION: What is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women? SUMMARY ANSWER: The incidence of POI increased among females aged 15-19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased. WHAT IS KNOWN ALREADY: So far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause. STUDY DESIGN, SIZE, DURATION: Population-based study with 5011 women diagnosed with POI in 1988-2017. The data were collected from national registries and covers POI subjects in entire Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence was highest in the 35-39 age group, ranging from 73.8/100 000 women-years in 1993-1997 to 39.9/100 000 women-years in 2013-2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015-2017. Cumulative incidence of POI for women under 40 years in 1988-2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3-6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls. LIMITATIONS, REASONS FOR CAUTION: For some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria. WIDER IMPLICATIONS OF THE FINDINGS: The risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis. STUDY FUNDING/COMPETING INTEREST(S): This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare.publishedVersionPeer reviewe

Fashion consumption during COVID-19: Comparative analysis of changing acquisition practices across nine countries and implications for sustainability

The COVID-19 pandemic caused and still causes unprecedented disruptions in daily lives of billions of people globally. It affects practices and routines across all household consumption domains, including clothing consumption. Drawing on Social Practice Theory, this article explores and compares changes in clothing acquisition practices during COVID-19 across nine countries: the USA, the UK, Finland, Germany, Switzerland, Iran, Czech Republic, India, and Hong Kong SAR. Data was obtained through a standardized survey containing rated and open-ended questions, which were analyzed through descriptive quantitative analysis and inductive qualitative content analysis of open-ended questions. The results of this cross-country research indicate that all forms of fashion consumption, including more sustainable practices, have decreased during the pandemic. The most visible impacts have occurred in the material arrangements associated with fashion acquisition practices (e.g., closed physical shops, shipping disruptions, cancelled events, remote work, etc.). However, changes that result from these disruptions may be shorter-lived that changes that happened as a result of changing meanings associated with fashion consumption and its more sustainable forms and new competencies and skills acquired during the pandemic that could ensure more lasting practicing of more sustainable forms of fashion consumption

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations

Designing Products for the Circular Economy

Until recent years, apparel product design has been undertaken with very little reference to environmental sustainability. However, the legislative framework has increasingly constrained design decisions relating to the use of hazardous chemicals, especially with the advent of REACH regulations within the EU. Most companies now recognise a large number of chemical substances that are prohibited in the dyeing and finishing of textiles. This dominates thinking about design for the environment. The increasing adoption of environmental management systems has expanded the vision for initiatives promoting sustainability, including laundering and care. Principles are recognised for product design and development that lead to more sustainable goods and services. In some industries, regulations require producer to take responsibility for the disposal of products companies release to the market. This obligation has triggered thinking about design for disassembly and design for disposal. This development has accelerated the adoption of circular economy concepts. The EU has not implemented producer responsibility in apparel, although some companies have voluntarily championed circular economy initiatives. However, the business models of most apparel companies have nothing to say about end-of-life issues. This chapter is concerned with new product development processes that incorporate Design for Environment and Design for Disassembly and Disposal. As there are numerous technical issues to address, a team-based product development process has many advantages, whereby garment designers work alongside specialists from other disciplines. This process requires culture change to be embraced by most brand owners, and a departure from the practice of separating the design process from the product development process. In most cases, changes of this nature bring disruption to a globalised industrial sector. Case studies will be considered that illustrate the concepts developed in this chapter. In particular, the French experience of adopting producer responsibility for apparel goods is considered. The accredited organisation ECO TLC exhibits strength in the promotion of sustainability projects, but there is a fundamental weakness in that culture change in the design process of brand owners is hard to discern