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Sustainable bioeconomy is a promising pathway towards the transition to a circular and climate-neutral economy. The valorization of biowaste is a key player in this direction. This paper presents the design and development of the AgriPLaCE Platform, which aims to promote synergies that enable the utilization of biowaste from the fruit and vegetable supply chain. The platform consists of the AgriPLaCE Waste Management Database, which provides users with an extended list of potential utilization methods for various types of fruit and vegetable biowaste streams, and the AgriPLaCE Synergies Tool, which facilitates synergies between different actors involved in the biowaste-to-resource value chain from agricultural waste production to waste treatment and new valuable products’ exploitation. Initially, the conceptual design of both tools took place based on analysis of user needs and services alongside the system architecture. Following this, the AgriPLaCE Platform was developed with the implementation of all the necessary subsystems. The results of the platform’s implementation demonstrated its potential to generate multiple collaborations and synergies while users can also deepen their knowledge about alternative and emerging treatment technologies and valuable products from a wide range of fruit and vegetable biowaste streams.

Kyriakos Souliotis,1,2 Christina Golna,2 Christina Poimenidou,2 Tatiana Drakopoulou,3 Memi Tsekoura,2 Damon Willems,4 Vasileios Kountouris,5 Polyzois Makras6 1Department of Social and Education Policy, University of Peloponnese, Corinth, Greece; 2Research Department, Health Policy Institute, Maroussi, Greece; 3Greek Bone Health Association “Petalouda”, Perama, Greece; 4Market Access Lead, UCB Pharma, Brussels, Belgium; 5External Engagement Lead, UCB Pharma, Athens, Greece; 6Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, GreeceCorrespondence: Kyriakos Souliotis, Email info@ksouliotis.grObjective: The objectives of this study were to elicit self-reported health status, quantify osteoporosis-related burden, and understand preferences for treatment attributes among postmenopausal women with severe osteoporosis in Greece.Methods: Postmenopausal women with self-reported severe osteoporosis, defined as having suffered at least one osteoporotic fracture and reporting a T-score of ≤− 2.5, were asked to evaluate their health status, osteoporosis management, and disease-related physical, emotional, and financial burden. Participants were also asked to rate a series of treatment attributes and state their preference for unlabeled anabolic treatments, based on scenarios describing key treatment characteristics.Results: Approximately one third (31%) of the 186 participants who responded to the survey in full had been living with severe osteoporosis for more than 10 years. Three quarters of participants (72%) considered their overall quality of life (QoL) to be worse than it had been 10 years prior, and the vast majority (89%) attributed this deterioration to osteoporosis. Direct, out of pocket, disease-related costs of at least € 100 per month were reported by 86% of participants. Patients attached the greatest value to a treatment that would decrease probability of future fractures, followed by increase in bone density, safety, and mode and frequency of administration. When asked to select their preferred treatment scenario between two anabolic treatments, 70% of participants opted for the scenario that shared treatment characteristics with romosozumab over a scenario that shared treatment characteristics with teriparatide.Conclusion: Our study revealed that osteoporosis placed a considerable burden on QoL for postmenopausal women with severe osteoporosis in Greece. Patients reported valuing treatment efficacy, measured through reduction in future fractures and increase in bone density, and safety, as key treatment attributes.Keywords: osteoporosis, patient preference, burden of disease, quality of life

Introduction: We aimed to compare annual changes in the bone mineral density (BMD) at the lumbar spine (LS) and the femoral neck (FN) in males with HIV-associated osteoporosis treated with either zoledronate (ZOL) or denosumab (Dmab). Methods: In this open label, 12-month, prospective, multicenter, cohort study, 23 male people living with HIV (PLWH) under antiretroviral therapy (ART) with low BMD were administered either a single iv infusion of ZOL 5 mg (n = 10) or Dmab 60 mg sc injections biannually (n = 13). Fourteen age-matched male PLWH with normal BMD served as controls. BMD was measured at baseline and at 12 months. Results: LS-BMD increased within both treatment groups at 12 months (ZOL 5.43% ± 3.60%, p = 0.001; Dmab 5.76% ± 3.44%, p

ABSTRACT We investigated the expression profile of selected microRNAs (miRs) in serum and tissue samples from patients with sporadic parathyroid adenomas (sPAs). This was a prospective, controlled cohort study. Forty patients with sPAs who had undergone parathyroidectomy (PTX) were included. MiR extraction was performed from (i) 40 formalin‐fixed paraffin‐embedded samples (FFPEs) of sPAs, (ii) 10 FFPEs of normal parathyroid tissue (NPT), (iii) serum samples of the 40 patients with sPAs (t1 = baseline; t2 = 2 months post‐PTX), and (vi) serum samples of 10 healthy individuals (controls; t1 = baseline and t2 = 2 months later). Ten miRs were selected based on their interaction with genes related to parathyroid tumorigenesis (miR‐17‐5p, miR‐24‐3p, miR‐29b‐3p, miR‐31‐5p, miR‐135b‐5p, miR‐186‐5p, miR‐195‐5p, miR‐330‐3p, miR‐483‐3p, and miR‐877‐5p). At tissue level, the relative expression of miR‐17‐5p, miR‐31‐5p, miR‐135b‐5p, miR‐186‐5p, and miR‐330‐3p was significantly decreased (fold change [FC]: 0.17, FC: 0.03, FC: 0.01, FC: 0.10, FC: 0.10, respectively; all p values

Denosumab discontinuation has been associated with increased risk of rebound-associated multiple vertebral fractures. We report the cases of three patients, two females and one male, who had manifested rebound-associated vertebral fractures after denosumab discontinuation and sustained new vertebral fractures a few months later. Two of the patients had been previously treated with bisphosphonates. Patients discontinued denosumab after 2 to 8 years of treatment. One of the female patients was receiving prednisolone 7.5 mg daily for an unspecified connective tissue disorder and the male patient methylprednisolone 8 mg daily for dermatomyositis. We hypothesize that rebound-associated multiple vertebral fractures after denosumab discontinuation may occur, at least in some cases, sequentially instead of simultaneously. Our cases further underpin the need for prompt initiation of potent antiresorptives in patients who sustained rebound-associated vertebral fractures, in order to prevent not only bone loss but also a second round of fractures.

Abstract. Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). We prospectively evaluated bone remodeling pre- and post-chemotherapy in 61 patients with newly diagnosed NHL. First-line chemotherapy resulted in high bone turnover, which led to increased bone loss and reduced bone mineral density (BMD) of lumbar spine (L1-L4) and femur neck (FN). The reduction of L1-L4 and FN BMD post-chemo was more profound in males and in older patients (>55 years). Patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 and FN BMD as compared to 6 cycles. The administration of chemotherapy also resulted in a dramatic increase of bone resorption markers (CTX and TRACP-5b), bone formation markers, (bALP and Osteocalcin) and of osteoblast regulator Dickkopf-1. During study period, one patient had a pathological fracture in his right FN.

Individuals consistently report preferring humour in a romantic partner; but it is unclear why. The 'fitness indictor hypothesis' proposes that attraction to humour evolved because it is an indicator of genetic fitness. Studies testing predictions from this hypothesis, mostly based on stated preferences regarding a hypothetical ideal partner or on artificial tasks or scenarios, have so far yielded conflicting evidence. Here, we assessed a sample of 554 participants' (291 women) stated preferences for various traits including humour production and receptiveness, and their revealed preferences for the same traits through speed dates (i.e. a naturalistic, face-to-face setting). Dates were audio-recorded for a subset of 350 participants (188 women), enabling additional assessment of revealed preferences based on an objective measure of humour in the form of laughter frequency. We tested the predictions that 1) humour is an attractive trait, and 2) men are more attracted to humour receptivity compared to women, and women are more attracted to humour production compared to men. Stated preferences from men and women largely replicated those found in the existing literature and are consistent with the fitness indicator hypothesis. Results from revealed preferences found a main effect of funniness on ratings of overall partner attractiveness, but there was no significant effect of laughter on attractiveness. Revealed preferences, using both funniness ratings and laughter, also found no main effect of humour receptivity on overall attractiveness. Finally, we observed no sex differences in the effects of humour production and humour receptivity, as measured by both funniness ratings and laughter, on ratings of overall attractiveness. [ABSTRACT FROM AUTHOR]

The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP−) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV−), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower (p < 0.001) while the expression of miRNA-24-2-5p was significantly higher (p = 0.030) in HIV+/OP+ compared to HIV+/OP−. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.

The pathophysiology of chronic kidney disease–mineral and bone disorder (CKD-MBD) is complex and multifactorial. Recent studies have identified a link between microRNAs (miRNAs) and bone loss. In this study, we investigated the expression of miRNAs in CKD-MBD. In this case-control study, we included thirty patients with CKD-MBD (cases) and 30 age- and gender-matched healthy individuals (controls). Bone mineral density (BMD) and trabecular bone score (TBS) evaluation was performed with dual X-ray absorptiometry. The selected panel of miRNAs included: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3; hsa-miRNA-124-3p; hsa-miRNA-2861. The majority of cases had low BMD values. The relative expression of miRNA-21-5p was 15 times lower [fold regulation (FR): −14.7 ± 8.1, p = 0.034), miRNA-124-3p, 6 times lower (FR: −5.9 ± 4, p = 0.005), and miRNA-23a-3p, 4 times lower (FR: −3.8 ± 2.0, p = 0.036) in cases compared to controls. MiRNA-23a-3p was significantly and inversely correlated with TBS, adjusted for calcium metabolism and BMD values (beta = −0.221, p = 0.003, 95% CI −0.360, −0,081) in cases. In a receiver operating characteristic (ROC) analysis, expression of miRNA-124-3p demonstrated 78% sensitivity and 83% specificity in identifying CKD patents with osteoporosis. Serum expression of miRNAs related to osteoblasts (miRNA-23a-3p) and osteoclasts (miRNA-21-5p, miRNA-124-3p) is significantly altered in patients with CKD-MBD.

Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas.

Langerhans cell histiocytosis (LCH) is a rare disease of not well-defined etiology that involves immune cell activation and frequently affects the skeleton. Bone involvement in LCH usually presents in the form of osteolytic lesions along with low bone mineral density. Various molecules involved in bone metabolism are implicated in the pathogenesis of LCH or may be affected during the course of the disease, including interleukins (ILs), tumor necrosis factor α, receptor activator of NF-κB (RANK) and its soluble ligand RANKL, osteoprotegerin (OPG), periostin and sclerostin. Among them IL-17A, periostin and RANKL have been proposed as potential serum biomarkers for LCH, particularly as the interaction between RANK, RANKL and OPG not only regulates bone homeostasis through its effects on the osteoclasts but also affects the activation and survival of immune cells. Significant changes in circulating and lesional RANKL levels have been observed in LCH patients irrespective of bone involvement. Standard LCH management includes local or systematic administration of corticosteroids and chemotherapy. Given the implication of RANK, RANKL and OPG in the pathogenesis of the disease and the osteolytic nature of bone lesions, agents aiming at inhibiting the RANKL pathway and/or osteoclastic activation, such as bisphosphonates and denosumab, may have a role in the therapeutic approach of LCH although further clinical investigation is warranted.

Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series. Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

Athanasios D Anastasilakis,1 Konstantinos A Toulis,1 Stergios A Polyzos,2 Chrysostomos D Anastasilakis,3 Polyzois Makras41Department of Endocrinology, 424 General Military Hospital, 2Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, 3Department of Pharmacology, 424 General Military Hospital, Thessaloniki; 4Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, GreeceAbstract: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised.Keywords: adverse event, denosumab, efficacy, fracture, osteoporosis, safety