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The aim of this study was developing and testing a new tool for measuring quality of life (QoL) in patients with osteoporosis who had experienced nonvertebral fractures (NVFXs). Two main phases were carried out. First, the tool was developed based on expert opinion through three focus groups. Second, the tool was tested with exploratory factor analysis and confirmatory factor analysis in a sample of 458 postmenopausal women. The reliability of the developed Quality of Life Osteoporosis Scale-Nonvertebral Fractures (QoLOS-NVFX) was measured using Cronbach's α, maximal reliability (MR), composite reliability (CR), and average variance extracted (AVE). The QoLOS-NVFX resulted in a unidimensional scale with 23 items and showed good reliability, with a Cronbach's α of 0.94, an MR of 0.96, a CR of 0.96, and an AVE of 0.70. The QoLOS-NVFX shows good psychometric properties and can be used to assess the impact of NVFX on QoL in osteoporotic women. Furthermore, it can be easily used in clinical practice and research.

Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T-cell co-stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL). Predictably, LIGHT-deficient (Tnfsf14-/- ) mice are protected from ovariectomy-dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag -/- Tnfsf14 -/- ) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Bacillus thuringiensis (Bt) è considerato un potenziale batterio entomopatogeno per la lotta al Rhynchophorus ferrugineus, coleottero da quarantena infestante le palme. In questo lavoro si considerano gli effetti dell’infezione di Bt in larve, maschi e femmine del punteruolo rosso. La patogenicità è stata valutata stimando la LD50 (Lethal Median Dose) e la LT50 (Lethal Median Time), il numero totale di emociti ed il tipo di emociti (Differential Haemocytes counts) ed inoltre l’espressione delle proteine Heat Shock Protein 70 (HSP70) negli emociti e nel cerebro. La mortalità di entrambi i sessi e delle larve aumentava all’aumentare della dose e del tempo di esposizione. Tuttavia le larve hanno mostrato una maggiore mortalità, quasi doppia di quella degli adulti, mentre i valori di LT50 erano superiori nelle femmine rispetto ai maschi e alle larve. Trattamenti con dosi sub letali di Bt inducevano un decremento nel numero di emociti sia per larve che per gli adulti. Nelle larve, tuttavia, vi era un incremento dei plasmatociti e un decremento di enociti e sferulociti. Nelle femmine invece diminuivano tutti i tipi di emociti mentre nei maschi diminuiva il numero di plasmatociti ed incrementava quello dei granulociti. La risposta fisiologica alla infezione da Bt è stata valutata anche mediante la modulazione delle HSP70 negli emociti, mostrando che già dopo 3 ore dall’ingestione di Bt, si poteva notare un incremento delle stesse. Nel cerebro il massimo picco di modulazione delle HSP70 si è registrato a 6 ore dall’ingestione. I risultati confermano che il Bt induce uno stato di patogenesi nel punteruolo rosso sia negli adulti che nelle larve già a poche ore dall’ingestione tuttavia gli effetti sono diversi come livello e tipo di risposta. Bacillus thuringiensisis considered a potential useful entomopathogen of Rhynchophorus ferrugineus(RPW), a quarantine pest that attacks the palm trees. We compare the effects of Bt in mature larvae, females and males. The pathogenicity activity of Bt was evaluated estimating: Median Lethal Dose (LD50), Median Lethal Time (LT50), and Total Haemocytes Count (THC) and Differential Haemocytes count (DHC), and finally the expression of the stress protein Heat Shock Protein 70 in the haemocytes and in the brains. RPW mortality exhibited a positive trend with the dosage and duration of exposure to Bt. The larvae were more susceptible than adults and the LD50 of females was even the double value of the one of larvae. Similarly, the LT50 value was higher for females than males and larvae. Treatment with sub-lethal dose of Bt induces a decrement in THC in larvae, females, and males. In treated larvae plasmatocytes decrease while oenocytes and spherulocytes increase. In treated females all type of haemocytes decrease, while in males the number of plasmatocytes decreases and the granulocytes increase. We also registered the stress answer directly on hemocytes, showing that already at 3, hours after eating Bt, it modulates the expression of the stress protein Hsp 70. This effect was also observed in the brain tissue at 6 hours after treatment. The results confirm that the Bt treatment induces a pathogenic state in RPW larvae and adult of both genders, that answer only after few hours from ingestion, however, the effects are different in magnitude and in type of target. The highlights can be useful to understand better the relationship pathogen-host and to implement the integrated control of phytophagous.

In this study, we investigated the relationship between sarcopenia (evaluated in term of fibers atrophy), vitamin d receptor protein expression and TaqI/Cdx2/FokI VDR genotypes in an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) patients. Muscle biopsies were fixed and investigated by both immunohistochemistry (vitamin d receptor expression) and transmission electron microscopy (satellite stem cells niches). Vitamin d receptor polymorphisms were studied on DNA extracted from muscle paraffin sections. For the first time, we reported that aging differently affects the VDR activation in OA and OP patients. In particular, while in OP patients we observed a significant reduction of VDR positive myonuclei with age, no "age effect" was observed in OA patients. The frequent activation of VDR could explain the lower number of atrophic fiber that we observed in OA patients respect to OP. From genetic point of view, we showed a putative association among polymorphisms FokI and Cdx2 of VDR gene, vitamin d receptor activation and the occurrence of sarcopenia. Altogether these data open new prospective for the prevention and cure of age-related muscle disorders.

The aim of this study was developing and testing a new tool for measuring quality of life (QoL) in patients with osteoporosis who had experienced nonvertebral fractures (NVFXs). Two main phases were carried out. First, the tool was developed based on expert opinion through three focus groups. Second, the tool was tested with exploratory factor analysis and confirmatory factor analysis in a sample of 458 postmenopausal women. The reliability of the developed Quality of Life Osteoporosis Scale-Nonvertebral Fractures (QoLOS-NVFX) was measured using Cronbach's α, maximal reliability (MR), composite reliability (CR), and average variance extracted (AVE). The QoLOS-NVFX resulted in a unidimensional scale with 23 items and showed good reliability, with a Cronbach's α of 0.94, an MR of 0.96, a CR of 0.96, and an AVE of 0.70. The QoLOS-NVFX shows good psychometric properties and can be used to assess the impact of NVFX on QoL in osteoporotic women. Furthermore, it can be easily used in clinical practice and research.

Sources Airguns and Waterguns are used in seismic exploration the marine seafloor for different purposes such as oil and gas search, or geological-geodynamic reconstruction. In this technique a bubble of compressed air is produced with a consequently production of loud sound wave penetrating the ocean floor. The impact of seismic Airguns was assessed in some cetaceans (Kyhn et al. 2019), fish species and invertebrate (Carroll et al. 2017), but we need to know more. In this study we evaluate the biochemical changes in sea urchin (Arbacia lixula) and sea cucumber (Holothuria tubulosa) exposed to a 20 minutes of watergun noise (1 pulse each 10 s) at a distance of 50 m. For each species 40 individuals were captured and caged in the sea in groups of 10. After four days of acclimation we started the experimental test that previewed these 4 samplings phases: T0-control group before the Watergun sound exposition; T1-post group soon after the end of sound exposition; T2-post group after 3 hour of exposition; T3- post group after 24 hour of exposition. Watergun pulse was characterized by measuring pressure (SM2U, Wildlife Acoustics) and particle speed (M20- 105, Geospectrum) in the three dimensions at the same position of the caged animals. Watergun pulses Power Spectral Density for pressure and particle speed showed respectively a peak of 122 dB re1μPa2/Hz at 850 Hz and a peak of 207 dB re(1nm/s)2 at 550 Hz for x component (direction parallel to the sea surface and forward the caged animals). The coelomatic fluid was extracted by each animal for the following successive analysis: total volume withdrawn, Total Hemocytes Counts (THC), total protein, phosphatase, esterase and peroxidase activity. In the sea urchin we observed significant differences in esterase (T0 < T2 and T3), and peroxidase (T0 < T2 and T3). Concerning sea cucumber we found significant differences for THC (T0 T2; T1 < T2). This is the first attempt to study the effects of a short loud low frequencies sound exposition in echinoderms species and results show that these animals reacted to the noise with an alteration of some coelomic fluid parameters indicators of stress.

Growing evidence has demonstrated that the extracts of different holothurian species exert beneficial effects on human health. Triple negative breast cancers (TNBC) are highly malignant tumors that present a poor prognosis due to the lack of effective targeted therapies. In the attempt to identify novel compounds that might counteract TNBC cell growth, we studied the effect of the exposure of the TNBC cell line MDA-MB231 to total and filtered aqueous extracts of the coelomic fluid obtained from the sea cucumber Holoturia tubulosa, a widespread species in the Mediterranean Sea. In particular, we examined cell viability and proliferative behaviour, cell cycle distribution, apoptosis, autophagy, and mitochondrial metabolic/cell redox state. The results obtained indicate that both total and fractionated extracts are potent inhibitors of TNBC cell viability and growth, acting through both an impairment of cell cycle progression and mitochondrial transmembrane potential and a stimulation of cellular autophagy, as demonstrated by the increase of the acidic vesicular organelles and of the intracellular protein markers beclin-1, and total LC3 and LC3-II upon early exposure to the preparations. Identification of the water-soluble bioactive component(s) present in the extract merit further investigation aiming to develop novel prevention and/or treatment agents efficacious against highly metastatic breast carcinomas.

Osteoporosis (OP) is a multifactorial disease influenced by genetic, epigenetic, and environmental factors. One of the main causes of the bone homeostasis alteration is inflammation resulting in excessive bone resorption. Long non-coding RNAs (lncRNAs), have a crucial role in regulating many important biological processes in bone, including inflammation. We designed our study to identify lncRNAs misregulated in osteoblast primary cultures derived from OP patients (n = 4), and controls (CTRs, n = 4) with the aim of predicting possible RNA and/or protein targets implicated in this multifactorial disease. We focused on 84 lncRNAs regulating the expression of pro-inflammatory and anti-inflammatory genes and miRNAs. In silico analysis was utilized to predict the interaction of lncRNAs with miRNAs, mRNAs, and proteins targets. Six lncRNAs were significantly down-regulated in OP patients compared to controls: CEP83-AS1, RP11-84C13.1, CTC-487M23.5, GAS5, NCBP2-AS2, and SDCBP2-AS1. Bioinformatic analyses identified HDCA2, PTX3, and FGF2 proteins as downstream targets of CTC-487M23.5, GAS5, and RP11-84C13.1 lncRNAs mediated by the interaction with miRNAs implicated in OP pathogenesis, including miR-21-5p. Altogether, these data open a new regulatory mechanism of gene expression in bone homeostasis and could direct the development of future therapeutic approaches.

Background: Osteoarthritis and osteoporosis are strongly coupled with alterations of muscles quality and fats metabolism. However, there are no studies for investigating possible differences between osteoporotic and osteoarthritic muscles. Understanding muscle-bone and muscle-cartilage interactions would be of high clinical value. Aim: Investigate potential microstructural and physiological differences between osteoporotic and osteoarthritic muscles by diffusion Nuclear Magnetic Resonance (NMR) imaging (diffusion MRI) and histological findings. Methods: Vastus-lateralis muscles excised from osteoporotic (n = 26, T Score < - 2.5, Kellgren-Lawrence - 2.5, Kellgren--Lawrence 3 and 4) age-matched women were investigated by NMR relaxometry, diffusion-tensor imaging (DTI) at 9.4 T, and histological techniques. Intramyocellular (IMCL) and extramyocellular (EMCL) lipid were quantified. The percentage and mean diameters of fibers I and II were evaluated. Relationship between mean diffusivity (MD), fractional anisotropy (FA), the DTI eigenvalues (?1, ?2, ?3), histological findings in muscles and clinical data (Kellgren-Lawrence and T score, age, menopausal age, body mass index) were studied. Pairwise comparisons between groups were made using one-way analysis of variance and correlation between variables was assessed with linear correlation analysis (Pearson's r coefficient). Results: Osteoporotic muscles showed higher MD, ?1,?2, ?3 compared to osteoarthritis ones. This is explainable with a significant higher density of IMCL droplets found inside the osteoarthritic muscles and a large amount of fibrotic tissue and IMCL infiltration between fibers, i.e. in endomysium and perimysium that lead to a more hindered diffusion. Furthermore, histological analysis suggests mitochondrial degeneration as the origin of the greatest amount of IMCL droplets in osteoarthritic muscles. Conclusion: This work highlights differences between muscles of osteoporotic and osteoarthritic subjects that can be quantified by NMR DTI investigations.

With increasing longevity in males, osteoporosis will become of increasing importance in both males and females. Men undergo gradual bone loss with aging, resulting in fragile bones. It is estimated that one in five men will suffer an osteoporotic fracture during their lifetime. The prognosis for men after a hip fracture is very grim. Many other factors result in secondary osteoporosis, including treatment for other diseases such as cancer and diabetes. Hip fracture is a common fracture, particularly in older female patients. However, about one-third of hip fractures occur in men. The causes underlying osteoporosis and susceptibility to falling differ between women and men, as do mortality rates; male patients appear to have higher standardized mortality ratios compared to female patients. The surgical treatment of the fractures of the upper extremity of the femur in the elderly is a challenge. The main problem is to conciliate the huge advancement of the biometrial technology with the incomplete knowledge of bone properties. After an initial low-trauma fracture, the absolute risk of subsequent fracture was similar for men and women. This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years.

Peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) is a transcription coactivator that interacts with a broad range of transcription factors involved in several biological responses. Here, we show that PGC1α plays a role in skeletal homeostasis since aged PGC1α-deficient mice (PGC1α−/−) display impaired bone structure. Micro-CT of the tibial mid-shaft showed a marked decrease of cortical thickness in PGC1α−/− (− 11.9%, p

This study examined the effects of lab-generated acoustic signals on the behaviour and biochemistry of Mediterranean mussels (Mytilus galloprovincialis). The experiment was carried out in a tank equipped with a video-recording system using six groups of five mussels exposed to five acoustic treatments (each treatment was replicated three times) for 30min. The acoustic signals, with a maximum sound pressure level of 150dB rms re 1μPa, differed in frequency range as follows: low (0.1–5kHz), mid-low (5–10kHz), mid (10–20kHz), mid-high (20–40kHz) and high (40–60kHz). The exposure to sweeps did not produce any significant changes in the mussels' behaviour. Conversely, the specimens exposed to the low frequency band treatment showed significantly higher values of the following biochemical stress parameters measured in their plasma and tissues: glucose, total proteins, total haemocyte number (THC), heat shock protein 70 (Hsp70) expression, and Acetylcholinesterase (AChE) activity. The responses observed in the mussels exposed to low frequency sweeps enable us to suppose a biological and ecological role for this sound, which contains the main frequencies produced by both shipping traffic and the acoustic emissions of fish.

Background Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. Methods Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. Results We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p

This study examined the effects of recorded boat noises on the behaviour and biochemistry of the common prawn ( Palaemon serratus ) in laboratory settings. The experiment was carried out in a tank equipped with a video-recording system using six groups (three control and three tested) of eight common prawns (48 animals in total). After habituation for 1 h, the behaviour of the prawns was monitored for 1 h. During the last 30 min, the animals in the test groups were exposed to noise resembling a marine area with high anthropogenic acoustic pollution. The exposure to noise produced significant changes in locomotor patterns, presence inside or outside a shelter, total protein concentrations in the haemolymph and brain, DNA integrity, and the expression protein levels of HSP 27 and 70 in brain tissues, revealing a stressful effect of noise on this crustacean species. This study clearly reveals that invertebrates are likely to be susceptible to acoustic stimuli from boat's noise and that they are potential valuable targets for further and detailed investigations into the effects of the anthropogenic noise pollution.

This study examined the effects of boat noise pollution on the stress indices of gilthead sea bream (Sparus aurata, Linnaeus 1758). To assess the stress response in these fish, biometric values and plasma parameters such as ACTH, cortisol, glucose, lactate, haematocrit, Hsp70, total protein, cholesterol, triglycerides and osmolarity were analysed. After acclimatization of the animals, the experiment was carried out in a tank fitted with underwater speakers where the fish were exposed to sound treatments (in duplicate) consisting of: 10days of no sound (control treatment; the animals were only exposed to the experimental tank’s background noise) and 10days of noise derived from original recordings of motor boats, including recreational boats, hydrofoil, fishing boat and ferry boat (vessel noise treatment). The exposure to noise produced significant variations in almost all the plasma parameters assessed, but no differences were observed in weights and fork lengths. A PERMANOVA analysis highlighted significantly increased values (p&nbsp

Irisin is a new peptide produced mainly by the skeletal muscle playing an important role both in glucose/energy homeostasis and bone metabolism. Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. We aimed to evaluate irisin levels in TD1M children and their correlation with bone metabolism and glycaemic control.Ninety-six T1DM subjects (12.2 ± 4 years), 56 on multiple daily injections (MDI), 40 on continuous subcutaneous insulin infusion (CSII), and 34 controls were included in the study. Irisin and bone remodeling markers were quantified in sera from patients and controls. Bone mineral density (BMD) was evaluated by QUS.Increased irisin levels were found in T1DM patients respect to controls (p 0.001). With adjustment for age, irisin levels significantly correlated negatively with HbA1c% (r = -0.105, p 0.001), years of diabetes (r = -0.07, p 0.04), 25(OH)-Vitamin D (r = -0.175, p 0.0001), and positively with BTT-Z-score (r = 0.088, p = 0.016), and osteocalcin (r = 0.059, p 0.04). We detected the highest levels of irisin in CSII patients compared to MDI and controls (p 0.001 and p 0.007 respectively).We demonstrated high irisin levels in T1DM children and the association of highest irisin amounts to a better glycaemic control and bone health in TDM1 subjects on CSII.

Marine crustaceans are influenced by numerous environmental factors. Environmental stress from pollutants seems to affect their metabolism, growth, moulting, survival, and immune defence. Recently, it has become clear that there is an impact of the global increase in sea noise levels due to shipping traffic on crustacean welfare. Considering the ecological and commercial importance of the European spiny lobster (Palinurus elephas (Fabricius, 1787)) in most parts of the Mediterranean coastal area, in the present study we investigated whether shipping noise pollution contribute to changing the immune parameters of stress in the European spiny lobster. The animals were exposed to a mix of noises produced by different typologies of the boat played back in a tank, and the values of cellular and humeral parameters were evaluated. Total haemocyte count (THC), haemolymphatic protein concentration, phenoloxidase (PO) activity in cell-free haemolymph, and heat shock protein 27 (Hsp27) expression in haemocyte lysate were considered potential biomarkers of stress. THC and PO activity decreased significantly, whereas total protein and Hsp27 expression increased significantly. Overall, the results demonstrate that the stressful conditions investigated in this study affect both cellular and biochemical parameters in the European spiny lobster.

The immune system of marine invertebrates, in particular that of holothurians, still requires further study. Our research showed that coelomocyte cells contained in the coelomic fluid of the sea cucumber, Holothuria tubulosa, are able to lyse, in vitro, red blood cells in rabbits and sheep. A plaque-forming assay showed spherule cells to be the effector cells, able to release cytotoxic molecules after xenogenic cell contact. The coelomocyte lysate supernatant, analysed by polyacrylamide gel electrophoresis overlay technique, using rabbit and sheep erythrocytes, showed two different haemolytic protein patterns: one calcium dependent and the other calcium independent. The fractions of each pattern were resolved on a polyacrylamide gel and calcium-dependent and independent coelomocyte lysate patterns were compared.

In the last few decades, technological developments and the widespread rise of anthropic activities have increased the exposure of organisms to noise pollution, thus evoking great interest in its biological effects, particularly on the immune system. The aim of the present work was to investigate some of the biochemical parameters in the blood of Chromis chromis (Linnaeus, 1758) following in vivo exposure to noise levels of 200 and 300 Hz. Our results revealed that, compared to the control specimens, the fish exposed to noise had significantly increased levels of stress biomarkers such as glucose, lactate and total proteins in plasma, as well as a rise in the expression of heat shock protein 70 (HSP70).

Currently, an increasing number of younger patients undergo total hip arthroplasty surgery. This has led to a minimal invasive approach and the use of short, bone preserving, femoral stems. In this study, we sought to evaluate osseointegration of the Fitmore stem (Zimmer, Inc; Warsaw, IN) during the first 12 mo after surgery, which reflects the biological phenomenon of osseointegration with radiographic evaluation and bone densitometry (dual-energy X-ray absorptiometry). We evaluated 33 patients (mean age 62.3) using dual-energy X-ray absorptiometry scan around the stem and X-ray. Moreover, we studied functional recovery using the Harris Hip Score, timed up and go test, and a quality of life form (SF-36), during the follow-up period. At 12 mo, we observed an increased periprosthetic bone mineral density in region of interest 1 (1.7%) and region of interest 7 (8.3%), where there is usually a greater amount of bone resorption. Also Harris Hip Score, timed up and go test, and SF-36 showed an improvement of clinical conditions of all patients. We also used a control group with a standard stem implanted. Because this is the first study correlating osseointegration and clinical outcome of the Fitmore stem, further clinical studies will be necessary to confirm good/positive results and a long stable fixation.

Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide [PTH (1–34)], is a drug with a proven anabolic action on the bone, effective in preventing vertebral and non-vertebral fragility fractures. Recent publications have investigated in great detail the TPTD action on the cortical bone, highlighting the increased strength in the critical zone of the hip with high risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In November 2002, TPTD was approved by the FDA for use in post-menopausal women and men with osteoporosis at high risk of fracture and in patients with glucocorticoid-induced osteoporosis and, since then, has been used to treat more than 1 million patients worldwide (J Bone Miner Res 27(12):2429-2437, 2012). The unchanged safety profile and the well-known mechanism of action of this drug have led doctors to explore the use of TPTD in other conditions such as delayed fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports that have resulted from these studies are helping to hypothesize a new perspective on the wider use of this drug, but warrant further clinical investigation to consolidate these results.

An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future. © 2013 Springer International Publishing Switzerland. An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future. © 2013 Springer International Publishing Switzerland.

Recently has been highlighted that topological properties of trabecular microstructure and microarchitectural deterioration of bone tissue are important factors in determining bone strength and its resistance to fracture. Magnetic resonance (MR) techniques allow investigation of both trabecular networks and bone marrow providing precious information on the physiological and functional changes associated with osteoporosis. The aim of the present work was to show the ability of MR micro-imaging investigation to describe cancellous bone status as related to its trabecular bone density and quality. For this purpose we measured in vitro, at high magnetic field (9.4T), the MR parameter $$ T_{2}^{\text{APP}} $$ of cancellous bone samples extracted from femoral head of osteoporotic and osteoarthritic women as classified by dual energy X ray absorptiometry bone mineral density. We assessed $$ T_{2}^{\text{APP}} $$ associations with T-scores, Harris Hip score and age. Results show that $$ T_{2}^{\text{APP}} $$ is able to discriminate between osteoarthritic and osteoporotic bone samples. Moreover, the micro-imaging $$ T_{2}^{\text{APP}} $$ investigation has highlighted a different trabecular bone density in cancellous bone specimens of osteoarthritic patients only, which is higher in subchondral compared to metaphysis section of each sample.

Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status.

Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship.The sample was made of 101 postmenopausal women, 49 with MDD and 52 age-matched healthy volunteers. Structured clinical interview and Beck Depression Inventory (BDI) were performed to assesse MDD. AS was evaluated using the Relationship Questionnaire (RQ). BMD was measured by dual energy X-ray absorptiometry.The univariate analysis showed that women with MDD had lower BMD values as compared to healthy volunteers. In the regression models MDD diagnosis and BDI score were not significant predictors of low BMD. The “preoccupied” pattern of insecure AS was a significant, independent predictor of decreased BMD in all skeletal sites: lumbar spine (p=0.008), femoral neck (p=0.011), total hip (p=0.002).This is the first study exploring the relationship between AS, MDD and BMD. Our results support the link between MDD and low BMD. We found that insecure AS was a risk factor for decreased BMD, regardless of depression. Insecure AS may play a role in the relationship between MDD and BMD or may constitute a risk factor itself. Therapeutic interventions focused on AS could improve psychiatric disorders and physical diseases related to low BMD.

Submersible sea-cages represent an alternative method to standard surface-based cages, and could help solve several production problems that exist in surface-based farming, such as heavy storms, algal and jellyfish blooms and attacks by predators. In this study, we investigated growth, haematological, biochemical and immunological parameters of European sea bass ( Dicentrarchus labrax ) farmed in surface and submersible cages, to compare the physiological status under different rearing conditions. In addition, we evaluated the use of erythrocyte HSP70 levels as a biomarker of fish welfare. The study was conducted in two submerged and two surface cages filled with D. labrax . No significant differences were observed in the growth rate and the relative condition factor between the two groups. Significantly higher levels of serum cortisol, haematocrit plasma glucose and total plasma proteins were measured in surface-based cages. Conversely, fish in submerged cages showed higher haemolytic activity and lysozyme levels in both mucus and kidney than surface reared sea bass. Results obtained in this study indicate that submergence could be a favorable condition for sea bass farming, suggesting mariculture in submerged net cages as a promising system that allows producers to minimize stress (included that from predation by fish-eating birds) and therefore favor animal welfare.

Since glucocorticoids have a role in maintaining the homeostatic status in fish, in the present paper mRNA expression (in situ hybridization) and tissue immunohistochemical localization of a glucocorticoid receptor (DlGR1) in several Dicentrarchus labrax organs are reported. Riboprobe and specific antibodies were prepared by using the DlGR1 that has been previously cloned and sequenced from peritoneal cavity leukocytes. Both mRNA and receptor were identified in head kidney, spleen, gills, intestine, heart and liver tissues. The functional roles of DlGR1 localization are discussed.

To assess the effects of a moderately hypoenergetic Mediterranean diet (MHMD) and exercise program on body cell mass (BCM) and cardiovascular disease risk factors in obese women.Forty-seven obese women, 39.7+/-13.2 years of age, with a body mass index (BMI)=30.7+/-6.0 kg/m(2), completed the study. The following were measured at baseline, 2 and 4 months: BCM, BCM index (BCMI), body weight, BMI, fat-free mass (FFM), fat mass (FM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) using bioelectrical impedance analysis; fasting blood glucose (FBG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations; systolic (SBP) and diastolic (DBP) blood pressure.Body weight, BMI, FM, TC and TG significantly decreased (P0.001; P0.002 (TG)) at 2 and 4 months. FFM, TBW, ECW, FBG and DBP significantly decreased at 2 months (P0.05 (FFM); P0.001). LDL-C significantly decreased (P0.001), while HDL-C significantly increased (P0.002) at 4 months. BCM, BCMI, ICW and SBP remained stable over time.BCM was preserved and cardiovascular disease risk factors improved in obese women placed on a MHMD and exercise program for 4 months.

This study examined the effects of boat noise on the behavioural and biochemical parameters of the Mediterranean spiny lobster (Palinurus elephas).The experiment was conducted in a tank equipped with a video and audio recording system. 18 experimental trials, assigned to boat noise and control conditions, were performed using lobsters in single and group of 4 specimens. After a 1. h habituation period, we audio- and video-recorded the lobsters for 1. h. During the experimental phase, the animals assigned to the boat groups were exposed to boat noise pollution (a random sequence of boat noises). Exposure to the noise produced significant variations in locomotor behaviours and haemolymphatic parameters. Our results indicate that the lobsters exposed to boat noises increased significantly their locomotor activities and haemolymphatic bioindicator of stressful conditions such as glucose, total proteins, Hsp70 expression and THC when tested both singly and in groups. © 2014 Elsevier Ltd.

Wound repair is a key event in the regeneration mechanisms of echinoderms. We studied, at the behavioural, cellular and molecular levels, the wound healing processes in Holothuria tubulosa after injuries to the body wall. The experiments were performed for periods of up to 72 h, and various coelomocyte counts, as well as the expression of heat shock proteins (HS27, HSP70 and HSP90), were recorded. Dermal wound healing was nearly complete within 72 h. In the early stages, we observed the injured animals twisting their bodies to keep their injuries on the surface of the water for the extrusion of the buccal pedicles. At the cellular level, we found time-dependent variations in the circulating coelomocyte counts. After injury, in particular, we observed a significant increase in spherule cells at 2.5 h post-injury. Using the western blot method, we observed and reported that the wounds produced, compared with controls, a significant increase in HSP27 and HSP70 expression in coelomocytes, whereas HSP70 was increased in scar tissue and HSP90 was increased only in cell-free coelomic fluid. These results highlight that the wounds were responsible for the stress condition with the induction of cellular and biochemical responses.

Fracture healing is a complex event that involves the coordination of different processes: initial inflammatory response, soft and hard callus formation, initial bony union and bone remodeling. This well-orchestrated series of biological events follows a specific temporal and spatial sequence that can be affected by biological factors, such as age and bone quality. There is some evidence that increased age is a considerable factor in the inhibition of fracture repair in human subjects. During aging there is an accumulation of damage that depends on the activation of inflammation processes and on changes in the circulating levels of inflammatory cytokines. In addition to the physiological slow down in the repair process, other conditions such as multiple comorbidities leading to polymedication are a frequent occurrence in elderly patients and can have an influence on this process. A further factor that affects bone metabolism is nutrition: bone quality, fragility fractures risk and fracture healing process are all influenced by the nutritional status. This review provides a summary of the immunological aspects of physiological fracture healing and of those nutritional factors which might play an important role in this process.

Sulfamethoxazole (SMZ) is one of the most widely employed sulfonamides. Because of the widespread use of SMZ, a considerable amount is indeed expected to be introduced into the environment. The cytotoxicity of SMZ relies mainly on arylhydroxylamine metabolites (S-NOH) of SMZ and it is associated with the production of reactive oxygen species (ROS). There is limited information about the toxic potential of SMZ at the cellular and molecular levels, especially in aquatic and/or non-target organisms. In the present study, the red swamp crayfish (Procambarus clarkii), being tolerant to extreme environmental conditions and resistant to disease, was used as a model organism to profile the molecular and physiological response to SMZ. Haemolymphatic-immunological parameters such as glucose serum levels and total haemocyte counts were altered; moreover, a significant increase in Hsp70 plasma levels was detected for the first time. Variations at the transcriptional level of proinflammatory genes (cyclooxygenase-1, COX 1, and cyclooxygenase-2, COX 2), antioxidant enzymes (glutathione-S-transferase, GST and manganese superoxide dismutase MnSOD), stress response and Fenton reaction inhibitor genes (heat-shock protein 70 HSP70, metallothionein, MT and ferritin, FT) were evaluated, and alterations in the canonical gene expression patterns emerged. Considering these results, specific mechanisms involved in maintaining physiological homeostasis and adaptation in response to perturbations are suggested. (C) 2014 Elsevier Inc. All rights reserved.

The immunotoxic effects of heavy metals on blood leukocytes of sea bass (Dicentrarchus labrax) were examined. The cells, separated by a discontinuous Percoll-gradients, were exposed in vitro to various sublethal concentrations of cadmium and copper (10(-7) M, 10(-5) M, and 10(-3) M) and their immunotoxic effect was then evaluated by measuring neutral red uptake, MU assay, DNA fragmentation and Hsp70 gene expression. First of all, we demonstrated that the cells treated in vitro could incorporate Cd and Cu. A relationship between heavy metal exposure and dose-time-dependent alterations in responses of leukocytes from blood was found for both metals, but copper was more immunotoxic than cadmium in all assays performed. A significant reduction in the cells' ability to uptake neutral red and viability by MU assay was recorded, indicating that both cadmium and copper could change the membrane permeability, inducing cellular apoptosis when the concentration of metals reached 10(-3) M. The apoptotic effect may also explain the high level of cytotoxicity found when the leukocytes were exposed to higher concentration of metals. These results demonstrated that toxic effect of copper and cadmium affect on the mechanisms of cell-mediated immunity reducing the immune defences of the organism. (C) 2014 Elsevier Inc. All rights reserved.

Aim: To evaluate the hospitalization rate of femoral neck fractures in the elderly Italian population over ten years. Methods: We analyzed national hospitalizations records collected at central level by the Ministry of Health from 2000 to 2009. Age- and sex-specific rates of fractures occurred at femoral neck in people ≥ 65 years old. We performed a sub-analysis over a three-year period (2007-2009), presenting data per five-year age groups, in order to evaluate the incidence of the hip fracture in the oldest population. Results: We estimated a total of 839008 hospitalizations due to femoral neck fractures between 2000 and 2009 in people ≥ 65, with an overall increase of 29.8% over 10 years. The incidence per 10000 inhabitants remarkably increased in people ≥ 75, passing from 158.5 to 166.8 (+5.2%) and from 72.6 to 77.5 (+6.8%) over the ten-year period in women and men, respectively. The oldest age group (people > 85 years old) accounted for more than 42% of total hospital admissions in 2009 (n = 39000), despite representing only 2.5% of the Italian population. Particularly, women aged > 85 accounted for 30.8% of total fractures, although they represented just 1.8% of the general population. The results of this analysis indicate that the incidence of hip fractures progressively increased from 2000 to 2009, but a reduction can be observed for the first time in women ≤ 75 (-7.9% between 2004 and 2009). Conclusion: Incidence of hip fractures in Italy are continuously increasing, although women aged 65-74 years old started showing a decreasing trend. © 2014 Baishideng Publishing Group Inc.

A 20-year-old man sustained an open medial dislocation of the ankle without an associated fracture after a low-energy inversion injury. Prompt debridement and reduction with primary wound closure of the skin were performed without suture of the capsule. Immobilisation in a non-weight-bearing cast for 30 days followed by ankle bracing for two weeks and subsequent physiotherapy, produced full functional recovery by three months. At follow-up at one year there was a full range of pain-free movement, although the radiographs and MR scan showed early post-traumatic degenerative change at the medial aspect of the tibiotalar and the calcaneocuboid joints.