Determination and investigation of defect domains in multi-shape monolayer tungsten disulfide.

Single-layer tungsten disulfide (WS2) is among the most widely investigated two-dimensional materials. Synthesizing it over large areas would enable the exploitation of its appealing optical and electronic properties in industrial applications. However, defects of different nature, concentration and distribution profoundly affect the optical as well as the electronic properties of this crystal. Controlling the defect density distribution can be an effective way to tailor the local dielectric environment and therefore the electronic properties of the system. In this work we investigate the defects in single-layer WS2, grown in different shapes by liquid phase chemical vapor deposition, where the concentration of certain defect species can be controlled by the growth conditions. The properties of the material are surveyed by means of optical spectroscopy, photoelectron spectroscopy and Kelvin probe force microscopy. We determine the chemical nature of the defects and study their influence on the optical and electronic properties of WS2. This work contributes to the understanding of the microscopic nature of the intrinsic defects in WS2, helping the development of defect-based technologies which rely on the control and engineering of defects in dielectric 2D crystals.

Heart transplantation and biomarkers: a review about their usefulness in clinical practice.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Analysis of the risk of a secondary displacement in conservati- vely treated paediatric distal radius metaphyseal fractures. A multicentric study.

OBJECTIVES: Distal radius fractures represent one of the most fre-quent injuries in children. The treatment of choice is a closed reduction followed by immobilisation in plaster cast; the immediate recourse to osteosynthesis with Kirschner wires is only reserved for certain cases. The displacement rate reported in the literature is 21-39%. The aim of this study is to retrospectively evaluate the risk factors for a secondary displacement of metaphyseal radius fractures in a paediatric population treated in three different centres. MATERIALS AND METHODS: The initial treatment for all 360 patients examined was a closed reduction under general anaesthesia and im-mobilisation in an above elbow cast for 4 weeks. The pre-operative displacement, residual post-reduction displacement and possible di-splacement at 7 and 14 days of follow-up were all assessed clinically and radiographically. RESULTS: A loss of reduction was reported in 102 cases; 51 under-went an additional reduction procedure - some followed by osteo-synthesis - while in the remaining 51 cases, the loss of reduction was acceptable in relation to the expectation of remodelling. The most statistically significant variable for the occurrence of a secondary displacement is a severe primary displacement. The association with the ulna fracture is not significantly correlated. The quality of the plaster cast is important for maintaining the reduction. There are a few things to consider as indicators for a second procedure: age, time elapsed from moment of fracture, fracture site and the absence of an acceptable reduction. CONCLUSIONS: In our experience, a reduction followed by osteo-synthesis with Kirschner wires should be considered the treatment of choice in fractures with a high risk of secondary displacement, namely those with severe initial displacement or unsatisfactory reduction.

Prospects on the Potential In Vitro Regenerative Features of Mechanically Treated-Adipose Tissue for Osteoarthritis Care.

Gathering a better grasp on the adipose stromal vascular fraction (SVF) is demanding among clinicians for osteoarthritis (OA) care because of its promising but multifaceted clinical outcomes. The aim of this preclinical in vitro study was to test whether the mechanical approach with Hy-Tissue SVF system, a class IIa CE marked device of adipose tissue micro-fragmentation, influences the biological features and functions of SVF. We compared mechanical generated-SVF (mSVF) with the enzymatic generated-SVF (eSVF) by testing cell survival, phenotype, differentiation, and paracrine properties using ELISA assays. Both adipose SVF showed 80% viable cells and enrichment for CD-44 marker. The mSVF product preserved the functions of cell populations within the adipose tissue; however, it displayed lowered nucleated cell recovery and CFU-F than eSVF. As for multipotency, mSVF and eSVF showed similar differentiation commitment for osteochondral lineages. Both adipose SVF exhibited an increased release of VEGF, HGF, IGF-1 and PDGF-bb, involved in pathways mediating osteochondral repair and cell migration. Both mSVF and eSVF also displayed high release for the anti-inflammatory cytokine IL-10. After in vitro culture, supernatants from both mSVF and eSVF groups showed a low release of cytokines except for IL-10, thereby giving evidence of functional changes after culture expansion. In this study, mSVF showed active cell populations in the adipose tissue comparable to eSVF with excellent survival, differentiation and paracrine properties under a new mechanical adipose tissue micro-fragmentation system; thereby suggesting its potential use as a minimally invasive technique for OA treatment.

Spinal fusion procedures in the adult and young population: a systematic review on allogenic bone and synthetic grafts when compared to autologous bone.

This systematic review aims to compare clinical evidences related to autologous iliac crest bone graft (ICBG) and non-ICBG (local bone) with allografts and synthetic grafts for spinal fusion procedures in adult and young patients. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials) to identify clinical studies in the last 10 years. The initial search retrieved 1085 studies, of which 24 were recognized eligible for the review. Twelve studies (4 RCTs, 5 prospective, 3 retrospective) were focused on lumbar spine, 9 (2 RCTs, 2 prospective, 4 retrospective, 1 case-series) on cervical spine and 3 (1 RCT, 2 retrospective) on spinal fusion procedures in young patients. Calcium phosphate ceramics, allografts, bioglasses, composites and polymers have been clinically investigated as substitutes of autologous bone in spinal fusion procedures. Of the 24 studies included in this review, only 1 RCT on cervical spine was classified with high level of evidence (Class I) and showed low risk of bias. This RCT demonstrated the safety and efficacy of the proposed treatment, a composite bone substitute, that results in similar and on some metrics superior outcomes compared with local autograft bone. Almost all other studies showed moderately or, more often, high incidence of bias (Class III), thus preventing ultimate conclusion on the hypothesized beneficial effects of allografts and synthetic grafts. This review suggests that users of allografts and synthetic grafting should carefully consider the scientific evidence concerning efficacy and safety of these bone substitutes, in order to select the best option for patient undergoing spinal fusion procedures.

A solution based on melatonin, tryptophan, and vitamin B6 (Melamil Tripto©) for sedation in newborns during brain MRI.

INTRODUCTION: Melatonin has been studied and used for several years as a sleep-wake cycle modulator in patients with sleep disorders. Experimental evidence has demonstrated the multiple neuroprotective benefits of this indoleamine secreted by the pineal gland. Melatonin is also used in neurological investigations, for its ability to induce sleep in children. In fact, it favors falling asleep during electroencephalogram, Magnetic Resonance Imaging (MRI), and during brainstem auditory evoked potentials. Previous studies are focused on infants and children. No investigation have been performed in neonates, before or during instrumental assessments. MATERIAL AND METHODS: One hundred ten newborns (term and preterm) undergoing brain MRI were enrolled in the study. Thirty minutes before the planned time for the examination, we administered a single dose solution of melatonin- tryptophan-vitamin B6. Twenty minutes after the initial administration of 2 mg, a second dose of 1 mg was administered, if the baby was still awake. If after further 15 min the baby was still not sleeping, an additional dose of 1 mg was administered. RESULTS: In 106 patients we obtained adequate sedation without adverse events, allowing us to perform an adequate quality MRI, with a median time of 25 min to reach sleeping. Only in three patients MRI could not be performed. In patients having a large weight, higher doses of melatonin were necessary to reach sleeping. Considering the pro kg dose of melatonin, the average dose that induced sleepiness in neonates was 0,64 ± 0.16 mg/Kg. CONCLUSION: A solution based on Melatonin- tryptophan-vitamin B6 can be a helpful sedative to administer to neonates undergoing brain MRI, avoiding the use of anesthetics and achieving adequate assessments.

Fixed Dose Combination Formulations: Multilayered Platforms Designed for the Management of Cardiovascular Disease.

Hyperlipidaemia is considered as one of the main risk factors associated with cardiovascular diseases (CVDs). Among different lipid-lowering agents used to manage hyperlipidaemia, statins are highly prescribed for management of hyperlipidaemia with simvastatin being one of the most common. Simvastatin is susceptible to extensive metabolism by CYP450 3A4 and 3A5, which are expressed both in the liver and the gastrointestinal tract. Nevertheless, the localization of these enzymes is site-dependent with lower concentration at the distal/proximal regions of the small intestine/colon. In addition to statins, medications such as antihypertensive agents and anticoagulants are introduced as adjuvants, for the treatment of cardiovascular disease. The aim of this study was to design a bilayer delivery system capable of delivering biphasic release of simvastatin and aspirin, within a fixed dose combination. A delayed release platform based on a combination of anionic polymers prepared using hot-melt extrusion was developed to delay the release of simvastatin. An optimized formulation tested for dissolution performance clearly demonstrated an ability to delay the release of simvastatin. In addition, an immediate release layer based on Kollidon VA64 was successfully developed to deliver aspirin. Both formulations were then manufactured as a bilayer drug delivery system (tablets and coextrudates), and the release performance was examined. On the basis of the obtained results, these formulations may be used as a platform for delivering a wide range of medications in a biphasic manner.

Pulsed electromagnetic fields and platelet rich plasma alone and combined for the treatment of wear-mediated periprosthetic osteolysis: An in vivo study.

Wear-mediated osteolysis is a common complication occurring around implanted prosthesis, which ultimately leads to bone loss with mechanical instability and the need for surgical revision. At the moment, revision surgery is the only effective treatment. The aim of this study was to assess the efficacy of pulsed electromagnetic fields (PEMFs) and platelet rich plasma (PRP), alone and in association, in a clinically relevant in vivo model of periprosthetic osteolysis. Titanium alloy pins were implanted intramedullary in distal femurs of male inbred rats and, after osseointegration, polyethylene particles were injected intra-articularly to induce osteolysis. Animals were divided in four groups of treatment: PEMFs, PRP, PEMFs + PRP and no treatment. Microtomography was performed during the course of experiments to monitor bone stock and microarchitecture. Histology, histomorphometry, immunohistochemistry and biomechanics were evaluated after treatments. Biophysical and biological stimulations significantly enhanced bone to implant contact, bone volume and bone microhardness and reduced fibrous capsule formation and the number of osteoclasts around implants. Among treatments, PEMFs alone and in association with PRP exerted better results than PRP alone. Present data suggest that biophysical stimulation, with or without the enrichment with platelet derived growth factors, might be a safe, mini-invasive and conservative therapy for counteracting osteolysis and prompting bone formation around implants. STATEMENT OF SIGNIFICANCE: Pulsed electromagnetic fields (PEMFs) and platelet rich plasma (PRP) show anabolic and anti-inflammatory effects and they are already been used in clinical practice, but separately. To date, there are no preclinical in vivo studies evaluating their combined efficacy in periprosthetic osteolysis, in bone tissue microarchitecture and in biomechanics. The aim of the present study was to evaluate the effects of PEMFs and PRP in vivo, when administered individually and in combination in the treatment of periprosthetic wear mediated ostelysis, and in restoring the osteogenetic properties of perimplant bone tissue and its biomechanical competence. The combination of PEMFs and PRP could be employed for counteracting the ostelysis process in a conservative and non surgical manner.

A novel technique for decellularization of allogenic nerves and in vivo study of their use for peripheral nerve reconstruction.

Autografts represent the gold standard for peripheral nerve reconstruction but their limited availability, the discrepancy of nerve caliber, and long surgical times are drawbacks. Allografts have therefore become a valid alternative option. In particular, acellular nerve allografts (ANAs) rather than fresh allografts do not need immunosuppression and appear to be safe and effective based on recent studies. An innovative method was conceived to obtain ANAs, so as to speed up nerve decellularization, without compromising nerve architecture, and without breaking the asepsis chain. Several detergent-based techniques, integrated with sonication and mechanical stirring, were tested in vitro on rabbit nerves, to identify, by microscopy and immunohistochemistry, the most effective protocol in terms of cell lysis and cellular debris clearance, while maintaining nerve architecture. Furthermore, a pilot in vivo study was performed: ANAs were implanted into tibial nerve defects of three rabbits, and autografts, representing the gold standard, in other three animals. Twelve weeks postoperatively, rabbits were clinically evaluated and euthanasized; grafts were harvested and microscopically and histomorphometrically analyzed. The method proved to be effective in vitro: the treatment removed axons, myelin and cells, without altering nerve architecture. The in vivo study did not reveal any adverse effect: animals maintained normal weight and function of posterior limb during the entire experimental time. A mild fibrotic reaction was observed, macrophages and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were comparable versus autografts. Based on these results, this decellularization protocol is encouraging and deserves deeper investigations with further preclinical and clinical studies. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2228-2240, 2017.

Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model.

Although articular cartilage is the target of osteoarthritis (OA), its deterioration is not always clearly associated with patient symptoms. Because a functional interaction between cartilage and bone is crucial, the pathophysiology of OA and its treatment strategy must focus also on subchondral bone. We investigated whether adipose-derived stromal cells (ASCs) injected into a joint at two different concentrations could prevent subchondral bone damage after the onset of mild OA in a rabbit model. We measured both volumetric and densitometric aspects of bone remodeling. Although OA can stimulate bone remodeling either catabolically or anabolically over time, the accelerated turnover does not allow complete mineralization of new bone and therefore gradually reduces its density. We measured changes in morphometric and densitometric bone parameters using micro-CT analysis and correlated them with the corresponding parameters in cartilage and meniscus. We found that ASCs promoted cartilage repair and helped counteract the accelerated bone turnover that occurs with OA.

Mesenchymal Stem Cells for the Treatment of Spinal Arthrodesis: From Preclinical Research to Clinical Scenario.

The use of spinal fusion procedures has rapidly augmented over the last decades and although autogenous bone graft is the "gold standard" for these procedures, alternatives to its use have been investigated over many years. A number of emerging strategies as well as tissue engineering with mesenchymal stem cells (MSCs) have been planned to enhance spinal fusion rate. This descriptive systematic literature review summarizes the in vivo studies, dealing with the use of MSCs in spinal arthrodesis surgery and the state of the art in clinical applications. The review has yielded promising evidence supporting the use of MSCs as a cell-based therapy in spinal fusion procedures, thus representing a suitable biological approach able to reduce the high cost of osteoinductive factors as well as the high dose needed to induce bone formation. Nevertheless, despite the fact that MSCs therapy is an interesting and important opportunity of research, in this review it was detected that there are still doubts about the optimal cell concentration and delivery method as well as the ideal implantation techniques and the type of scaffolds for cell delivery. Thus, further inquiry is necessary to carefully evaluate the clinical safety and efficacy of MSCs use in spine fusion.

When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential.

Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, <0.5 mm). After demineralization, the chemical-physical analysis clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

RAW 264.7 co-cultured with ultra-high molecular weight polyethylene particles spontaneously differentiate into osteoclasts: an in vitro model of periprosthetic osteolysis.

Wear-particle osteolysis affects prosthesis survival leading to implant loosening up to 70% of revisions. Therapeutic strategies are increasing, however alternative testing methods to experimentally evaluate such treatments are lacking. The aim of this study was to reproduce an in vitro osteolysis model recapitulating the events that, starting from the exposure of macrophages to polyethylene, lead to the establishment of osteoclastogenesis and inflammation. Responses to polyethylene, at 3 and 7 days, in a macrophage cell line, RAW 264.7, were determined by DNA quantification, immunofluorescence, pit assay, gene expression, cytokine production and NF-kB activation. Results showed that 3 days exposure to particles could induce a significant production of Tumor Necrosis Factor alpha (p < 0.0005) and Prostaglandin E2 (p < 0.005) compared to controls. Particles also induced macrophages to spontaneously differentiate into mature and active osteoclasts, in terms of identification of multinucleated cells by Phalloidin staining and by the analysis of osteoclast-specific gene markers. In particular, at 3 days polyethylene induced a significant up-regulation of Nuclear Factor of Activated T-cells, cytoplasmic 1, Receptor Activator of Nuclear factor Kappa-B and Receptor Activator of Nuclear Factor Kappa-B Ligand genes (p < 0.0005) compared to controls. At protein level, the particles induced a significant increase of Receptor Activator of Nuclear Factor Kappa-B Ligand at day 7 over controls (p < 0.0005). Osteoclasts were capable to resorb bone even in absence of differentiating factors. The possible mechanism, beside spontaneous osteoclastogenesis mediated by wear debris, was identified in an autocrine up-regulation of Receptor activator of nuclear factor kappa-B ligand gene expression and protein synthesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 510-520, 2017.

Comparisons of physical activity, adipokines, vitamin D status and dietary vitamin D intake among adolescents.

BACKGROUND: Considering that lifestyle and diet are key factors responsible for the increases in adiposity in youth, it is important to understand how vitamin D, adipokines and markers of glucose metabolism are related to physical activity level (PAL) during growth. The present study aimed to investigate associations between physical activity level, adiponectin/leptin ratio, vitamin D status and dietary vitamin D intake among adolescents. METHODS: A cross-sectional study was conducted with adolescents aged 14-18 years old who were living in São Paulo, Brazil. Serum 25 hydroxyvitamin D [25(OH)D], adiponectin (A), leptin (L), glucose and insulin were obtained after 12 h of fasting. Dietary calcium and vitamin D intake were measured by 24-h food record, as repeated in 62.6% of the sample. PAL was measured by the International Physical Activity Questionnaire (IPAQ). Pearson's chi-square test, Pearson correlation and linear regression analysis were performed. RESULTS: A total of 198 subjects, mean (SD) age 16.3 (1.4) years, 51% male, were enrolled in the study. Some 9% of participants were sedentary, 22% were insufficiently active (IA), 51% were active and 18% were very active (VA). The A/L ratio was lower among sedentary/IA subjects [2.2 (4.0) versus 5.6 (12.3); P = 0.01] compared to active/VA subjects. PAL was not associated with vitamin D status or markers of glucose metabolism. Serum 25(OH)D positively associated with vitamin D intake, after adjusting for sex, sun exposure and season of the year in regression analysis (partial r2 =0.026, P = 0.02). CONCLUSIONS: Low PAL was associated with a lower A/L ratio. Vitamin D status was not associated with sun exposure habits, although it was positively correlated with vitamin D intake.

A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations.

Current treatments for acute or degenerative chondral and osteochondral lesions are in need of improvement, as these types of injuries lead to disability and worsen the quality of life in a high percentage of patients. The aim of this study was to develop a new bi-layered scaffold for osteochondral tissue regeneration through a "biomimetic" and "bioinspired" approach. For chondral regeneration, the scaffold was realized with an organic compound (type I collagen), while for the regeneration of the subchondral layer, bioactive magnesium-doped hydroxyapatite (Mg/HA) crystals were co-precipitated with the organic component of the scaffold. The entire scaffold structure was stabilized with a cross-linking agent, highly reactive bis-epoxyde (1,4-butanediol diglycidyl ether - BDDGE 1wt%). The developed scaffold was then characterized for its physico-chemical characteristics. Its structure and adhesion strength between the integrated layers were investigated. At the same time, in vitro cell culture studies were carried out to examine the ability of chondral and bone scaffold layers to separately support adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes and osteoblasts, respectively. Moreover, an in vivo study with nude mice, transplanted with osteochondral scaffolds plain or engineered with undifferentiated hMSCs, was also set up with 4 and 8-week time points. The results showed that chondral and bone scaffold layers represented biocompatible scaffolds able to sustain hMSCs attachment and proliferation. Moreover, the association of scaffold stimuli and differentiation medium, induced hMSCs chondrogenic and osteogenic differentiation and deposition of extracellular matrix (ECM). The ectopic implantation of the engineered osteochondral scaffolds indicated that hMSCs were able to colonize the osteochondral scaffold in depth. The scaffold appeared permissive to tissue growth and penetration, ensuring the diffusion of nutrients and oxygen, as also suggested by the presence of a neo-angiogenesis process, especially at 4weeks. Moreover, the in vivo results further confirmed the great potential of the scaffold in tissue engineering, as it was able to support the initial formation of new bone and chondral tissue, confirming the importance of combined and innovative strategies to improve the available therapeutic strategies for chondral and osteochondral regeneration.

Production of nabumetone nanoparticles: Effect of molecular weight, concentration and nature of cellulose ether stabiliser.

The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely methylhydroxethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to prepare stable nabumetone nanoparticles (<1000nm, as measured by laser diffraction) using wet-bead milling has been investigated. Due to the limited range of CE molecular weights commercially available, the CEs were degraded using ultrasonication for varying lengths of time to yield CEs of lower molecular weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise the production of nabumetone nanoparticles at any of the molecular weights tested, namely viscosity average molecular weights (Mv) in the range of 236-33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with the lower molecular weight/viscosity polymers within a series being more likely to result in nanoparticle production than their higher molecular weight counterparts. Unfortunately due to the nature of the ultrasonication process, it was not possible to compare the size of nabumetone particles produced using polymers of identical Mv. There was, however, enough similarity in the Mv of the various polymers to draw the general conclusion that there was no strong correlation between the Mv of the various polymers and their ability to produce nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less successfully produced nanoparticles while only ethylhydroxyethylcellulose and hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles. These results suggest that polymer molecular weight is not the only determinant of nanoparticle production and that structure of the polymer is at least as important as its molecular weight. In particular the hydrophobic nature of the CE was thought to be an important factor in the production of nabumetone nanoparticles: the more hydrophobic the polymer, the stronger its interaction with nabumetone and the greater its ability to produce nanoparticles. In this context HPC was the most hydrophobic polymer and HEC the least hydrophobic.

Dietary patterns and bone mineral density in Brazilian postmenopausal women with osteoporosis: a cross-sectional study.

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the association between dietary patterns and bone mineral density (BMD) in postmenopausal women with osteoporosis. SUBJECTS/METHODS: This cross-sectional study included 156 postmenopausal and osteoporotic Brazilian women aged over 45 years. BMD of lumbar spine, total femur (TF), femoral neck and of total body (TB), as well as body composition (fat and lean mass), was assessed by dual-energy X-ray absorptiometry. Body mass index and lifestyle information were also obtained. Dietary intake was assessed by using a 3-day food diary. Dietary patterns were obtained by principal component factor analysis. Adjusted multiple linear regression analysis was applied in order to evaluate the predictive effect of dietary patterns on BMD. Significance was set at P<0.05. RESULTS: Five patterns were retained: 'healthy', 'red meat and refined cereals', 'low-fat dairy', 'sweet foods, coffee and tea' and 'Western'. The 'sweet foods, coffee and tea' pattern was inversely associated with TF BMD (ß=-0.178; 95% CI: -0.039 to -0.000) and with TB BMD (ß=-0.320; 95% CI: -0.059 to -0.017) even after adjusting for energy and calcium intake, lean mass, age and postmenopausal time. CONCLUSIONS: A concomitant excessive consumption of sweet foods and caffeinated beverages appears to exert a negative effect on BMD even when the skeleton already presents some demineralization. Food and beverage intake is a modifiable factor that should not be neglected in the treatment of individuals with osteoporosis.

Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1ß, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1ß was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.