Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation.

Biomaterials play a pivotal role in cell-free cartilage repair approaches, where cells must migrate through the scaffold, fill the defect, and then proliferate and differentiate facilitating tissue remodeling. Here we used multiple assays to test the influence of chemokines and growth factors on cell migration and cartilage repair in two different hyaluronan (HA)-based hydrogels. We first investigated bone marrow Mesenchymal Stromal Cells (BMSC) migration in vitro, in response to different concentrations of platelet-derived growth factor-BB (PDGF-BB), chemokine ligand 5 (CCL5/RANTES) and stromal cell-derived factor 1 (SDF-1), using a 3D spheroid-based assay. PDGF-BB was selected as most favourable chemotactic agent, and MSC migration was assessed in the context of physical impediment to cell recruitment by testing Fibrin-HA and HA-Tyramine hydrogels of different cross-linking densities. Supplementation of PDGF-BB stimulated progressive migration of MSC through the gels over time. We then investigated in situ cell migration into the hydrogels with and without PDGF-BB, using a cartilage-bone explant model implanted subcutaneously in athymic mice. In vivo studies show that when placed into an osteochondral defect, both hydrogels supported endogenous cell infiltration and provided an amenable microenvironment for cartilage production. These processes were best supported in Fibrin-HA hydrogel in the absence of PDGF-BB. This study used an advanced preclinical testing platform to select an appropriate microenvironment provided by implanted hydrogels, demonstrating that HA-based hydrogels can promote the initial and critical step of endogenous cell recruitment and circumvent some of the clinical challenges in cartilage tissue repair. STATEMENT OF SIGNIFICANCE: The challenge of articular cartilage repair arises from its complex structure and architecture, which confers the unique mechanical behavior of the extracellular matrix. The aim of our research is to identify biomaterials for implants that can support migration of endogenous stem and progenitor cell populations from cartilage and bone tissue, in order to permanently replace damaged cartilage with the original hyaline structure. Here, we present an in vitro 3D spheroid-based migration assay and an osteochondral defect model, which provide the opportunity to assess biomaterials and biomolecules, and to get stronger experimental evidence of the not well-characterized dynamic process of endogenous cells colonization in an osteochondral defect. Furthermore, the delicate step of early cell migration into biomaterials towards functional tissue engineering is reproduced. These tests can be used for pre-clinical testing of newly developed material designs in the field of scaffold engineering.

Slug transcription factor and nuclear Lamin B1 are upregulated in osteoarthritic chondrocytes.

OBJECTIVE: To contribute to clarify molecular mechanisms supporting senescence and de-differentiation of chondrocytes in chondrocyte pathologies such as osteoarthritis (OA). Specifically, we investigated the relationship between the nuclear lamina protein Lamin B1 and the negative regulator of chondrogenesis Slug transcription factor in osteoarthritic chondrocytes. METHODS: Lamin B1 and Slug proteins were analyzed in cartilage explants from normal subjects and OA patients by immunohistochemical technique. Their expression was confirmed on isolated chondrocytes both at passage 0 and passage 2 (de-differentiated chondrocytes) by immunofluorescence and western blot. Subsequently, we explored the "in vivo" binding of Slug on LMNB1 promoter by chromatin immunoprecipitation assay (ChIP). RESULTS: In this study we demonstrated that nuclear lamina protein Lamin B1 and anti-chondrogenic Slug transcription factor are upregulated in cartilage and OA chondrocytes. Furthermore, we found that Slug is "in vivo" recruited by LMNB1 gene promoter mostly when chondrocytes undergo de-differentiation or OA degeneration. CONCLUSIONS: We described for the first time a potential regulatory role of Slug on the LMNB1 gene expression in OA chondrocytes. These findings may have important implications for the study of premature senescence, and degeneration of cartilage, and may contribute to develop effective therapeutic strategies against signals supporting cartilage damage in different subsets of patients.

Difficult hospital discharges in internal medicine wards.

OBJECTIVE: Investigate the prevalence of difficult hospital discharges (DHD), describe clinical and social patients' characteristics as potential reasons for discharge delays in an internal medicine ward and implement tailored post-discharge care. METHODS: During the year 2005 we analysed, in a middle-sized country hospital, all the patients for which some delay for discharge, owing to their whole complexity, was presumable. Comprehensive multidimensional assessment, clinical-social risk score, specific needs of care, mean of stay and outcomes were evaluated. RESULTS: 68.5% of DHD patients were >/=80 years old, with 3.8 the mean number of diseases per patient; 57.5% presented a loss of autonomy (ADL) just before acute deterioration; 80% were functionally and/or cognitively impaired. Only 5% had suitable family support; 5.1% were living at a nursing home; 2% were living alone. The most frequent causes of admission were stroke, cognitive impairment-dementia, cardiovascular diseases, fractures and cancer. Mean length of stay was 12 days. Fifty-two percent of patients were discharged home, 30% were admitted to a long-term care facility, 1% to hospice and 17% died during their hospital stay. CONCLUSIONS: The aim of "coordinated care" (i.e., targeting "at-risk" patients with assessment of medical, functional, social and emotional needs; provision of optimal medical treatment, self-care education, integrated services, monitoring of progress and early signs of problems) is to improve health outcomes and reduce costs. More than 80% of DHDs patients, with specific tailored programmes, may be discharged from hospital, with satisfactory solutions for them and their families.

Professional clinical bleaching with Pola Office: 6-month clinical results with spectrophotometric analysis.

AIM: The aim of the study was to evaluate the efficacy of the professional bleaching treatment with Pola Office (SDI): the shade, chroma and value parameters of the anterior upper elements were analysed. METHODS: At the Prosthetic Unit of the Modena and Reggio Emilia University, 10 patients were selected. All patients underwent oral hygiene treatment and spectrophotometric analysis (Spectro-Shade) of the 6 front elements: the variables L (value), c (chroma), and h (shade) were examined in the cervical, mesial and incisal sections. Spectrophotometric analysis was repeated 6 months after initial bleaching. The patients were asked to report the degree of sensitivity after 3, 6, 12 and 24 h and after 3, 6, 7, and 10 days. RESULTS: The value (L) of the treated elements increases after bleaching, the chroma parameter (c) showed lower values than those prior to treatment (except for the first patient); this means a shift towards a lower degree of saturation. The course of the shade parameter is uniform and constant for all patients, with a shift towards yellow chroma values. Postoperative sensitivity was confined to the first 3 h after treatment, after which it showed a steady decrease over 24 h. CONCLUSIONS: Esthetic results obtained using the Pola Office bleaching procedure were visibly significant; confirmed by colorimeter analysis. The harmony between chroma, shade and value remained 6 months after the bleaching treatment; the sensitivity is particularly high in the first hour, however after 24 h sensitivity is greatly reduced.

[Home care service integrated into community nursing service in milan: 5 years of experience]. / Il servizio di assistenza domiciliare integrata nell'ambito di un'azienda ussl milanese: 5 anni di attività.

In Italy the "Elderly Objective Project"--approved with a special resolution of Chamber and Senate in January 1992 out of the National Health Plan"--placed the domiciliary assistance within a network of territorial services, with the purpose to answer to the elderly needs, in social-welfare and health, in their own home context, looking over to avoid unnecessary admissions in hospital and promote early admissions. The achievement of these directions of these directions have created a kind of services which shows an extreme heterogeneity in organization, typology and intensity of service delivered, as well as in the monitoring strategy, beside the estimation of efficiency and quality of interventions. To contribute to knowledge and progress of efficacy interventions for domiciliary cares, the author suggests a descriptive analysis of domiciliar assistance, existing since 1993 in the USSL 41 of Milan, and a consideration, from a nursing pont of view, about the collected data.

[An active way for professional autonomy]. / Percorsi operativi per l'autonomia nell'esercizio professionale.

Authonomy, competence, specificity. What is nowadays the situation of the professional practice authonomy? To answer the question, the author presents an outline of the present condition in this field. Different possible developments and solutions are shown, starting from some interventions at a personal level to demonstrate nursing specificity to go up to superior levels, belonging to the professional organs.

[Analysis of the activities of ambulatory care nurses and a methodology for the definition of nurses' workload]. / Analisi delle attività infermieristiche in ambito ambulatoriale ed identificazione di una metodologia per la rilevazione del fabbisogno infermieristico.

Patients need medical and qualified surgery care for different purposes: to begin a diagnostic investigation, to monitor a medical therapy, to execute controls in view of or after a surgical operation, etc. Medical care becomes the heart of patient interest, the direct consequence is a lacking reflection about the purpose of nursery activity in this area and, therefore, on the method to be used to define the staff needed. On this particular subject is based the contribute of this article, considering it of particular interest, being the growing attention on the management of human resource in the health word.

[Management instruments for nursing care: experiences in a local Milano health facility]. / Alcuni strumenti di gestione per l'assistenza infermieristica: un'esperienza condotta in un'azienda sanitaria locale di Milano.

The present article brings into focus the problems rising from the changes required to achieve an efficient use of resources in the health world. How do the nursing services deal with the organizational changes? How to program nurses activities within the nursing services? The article tries to discuss some answers to these problems.