Do Personal Nurse-Initiated Medication Boxes Work in Prison? A Cross-Sectional Study Involving Incarcerated Persons and Prison Officers in a Swiss Prison.

INTRODUCTION: Daily in-hand medication dispensing in prisons and jails is resource intensive, disempowering, and nonconfidential. This research aimed to assess a nurse-initiated, low-frequency medication dispensing system using personal lockable boxes. METHODS: A cross-sectional study was carried out in a Swiss prison involving 47 box users and 19 custodial officers. FINDINGS: Box users agreed or strongly agreed about the perceived advantages of the box system, including user-friendliness, lower theft risk, and increased dignity, confidentiality, compliance, and autonomy to self-manage medication. Officers, who must accompany nurses during dispensing rounds, concurred that medication boxes were more time-efficient and improved role differentiation between custodial and clinical staff. Patients and officers were overall satisfied with the system and would recommend scaling it up in other facilities. DISCUSSION: This study suggests that medication boxes are feasible, acceptable, easy to use, and secure. Boxes could promote patients' autonomy, protect confidentiality, and allow nurses to dedicate more time to individual visits and health promotion and prevention activities.

Access to treatment in prison: an inventory of medication preparation and distribution approaches.

The preparation and distribution of medication in prisons or jails are critical for individuals to access their treatment. This process is resource-intensive for healthcare professionals and may violate principles of confidentiality, autonomy, respect, and dignity if non-qualified staff are involved. However, there are no published best practices on the topic. This report aims to bridge this gap by presenting the results of a mapping exercise on different models of medication preparation and delivery. Authors call upon healthcare professionals to enrich this live document to inform health services research further and improve access to prescribed medications for people experiencing incarceration.

Nurse-led mind-body relaxation intervention in prison: A multiperspective mixed-method evaluation.

BACKGROUND: Mind-body relaxation techniques are complementary or alternative to medication to manage high stress and anxiety levels in prisons. PURPOSE: To assess the motivation to attend and perceived benefits of a nurse-led group relaxation intervention in prison, investigate the experience of participants, prison officers, and health professionals, and identify improvements. METHOD: Exploratory study was conducted in a post-trial facility in Switzerland using a multiperspective convergent parallel mixed method drawing from participatory action research principles. FINDINGS: Reasons for attendance included back problems, mental tension, physical fitness, relaxation, and sleep problems. Perceived benefits comprised autonomy in self-practice, decreased physical tensions and anxiety, and improvement of sleep and physical fitness. Qualitative findings converged highlighting the importance of body-centering, relaxation as an alternative to medication, negative representations about relaxation sessions (useless, effeminate), and recommendations for improvement, including audio-visual support for self-practice. DISCUSSION: Long-standing mind-body relaxation interventions led by nurses in groups may offer participants a beneficial and operationally feasible complement to stress management in prisons.

A Developmental Engineering-Based Approach to Bone Repair: Endochondral Priming Enhances Vascularization and New Bone Formation in a Critical Size Defect.

There is a distinct clinical need for new therapies that provide an effective treatment for large bone defect repair. Herein we describe a developmental approach, whereby constructs are primed to mimic certain aspects of bone formation that occur during embryogenesis. Specifically, we directly compared the bone healing potential of unprimed, intramembranous, and endochondral primed MSC-laden polycaprolactone (PCL) scaffolds. To generate intramembranous constructs, MSC-seeded PCL scaffolds were exposed to osteogenic growth factors, while endochondral constructs were exposed to chondrogenic growth factors to generate a cartilage template. Eight weeks after implantation into a cranial critical sized defect in mice, there were significantly more vessels present throughout defects treated with endochondral constructs compared to intramembranous constructs. Furthermore, 33 and 50% of the animals treated with the intramembranous and endochondral constructs respectively, had full bone union along the sagittal suture line, with significantly higher levels of bone healing than the unprimed group. Having demonstrated the potential of endochondral priming but recognizing that only 50% of animals completely healed after 8 weeks, we next sought to examine if we could further accelerate the bone healing capacity of the constructs by pre-vascularizing them in vitro prior to implantation. The addition of endothelial cells alone significantly reduced the healing capacity of the constructs. The addition of a co-culture of endothelial cells and MSCs had no benefit to either the vascularization or mineralization potential of the scaffolds. Together, these results demonstrate that endochondral priming alone is enough to induce vascularization and subsequent mineralization in a critical-size defect.

Inferior In Vivo Osteogenesis and Superior Angiogenesis of Human Adipose­Derived Stem Cells Compared with Bone Marrow­Derived Stem Cells Cultured in Xeno­Free Conditions.

The possibility of using adipose tissue-derived stromal cells (ATSC) as alternatives to bone marrow-derived stromal cells (BMSC) for bone repair has garnered interest due to the accessibility, high cell yield, and rapid in vitro expansion of ATSC. For clinical relevance, their bone forming potential in comparison to BMSC must be proven. Distinct differences between ATSC and BMSC have been observed in vitro and comparison of osteogenic potential in vivo is not clear to date. The aim of the current study was to compare the osteogenesis of human xenofree-expanded ATSC and BMSC in vitro and in an ectopic nude mouse model of bone formation. Human MSC were implanted with biphasic calcium phosphate biomaterials in subcutis pockets for 8 weeks. Implant groups were: BMSC, ATSC, BMSC and ATSC mixed together in different ratios, as well as MSC primed with either osteogenic supplements (250 µM ascorbic acid, 10 mM ß-glycerolphosphate, and 10 nM dexamethasone) or 50 ng/ml recombinant bone morphogenetic protein 4 prior to implantation. In vitro results show osteogenic gene expression and differentiation potentials of ATSC. Despite this, ATSC failed to form ectopic bone in vivo, in stark contrast to BMSC, although osteogenic priming did impart minor osteogenesis to ATSC. Neovascularization was enhanced by ATSC compared with BMSC; however, less ATSC engrafted into the implant compared with BMSC. Therefore, in the content of bone regeneration, the advantages of ATSC over BMSC including enhanced angiogenesis, may be negated by their lack of osteogenesis and prerequisite for osteogenic differentiation prior to transplantation. Stem Cells Translational Medicine 2017;6:2160-2172.

3D cell culture and osteogenic differentiation of human bone marrow stromal cells plated onto jet-sprayed or electrospun micro-fiber scaffolds.

A major limitation of the 2D culture systems is that they fail to recapitulate the in vivo 3D cellular microenvironment whereby cell-cell and cell-extracellular matrix (ECM) interactions occur. In this paper, a biomaterial scaffold that mimics the structure of collagen fibers was produced by jet-spraying. This micro-fiber polycaprolactone (PCL) scaffold was evaluated for 3D culture of human bone marrow mesenchymal stromal cells (MSCs) in comparison with a commercially available electrospun scaffold. The jet-sprayed scaffolds had larger pore diameters, greater porosity, smaller diameter fibers, and more heterogeneous fiber diameter size distribution compared to the electrospun scaffolds. Cells on jet-sprayed constructs exhibited spread morphology with abundant cytoskeleton staining, whereas MSCs on electrospun scaffolds appeared less extended with fewer actin filaments. MSC proliferation and cell infiltration occurred at a faster rate on jet-sprayed compared to electrospun scaffolds. Osteogenic differentiation of MSCs and ECM production as measured by ALP, collagen and calcium deposition was superior on jet-sprayed compared to electrospun scaffolds. The jet-sprayed scaffold which mimics the native ECM and permits homogeneous cell infiltration is important for 3D in vitro applications such as bone cellular interaction studies or drug testing, as well as bone tissue engineering strategies.

Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury.

Different macrophage depletion strategies have demonstrated a vital role of macrophages in bone healing, but the underlying molecular mechanisms are poorly understood. Here, with the use of a mouse model of tibia injury, we found that the cytokine oncostatin M [OSM or murine (m)OSM] was overexpressed during the initial inflammatory phase and that depletion of macrophages repressed mOSM expression. In Osm(-/-) mice, by micro-computed tomography and histology we observed a significant reduction in the amount of new intramedullar woven bone formed at the injured site, reduced number of Osterix(+) osteoblastic cells, and reduced expression of the osteoblast markers runt-related transcription factor 2 and alkaline phosphatase. In contrast, osteoclasts were normal throughout the healing period. One day after bone injury, Stat3, the main transcription factor activated by mOSM, was found phosphorylated/activated in endosteal osteoblastic cells located at the hedge of the hematoma. Interestingly, we observed reduced activation of Stat3 in Osm(-/-) mice. In addition, mice deficient in the mOSM receptor (Osmr(-/-)) also had reduced bone formation and osteoblast number within the injury site. These results suggest that mOSM, a product of macrophages, sustains intramembranous bone formation by signaling through Osmr and Stat3, acting on the recruitment, proliferation, and/or osteoblast differentiation of endosteal mesenchymal progenitor cells. Because bone resorption is largely unaltered, OSM could represent a new anabolic treatment for unconsolidated bone fractures.

Pre-clinical studies of bone regeneration with human bone marrow stromal cells and biphasic calcium phosphate.

INTRODUCTION: Repair of large bone defects remains a significant clinical challenge. Bone marrow stromal cells (BMSCs), a subset of which is known as bone marrow-derived mesenchymal stem cells, show therapeutic potential for bone regeneration. However, their isolation, expansion and implantation will need to be conducted under good manufacturing practices (GMP) at separate locations. An investigation which mimics this clinical scenario where large bone defects shall be regenerated is required before clinical trials can be initiated. METHODS: Seven batches of 100 million human ex-vivo expanded BMSCs from five donors were transported fresh in syringes from a GMP facility in Germany to France. BMSCs were mixed with biphasic calcium phosphate (BCP) biomaterial prior to subcutaneous implantation in nude mice. The capacity of BMSCs in unison with BCP to regenerate critical sized cranial bone defects was also evaluated. BMSCs expressing luciferase were used to assess the viability and bio-distribution of implanted cells. In situ hybridization, using the human-specific repetitive Alu sequence, was performed for the identification of human cells in explants. RESULTS: Eight weeks after implantation of BMSCs, mineralized bone containing mature bone marrow territories was formed in ectopic sites and in calvaria defects. Significant loss of cell viability was observed by bioluminescence imaging and only 1.5 percent of the initial number of transplanted cells remained after 37 days. After eight weeks, while explants were comprised primarily of host cells, there were also human cells attached along the periphery of BCP and embedded in osteocyte lacunae dispersed throughout the newly formed bone matrix. CONCLUSIONS: This study demonstrates the safety and efficacy of BMSC/BCP combinations and provides crucial information for the implementation of BMSC therapy for bone regeneration.

Osteoblastic and osteoclastic differentiation of human mesenchymal stem cells and monocytes in a miniaturized three-dimensional culture with mineral granules.

The pathologies of the skeleton have a significant socioeconomic impact on our population. Although therapies have improved the treatment of osteosarcoma and osteoporosis, their efficacy still remains limited. In this context, we developed a miniaturized 3-D culture model of bone cells on calcium phosphate ceramics. Human bone marrow mesenchymal stem cells (MSCs) were three-dimensionally cultured on particles of biphasic calcium phosphate (BCP, 125-200µm) in osteogenic media. The MSCs seeded on the BCP particles adhered and proliferated, producing abundant collagenous extracellular matrix (ECM). Light and confocal laser scanning microscopy showed that the MSCs created bridges between the BCP particles and formed a 3-D structure. Energy dispersive X-ray analysis in a scanning electron microscope confirmed the mineralization of the collagen matrix. The 96-well sized bone constructs were tested by immunohistology and transcription analysis, proving cell differentiation. Both techniques corroborated the osteoblastic differentiation with high production of bone sialoprotein and osteocalcin. Peripheral blood CD14-positive monocytes (MOs) were pre-differentiated into osteoclasts prior to seeding on the 3-D constructs. Multinucleated and tartrate-resistant acid phosphatase-positive cells were also identified at the surface of the 3-D constructs after 90days of culture. In addition, cell viability within these constructs was measured by flow cytometry. In summary, we have developed a miniaturized 3-D culture of bone cell precursors with osteoblasts and osteoclasts. This 3-D culture may make it possible to test the effects of new drugs for bone healing, osteoporosis and osteosarcomas, in more appropriate cell-cell and cell-matrix interactions than conventional 2-D cultures.

Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages.

Human mesenchymal stem cells (hMSC) have immunomodulative properties and, associated with calcium phosphate (CaP) ceramics, induce bone tissue repair. However, the mechanisms of osteoinduction by hMSC with CaP are not clearly established, in particular the role of osteoclasts and macrophages. Biphasic calcium phosphate (BCP) particles were implanted with or without hMSC in the paratibial muscles of nude mice. hMSC increased osteoblastic gene expression at 1 week, the presence of macrophages at 2 and 4 weeks, osteoclastogenesis at 4 and 8 weeks, and osteogenesis at 4 and 8 weeks. hMSC disappeared from the implantation site after 2 weeks, indicating that hMSC were inducers rather than effectors of bone formation. Induced blockage of osteoclastogenesis by anti-Rankl treatment significantly impaired bone formation, revealing the pivotal role of osteoclasts in bone formation. In summary, hMSC positively influence the body foreign reaction by attracting circulating haematopoietic stem cells and inducing their differentiation into macrophages M1 and osteoclasts, thus favouring bone formation.

Osteoblastic differentiation and potent osteogenicity of three-dimensional hBMSC-BCP particle constructs.

Bone tissue engineering usually consists of associating osteoprogenitor cells and macroporous scaffolds. This study investigated the in vitro osteoblastic differentiation and resulting in vivo bone formation induced by a different approach that uses particles as substrate for human bone marrow stromal cells (hBMSCs), in order to provide cells with a higher degree of freedom and allow them to synthesize a three-dimensional (3D) environment. Biphasic calcium phosphate (BCP) particles (35 mg, ~175 µm in diameter) were therefore associated with 4 × 10(5) hBMSCs. To discriminate the roles of BCP properties and cell-synthesized 3D environments, inert glass beads (GBs) of similar size were used under the same conditions. In both cases, high cell proliferation and extensive extracellular matrix (ECM) production resulted in the rapid formation of thick cell-synthesized 3D constructs. In vitro, spontaneous osteoblastic differentiation was observed in the 3D constructs at the mRNA and protein levels by monitoring the expression of Runx2, BMP2, ColI, BSP and OCN. The hBMSC-BCP particle constructs implanted in the subcutis of nude mice induced abundant ectopic bone formation after 8 weeks (~35%, n = 5/5). In comparison, only fibrous tissue without bone was observed in the implanted hBMSC-GB constructs (n = 0/5). Furthermore, little bone formation (~3%, n = 5/5) was found in hBMSC-macroporous BCP discs (diameter 8 × 3 mm). This study underlines the lack of correspondence between bone formation and in vitro differentiation assays. Furthermore, these results highlight the importance of using BCP as well as a 3D environment for achieving high bone yield of interest for bone engineering.