Beyond good intentions: lessons on equipment donation from an African hospital.

OBJECTIVE: In 2000, a referral hospital in the Gambia accepted a donation of oxygen concentrators to help maintain oxygen supplies. The concentrators broke down and were put into storage. A case study was done to find the reasons for the problem and to draw lessons to help improve both oxygen supplies and the success of future equipment donations. METHODS: A technical assessment of the concentrators was carried out by a biomedical engineer with relevant expertise. Semi-structured interviews were undertaken with key informants, and content analysis and inductive approaches were applied to construct the history of the episode and the reasons for the failure. FINDINGS: Interviews confirmed the importance of technical problems with the equipment. They also revealed that the donation process was flawed, and that the hospital did not have the expertise to assess or maintain the equipment. Technical assessment showed that all units had the wrong voltage and frequency, leading to overheating and breakdown. Subsequently a hospital donations committee was established to oversee the donations process. On-site biomedical engineering expertise was arranged with a nongovernmental organization (NGO) partner. CONCLUSION: Appropriate donations of medical equipment, including oxygen concentrators, can be of benefit to hospitals in resource-poor settings, but recipients and donors need to actively manage donations to ensure that the donations are beneficial. Success requires planning, technical expertise and local participation. Partners with relevant skills and resources may also be needed. In 2002, WHO produced guidelines for medical equipment donations, which address problems that might be encountered. These guidelines should be publicized and used

Ischemic preconditioning in the liver is independent of regulatory T cell activity

Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. We explored the role of Treg in hepatic IRI and IPC in detail. IPC significantly reduced injury following ischemia reperfusion insults. Treg were mobilized rapidly to the circulation and liver after IRI, but IPC did not further increase Treg numbers, nor was it associated with modulation of circulating pro-inflammatory chemokine or cytokine profiles. We used two techniques to deplete Treg from mice prior to IRI. Neither Treg depleted FoxP3.LuciDTR mice, nor wildtyoe mice depleted of Tregs with PC61, were more susceptible to IRI compared with controls. Despite successful enrichment of Treg in the liver, by adoptive transfer of both iTreg and nTreg or by in vivo expansion of Treg with IL-2/anti-IL-2 complexes, no protection against IRI was observed.We have explored the role of Treg in IRI and IPC using a variety of techniques to deplete and enrich them within both the liver and systemically. This work represents an important negative finding that Treg are not implicated in IPC and are unlikely to have translational potential in hepatic IRI

Are point measurements in a bog representative of their surrounding area?

Descriptions of abiotic properties in bogs are often based on point measurements. To assess whether these point measurements are representative of their surrounding area, depth to water table (DTW), soil moisture, pH, electrical conductivity (EC), the degree of peat humification and ash content were measured at 25 points in a 4 m × 4 m study site. The gravimetric moisture content of the peat samples varied little (coefficient of variation (CV): 2–4 %), while the volumetric moisture content (CV: 11 %) and DTW (CV: 48 %) were more variable. Pore water pH also varied little throughout the study site (CV: 1 %), but pore water EC was more variable (CV: 84 %). The degree of humification was generally within 1–2 points on the von Post scale. Ash content was fairly variable (CV: 61–100 %). Plant species composition varied across the study site in relation to microtopography and was, not surprisingly, most strongly influenced by DTW and near-surface soil moisture. Some point measurements in bogs (e.g. pH, gravimetric moisture content) are likely to be representative for an area of at least several square metres, while other variables (e.g. EC, volumetric moisture content, degree of humification, ash content) may need to be measured at more than one point to obtain a representative average

Septic arthritis in an in vivo murine model induced by Staphylococcus aureus:a comparison between actions of the haemolysin toxin and the effects of the host immune response

AIMS: Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. METHODS: Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10(7) colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. RESULTS: Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. CONCLUSION: Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678

Intrapulmonary Autoantibodies to HSP72 Are Associated with Improved Outcomes in IPF

Rationale. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease, with high mortality. Currently, the aetiology and the pathology of IPF are poorly understood, with both innate and adaptive responses previously being implicated in the disease pathogenesis. Heat shock proteins (Hsp) and antibodies to Hsp in patients with IPF have been suggested as therapeutic targets and prognostic biomarkers, respectively. We aimed to study the relationship between the expression of Hsp72 and anti-Hsp72 antibodies in the BAL fluid and serum Aw disease progression in patients with IPF. Methods. A novel indirect ELISA to measure anti-Hsp72 IgG was developed and together with commercially available ELISAs used to detect Hsp72 IgG, Hsp72 IgGAM, and Hsp72 antigen, in the serum and BALf of a cohort of IPF (n=107) and other interstitial lung disease (ILD) patients (n=66). Immunohistochemistry was used to detect Hsp72 in lung tissue. The cytokine expression from monocyte-derived macrophages was measured by ELISA. Results. Anti-Hsp72 IgG was detectable in the serum and BALf of IPF (n=107) and other ILDs (n=66). Total immunoglobulin concentrations in the BALf showed an excessive adaptive response in IPF compared to other ILDs and healthy controls (p=0.026). Immunohistochemistry detection of C4d and Hsp72 showed that these antibodies may be targeting high expressing Hsp72 type II alveolar epithelial cells. However, detection of anti-Hsp72 antibodies in the BALf revealed that increasing concentrations were associated with improved patient survival (adjusted HR 0.62, 95% CI 0.45-0.85; p=0.003). In vitro experiments demonstrate that anti-Hsp72 complexes stimulate macrophages to secrete CXCL8 and CCL18. Conclusion. Our results indicate that intrapulmonary anti-Hsp72 antibodies are associated with improved outcomes in IPF. These may represent natural autoantibodies, and anti-Hsp72 IgM and IgA may provide a beneficial role in disease pathogenesis, though the mechanism of action for this has yet to be determined

Treatment of the fixation surface improves glenoid prosthesis longevity in-vitro

Many commercial cemented glenoid components claim superior fixation designs and increased survivability. However, both research and clinical studies have shown conflicting results and it is unclear whether these design variations do improve loosening rates. Part of the difficulty in investigating fixation failure is the inability to directly observe the fixation interface, a problem addressed in this study by using a novel experimental set-up.Cyclic loading-displacement tests were carried out on 60 custom-made glenoid prostheses implanted into a bone substitute. Design parameters investigated included treatment of the fixation surface of the component resulting in different levels of back-surface roughness, flat-back versus curved-back, keel versus peg and more versus less conforming implants. Visually-observed failure and ASTM-recommended rim-displacements were recorded throughout testing to investigate fixation failure and if rim displacement is an appropriate measure of loosening. Roughening the implant back (Ra > 3 µm) improved resistance to failure (P < 0.005) by an order of magnitude with the rough and smooth groups failing at 8712 ± 5584 cycles (mean ± SD) and 1080 ± 1197 cycles, respectively. All other design parameters had no statistically significant effect on the number of cycles to failure. All implants failed inferiorly and 95 % (57/60) at the implant/cement interface. Rim-displacement correlated with visually observed failure. The most important effect was that of roughening the implant, which strengthened the polyethylene-cement interface. Rim-displacement can be used as an indicator of fixation failure, but the sensitivity was insufficient to capture subtle effects.Level of Evidence: Basic Science Study, Biomechanical Analysis

Metal Oxide Nanoparticles Induce Unique Inflammatory Footprints in the Lung: Important Implications for Nanoparticle Testing

BACKGROUND: Metal oxide nanoparticles (NPs) have been widely used in industry, cosmetics, and biomedicine. OBJECTIVES: We examined hazards of several well-characterized high production volume NPs because of increasing concern about occupational exposure via inhalation. METHODS: A panel of well-characterized NPs [cerium oxide (CeO(2)NP), titanium dioxide (TiO(2)NP), carbon black (CBNP), silicon dioxide (SiO(2)NP), nickel oxide (NiONP), zinc oxide (ZnONP), copper oxide (CuONP), and amine-modified polystyrene beads] was instilled into lungs of rats. We evaluated the inflammation potencies of these NPs 24 hr and 4 weeks postinstillation. For NPs that caused significant inflammation at 24 hr, we then investigated the characteristics of the inflammation. All exposures were carried out at equal-surface-area doses. RESULTS: Only CeO(2)NP, NiONP, ZnONP, and CuONP were inflammogenic to the lungs of rats at the high doses used. Strikingly, each of these induced a unique inflammatory footprint both acutely (24 hr) and chronically (4 weeks). Acutely, patterns of neutrophil and eosinophil infiltrates differed after CeO(2)NP, NiONP, ZnONP, and CuONP treatment. Chronic inflammatory responses also differed after 4 weeks, with neutrophilic, neutrophilic/lymphocytic, eosinophilic/fibrotic/granulomatous, and fibrotic/granulomatous inflammation being caused respectively by CeO(2)NP, NiONP, ZnONP, and CuONP. CONCLUSION: Different types of inflammation imply different hazards in terms of pathology, risks, and risk severity. In vitro testing could not have differentiated these complex hazard outcomes, and this has important implications for the global strategy for NP hazard assessment. Our results demonstrate that NPs cannot be viewed as a single hazard entity and that risk assessment should be performed separately and with caution for different NPs