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Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the “don’t eat me” signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47 −/− -mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.

The aim of this work study was to evaluate the cytophysiological activity of equine adipose-derived stem cells (ASCs) cultured under conditions of static magnetic field. Investigated cells were exposed to a static magnetic field (MF) with the intensity of 0.5 T. In order to investigate the effects of magnetic field on stem cell signaling, the localization and density and content of microvesicles (MVs) as well as morphology, ultrastructure, and proliferation rate of equine ASCs were evaluated. Results showed that potential of equine adipose-derived mesenchymal stem cells was accelerated when magnetic field was applied. Resazurin-based assay indicated that the cells cultured in the magnetic field reached the population doubling time earlier and colony-forming potential of equine ASCs was higher when cells were cultured under magnetic field conditions. Morphological and ultrastructural examination of equine ASCs showed that the exposure to magnetic field did not cause any significant changes in cell morphology whereas the polarity of the cells was observed under the magnetic field conditions in ultrastructural examinations. Exposition to MF resulted in a considerable increase in the number of secreted MVs—we have clearly observed the differences between the numbers of MVs shed from the cells cultured under MF in comparison to the control culture and were rich in growth factors. Microvesicles derived from ASCs cultured in the MF condition might be utilized in the stem cell-based treatment of equine musculoskeletal disorders and tendon injuries.

Introduction Laminar flow (LF) in theatres has become the standard of care in orthopaedic implant surgery. Most of the evidence for laminar flow use is based on arthroplasty surgery, with early studies showing a significant reduction in infections. We conducted a retrospective comparative study to assess surgical site infection (SSI) rates in consecutive patients undergoing surgery for trauma in LF and non-laminar flow (NLF) theatres. Methods Due to COVID-19 safety restrictions, trauma surgery was performed in non-laminar flow theatres during the pandemic. We identified consecutive patients who had trauma surgery pre- and post-pandemic from February 2019 to June 2021 to avoid selection bias. A total of 1809 patients were identified for the study, and the relevant patient details were collected through the hospital operating theatre software (Bluespier) and patient records (Welsh Clinical Portal). There were 917 in the laminar theatre group and 892 in the non-laminar theatre group. For the purpose of this study, we recorded SSI rates within the first 90 days. The two groups were statistically similar in terms of age and gender of the patients. Results Nineteen patients developed surgical site infections in non-laminar flow theatres and 25 patients in laminar flow theatres. There was no significant difference between the SSI rate in laminar flow theatres (2.72%) as compared to non-laminar flow theatres (2.13%) (p=0.399). There was no link between infections and the duration of surgery. Two patients in the laminar flow group were MRSA-positive and were excluded. Conclusion In our study, the laminar flow theatres did not show a statistically significant reduction in surgical site infections. We conclude in the practical environment of trauma theatres the theoretical advantage of laminar flow does not translate to an observable reduction of infections.

Hip fractures are common in patients with poor bone quality and are seen to affect the elderly and frail population. We report a case of implant failure after fixing an unstable intertrochanteric fracture with a dynamic hip screw (DHS). The patient presented with a DHS that had migrated into the pelvis approximately six months after surgery. Plain radiographs showed migration of the DHS through the acetabulum and into the pelvis. Migration of DHS into the pelvis is an extremely rare complication and has only been reported a few times. A 71-year-old man presented with a fall and confusion. The patient reported having a fall but could not recall the exact events. Past medical history included Alzheimer's dementia, osteoporosis, left total hip replacement, right DHS, peripheral neuropathy, and recurrent falls. He had undergone reduction and fixation of a right intertrochanteric fracture with DHS implant via direct lateral approach six months before hospital admission. On examination, he had right-sided hip pain and was unable to straighten leg raise. His abdomen was soft and non-tender, with no distension or palpable masses. Neurovascular status was normal, and no signs of infection were detected. On the anteroposterior radiograph, the implant seemed to have migrated through the acetabulum and into the abdomen. A CT of the abdomen and pelvis was performed to identify any visceral injuries (negative) and for surgical planning. The patient underwent a midline laparotomy to remove the implant. Although the exact reason for the implant failure is unknown, the migration of an unbroken hip screw into the abdomen and pelvis requiring laparotomy has not been reported in literature.

The aim of this study was to evaluate the influence of increase in intraocular pressure (IOP) and cooccurring changes in ocular biometry parameters on the corneal optical coherence tomography (OCT) speckle distribution in ex-vivo experiments on porcine intact eyes. Twenty-three eyeballs were used in the inflation test where IOP in the anterior chamber was precisely set from 10 mmHg to 40 mmHg in steps of 5 mmHg and where eye biometry was utilized (IOL Master 700). To assess the influence of the duration of the experiment on the OCT speckle statistics, the second experiment was performed with 10 eyeballs at the constant IOP of 15 mmHg. Based on the OCT scans of central cornea (Copernicus REVO), spatial maps of the scale parameter ( a ) and the shape parameter ( v ) of the gamma distribution speckle model were estimated. The means of both parameters for each spatial map were computed within the 2 mm of the central stroma. Both distributional parameters statistically significantly varied with IOP and time (one way repeated measures ANOVA, all p -values < 0.001). The a parameter revealed a faster statistically significant increase in IOP up to 25 mmHg, regardless of time. Central corneal thickness (CCT), the anterior chamber depth, and the mean equivalent spherical power varied significantly with IOP, whereas CCT and axial length changed statistically significantly with time. Statistically significant correlation was found between CCT and the a parameter, after removing IOP as a confounding factor (r = −0.576, p < 0.001). The parameters of the gamma distribution can be used not only for identifying IOP induced changes in the optical scattering within the corneal stroma, but also in corneal geometry. The approach of corneal speckle analysis could be potentially utilized for an indirect and noninvasive assessment of some properties of corneal stroma.

Background Hip fractures are one of the most common serious injuries seen today and constitute one of the most serious healthcare problems affecting the elderly worldwide. Due to the elderly population, associated falls and osteoporosis increase the incidence of hip fractures. Patients may remain hospitalized for several weeks, leading to one and a half million hospital bed days used each year. The reported incidence of a concurrent upper limb and a lower limb fracture is between 3% and 5%. It has been shown in the literature that patients who sustain both a hip fracture and an upper limb fracture have difficulties with rehabilitation which causes prolonged stays. The available literature on concomitant hip fracture and upper extremity fracture is limited. This study aimed to review patients with concurrent upper limb injury and hip fractures and to analyse the pattern of associated upper limb fractures, management of these fractures, length of hospital stay, mortality rates, and complications. Methodology We performed a retrospective data collection of all patients with a concomitant upper limb fracture and hip fracture from January 2017 to December 2020 at the University Hospital of Wales, Cardiff, United Kingdom. Patients were identified from the registers maintained in the ward. All patients aged over 60 years with a fragility hip fracture (managed operatively) and a concurrent upper limb fracture were included in the study. Patients aged less than 60 years were excluded. The local research department registered and approved this study as a service evaluation and therefore did not need ethical committee approval. The anatomical location of the upper limb and hip fractures was confirmed using the imaging database (Synapse). Results Of the 760 patients admitted with neck of femur fractures during this period, 39 (5.1%) patients had concomitant upper limb fractures. Only one upper limb fracture was managed with fixation, and for this study, that patient was excluded. Our retrospective search identified 38 patients, of whom 11 were men and 27 were women. Distal radius fractures were the most commonly associated upper limb fractures (55%). There was a significant increase in length of stay (43.6 days vs. 16.6 days) and delay in mobilization (58.9% vs. 81%) compared to an isolated hip fracture. There was no difference in the 30-day mortality rates. We were unable to collect the data for the Key Performance Indicator (KPI) of the National Institute for Health and Care Excellence compliant surgery, and this KPI was excluded from our study. Of the remaining five KPIs, our group of patients displayed better averages in three of the five categories, including prompt orthogeriatric review (92%), not delirious postoperatively (87%), and return to original residence (79%). Conclusions Due to the ageing population, hip fractures are increasing, and within one year of operation, have shown higher mortality rates. Annually, reports show that the worldwide incidence of fractures in the adult population ranges between 9.0 and 22.8 per 1,000. These fractures are more frequent in osteoporotic patients with weak bone quality. Following hip fractures, upper extremity fractures are the second most common among the osteoporotic, elderly population, with distal radius fractures being the most common. With the length of stay almost tripled (from 16.6 to 44.4 days), one can see this has a very big effect on costs in the National Health Service system.

Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene ( Ifnb1 ) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shutdown. Transcriptional regulation of the interferon-β gene ( Ifnb1 ) in macrophages is a critical immune event. Here, Ferri et al . show that, at late phases of macrophages activation, TRIM33 bound to a distal repressor element suppresses Ifnb1 transcription by preventing recruitment of CBP/p300.

The purpose of this study was to ascertain the relationships between the amplitude of the corneal pulse (CP) signal and the parameters of corneal biomechanics during ex-vivo intraocular pressure (IOP) elevation experiments on porcine eyes with artificially induced ocular pulse cycles. Two experiments were carried out using porcine eyes. In the first one, a selected eye globe was subjected to three IOP levels (15, 30 and 45 mmHg), where changes in physical ocular pulse amplitude were controlled by infusion/withdrawal volumes (ΔV). In the second experiment, six eyes were subjected to IOP from 15 mmHg to 45 mmHg in steps of 5 mmHg with a constant ΔV, where corneal deformation parameters were measured using Corvis ST. In both experiments, at each IOP, the CP and IOP signals were acquired synchronically using a non-contact ultrasonic distance sensor and a pressure transmitter, respectively. Based on the amplitudes of the CP and IOP signals ocular pulse based corneal rigidity index (OPCRI) was calculated. Results indicate positive correlations between ΔV and the physical ocular pulse amplitude, and between ΔV and the corneal pulse amplitude (both p < 0.001). OPCRI was found to increase with elevated IOP. Furthermore, IOP statistically significantly differentiated changes in OPCRI, the amplitudes of CP and IOP signals and in most of the corneal deformation parameters (p < 0.05). The partial correlation analysis, with IOP as a control variable, revealed a significant correlation between the length of the flattened cornea during the first applanation (A1L) and the corneal pulse amplitude (p = 0.002), and between A1L and OPCRI (p = 0.003). In conclusion, this study proved that natural corneal pulsations, detected with a non-contact ultrasonic technique, reflect pressure-volume dynamics and can potentially be utilized to assess stiffness of the cornea. The proposed new rigidity index could be a simple approach to estimating corneal rigidity.

Background Human multilineage-differentiating stress enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be easily obtained from various adult or fetal tissues. Regenerative effects of Muse cells have been shown in some disease models. Muse cells specifically home in damaged tissues where they exert pleiotropic effects. Exposition of the small intestine to high doses of irradiation (IR) delivered after radiotherapy or nuclear accident results in a lethal gastrointestinal syndrome (GIS) characterized by acute loss of intestinal stem cells, impaired epithelial regeneration and subsequent loss of the mucosal barrier resulting in sepsis and death. To date, there is no effective medical treatment for GIS. Here, we investigate whether Muse cells can prevent lethal GIS and study how they act on intestinal stem cell microenvironment to promote intestinal regeneration. Methods Human Muse cells from Wharton’s jelly matrix of umbilical cord (WJ-Muse) were sorted by flow cytometry using the SSEA-3 marker, characterized and compared to bone-marrow derived Muse cells (BM-Muse). Under gas anesthesia, GIS mice were treated or not through an intravenous retro-orbital injection of 50,000 WJ-Muse, freshly isolated or cryopreserved, shortly after an 18 Gy-abdominal IR. No immunosuppressant was delivered to the mice. Mice were euthanized either 24 h post-IR to assess early small intestine tissue response, or 7 days post-IR to assess any regenerative response. Mouse survival, histological stainings, apoptosis and cell proliferation were studied and measurement of cytokines, recruitment of immune cells and barrier functional assay were performed. Results Injection of WJ-Muse shortly after abdominal IR highly improved mouse survival as a result of a rapid regeneration of intestinal epithelium with the rescue of the impaired epithelial barrier. In small intestine of Muse-treated mice, an early enhanced secretion of IL-6 and MCP-1 cytokines was observed associated with (1) recruitment of monocytes/M2-like macrophages and (2) proliferation of Paneth cells through activation of the IL-6/Stat3 pathway. Conclusion Our findings indicate that a single injection of a small quantity of WJ-Muse may be a new and easy therapeutic strategy for treating lethal GIS.

Universally accepted guidelines to predict futile resuscitation in severely bleeding trauma patients with traumatic brain injury do not exist. These patients may consume vast volumes of blood products in futile cases, which is especially problematic during times of local and national blood scarcity. However, determining which patients have no chance of survival is complicated and often reliant on the traumatologist’s individual judgment, which may be inconsistent. Traumatologists often face the ethical dilemma of balancing their obligations to provide appropriate care for patients and to conserve blood products for other patients. To assist physicians, bedside futility algorithms have been developed, some of which emphasize the negative effects of traumatic brain injury on survival. Bedside futility algorithms may be used during futility time-outs early in the treatment of severely bleeding trauma patients who are unlikely to survive, potentially preventing blood product waste by providing guidance to clinicians in the early determination of futility and the withdrawal of life-sustaining treatment. These algorithms are steps toward the development of ethically grounded, data-driven clinical guidelines regarding the use of blood products in severely bleeding trauma patients. We compare historical and nascently proposed futility algorithms in the context of the ethical challenges of declaring futility in the severely injured population.