764 research outputs found

    Assessing the waiting time for emergency orthopedic surgery for open fractures – A 6-month review of records at one of the largest referral public hospitals in Rwanda

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    INTRODUCTION: The delay in surgical intervention for open fractures can have severe negative consequences. However, the delay for patients with open fractures presenting at Centre Hospitalier Universitaire de Kigali (CHUK), one of the largest public hospitals in Kigali, Rwanda, had not been studied. This study assessed the waiting time for surgery and compared it against the 6-hour (ideal time) and 24-hours (acceptable time) standards.METHODS: A review of the postoperative register and patients’ records was conducted. All medical charts of open fracture cases between April and September 2018 were audited. A surgical case was considered significantly delayed if the time interval from patient arrival at the emergency room to the operation theater was longer than 24 hours. The demographics, acuity level, insurance status and work shifts, were assessed using bi- and multivariate analysis.RESULTS: A total of 115 open fracture case files were audited. From arrival at the emergency room to surgery, the median time was 41 hours (IQR 21, 93). Only 3 (2.6%) were operated within 6 hours and 38 (33%) within 6 to 24 hours. The main factor contributing to the delay was obtaining orthopedic consultation note and documenting the decision to operate (median 10 hours, IQR 4 to 17). Meanwhile, the designated emergency theater was not utilized for a total of 18 hours per day, especially during night shifts.CONCLUSION: There was a significant delay in obtaining emergency orthopedic consultation and, thus, the timing of the surgical treatment. Examining the patient flow system in orthopedic surgical care delivery is needed in order to maximize theater utilization at this urban university hospital

    Tendon-like Electrospun PLGA Scaffolds with Optimized Physical Cues Induced Tenogenic Differentiation and Boosted Immunomodulatory Properties on Amniotic Epithelial Stem Cells.

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    Introduction: The advanced strategies in the field of Tissue Engineering might render possible overcoming the unsatisfactory results of conventional treatments to deal with tendinopathies. In this context, the design of tendon biomimetic electrospun scaffolds engineered with Amniotic Epithelial Stem Cells (AECs), which have shown a high teno-regenerative and immunomodulatory potential in tendon-defect models, can represent a promising solution for tendon regeneration. Methods: Poly(lactide-co-glycolic) acid (PLGA) scaffolds were fabricated using the electrospinning technique to mimic the native tendon biomechanics and extracellular matrix by optimizing: fiber alignment and diameter size (1.27 and 2.5 µm), and surface chemistry using the Cold Atmospheric Plasma (CAP) Technique. Moreover, the teno-inductive and immunomodulatory effects of these parameters on AECs have been also assessed. Results: The fabricated PLGA scaffolds with highly aligned fibers and small diameter size (1.27 µm) induced a stepwise tenogenic differentiation on AECs with an early epithelial-mesenchymal transition (EMT), followed by their tenogenic differentiation. Indeed, SCX, an early tendon marker, was significantly more efficiently translated into the downstream effector TNMD, a mature tendon marker. Moreover, 1.27 µm fiber diameter induced on AECs a higher expression of anti-inflammatory interleukin mRNAs (IL-4 and IL-10). The CAP treated PLGA scaffolds showed an improved cell adhesion and infiltration without altering their topological structure and teno-inductive properties. In fact, AECs engineered with CAP treated fibers, expressed in their cytoplasm TNMD. Moreover, CAP treatment did not alter the mechanical properties of PLGA scaffolds. Conclusions: The developed electrospun PLGA scaffolds with the optimized features represent an ideal tendon-like construct that could be applied in in-vivo models to evaluate their biosafety and teno-regenerative potential

    A geospatial framework to support integrated biogeochemical modelling in the United Kingdom

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    Anthropogenic impacts on the aquatic environment, especially in the context of nutrients, provide a major challenge for water resource management. The heterogeneous nature of policy relevant management units (e.g. catchments), in terms of environmental controls on nutrient source and transport, leads to the need for holistic management. However, current strategies are limited by current understanding and knowledge that is transferable between spatial scales and landscape typologies. This study presents a spatially-explicit framework to support the modelling of nutrients from land to water, encompassing environmental and spatial complexities. The framework recognises nine homogeneous landscape units, distinct in terms of sensitivity of nutrient losses to waterbodies. The functionality of the framework is demonstrated by supporting an exemplar nutrient model, applied within the Environmental Virtual Observatory pilot (EVOp) cloud cyber-infrastructure. We demonstrate scope for the use of the framework as a management decision support tool and for further development of integrated biogeochemical modelling

    Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

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    Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

    Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving their Immunomodulatory Profile In Vitro

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    Electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds with highly aligned fibers (ha-PLGA) represent promising materials in the field of tendon tissue engineering (TE) due to their characteristics in mimicking fibrous extracellular matrix (ECM) of tendon native tissue. Among these properties, scaffold biodegradability must be controlled allowing its replacement by a neo-formed native tendon tissue in a controlled manner. In this study, ha-PLGA were subjected to hydrolytic degradation up to 20 weeks, under di-H2 O and PBS conditions according to ISO 10993-13:2010. These were then characterized for their physical, morphological, and mechanical features. In vitro cytotoxicity tests were conducted on ovine amniotic epithelial stem cells (oAECs), up to 7 days, to assess the effect of non-buffered and buffered PLGA by-products at different concentrations on cell viability and their stimuli on oAECs’ immunomodulatory properties. The ha-PLGA scaffolds degraded slowly as evidenced by a slight decrease in mass loss (14%) and average molecular weight (35%), with estimated degradation half-time of about 40 weeks under di-H2 O. The ultrastructure morphology of the scaffolds showed no significant fiber degradation even after 20 weeks, but alteration of fiber alignment was already evident at week 1. Moreover, mechanical properties decreased throughout the degradation times under wet as well as dry PBS conditions. The influence of acid degradation media on oAECs was dose-dependent, with a considerable effect at 7 days’ culture point. This effect was notably reduced by using buffered media. To a certain level, cells were able to compensate the generated inflammation-like microenvironment by upregulating IL-10 gene expression and favoring an anti-inflammatory rather than pro-inflammatory response. These in vitro results are essential to better understand the degradation behavior of ha-PLGA in vivo and the effect of their degradation by-products on affecting cell performance. Indeed, buffering the degradation milieu could represent a promising strategy to balance scaffold degradation. These findings give good hope with reference to the in vivo condition characterized by physiological buffering systems

    Tendon biomimetic 3D scaffold enhance amniotic epithelial stem cells biological potential

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    Tendon tissue engineering represents an emerging field whose aim focuses on the design of 3D tendon biomimetic scaffolds that should ideally combine adequate physical, mechanical, biological and functional properties of the native tissue. In this research, it was designed a bundle tendon-like PLGA 3D scaffold with highly aligned fibers on which the structure and mechanical properties were evaluated. Moreover, it was assessed scaffold’s teno-differentiative and immuno-inductive ability on amniotic epithelial stem cells (AECs). The fabricated PLGA 3D scaffolds mimic macroscopically and microscopically the structure of native tendon tissue and its biomechanical properties. Biologically, AECs seeded on the fabricated 3D scaffolds acquired a spindle tenocyte-like morphology after just 24h compared to the AECs cultured on petri dishes (CTR) which maintained their cobblestone morphology. The phenotypic change of the engineered AECs was also confirmed by visualizing TNMD protein expression, a mature tendon marker, within their cytoplasm and supported by the analysis of tendon-related genes (SCX, COL1, and TNMD) that were significantly upregulated at 7-day culture, while no TNMD protein expression or significant increase in tendon-related genes was found in CTR cells. Moreover, the 3D construct induced on AECs an upregulation of IL-10, an anti-inflammatory cytokine, maintaining basal levels of IL-12, a pro-inflammatory cytokine, showing a favorable IL10/IL12 ratio. In conclusion, the fabricated PLGA 3D scaffolds are tendon biomimetic in terms of ultrastructure and biomechanics, making them also suitable for surgical purposes. Moreover, these constructs revealed a high teno- and immuno-inductive potential on AECs and thus represent potential candidates for tendon regeneration

    Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

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    Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials. However, any technological advancement must take into consideration the role of the immune system in tissue regeneration and the potential of biomaterial scaffolds to control the immune signaling, creating a pro-regenerative environment. In this context, immunoengineering has emerged as a new discipline, developing innovative strategies for tendon injuries. It aims at designing scaffolds, in combination with engineered bioactive molecules and/or stem cells, able to modulate the interaction between the transplanted biomaterial-scaffold and the host tissue allowing a pro-regenerative immune response, therefore hindering fibrosis occurrence at the injury site and guiding tendon regeneration. Thus, this review is aimed at giving an overview on the role exerted from different tissue engineering actors in leading immunoregeneration by crosstalking with stem and immune cells to generate new paradigms in designing regenerative medicine approaches for tendon injuries
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