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Condition monitoring is a cost-effective means to reduce the unscheduled maintenance cost of insulated gate bipolar transistor (IGBT) modules. The junction to case thermal resistance $R_{\mathrm {thjc}}$ is considered as a critical health indicator of IGBT module solder layer. However, thermal interface materials’ (TIMs) deterioration will not only reduce the heat dissipation performance but also affects the accuracy of $R_{\mathrm {thjc}}$ monitoring of IGBT modules. This article investigates the effect of thermal grease deterioration on $R_{\mathrm {thjc}}$ monitoring of IGBT module. First, it is found that the thermal grease deterioration will lead to the decrease of monitored $R_{\mathrm {thjc}}$ of IGBT module under the same health status of IGBT solder layer, despite that the thermal resistance of TIM increasing as deterioration of the TIM takes place. That is, the same monitored increment ratio of $R_{\mathrm {thjc}}$ caused by the solder fatigue may correspond to different health status of the IGBT module, which cannot accurately reflect its actual health status. Then, a compensation strategy for thermal resistance monitoring based on the TIM aging rate is proposed, which uses the established mapping relationship to decouple the negative coupling part of TIM degradation. The compensated thermal resistance can better reflect the actual health status of the IGBT module and approximately eliminate the negative impact. Finally, the feasibility of the proposed compensation strategy is verified by finite element model (FEM) analysis and experiments. [ABSTRACT FROM AUTHOR]

With the emergence and rapid development of super-resolution fluorescence microscopy, monitoring of mitochondrial morphological changes has aroused great interest for exploring the role of mitochondria in the process of cell metabolism. However, in the absence of water-soluble, photostable and low-toxicity fluorescent dyes, ultra-high-resolution mitochondrial imaging is still challenging. Herein, we designed two fluorescent BODIPY dyes, namely Mito-BDP 630 and Mito-BDP 760, for mitochondrial imaging. The results proved that Mito-BDP 760 underwent aggregation-caused quenching (ACQ) in the aqueous matrix owing to its hydrophobicity and was inaccessible to the cells, which restricted its applications in mitochondrial imaging. In stark contrast, water-soluble Mito-BDP 630 readily penetrated cellular and mitochondrial membranes for mitochondrial imaging with high dye densities under wash-free conditions as driven by membrane potential. As a comparison, Mito Tracker Red presented high photobleaching (the fluorescence intensity dropped by nearly 50%) and high phototoxicity after irradiation by a laser for 30 min. However, Mito-BDP 630 possessed excellent biocompatibility, photostability and chemical stability. Furthermore, clear and bright mitochondria distribution in living HeLa cells after incubation with Mito-BDP 630 could be observed by CLSM. Convincingly, the morphology and cristae of mitochondria could be visualized using an ultra-high-resolution microscope. In short, Mito-BDP 630 provided a powerful and convenient tool for monitoring mitochondrial morphologies in living cells. Given the facile synthesis, photobleaching resistance and low phototoxicity of Mito-BDP 630, it is an alternative to the commercial Mito Tracker Red. [ABSTRACT FROM AUTHOR]

This paper mainly proposes a capacity configuration strategy for a hybrid wind farm with fixed-speed induction generator (FSIG)-based and permanent magnet synchronous generator (PMSG)-based wind farms during grid faults. In this paper, FSIG-based wind farm realizes low voltage ride through (LVRT) with the associated control of nearby PMSG systems as StatComs to provide the required reactive power. By establishing the mathematical model of hybrid wind farm containing network parameters, the operation characteristics of the FSIG-based wind farm during grid faults are analyzed in detail. Based on the characteristics and the critical clearing time of FSIG-based wind farm, a novel capacity configuration method for the hybrid wind farm is proposed to calculate the required reactive power of FSIG-based wind farm for a LVRT operation. Based on the capacity configuration result, the minimum installed capacity of PMSG-based wind farm could be determined. Taking into account the impact of reactive power compensation capacity and grid transmission line parameters, the coordinated LVRT capability of the hybrid wind farm is then analyzed. Finally, simulation and experimental results demonstrate the effectiveness of the proposed capacity configuration method and the coordinated operation performance of the hybrid wind farm respectively. [ABSTRACT FROM PUBLISHER]

This paper investigates a control strategy for a wind farm with the direct-driven permanent-magnet synchronous generators (PMSG)-based wind turbines and the fixed speed induction generators (FSIG)-based wind turbines under unbalanced grid voltage condition. By controlling the PMSG-based wind farm to inject negative-sequence current for decreasing voltage unbalance factor (VUF) at point of common coupling (PCC), the double grid frequency oscillations in electromagnetic torque, active, and reactive power output from the FSIG-based wind farm can be suppressed. In this paper, the maximum amplitude of the negative-sequence current provided by the PMSG-based wind farm under different average active power output and different VUF conditions is deduced, and the impacts of its phase angle on the VUF mitigation control effect are further studied. The improved control strategy of injecting negative-sequence current from the PMSG-based wind farm by the modified negative-sequence voltage and current double closed-loop control system is then developed. Finally, the correctness of theoretical analysis and the effectiveness of the proposed control strategy are validated by the experimental results. [ABSTRACT FROM PUBLISHER]

Abstract—This article presents an enhanced control strategy for a direct-driven permanent synchronous generator based wind-power generation system with a flywheel energy storage unit. The behaviors of the direct-driven permanent magnet synchronous generator system with a flywheel energy storage unit under unbalanced grid fault conditions are investigated. Three control targets for the grid-side converter during network unbalance conditions are identified, including eliminating the oscillations in the total active power or reactive power or no negative-sequence current injecting into the grid. Meanwhile, the DC-link voltage oscillations can be effectively suppressed during the unbalanced grid fault by controlling the flywheel energy storage unit. Furthermore, a proportional–integral-resonant controller is designed for the flywheel motor to eliminate the oscillations in the DC-link voltage. Finally, the proposed coordinated control strategy for the direct-driven permanent magnet synchronous generator system with a flywheel energy storage unit has been validated by the simulation results of a 1-MW direct-driven permanent magnet synchronous generator wind power generation system with a flywheel energy storage unit under unbalanced grid fault. [ABSTRACT FROM AUTHOR]

Objective. Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the inflammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis. Materials and method. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements. Results. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor- κB ligand (RANKL), receptor activator of nuclear factor- κB (RANK), osteoprotegerin (OPG), tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. Conclusions. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the pathophysiological processes that take place before and after repair. Summarizing key concepts using animal studies may allow for a better assessment of common pre- and postoperative microstructural abnormalities in RD. We performed a systematic literature review on Ovid MEDLINE, EMBASE, and Cochrane Controlled Register of Trials from January 1968 to January 2022, searching animal or human studies reporting retinal histologic changes following primary or induced RD. Thirty-two studies were included. Main cellular events were summarized: photoceptor apoptosis occurs as early as 12 hours after RD and, although most cells survive, there is extensive remodeling. Outer segments progressively degenerate, while inner segments are reorganized. Rod and cone opsins are redistributed, and rod axons retract while cones undergo changes in shape. Second- and third-order neurons rearrange their dendritic processes, and Müller cells become hypertrophic, growing into the subretinal space. Finally, retinal pigment epithelium cells undergo a change in their morphology. Acknowledging critical morphologic changes following RD is crucial in understanding why anatomical and functional outcomes can vary. Insights from histological studies, together with high-resolution imaging, may be key in identifying novel biomarkers in RD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to compare the outcomes of ProKera versus amniotic membrane transplantation (AMT) in managing ocular surface disease., Methods: This study is a retrospective case series of patients who received either ProKera or sutured AMT for ocular surface disease. Patient demographics, treatment indications, retention time, percentage healed area, changes in visual acuity, and costs to the health care system were analyzed., Results: Fourteen patients were identified and analyzed for each group. The main indications for using ProKera and AMT were similar, including corneal ulcer or epithelial defect due to chemical burns, neurotropic state, or herpes zoster keratitis. The average time to dissolution or removal was 24.8 days in the ProKera group, compared with 50.1 days in the AMT group. The average percentage of healed corneal area was 59% for ProKera and 73% for AMT. There was no significant difference between the initial and the final visual acuity within groups and when comparing both groups. In our expense analysis, ProKera had a total cost of 699.00 Canadian dollars (CAD), whereas the cost of suture AMT was 1561.52 CAD. ProKera priced at 11.85 CAD for each percentage healed surface area and at 21.39 CAD for AMT., Conclusions: ProKera allowed for a faster corneal healing than sutured AMT, although its total healed area was less than the latter. Moreover, ProKera is more cost-effective than AMT, thus reducing financial burden to our health care system., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The 2019 Annual General Meeting and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherche Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada / Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was held in Banff, Alberta on November 8-10th, 2019. The theme was "Positioning Early Career Investigators for Success: Strategy and Resilience". Lectures and workshops provided knowledge and tools to facilitate the attendees' development as clinician investigators. Dr. Jason Berman (President of CSCI/SCRC), Elina Cook (President of CITAC/ACCFC) and Drs. Doreen Rabi and Zelma Kiss (University of Calgary Organizing Co-Chairs) gave opening presentations. The keynote speakers were Dr. William Foulkes (McGill University) (Distinguished Scientist Award winner) and Dr. Andrés Finzi (Université de Montréal) (Joe Doupe Young Investigator Award winner). Dr. Robert Bortolussi (Dalhousie University) received the Distinguished Service Award for his work as the Editor-in-Chief of Clinical and Investigative Medicine and for being instrumental in the development of the Canadian Child Health Clinician Scientist Program. This meeting was the first to host a panel discussion with Drs. Stephen Robbins and Marcello Tonelli from the Canadian Institutes of Health Research. Workshops on communication, career planning and work-life balance were hosted by André Picard and Drs. Todd Anderson, Karen Tang, William Ghali, May Lynn Quan, Alicia Polachek and Shannon Ruzycki. The AGM showcased 90 presentations from clinician investigator trainees from across Canada. Most of the abstracts are summarized in this review. Eight outstanding abstracts were selected for oral presentation at the President's Forum.

Retinopathy of prematurity (ROP) is the leading cause of blindness in neonates. Inflammation, in particular interleukin-1β (IL-1β), is increased in early stages of the disorder, and contributes to inner and outer retinal vasoobliteration in the oxygen-induced retinopathy (OIR) model of ROP. A small peptide antagonist of IL-1 receptor, composed of the amino acid sequence, rytvela, has been shown to exert beneficial anti-inflammatory effects without compromising immunovigilance-related NF-κB in reproductive tissues. We conducted a longitudinal study to determine the efficacy of "rytvela" in preserving the integrity of the retina in OIR model, using optical coherence tomography (OCT) which provides high-resolution cross-sectional imaging of ocular structures in vivo . Sprague-Dawley rats subjected to OIR and treated or not with "rytvela" were compared to IL-1 receptor antagonist (Kineret). OCT imaging and custom automated segmentation algorithm used to measure retinal thickness (RT) were obtained at P14 and P30; gold-standard immunohistochemistry (IHC) was used to confirm retinal anatomical changes. OCT revealed significant retinal thinning in untreated animals by P30, confirmed by IHC; these changes were coherently associated with increased apoptosis. Both rytvela and Kineret subsided apoptosis and preserved RT. As anticipated, Kineret diminished both SAPK/JNK and NF-κB axes, whereas rytvela selectively abated the former which resulted in preserved monocyte phagocytic function. Altogether, OCT imaging with automated segmentation is a reliable non-invasive approach to study longitudinally retinal pathology in small animal models of retinopathy., (Copyright © 2020 Sayah, Zhou, Omri, Mazzaferri, Quiniou, Wirth, Côté, Dabouz, Desjarlais, Costantino and Chemtob.)

Retinopathy of prematurity (ROP) is characterized by an initial retinal avascularization, followed by pathologic neovascularization. Recently, choroidal thinning has also been detected in children formerly diagnosed with ROP; a similar sustained choroidal thinning is observed in ROP models. But the mechanism underlying the lack of choroidal revascularization remains unclear and was investigated in an oxygen-induced retinopathy (OIR) model. In OIR, evidence of senescence was detected, preceded by oxidative stress in the choroid and the retinal pigment epithelium. This was associated with a global reduction of proangiogenic factors, including insulin-like growth factor 1 receptor (Igf1R). Coincidentally, tumor suppressor p53 was highly expressed in the OIR retinae. Curtailing p53 activity resulted in reversal of senescence, normalization of Igf1r expression, and preservation of choroidal integrity. OIR-induced down-regulation of Igf1r was mediated at least partly by miR-let-7b as i) let-7b expression was augmented throughout and beyond the period of oxygen exposure, ii) let-7b directly targeted Igf1r mRNA, and iii) p53 knock-down blunted let-7b expression, restored Igf1r expression, and elicited choroidal revascularization. Finally, restoration of Igf1r expression rescued choroid thickness. Altogether, this study uncovers a significant mechanism for defective choroidal revascularization in OIR, revealing a new role for p53/let-7b/IGF-1R axis in the retina. Future investigations on this (and connected) pathway could further our understanding of other degenerative choroidopathies, such as geographic atrophy., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

A decade of CITAC Annual General Meetings: 2007-2017 In 2007, the Clinician Investigator Trainee Association of Canada (CITAC) launched its inaugural Annual General Meeting (AGM). The AGM has since become a major annual event, jointly organized by CITAC and leaders from the Canadian Society for Clinical Investigation (CSCI), and continues to provide a forum for clinician investigator (CI) trainees to exchange ideas, advance career prospects and engage with the broader community. Indeed, since its inception, all Canadian institutions with medical doctor and clinician investigator (MD+CI) training programs have participated in the AGM, while more than 1,000 trainees have registered as CITAC members. The 10th CITAC-CSCI AGM was recently held in Toronto (November 20-22, 2017). There were nearly 200 attendees, including CI trainees, faculty member and physician leaders from across Canada (Figure 1A, 1B). Trainees spanning diverse career stages had opportunities to participate in interactive poster sessions, workshops and lectures by leading physician-scientists. These exercises were designed to encourage and enhance networking, career development and mentorship for prospective physician-scientists.

The 2016 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national conference held in Toronto November 21-23, 2016, in conjunction with The University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Mapping Your Career as a Clinician-Scientist"; emphasizing essential skills for developing a fruitful career as clinician-scientist. The meeting featured an opening presentation by Dr. Alan Underhill, Dr. Nicola Jones and Alexandra Kuzyk. The keynote speakers were Dr. Nada Jabado (McGill University), who discussed the association between cancer and histones, Dr. Norman Rosenblum (University of Toronto), who addressed the career path and the "calling" of the Clinician Scientist, Dr. Martin Schmeing (McGill University), who was the 2016 Joe Doupe Award recipient, and Dr. Linda Rabeneck (Cancer Care Ontario and University of Toronto), who received the Friends of CIHR lectureship. The workshops, focusing on career development for clinician scientists, were hosted by Drs. Alan Underhill, Nicola Jones, Lynn Raymond, Michael Schlossmacher and Norman Rosenblum, as well as University of Toronto communication specialists, Caitlin Johannesson and Suzanne Gold. In addition, the Young Investigators' Forum included presentations from clinician investigator trainees from across the country. The research topics were diverse and comprehensive: from basic sciences to clinical practice; from epidemiology to medical engineering. All scientific abstracts are summarized in this review. Over 70 abstracts were showcased at this year's meeting during two poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Clinician-scientists are physicians with training in both clinical medicine and research that enables them to occupy a unique niche as specialists in basic and translational biomedical research. While there is widespread acknowledgement of the importance of clinician-scientists in today's landscape of evidence-based medical practice, training of clinician-scientists in Canada has been on the decline, with fewer opportunities to obtain funding. With the increasing length of training and lower financial compensation, fewer medical graduates are choosing to pursue such a career. MD-PhD programs, in which trainees receive both medical and research training, have the potential to be an important tool in training the next generation of clinician-scientists; however, MD-PhD trainees in Canada face barriers that include an increase in medical school tuition and a decrease in the amount of financial support. We examined the available data on MD-PhD training in Canada and identified a lack of oversight, a lack of funding and poor mentorship as barriers experienced by MD-PhD trainees. Specific recommendations are provided to begin the process of addressing these challenges, starting with the establishment of an overseeing national body that would track long-term outcome data for MD-PhD trainees. This national body could then function to implement best practices from individual programs across the country and to provide further mentorship and support for early-career physician-scientists. MD-PhD programs have the potential to address Canada's growing shortage of clinician-scientists, and strengthening MD-PhD programs will help to effect positive change.

Background: The present study was conducted to compare 2 purification methods for isolation of human adipose-derived stromal vascular fraction or stem cells (ADSCs) based on red blood cell (RBC) lysis with 155 mM ammonium chloride (NH4Cl) and hypotonic sodium chloride (NaCl) solution, and try to develop a safe, convenient, and cost-effective purification method for clinical applications., Methods: Adipose-derived stem cells and RBC were harvested from the fatty and fluid portions of liposuction aspirates, respectively. The suitable concentration of hypotonic NaCl solution on RBC lysis for purification of ADSCs was developed by RBC osmotic fragility test and flow cytometry analysis. The effects of 155 mM NH4Cl or 0.3% NaCl solution on ADSCs proliferation and RBC lysis efficiency were examined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and lysis efficiency test, respectively. In addition, the adipogenic and osteogenic capabilities, phenotype and genetic stability of ADSCs were evaluated by oil red staining, alkaline phosphatase activity measurement, flow cytometry, and karyotype analysis, respectively., Results: Sodium chloride solution in 0.3% concentration effectively removed RBCs and did not influence the survival of ADSCs in the 10-minute incubation time. The lysis efficiency did not differ significantly between 0.3% NaCl and 155 mM NH4Cl. Moreover, the adipogenic and osteogenic capabilities, surface marker expression and karyotype of the ADSCs were not affected by lysis solutions or by lysis per se. However, the proliferation capacity in the 0.3% NaCl group was superior to that in 155 mM NH4Cl group., Conclusions: Our data suggest that 0.3% NaCl solution is useful for isolating ADSCs from liposuction aspirate for clinical applications with safety, convenience, and cost-effect.

Purpose: Spectral-domain optical coherence tomography (SD-OCT) is widely used in clinical ophthalmology and recently gained popularity in laboratory research involving small rodents. Its noninvasive nature allows repeated measurements, thereby decreasing the number of animals required. However, when used at a conventional dosage, xylazine (an α2-adrenoceptor) can cause irreversible corneal calcification, especially among young rodents. In the present study, we test whether corneal calcification associated with xylazine is mediated by the α2-adrenoceptor., Methods: Our study tested Sprague-Dawley rats, Long-Evans rats, and CD-1 mice (postnatal day [P]14). Retinal images were captured by SD-OCT. Quantitative PCR (qPCR) was used to study gene expression, whereas receptor localization was examined by immunofluorescent staining followed by confocal microscopy. Calcium deposits were detected via von Kossa staining., Results: When used at dosages appropriate for adult animals, ketamine-xylazine anesthetics led to a high rate of respiratory failure, increased apoptotic activity in the corneal epithelium, and irreversible corneal calcification in P14 rat pups. Meanwhile, OCT image quality decreased drastically as a result of corneal calcification among animals recovering from anesthesia. α2-Adrenoceptor subtypes were highly expressed on P14, in line with rodents' age-specific sensitivity to xylazine. Clonidine, a potent α2-adrenoceptor agonist, dose-dependently induced corneal calcification, which could be prevented by an α2-adrenoceptor antagonist., Conclusions: These data suggest that α2-adrenoceptors contribute to corneal calcification in young rodents. Therefore, we developed a suitable OCT imaging protocol for this cohort, including a carefully tailored ketamine-xylazine dosage (60 mg/kg and 2.5 kg/mg, respectively).

Retinopathy of prematurity (ROP), the most common cause of blindness in premature infants, has long been associated with inner retinal alterations. However, recent studies reveal outer retinal dysfunctions in patients formerly afflicted with ROP. We have recently demonstrated that choroidal involution occurs early in retinopathy. Herein, we investigated the mechanisms underlying the choroidal involution and its long-term impact on retinal function. An oxygen-induced retinopathy (OIR) model was used. In vitro and ex vivo assays were applied to evaluate cytotoxic effects of IL-1β on choroidal endothelium. Electroretinogram was used to evaluate visual function. We found that proinflammatory IL-1β was markedly increased in retinal pigment epithelium (RPE)/choroid and positively correlated with choroidal degeneration in the early stages of retinopathy. IL-1β was found to be cytotoxic to choroid in vitro, ex vivo, and in vivo. Long-term effects on choroidal involution included a hypoxic outer neuroretina, associated with a progressive loss of RPE and photoreceptors, and visual deterioration. Early inhibition of IL-1β receptor preserved choroid, decreased subretinal hypoxia, and prevented RPE/photoreceptor death, resulting in life-long improved visual function in IL-1 receptor antagonist-treated OIR animals. Together, these findings suggest a critical role for IL-1β-induced choroidal degeneration in outer retinal dysfunction. Neonatal therapy using IL-1 receptor antagonist preserves choroid and prevents protracted outer neuroretinal anomalies in OIR, suggesting IL-1β as a potential therapeutic target in ROP., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder., Conclusion: Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Platelet-activating factor (PAF) is a pleiotropic phospholipid with proinflammatory, procoagulant and angiogenic actions on the vasculature. We and others have reported the presence of PAF receptor (Ptafr) at intracellular sites such as the nucleus. However, mechanisms of localization and physiologic functions of intracellular Ptafr remain poorly understood. We hereby identify the importance of C-terminal motif of the receptor and uncover novel roles of Rab11a GTPase and importin-5 in nuclear translocation of Ptafr in primary human retinal microvascular endothelial cells. Nuclear localization of Ptafr is independent of exogenous PAF stimulation as well as intracellular PAF biosynthesis. Moreover, nuclear Ptafr is responsible for the upregulation of unique set of growth factors, including vascular endothelial growth factor, in vitro and ex vivo. We further corroborate the intracrine PAF signaling, resulting in angiogenesis in vivo, using Ptafr antagonists with distinct plasma membrane permeability. Collectively, our findings show that nuclear Ptafr translocates in an agonist-independent manner, and distinctive functions of Ptafr based on its cellular localization point to another dimension needed for pharmacologic selectivity of drugs.

Background: Sepsis has become the greatest threat to in-patients, with a mortality of over 25%. The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture., Methods: Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected., Results: The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P<0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P<0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group., Conclusion: The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.