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Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of intra-bursal injection of single-dose platelet-rich plasma (PRP) against corticosteroids under ultrasonography guidance in shoulder impingement syndrome (SIS). Materials and methods: This single-blind randomized controlled trial was conducted on 60 participants with a clinical diagnosis of SIS from a selected orthopedic clinic. Thirty participants in each arm were given a single dose of either PRP or triamcinolone acetonide into the subacromial sub-deltoid bursa (SASD) under ultrasonography guidance. The outcome variables assessed were the severity score of pain and the degree of shoulder abduction. Post-treatment follow-up was done in 1 week, 3 months, 6 months, and 1 year. Results: At 1 week, the triamcinolone arm showed a statistically significant reduction of pain (p = 0.039) when compared to PRP. In the long term, PRP showed statistically significant improvement in shoulder abduction, compared to the triamcinolone injection (p = 0.012). Conclusion: PRP and triamcinolone in the SASD bursa could be considered as safe treatment options for SIS under ultrasonography guidance. While triamcinolone was effective in short-term pain reduction, PRP was effective in long-term improvement in shoulder abduction. [ABSTRACT FROM AUTHOR]

Copyright of Western North American Naturalist is the property of Monte L. Bean Life Science Museum and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

l-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of l-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral l-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length. Visual electrophysiology, acuity, and retinal morphology were measured at 4, 5, 6, 12 and 16 weeks PNA and compared to untreated C57BL/6 J (WT) and OCA1 mice. Quantification of PEDF, βIII-tubulin and syntaxin-3 expression was also performed. Our data showed impaired retinal morphology, decreased retinal function and lower visual acuity in untreated OCA1 mice compared to WT mice. These changes were diminished or eliminated when treated with higher doses of l-DOPA/Carbidopa. Our results demonstrate that oral l-DOPA/Carbidopa supplementation at human equivalent doses during the postnatal critical period of retinal neuroplasticity can rescue visual retinal morphology and retinal function, via PEDF upregulation and modulation of retinal synaptogenesis, providing a further step towards developing an effective treatment for albinism patients. [ABSTRACT FROM AUTHOR]

Residents of Ratnapura District's communities are seriously at risk from landslides. The creation of precise and timely landslide prediction systems is essential to reduce the risks and improve readiness for disasters. Landslide prediction in the Ratnapura District is the topic of a larger Pre-Disaster and Risk Detection AI Prediction System presented in this paper. The component seeks to offer the likelihood of possible landslides by utilizing cutting-edge machine learning techniques and geographical data. To build a complete landslide prediction model, the suggested system combines topographical and geological data sources. The system examines the correlations between numerous environmental parameters using machine learning methods. The program can produce probabilistic forecasts of landslide occurrences in the Ratnapura District since it has been trained to recognize patterns and trends that precede landslides. The Pre-Disaster and Risk Detection AI Prediction System, which has a dedicated landslide prediction module, makes use of AI and predictive analytics to enhance the Ratnapura District's disaster management approach. This component shows the significance of technology innovation in protecting vulnerable communities from natural disasters as part of a complete risk detection framework. [ABSTRACT FROM AUTHOR]

Introduction: The non-growing, meiotically-arrested oocytes housed within primordial follicles are exquisitely sensitive to genotoxic insults from endogenous and exogenous sources. Even a single DNA double-strand break (DSB) can trigger oocyte apoptosis, which can lead to accelerated depletion of the ovarian reserve, early loss of fertility and menopause. Therefore, repair of DNA damage is important for preserving the quality of oocytes to sustain fertility across the reproductive lifespan. This study aimed to evaluate the role of KU80 (encoded by the XRCC5 gene) - an essential component of the non-homologous end joining (NHEJ) pathway - in the repair of oocyte DNA DSBs during reproductive ageing, and following insult caused by the DNA-damaging chemotherapies cyclophosphamide and cisplatin. Methods: To investigate the importance of KU80 following endogenous and exogenous DNA damage, ovaries from conditional oocyte-specific Xrcc5 knockout (Xrcc5 cKO) and wildtype (WT) mice that were aged or exposed to DNA damage-inducing chemotherapy were compared. Ovarian follicles and oocytes were quantified, morphologically assessed and analysed via immunohistochemistry for markers of DNA damage and apoptosis. In addition, chemotherapy exposed mice were superovulated, and the numbers and quality of mature metaphase-II (MII) oocytes were assessed. Results: The number of healthy follicles, atretic (dying) follicles, and corpora lutea were similar in Xrcc5 cKO and WT mice at PN50, PN200 and PN300. Additionally, primordial follicle number and ovulation rates were similar in young adult Xrcc5 cKO and WT mice following treatment with cyclophosphamide (75mg/kg), cisplatin (4mg/kg), or vehicle control (saline). Furthermore, KU80 was not essential for the repair of exogenously induced DNA damage in primordial follicle oocytes. Discussion: These data indicate that KU80 is not required for maintenance of the ovarian reserve, follicle development, or ovulation during maternal ageing. Similarly, this study also indicates that KU80 is not required for the repair of exogenously induced DSBs in the prophase-arrested oocytes of primordial follicles. [ABSTRACT FROM AUTHOR]

Transcatheter cardiovascular interventions increasingly rely on advanced imaging. X-ray fluoroscopy provides excellent visualization of catheters and devices, but poor visualization of anatomy. In contrast, magnetic resonance imaging (MRI) provides excellent visualization of anatomy and can generate real-time imaging with frame rates similar to X-ray fluoroscopy. Realization of MRI as a primary imaging modality for cardiovascular interventions has been slow, largely because existing guidewires, catheters and other devices create imaging artifacts and can heat dangerously. Nonetheless, numerous clinical centers have started interventional cardiovascular magnetic resonance (iCMR) programs for invasive hemodynamic studies or electrophysiology procedures to leverage the clear advantages of MRI tissue characterization, to quantify cardiac chamber function and flow, and to avoid ionizing radiation exposure. Clinical implementation of more complex cardiovascular interventions has been challenging because catheters and other tools require re-engineering for safety and conspicuity in the iCMR environment. However, recent innovations in scanner and interventional device technology, in particular availability of high performance low-field MRI scanners could be the inflection point, enabling a new generation of iCMR procedures. In this review we review these technical considerations, summarize contemporary clinical iCMR experience, and consider potential future applications. [ABSTRACT FROM AUTHOR]

l-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of l-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral l-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length. Visual electrophysiology, acuity, and retinal morphology were measured at 4, 5, 6, 12 and 16 weeks PNA and compared to untreated C57BL/6 J (WT) and OCA1 mice. Quantification of PEDF, βIII-tubulin and syntaxin-3 expression was also performed. Our data showed impaired retinal morphology, decreased retinal function and lower visual acuity in untreated OCA1 mice compared to WT mice. These changes were diminished or eliminated when treated with higher doses of l-DOPA/Carbidopa. Our results demonstrate that oral l-DOPA/Carbidopa supplementation at human equivalent doses during the postnatal critical period of retinal neuroplasticity can rescue visual retinal morphology and retinal function, via PEDF upregulation and modulation of retinal synaptogenesis, providing a further step towards developing an effective treatment for albinism patients. [ABSTRACT FROM AUTHOR]

There are no disease-modifying treatments available for geographic atrophy (GA), the advanced form of dry age-related macular degeneration. Current murine models fail to fully recapitulate the features of GA and thus hinder drug discovery. Here we describe a novel mouse model of retinal degeneration with hallmark features of GA. We used an 810 nm laser to create a retinal lesion with central sparing (RLCS), simulating parafoveal atrophy observed in patients with progressive GA. Laser-induced RLCS resulted in progressive GA-like pathology with the development of a confluent atrophic lesion. We demonstrate significant changes to the retinal structure and thickness in the central unaffected retina over a 24-week post-laser period, confirmed by longitudinal optical coherence tomography scans. We further show characteristic features of progressive GA, including a gradual reduction in the thickness of the central, unaffected retina and of total retinal thickness. Histological changes observed in the RLCS correspond to GA pathology, which includes the collapse of the outer nuclear layer, increased numbers of GFAP + , CD11b + and FcγRI + cells, and damage to cone and rod photoreceptors. We demonstrate a laser-induced mouse model of parafoveal GA progression, starting at 2 weeks post-laser and reaching confluence at 24 weeks post-laser. This 24-week time-frame in which GA pathology develops, provides an extended window of opportunity for proof-of-concept evaluation of drugs targeting GA. This time period is an added advantage compared to several existing models of geographic atrophy. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-9 (MMP9) and total amyloid-beta (Aβ) are prospective biomarkers of ocular ageing and retinopathy. These were quantified by ELISA in the vitreous and blood from controls (n = 55) and in a subset of age-related macular degeneration (AMD) patients (n = 12) for insights and possible additional links between the ocular and systemic compartments. Vitreous MMP9 levels in control and AMD groups were 932.5 ± 240.9 pg/mL and 813.7 ± 157.6 pg/mL, whilst serum levels were 2228 ± 193 pg/mL and 2386.8 ± 449.4 pg/mL, respectively. Vitreous Aβ in control and AMD groups were 1173.5 ± 117.1 pg/mL and 1275.6 ± 332.9 pg/mL, whilst plasma Aβ were 574.3 ± 104.8 pg/mL and 542.2 ± 139.9 pg/mL, respectively. MMP9 and Aβ showed variable levels across the lifecourse, indicating no correlation to each other or with age nor AMD status, though the smaller AMD cohort was a limiting factor. Aβ and MMP9 levels in the vitreous and blood were unrelated to mean arterial pressure. Smoking, another modifiable risk, showed no association with vitreous Aβ. However, smoking may be linked with vitreous (p = 0.004) and serum (p = 0.005) MMP9 levels in control and AMD groups, though this did not reach our elevated (p = 0.001) significance. A bioinformatics analysis revealed promising MMP9 and APP/Aβ partners for further scrutiny, many of which are already linked with retinopathy. [ABSTRACT FROM AUTHOR]

We report our experience with transcatheter patent ductus arteriosus (PDA) closure in premature infants and compare patients grouped by the device used for closure: the Microvascular Plug, "MVP" (Medtronic, Minneapolis, MN); Micro Plug Set, "Micro Plug" (KA Medical, Minneapolis, MN); and Amplatzer Piccolo Occluder, "Piccolo" (Abbot, Santa Clara, CA). We also report trends in device selection over time. Studies examining outcomes according to device selection for PDA closure in premature infants are lacking. We performed a retrospective review of all percutaneous PDA closures in premature infants at a single center (June 2018–May 2021). Patients were grouped by initial device selected for PDA closure (intention to treat). Institutional Review Board approval was obtained. 58 premature infants [MVP (n = 25), Micro Plug (n = 25), and Piccolo (n = 8)] underwent successful transcatheter PDA closure (mean gestational age 27 weeks 2 days; mean weight at procedure 1.4 kg; mean age at procedure 28 days). Pre-procedural demographics, procedural data, and follow-up data were similar between groups. There were no significant procedural adverse events. Three devices (2 MVP, 0 Micro Plug, 1 Piccolo p = 0.27) embolized after the procedure. One other device was removed for concern for aortic obstruction. Device selection evolved with a clear trend toward the Micro Plug device over time. Demographic, procedural, and follow-up data were similar between the MVP, Micro Plug, and Piccolo groups. The Micro Plug did not require exchange for suboptimal fitting or embolize and became our preferred device in most cases. [ABSTRACT FROM AUTHOR]

We used citizen science and inexpensive methodology to assess the distribution of the jungle cat Felis chaus, a relatively common species in Sri Lanka but the least studied of the four wild cat species occurring in the country. We obtained three types of records of the jungle cat: geo-referenced photographs of the species from the public; sightings obtained from print and social media, and provided via an online sighting form; and sightings by field biologists. We combined the 112 unique records obtained in this way with the 21 records from the 2012 National Red List distribution map of the species, and used MaxEnt to predict habitat suitability for the species. The new sightings were primarily in drier regions, expanding the known extent of occurrence for this species in Sri Lanka. Of the new sightings, 7.1% were road kills. Distance to nearest riverine forest, annual precipitation and distance to the nearest reservoir were the most important variables explaining habitat suitability. These findings validate our hypotheses that the species is more widespread than demonstrated previously and also ranges in human-dominated landscapes outside protected areas. Our study provides a model for how ecological and behavioural information for common species can be obtained inexpensively and incorporated into species distribution models. Studies of species such as the jungle cat, which are neither threatened nor charismatic, will help ensure that we keep common species common. [ABSTRACT FROM AUTHOR]

Existing literature demonstrates that verbs are pivotal in legal information extraction tasks due to their semantic and argumentative properties. However, granting computers the ability to interpret the meaning of a verb and its semantic properties in relation to a given context can be considered as a challenging task, mainly due to the polysemic and domain specific behaviours of verbs. Therefore, developing mechanisms to identify behaviors of verbs and evaluate how artificial models detect the domain specific and polysemic behaviours of verbs can be considered as tasks with significant importance. In this regard, a comprehensive dataset that can be used as an evaluation resource, as well as a training data set, can be considered as a major requirement. In this paper, we introduce LeCoVe, which is a verb similarity dataset intended towards facilitating the process of identifying verbs with similar meanings in a legal domain specific context. Using the dataset, we evaluated both domain specific and domain generic embedding models, which were developed using state-of-the-art word representation and language modelling techniques. As a part of the experiments carried out using the announced dataset, Sense2Vec and BERT models were trained using a corpus of legal opinion texts in order to capture domain specific behaviours. In addition to LeCoVe, we demonstrate that a neural network model, which was developed by combining semantic, syntactic, and contextual features that can be obtained from the outputs of embedding models, can perform comparatively well, even in a low resource scenario. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac magnetic resonance imaging provides radiation-free, 3-dimensional soft tissue visualization with adjunct hemodynamic data, making it a promising candidate for image-guided transcatheter interventions. This review focuses on the benefits and background of real-time magnetic resonance imaging (MRI)-guided cardiac catheterization, guidance on starting a clinical program, and recent research developments. Recent Findings: Interventional cardiac magnetic resonance (iCMR) has an established track record with the first entirely MRI-guided cardiac catheterization for congenital heart disease reported nearly 20 years ago. Since then, many centers have embarked upon clinical iCMR programs primarily performing diagnostic MRI-guided cardiac catheterization. There have also been limited reports of successful real-time MRI-guided transcatheter interventions. Growing experience in performing cardiac catheterization in the magnetic resonance environment has facilitated practical workflows appropriate for efficiency-focused cardiac catheterization laboratories. Most exciting developments in imaging technology, MRI-compatible equipment and MRI-guided novel transcatheter interventions have been limited to preclinical research. Many of these research developments are ready for clinical translation. Summary: With increasing iCMR clinical experience and translation of preclinical research innovations, the time to make the leap to radiation-free procedures is now. [ABSTRACT FROM AUTHOR]

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1–9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p < 0.001) and a peak echo gradient increase of > 24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions. [ABSTRACT FROM AUTHOR]

Thickness of cotton fiber, referred to as fiber maturity, is a key determinant of fiber quality, lint yield, and textile performance. The cotton immature fiber (im) mutant has been used to study fiber maturity since its fiber is thinner than the wild type near isogeneic line (NIL), Texas Marker-1 (TM-1). The im phenotype is caused by a single recessive mutation of a pentatricopeptide repeat (PPR) gene that reduces the activity of mitochondrial complex I and up-regulates stress responsive genes. However, the mechanisms altering the stress responses in im mutant are not well understood. Thus, we characterized growth and gas exchange in im and TM-1 under no stress and also investigated their stress responses by comparing gas exchange and transcriptomic profiles under high temperature. Phenotypic differences were detected between the NILs in non-fiber tissues although less pronounced than the variation in fibers. At near optimum temperature (28±3°C), im maintained the same photosynthetic performance as TM-1 by means of greater stomatal conductance. In contrast, under high temperature stress (>34°C), im leaves reduced photosynthesis by decreasing the stomatal conductance disproportionately more than TM-1. Transcriptomic analyses showed that the genes involved in heat stress responses were differentially expressed between the NIL leaves. These results indicate that the im mutant previously reported to have low activity of mitochondrial complex I displays increased thermosensitivity by impacting stomatal conductance. They also support a notion that mitochondrial complex I activity is required for maintenance of optimal photosynthetic performance and acclimation of plants to high temperature stress. These findings may be useful in the future efforts to understand how physiological mechanisms play a role in determining cotton fiber maturity and may influence stress responses in other crops. [ABSTRACT FROM AUTHOR]

Background: The learning environment is a vital part of the undergraduate curriculum which enable to delivery of quality education in the stipulated time. Therefore, this study aimed to evaluate the learning environment among BSc. Nursing undergraduates in Sri Lankan state universities. Methods: A descriptive cross-sectional study was conducted among 161 final year BSc. Nursing undergraduates in six state universities. Socio-demographic characteristics were collected using a self-administered questionnaire. The Dundee Ready Educational Environment Measure (DREEM) questionnaire was used to evaluate the learning environment in Perception of learning (SPL), Perceptions of teaching (SPT), Academic self-perceptions (SASP), Perceptions of the atmosphere (SPA), and Social self-perceptions (SSP). Based on the SPL, SPT, SASP, SPA, and SSP domains, the overall score of learning environment was ranged from 0 to 200 and then the overall score was classified into four categories such as poor (0–50), many problems (51–100), more positive than negative (101–150) and excellent (151–200). One-way Analysis of Variance (ANOVA) and t-test were used to determine the difference in the subscales and the overall scale. Results: The mean age of the students was 24.9 ± 0.9 years. The overall score of the learning environment was 127.1 ± 14.3. Student's Perception of learning showed the highest mean score of 31.1 ± 3.9 while the social self-perception showed the lowest score (mean 16.4 ± 3.1). A significant group effect was observed in SPL and SPT subdomains among state universities while no significant group effect was observed in other subdomains. Furthermore, participating in extracurricular activities, travelling time to the faculty, and gender were observed as associated factors for the learning environment among BSc. Nursing undergraduates in state universities. Conclusions: Although the overall learning environment of BSc. Nursing undergraduates in state universities in Sri Lanka was within more positive than negative category, none of the university reaches to the excellent category. Therefore, each university should have improved their subdomains of learning environment to reach excellent category through addressing the gaps of curricular and extracurricular activities in the future. [ABSTRACT FROM AUTHOR]

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disease of the macula that leads to bilateral loss of central vision and is caused by mutations in the TIMP3 gene. However, the mechanisms by which TIMP3 mutations cause SFD are poorly understood. Here, we generated human induced pluripotent stem cell‐derived retinal pigmented epithelial (hiPSC‐RPE) cells from three SFD patients carrying TIMP3 p.(Ser204Cys) and three non‐affected controls to study disease‐related structural and functional differences in the RPE. SFD‐hiPSC‐RPE exhibited characteristic RPE structure and physiology but showed significantly reduced transepithelial electrical resistance associated with enriched expression of cytoskeletal remodelling proteins. SFD‐hiPSC‐RPE exhibited basolateral accumulation of TIMP3 monomers, despite no change in TIMP3 gene expression. TIMP3 dimers were observed in both SFD and control hiPSC‐RPE, suggesting that mutant TIMP3 dimerisation does not drive SFD pathology. Furthermore, mutant TIMP3 retained matrix metalloproteinase activity. Proteomic profiling showed increased expression of ECM proteins, endothelial cell interactions and angiogenesis‐related pathways in SFD‐hiPSC‐RPE. By contrast, there were no changes in VEGF secretion. However, SFD‐hiPSC‐RPE secreted higher levels of monocyte chemoattractant protein 1, PDGF and angiogenin. Our findings provide a proof‐of‐concept that SFD patient‐derived hiPSC‐RPE mimic mature RPE cells and support the hypothesis that excess accumulation of mutant TIMP3, rather than an absence or deficiency of functional TIMP3, drives ECM and angiogenesis‐related changes in SFD. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In recent years, interventional cardiac magnetic resonance imaging (iCMR) has evolved from attractive theory to clinical routine at several centers. Real-time cardiac magnetic resonance imaging (CMR fluoroscopy) adds value by combining soft-tissue visualization, concurrent hemodynamic measurement, and freedom from radiation. Clinical iCMR applications are expanding because of advances in catheter devices and imaging. In the near future, iCMR promises novel procedures otherwise unsafe under standalone X-Ray guidance. [ABSTRACT FROM AUTHOR]

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degeneration (AMD) and Sorsby fundus dystrophy, and potentially, through indirect mechanisms, with Alzheimer’s disease. Insights into TIMP-3 activities may be gleaned from studying Sorsby-linked mutations. However, recent findings do not fully support the prevailing hypothesis that a gain of function through the dimerisation of mutated TIMP-3 is responsible for retinopathy. Findings from Alzheimer’s patients suggest a hitherto poorly studied relationship between TIMP-3 and the Alzheimer’s-linked amyloid-beta (Aβ) proteins that warrant further scrutiny. This may also have implications for understanding AMD as aged/diseased retinae contain high levels of Aβ. Findings from TIMP-3 knockout and mutant knock-in mice have not led to new treatments, particularly as the latter does not satisfactorily recapitulate the Sorsby phenotype. However, recent advances in stem cell and in vitro approaches offer novel insights into understanding TIMP-3 pathology in the retina-brain axis, which has so far not been collectively examined. We propose that TIMP-3 activities could extend beyond its hitherto supposed functions to cause age-related changes and disease in these organs. [ABSTRACT FROM AUTHOR]

Alluvial fans record climate-driven erosion and sediment-transport processes and allow reconstructing past environmental conditions. Here we investigate the sedimentation history of two alluvial fans located in formerly glaciated valleys of the Cordillera Oriental, Peru. 10Be exposure ages from the fan surfaces and radiocarbon ages from the fan interiors constrain the final stages of fan formation. The 10Be and 14C ages cluster mainly between 13.3–9.3 ka and 11,500–9700 cal yr BP, respectively. Our age data set indicates that—after deglaciation—large amounts of fan sediment were deposited until ∼10 ka, when sedimentation rates declined rather abruptly. This pattern is supported by 10Be erosion rates for the fan catchments, because under the assumption of constant erosion the time needed to erode the material stored in the fans significantly exceeds their age. Correlating our ages with regional climate records indicates that precipitation exerts the primary control on fan sedimentation. Two periods with elevated lake levels and increased precipitation between 18 and 14.5 ka and from 13 to 11.5 ka resulted in rapid deposition of large fan lobes. Subsequently, lower precipitation rates decreased erosion in the catchments and sediment delivery to the fans, which have remained largely inactive since ∼9.5 ka. [ABSTRACT FROM AUTHOR]

Key points: The carotid body is a peripheral arterial chemoreceptor that regulates ventilation in response to both acute and sustained hypoxia. Type I cells in this organ respond to low oxygen both acutely by depolarization and dense core vesicle secretion and, over the longer term, via cellular proliferation and enhanced ventilatory responses. Using lineage analysis, the present study shows that the Type I cell lineage itself proliferates and expands in response to sustained hypoxia. Inactivation of HIF‐2α in Type I cells impairs the ventilatory, proliferative and cell intrinsic (dense core vesicle) responses to hypoxia. Inactivation of PHD2 in Type I cells induces multilineage hyperplasia and ultrastructural changes in dense core vesicles to form paraganglioma‐like carotid bodies. These changes, similar to those observed in hypoxia, are dependent on HIF‐2α. Taken together, these findings demonstrate a key role for the PHD2–HIF‐2α couple in Type I cells with respect to the oxygen sensing functions of the carotid body. Abstract: The carotid body is a peripheral chemoreceptor that plays a central role in mammalian oxygen homeostasis. In response to sustained hypoxia, it manifests a rapid cellular proliferation and an associated increase in responsiveness to hypoxia. Understanding the cellular and molecular mechanisms underlying these processes is of interest both to specialized chemoreceptive functions of that organ and, potentially, to the general physiology and pathophysiology of cellular hypoxia. We have combined cell lineage tracing technology and conditionally inactivated alleles in recombinant mice to examine the role of components of the HIF hydroxylase pathway in specific cell types within the carotid body. We show that exposure to sustained hypoxia (10% oxygen) drives rapid expansion of the Type I, tyrosine hydroxylase expressing cell lineage, with little transdifferentiation to (or from) that lineage. Inactivation of a specific HIF isoform, HIF‐2α, in the Type I cells was associated with a greatly reduced proliferation of Type I cells and hypoxic ventilatory responses, with ultrastructural evidence of an abnormality in the action of hypoxia on dense core secretory vesicles. We also show that inactivation of the principal HIF prolyl hydroxylase PHD2 within the Type I cell lineage is sufficient to cause multilineage expansion of the carotid body, with characteristics resembling paragangliomas. These morphological changes were dependent on the integrity of HIF‐2α. These findings implicate specific components of the HIF hydroxylase pathway (PHD2 and HIF‐2α) within Type I cells of the carotid body with respect to the oxygen sensing and adaptive functions of that organ. [ABSTRACT FROM AUTHOR]

Chronic degeneration of the Retinal Pigment Epithelium(RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as age-related macular degeneration, Stargardt disease and choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, α-synuclein pathologies and Alzheimer's disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived. [ABSTRACT FROM AUTHOR]

In X-ray fluoroscopy, static overlays are used to visualize soft tissue. We propose a system for cardiac and respiratory motion compensation of these overlays. It consists of a 3-D motion model created from real-time magnetic resonance (MR) imaging. Multiple sagittal slices are acquired and retrospectively stacked to consistent 3-D volumes. Slice stacking considers cardiac information derived from the ECG and respiratory information extracted from the images. Additionally, temporal smoothness of the stacking is enhanced. Motion is estimated from the MR volumes using deformable 3-D/3-D registration. The motion model itself is a linear direct correspondence model using the same surrogate signals as slice stacking. In X-ray fluoroscopy, only the surrogate signals need to be extracted to apply the motion model and animate the overlay in real time. For evaluation, points are manually annotated in oblique MR slices and in contrast-enhanced X-ray images. The 2-D Euclidean distance of these points is reduced from 3.85 to 2.75 mm in MR and from 3.0 to 1.8 mm in X-ray compared with the static baseline. Furthermore, the motion-compensated overlays are shown qualitatively as images and videos. [ABSTRACT FROM AUTHOR]

In a 19-year-old male with interrupted aortic arch and complex congenital heart disease, we report percutaneous repair of a compromised aortic conduit. The patient had aortic arch repair in childhood utilizing a 12 mm Hemashield Dacron conduit. CT angiography showed multiple segments of this conduit were dilated to 16 mm suggesting conduit degeneration and failure with pseudoaneurysm formation. We utilized a self-expanding aortic endograft supported by internal placement of bare metal stents to repair the conduit. Our repair was guided by 3D rotational angiography. This adult patient with complex congenital heart disease and interrupted aortic arch is an example of patients in whom endograft repair of compromised aortic conduits presents a much lower risk alternative than surgical revision. [ABSTRACT FROM AUTHOR]

Background: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety. Methods: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected. Results: During a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested. Conclusions: Comprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention. Trial registration: ClinicalTrials.gov registered February 17, 2016 [ABSTRACT FROM AUTHOR]

Background: Quantification of cardiac output and pulmonary vascular resistance (PVR) are critical components of invasive hemodynamic assessment, and can be measured concurrently with pressures using phase contrast CMR flow during real-time CMR guided cardiac catheterization. Methods: One hundred two consecutive patients underwent CMR fluoroscopy guided right heart catheterization (RHC) with simultaneous measurement of pressure, cardiac output and pulmonary vascular resistance using CMR flow and the Fick principle for comparison. Procedural success, catheterization time and adverse events were prospectively collected. Results: RHC was successfully completed in 97/102 (95.1%) patients without complication. Catheterization time was 20 ± 11 min. In patients with and without pulmonary hypertension, baseline mean pulmonary artery pressure was 39 ± 12 mmHg vs. 18 ± 4 mmHg (p < 0.001), right ventricular (RV) end diastolic volume was 104 ± 64 vs. 74 ± 24 (p = 0.02), and RV end-systolic volume was 49 ± 30 vs. 31 ± 13 (p = 0.004) respectively. 103 paired cardiac output and 99 paired PVR calculations across multiple conditions were analyzed. At baseline, the bias between cardiac output by CMR and Fick was 5.9% with limits of agreement -38.3% and 50.2% with r = 0.81 (p < 0.001). The bias between PVR by CMR and Fick was -0.02 WU.m² with limits of agreement -2.6 and 2.5 WU.m² with r = 0.98 (p <0. 001). Correlation coefficients were lower and limits of agreement wider during physiological provocation with inhaled 100% oxygen and 40 ppm nitric oxide. Conclusions: CMR fluoroscopy guided cardiac catheterization is safe, with acceptable procedure times and high procedural success rate. Cardiac output and PVR measurements using CMR flow correlated well with the Fick at baseline and are likely more accurate during physiological provocation with supplemental high-concentration inhaled oxygen. Trial registration: Clinicaltrials.gov NCT01287026, registered January 25, 2011. [ABSTRACT FROM AUTHOR]

Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the humanNOTCH1 and zebrafish notch1b genes. These enhancerswere able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SoxF binding sites established a clear requirement for members of this group of transcription factors (SOX7, SOX17 and SOX18) to drive the activity of these enhancers in vivo. Endogenous deletion of the notch1b enhancer led to a significant loss of arterial connections to the dorsal aorta in Notch pathway-deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for NOTCH1 and notch1b enhancer activity and for correct endogenous transcription of these genes. These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates. [ABSTRACT FROM AUTHOR]

Acute Pediatric VT Ablation Cardiac MRI Assessment Background Arrhythmia ablation with current techniques is not universally successful. Inadequate ablation lesion formation may be responsible for some arrhythmia recurrences. Periprocedural visualization of ablation lesions may identify inadequate lesions and gaps to guide further ablation and reduce risk of arrhythmia recurrence. Methods This feasibility study assessed acute postprocedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Ten pediatric patients who underwent ventricular tachycardia ablation were transferred immediately postablation to a 1.5T MRI scanner and late gadolinium enhancement (LGE) imaging was performed to characterize ablation lesions. Immediate and mid-term arrhythmia recurrences were assessed. Results Patient characteristics include median age 14 years (1-18 years), median weight 52 kg (11-81 kg), normal cardiac anatomy (n = 6), d-transposition of great arteries post arterial switch repair (n = 2), anomalous coronary artery origin post repair (n = 1), and cardiac rhabdomyoma (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 9/10 patients, all arrhythmia-free at median 7 months follow-up. LGE was not visible in 1 patient who had recurrence of frequent premature ventricular contractions within 2 hours, confirmed on Holter at 1 and 21 months post procedure. Conclusions Ventricular ablation lesion visibility by MRI in the acute post procedure setting is feasible. Lesions identifiable with MRI may correlate with clinical outcomes. Acute MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence. [ABSTRACT FROM AUTHOR]

Outdoor, hands-on and experiential learning, as opposed to instruction-based learning in classroom, increases student satisfaction and motivation leading to a deeper understanding of the subject. However, the use of outdoor exercises in undergraduate biology courses is declining due to a variety of constraints. Thus, the goal of this paper is to describe a convenient, no-cost and flexible exercise using an on-campus botanical tour for strengthening specific knowledge areas of major plant groups. Its assessment on conduct and coverage, and student-perceived and actual knowledge gain is also described. Data presented derived from traditional biology undergraduates in sophomore year over nine fall and three spring semesters. Conduct and coverage was assessed using a summative survey including open-ended questions administered to 198 students. A pre- and post-exercise survey addressing 10 knowledge categories was administered to 139 students to evaluate student-perceived knowledge gain. Quiz grades from the on-campus tour exercise were compared with average quiz grades from two in-class plant-related labs of 234 students to assess actual knowledge gain. Each student reporting on the conduct and coverage indicated either one or a combination of outcomes of the exercise as positive engagement, experiential learning, or of interest. Student-perceived improvement was evident in all ten knowledge categories with a greater improvement in categories learned anew during exercise compared to subjects reviewed. Quiz grades from the exercise were >11% greater than quiz grades from the two in-class plant-related labs. Active learning with interest likely contributed to the increased perceived and actual knowledge gains. Suggestions for adoption of the exercise in different settings are presented based on both student comments and instructor's experience. [ABSTRACT FROM AUTHOR]