185 research outputs found

    Localized outbreaks of coral disease on Arabian reefs are linked to extreme temperatures and environmental stressors

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    The Arabian Peninsula borders the hottest reefs in the world, and corals living in these extreme environments can provide insight into the effects of warming on coral health and disease. Here, we examined coral reef health at 17 sites across three regions along the northeastern Arabian Peninsula (Persian Gulf, Strait of Hormuz and Oman Sea) representing a gradient of environmental conditions. The Persian Gulf has extreme seasonal fluctuations in temperature and chronic hypersalinity, whereas the other two regions experience more moderate conditions. Field surveys identified 13 coral diseases including tissue loss diseases of unknown etiology (white syndromes) in Porites, Platygyra, Dipsastraea, Cyphastrea, Acropora and Goniopora; growth anomalies in Porites, Platygyra and Dipsastraea; black band disease in Platygyra, Dipsastraea, Acropora, Echinopora and Pavona; bleached patches in Porites and Goniopora and a disease unique to this region, yellow-banded tissue loss in Porites. The most widespread diseases were Platygyra growth anomalies (52.9% of all surveys), Acropora white syndrome (47.1%) and Porites bleached patches (35.3%). We found a number of diseases not yet reported in this region and found differential disease susceptibility among coral taxa. Disease prevalence was higher on reefs within the Persian Gulf (avg. 2.05%) as compared to reefs within the Strait of Hormuz (0.46%) or Oman Sea (0.25%). A high number of localized disease outbreaks (8 of 17 sites) were found, especially within the Persian Gulf (5 of 8 sites). Across all regions, the majority of variation in disease prevalence (82.2%) was associated with the extreme temperature range experienced by these corals combined with measures of organic pollution and proximity to shore. Thermal stress is known to drive a number of coral diseases, and thus, this region provides a platform to study disease at the edge of corals’ thermal range

    Adenovirus 5 fibers mutated at the putative HSPG-binding site show restricted retargeting with targeting peptides in the HI loop.

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    Adenoviral vectors are commonly used for liver-directed gene therapy following systemic administration owing to their strong propensity for hepatocyte transduction. However, many disease applications would benefit from the delivery of adenoviruses to alternate tissues via this route. Research has thus focused on stripping the virus of native hepatic tropism in conjunction with modifying virus capsid proteins to incorporate novel tropism. Recently, the KO1S* adenovirus serotype 5 fiber mutant, devoid of both coxsackie and adenovirus receptor binding in the fiber knob domain and mutated at the putative heparan sulphate proteoglycan binding site in the fiber shaft, was shown to possess strikingly poor hepatic tropism in mice, rats, and non-human primates. Thus, it is an ideal candidate for retargeting strategies. We therefore assessed the ability of peptide-modified KO1S* fibers to retarget adenovirus. Peptide insertions were well tolerated and virions produced to high titers. However, expected retargeting at the level of transduction was not observed, despite cell-binding studies showing enhanced vector targeting at the cell surface. Cy3 labeling studies showed retarded trafficking of S*-containing fibers. Taken together, our data demonstrates that KO1S* mutant fibers are ineffective for cell retargeting strategies

    UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings.

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    Assessment of outcome in preclinical studies of vascular cognitive impairment (VCI) is heterogenous. Through an ARUK Scottish Network supported questionnaire and workshop (mostly UK-based researchers), we aimed to determine underlying variability and what could be implemented to overcome identified challenges. Twelve UK VCI research centres were identified and invited to complete a questionnaire and attend a one-day workshop. Questionnaire responses demonstrated agreement that outcome assessments in VCI preclinical research vary by group and even those common across groups, may be performed differently. From the workshop, six themes were discussed: issues with preclinical models, reasons for choosing functional assessments, issues in interpretation of functional assessments, describing and reporting functional outcome assessments, sharing resources and expertise, and standardization of outcomes. Eight consensus points emerged demonstrating broadly that the chosen assessment should reflect the deficit being measured, and therefore that one assessment does not suit all models; guidance/standardisation on recording VCI outcome reporting is needed and that uniformity would be aided by a platform to share expertise, material, protocols and procedures thus reducing heterogeneity and so increasing potential for collaboration, comparison and replication. As a result of the workshop, UK wide consensus statements were agreed and future priorities for preclinical research identified

    Drug Delivery Strategies to Overcome the Blood‚ÄďBrain Barrier (BBB)

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    Parathyroidectomy in Chronic Kidney Disease

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    Chronic Kidney Disease (CKD) associates with disturbed modulation of hormones involved in calcium and phosphate homeostasis, with development of secondary hyperparathyroidism (SHPT). SHPT includes not only divalent ions derangements, but also renal bone disease (high turnover, low turnover and/or osteomalacia) and accelerated vascular and ectopic calcifications. In this way, SHPT resembles a true clinical syndrome named CKD-MBD, which is a recognized risk factor of all-causeand cardiovascular death. Long lasting stimulation of parathyroid hormone synthesis and secretion, as observed in CKD, causes specific and progressive histological changes responsible for the development of nodular hyperplastic glands unresponsive to physiologic inhibitors and thus characterized by hypercalcemia, elevated PTH levels and resistance to the available medical therapies. In these cases, surgicalparathyroidectomy (PTX) becomes the only therapeutic option. In this chapter we review current evidence on indications, types and clinical outcomes of PTX from a practical and clinical point of view

    Using patient‚Äźreported outcomes to understand the effectiveness of guideline‚Äźconcordant care for post‚Äźtraumatic stress disorder in clinical practice

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    RationaleIdentifying predictors of improvement amongst patients receiving routine treatment for post-traumatic stress disorder (PTSD) could provide information about factors that influence the clinical effectiveness of guideline-concordant care. This study builds on prior work by accounting for delivery of specific evidence-based treatments (EBTs) for PTSD while identifying potential predictors of clinical improvement using patient-reported outcomes measurement.MethodOur sample consisted of 2 643 US Department of Veterans Affairs (VA) outpatients who initiated treatment for PTSD between 2008 and 2013 and received at least four PTSD checklist (PCL) measurements over 12 weeks. We obtained PCL data as well as demographic, diagnostic, and health services use information from the VA corporate data warehouse. We used latent trajectory analysis to identify classes of patients based on PCL scores, then determined demographic, diagnostic, and treatment predictors of membership in each class.ResultsPatients who met our PCL-based inclusion criteria were far more likely than those who did not receive EBTs. We identified two latent trajectories of PTSD symptoms. Patients in the substantial improvement group (25.9%) had a mean decrease in PCL score of 16.24, whereas patients in the modest improvement group improved by a mean of 8.09 points. However, there were few differences between the groups, and our model to predict group membership was only slightly better than chance (area under the curve [AUC] = 0.55). Of the 64 covariates we tested, the only robust individual predictor of improvement was gender, with men having lower odds of being in the substantial improvement group compared with women (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.58-0.96).ConclusionVA patients with PTSD can realize significant improvement in routine clinical practice. Although available medical records-based variables were generally insufficient to predict improvement trajectory, this study did indicate that men have lower odds of substantial improvement than women
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