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Echinoderm mass mortality events shape marine ecosystems by altering the dynamics among major benthic groups. The sea urchin Diadema antillarum, virtually extirpated in the Caribbean in the early 1980s by an unknown cause, recently experienced another mass mortality beginning in January 2022. We investigated the cause of this mass mortality event through combined molecular biological and veterinary pathologic approaches comparing grossly normal and abnormal animals collected from 23 sites, representing locations that were either affected or unaffected at the time of sampling. Here, we report that a scuticociliate most similar to Philaster apodigitiformis was consistently associated with abnormal urchins at affected sites but was absent from unaffected sites. Experimentally challenging naïve urchins with a Philaster culture isolated from an abnormal, field-collected specimen resulted in gross signs consistent with those of the mortality event. The same ciliate was recovered from treated specimens postmortem, thus fulfilling Koch’s postulates for this microorganism. We term this condition D. antillarum scuticociliatosis.
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This report presents the highlights of the 7th European Meeting on Molecular Diagnostics held in Scheveningen, The Hague, The Netherlands, 12-14 October 2011. The areas covered included molecular diagnostics applications in medical microbiology, virology, pathology, hemato-oncology,clinical genetics and forensics. Novel real-time amplification approaches, novel diagnostic applications and new technologies, such as next-generation sequencing, PCR lectrospray-ionization TOF mass spectrometry and techniques based on the detection of proteins or other molecules, were discussed. Furthermore, diagnostic companies presented their future visions for molecular diagnostics in human healthcare.
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Author supplied Business rules play a critical role in an organization’s daily activities. With the increased use of business rules (solutions) the interest in modelling guidelines that address the manageability of business rules has increased as well. However, current research on modelling guidelines is mainly based on a theoretical view of modifications that can occur to a business rule set. Research on actual modifications that occur in practice is limited. The goal of this study is to identify modifications that can occur to a business rule set and underlying business rules. To accomplish this goal we conducted a grounded theory study on 229 rules set, as applied from March 2006 till June 2014, by the National Health Service. In total 3495 modifications have been analysed from which we defined eleven modification categories that can occur to a business rule set. The classification provides a framework for the analysis and design of business rules management architectures.
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Background: Follow‑up of curatively treated primary breast cancer patients consists of surveillance and aftercare and is currently mostly the same for all patients. A more personalized approach, based on patients’ individual risk of recurrence and personal needs and preferences, may reduce patient burden and reduce (healthcare) costs. The NABOR study will examine the (cost‑)effectiveness of personalized surveillance (PSP) and personalized aftercare plans (PAP) on patient‑reported cancer worry, self‑rated and overall quality of life and (cost‑)effectiveness. Methods: A prospective multicenter multiple interrupted time series (MITs) design is being used. In this design, 10 participating hospitals will be observed for a period of eighteen months, while they ‑stepwise‑ will transit from care as usual to PSPs and PAPs. The PSP contains decisions on the surveillance trajectory based on individual risks and needs, assessed with the ‘Breast Cancer Surveillance Decision Aid’ including the INFLUENCE prediction tool. The PAP contains decisions on the aftercare trajectory based on individual needs and preferences and available care resources, which decision‑making is supported by a patient decision aid. Patients are non‑metastasized female primary breast cancer patients (N= 1040) who are curatively treated and start follow‑up care. Patient reported outcomes will be measured at five points in time during two years of follow‑up care (starting about one year after treatment and every six months thereafter). In addition, data on diagnostics and hospital visits from patients’ Electronical Health Records (EHR) will be gathered. Primary outcomes are patient‑reported cancer worry (Cancer Worry Scale) and over‑all quality of life (as assessed with EQ‑VAS score). Secondary outcomes include health care costs and resource use, health‑related quality of life (as measured with EQ5D‑5L/SF‑12/EORTC‑QLQ‑C30), risk perception, shared decision‑making, patient satisfaction, societal participation, and cost‑effectiveness. Next, the uptake and appreciation of personalized plans and patients’ experiences of their decision‑making process will be evaluated. Discussion: This study will contribute to insight in the (cost‑)effectiveness of personalized follow‑up care and contributes to development of uniform evidence‑based guidelines, stimulating sustainable implementation of personalized surveillance and aftercare plans. Trial registration: Study sponsor: ZonMw. Retrospectively registered at ClinicalTrials.gov (2023), ID: NCT05975437.
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Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5-7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound epithelialization after 5-7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only. The relevance of cultured autologous cells in treatment of extensive burns is supported by our current findings.
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Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
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Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensivephylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2. Therefore, the cytosolically active CPT1 more closely resembles intramitochondrial ancestors than CPT2. The choline acetyltransferase is closely related to carnitine acetyltransferase and shows lower evolutionary rates than long chain acyltransferases. In the CPT1 family several duplications occurred during animal radiation, leading to the isoforms CPT1A, CPT1B and CPT1C. In addition, we found five CPT1-like genes in Caenorhabditis elegans that strongly group to the CPT1 family. The long branch leading to mammalian brain isoform CPT1C suggests that either strong positive or relaxed evolution has taken place on this node. The presented evolutionary delineation of carnitine/choline acyltransferases adds to current knowledge on their functions and provides tangible leads for further experimental research.
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