380 research outputs found
Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome
Chronic intestinal pseudo-obstruction syndrome (CIPS) is a severe motility disorder of the gastrointestinal tract that presents with continuous or recurrent symptoms and signs of intestinal obstruction without evidence of a structural lesion occluding the intestinal lumen. Mechanical obstruction might occur in these patients as well but is typically difficult to distinguish from an exacerbation of CIPS. We report two pediatric cases in which mechanical obstruction by volvulus mimicked an exacerbation of CIPS, requiring surgical intervention. Conclusion: Awareness of the possibility of true mechanical obstruction in CIPS patients during an exacerbation episode is needed, as this is a severe condition and usually requires surgical intervention
Large projected reductions in marine fish biomass for Kenya and Tanzania in the absence of climate mitigation
Climate change is projected to cause significant reductions in global fisheries catch during the 21st Century. Yet, little is understood of climate change impacts on tropical fisheries, which support many livelihoods, as is the case in the Western Indian Ocean region (WIO). Here, we focus on two central WIO countries ― Kenya and Tanzania ― and run a multi-species fish model (Size Spectrum Dynamic Bio-climate Envelope Model; SS-DBEM) for 43 species of commercial and artisanal importance, to investigate the effects of climate change. We include both national Exclusive Economic Zones (EEZs) as domains. The model was forced by data from a biogeochemical model (NEMO-MEDUSA), run under the high emissions scenario Representative Concentration Pathway (RCP) 8.5, until the end of the 21st century. Impacts of fisheries and climate change were investigated by running SS-DBEM under five scenarios of fishing pressures to predict a range of possible future scenarios. Fishing pressure was represented as the Maximum Sustainable Yield (MSY), expressed as MSY0, MSY1, MSY2, MSY3 and MSY4 representing fishing mortality of 0, 1, 2, 3 and 4 times MSY, respectively. Large reductions in average fish biomass were projected over the 21st Century, with median reductions of fish species biomass of 63–76% and 56–69% for the Kenyan and Tanzanian EEZs respectively across the fishing scenarios. Tunas were particularly impacted by future climate change, with the six modelled species exhibiting biomass reductions of at least 70% in both EEZs for all fishing scenarios during the 21st Century. Reductions in fish biomass were much more severe during the second half of the 21st Century, highlighting the benefits to tropical fisheries of global action on climate change
Key climate change stressors of marine ecosystems along the path of the east african coastal current
For the countries bordering the tropical Western Indian Ocean (TWIO), living marine resources are vital for food security. However, this region has largely escaped the attention of studies investigating potential impacts of future climate change on the marine environment. Understanding how marine ecosystems in coastal East Africa may respond to various climatic stressors is vital for the development of conservation and other ocean management policies that can help to adapt to climate change impacts on natural and associated human systems. Here, we use a high-resolution (1/4°) ocean model, run under a high emission scenario (RCP 8.5) until the end of the 21st century, to identify key regionally important climate change stressors over the East African Coastal Current (EACC) that flows along the coasts of Kenya and Tanzania. We also discuss these stressors in the context of projections from lower resolution CMIP5 models. Our results indicate that the main drivers of dynamics and the associated ecosystem response in the TWIO are different between the two monsoon seasons. Our high resolution model projects weakening of the Northeast monsoon (December–February) winds and slight strengthening of the Southeast monsoon (May–September) winds throughout the course of the 21st century, consistent with CMIP5 models. The projected shallower mixed layers and weaker upwelling during the Northeast Monsoon considerably reduce the availability of surface nutrients and primary production. Meanwhile, primary production during the Southeast monsoon is projected to be relatively stable until the end of the century. In parallel, a widespread warming of up to 5 °C is projected year-round with extreme events such as marine heatwaves becoming more intense and prolonged, with the first year-long event projected to occur as early as the 2030s. This extreme warming will have significant consequences for both marine ecosystems and the coastal populations dependent on these marine resources. These region-specific stressors highlight the importance of dynamic ocean features such as the upwelling systems associated with key ocean currents. This indicates the need to develop and implement a regional system that monitors the anomalous behaviour of such regionally important features. Additionally, this study draws attention to the importance of investment in decadal prediction methods, including high resolution modelling, that can provide information at time and space scales that are more directly relevant to regional management and policy making
Patterns of Gram-Stained Fecal Flora as a Quick Diagnostic Marker in Patients with Severe SIRS
A HIF-independent, CD133-mediated mechanism of cisplatin resistance in glioblastoma cells
Purpose
Glioblastoma Multiforme (GBM) is the commonest brain tumour in adults. A population of cells, known as cancer stem cells (CSCs), is thought to mediate chemo/radiotherapy resistance. CD133 is a cell surface marker to identify and isolate CSCs. However, its functional significance and the relevant microenvironment in which to study CD133 remain unknown. We examined the influence of hypoxia on CD133 expression and the potential functional significance of CD133 in glioblastoma chemoresistance.
Methods
Gene expression was analysed by qRT-PCR. siRNA technique was used to downregulate genes and confirmed by flow cytometry. IC50 values was evaluated with the Alamar blue assay.
Results
CD133 expression was upregulated in hypoxia in 2D and 3D models. There was increased resistance to chemotherapeutics, cisplatin, temozolomide and etoposide, in cells cultured in hypoxia compared to normoxia. siRNA knockdown of either HIF1a or HIF2a resulted in reduced CD133 mRNA expression with HIF2a having a more prolonged effect on CD133 expression. HIF2a downregulation sensitized GBM cells to cisplatin to a greater extent than HIF1a but CD133 knockdown had a much more marked effect on cisplatin sensitisation than knockdown of either of the HIFs suggesting a HIF-independent mechanism of cisplatin resistance mediated via CD133. The same mechanism was not involved in temozolomide resistance since downregulation of HIF1a but not HIF2a or CD133 sensitized GBM cells to temozolomide.
Conclusion
Knowledge of the mechanisms involved in the novel hypoxia-induced CD133-mediated resistance to cisplatin observed might lead to identification of new strategies that enable more effective use of current therapeutic agents
A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis
Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198C>G SNP (odds ratio=8.6; P=0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5′-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198C>G SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression
Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis
PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence
Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need
Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known
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