579 research outputs found
Surveillance of illness associated with pandemic (h1n1) 2009 virus infection among adults using a global clinical site network approach: The insight flu 002 and flu 003 studies
No full textThe novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection that experience clinically significant outcomes and to study factors related to these outcomes. Enrollment commenced in October 2009 and will continue until August 2011: as of the end of 2010, 62 sites in 14 countries in Australasia (12 sites), Europe (37) and North America (13) have enrolled 1365 adult patients, with 1049 enrollments into the FLU 002 outpatient study and 316 into the FLU 003 hospitalization study. These 'in progress' INSIGHT influenza observational studies may act as a model for obtaining epidemiological, clinical and laboratory information in future international disease outbreaks
Serum GRP-78 Levels Still Remain High 3 Months Later After the Treatment: A Cohort Study
No full textGRP-78 proteininin bat koronavirüs, Mers-Cov, ebola virüs, deng virüsü, japon ensefalit virüsü, influenza virüs ve zika virüs gibi birçok virüsün hücreye girişinde rol oynadığı bilinmektedir. Bu çalışmada COVID-19 enfeksiyonu geçirmiş ve tedavi almış ve tamamen iyileşmiş olan hastalarda tedavi başlangıcından üç ay sonrasındaki Glucose Regulated Protein-78 (GRP-78) düzeylerini incelemeyi amaçladık. Daha öncesinde Sabırlı ve ark. tarafından yapılan çalışma grubunda yer alan, COVID-19 hastalığı tanısı almış ve hastalığı geçirip tamamen iyileşmiş olan 20 hasta prospektif kohorta dahil edildi. Hastaların acil servise ilk tanıda başvurusu ve 3 ay sonra kontrole çağrıldığında alınan kanlardan enzyme-linked immunosorbent assay (ELISA) metodu ile GRP-78 düzeyi çalışıldı. Acil servise ilk başvuruda alınan kanda serum GRP-78 düzeyi 1393,31 ± 306,33 pg/ml; tedavi başlangıcından 90 gün sonra bakılan serum GRP-78 düzeyi ise 1451,73 ± 336,65 pg/ml olarak saptandı. İlk başvuru ve 3 ay sonraki kontrolde ölçülen GRP-78 düzeyleri açısından istatistiksel olarak anlamlı farklılık saptanmadı (p=0,451). Sonuç olarak bu çalışmada COVID-19 infeksiyonunda tedavi başlangıcından 3 ay sonrasında dahi yüksek seyrettiğini ortaya koyduk. GRP-78 düzeyinin yüksek olmasının kişinin Sars-CoV-2 virüsüne karşı immünitesi konusunda fikir verdirici olabilir fakat bu hususun gerek hücre kültürü çalışması ve gerekse daha uzun süreli kohort çalışması yapılarak incelenmesine ihtiyaç vardır.Glucose Regulated Protein (GRP-78) plays a role in the intrusion of many viruses such as bat coronavirus, MERS-CoV, ebola virus, dengue virus, Japanese encephalitis virus, influenza virus, and Zika virus. This study, however, aims to examine the GRP-78 levels in patients who were infected with COVID-19, treated and recovered completely three months after the initiation of treatment. A total of 20 patients who were diagnosed with the COVID-19 disease and fully recovered, and who had participated in a previous study conducted by Sabırlı et al., were included in this prospective cohort study. Using the enzyme-linked immunosorbent assay (ELISA) method, the GRP-78 levels were examined in the blood samples. The mean serum GRP-78 level was found to be 1393.31 ± 306.33 pg / ml in the blood samples drawn from the patients when they were first admitted to the emergency department while the mean serum GRP-78 level measured 90 days after the initiation of treatment was 1451.73 ± 336.65 pg / ml. No statistically significant differences were found between the GRP-78 levels measured during the first admission and the follow-up control 3 months later (p = 0.451). In conclusion, this study revealed that the GRP-78 levels remained high in patients with COVID-19 infections even after 3 months following the initiation of treatment. This high GRP-78 level may provide insight into the immunity of the person against the Sars-CoV-2 virus; however, this issue should be further examined both in a cell culture study and in a longer-term cohort study
Cellular Analysis Of Hepg2 Cells On Gastrin Releasing Peptide (Grp) Nanostructure
No full textArtificial juxtacrine stimulation arises from the covalent attachment of growth factors onto biomaterials. Incorporation of growth factors onto cell culture substrates has been found to enhance the functionality of cells in vitro. In this study, we describe how the immobilization of Gastrin Releasing Peptide (GRP) enhances the viability of hepatocarcinoma cell line, HepG2 up to 4 days. The biomaterial for immobilization of GRP was prepared using indium tin oxide (ITO) sputtered on polyethylene terephthalate (PET). A self-assembled monolayer (SAM) of 3-aminopropyl triethoxysilane (3-APTES) on ITO was covalently attached to GRP. Characterization of the substrates before and after immobilization of GRP was carried out using contact angle measurements, FTIR and AFM techniques. HepG2 cells were cultured on immobilized GRP-SAM-ITO substrate for 24, 48, 72 and 96 hours and compared to cell viability of soluble GRP under similar conditions. The cell viability on immobilized GRP-SAM-ITO after 48 hours was less than that of soluble GRP by 19%. Lactate dehydrogenase (LDH) production after 48 hours was significantly reduced by 44% for immobilized GRP when compared to that with soluble GRP. After 96 hours, cell viability increased and cytotoxicity decreased for HepG2 cells on GRP-SAM-ITO substrates, suggesting viability was successfully extended. A similar experiment (LDH assay) with immobilized epidermal growth facor (EGF), obtained by covalent attachment of EGF shows that the cell viability can be extended to 5 days. These data may provide insight towards the development of bioreactors for drug toxicity screening
Factors Associated with D-Dimer Levels in HIV-Infected Individuals
No full textBackground: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.
Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.
Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.
Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels
JOAO WANDERLEY GERALDI: THE LINGUIST RESEARCHER, TRAINING TEACHER AND UNIQUE BRAZILIAN READER OF BAKHTIN AND HIS STUDY CIRCLE
No full textThis article aims to honor and discuss our meeting with Joao Wanderley Geraldi, the linguist researcher, teacher trainer and unique reader of Bakhtin and his Study circle. Our subject matter in this paper is the meetings we held with the author in his research and teaching activities throughout his years of activism, and in specially during the Linguistics V program taken at Unicamp in 2005. From mediations with Geraldi on language studies, we chose to share our understanding of speech genres - involving life and education - that converge around this construction. Finally, we show how this knowledge guides us to maintain the inseparable relationship between language and literature in dialogue through a poem by Manoel de Barros, a poet who was also introduced to us by Geraldi.Univ Fed Santa Catarina UFSC, Programa Posgrad Linguist PPGL UFSC, Florianopolis, BrazilUniv Fed Santa Catarina, GEBAP Grp Estudos Bakhtinianos Pampa, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilUniv Fed Santa Catarina, NEPALP, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilNELA UFSC, Nucleo Estudos Linguist Aplicada, Florianopolis, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, BrazilUNIPAMPA Univ Fed Pampa, Curso Letras Linguas Adicionais, Campus Bage, RS, BrazilGEBAP Grp Estudos Bakhtinianos Pampa, Bage, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, Brazi
The Insulin/IGF Signaling Regulator Cytohesin/GRP-1 Modulates Sensitivity to Excitotoxicity in C. elegans
No full textExcitotoxicity is a form of neurodegeneration that serves as the main underlying cause of brain damage in stroke/brain ischemia, and a contributing factor in a range of neurological diseases such as Epilepsy, ALS, Alzheimer, and Huntington\u27s disease. In excitotoxicity, over-activation of glutamate receptors causes necrotic neuronal cell death. In spite of intense study of excitotoxicity, the molecular mechanisms that lead from glutamate receptor activation to necrotic death remain a mystery. Aging neurons are known to be more vulnerable to excitotoxicity and less likely to recover, but the underlying reasons for the increased cellular vulnerability are unknown. To gain insight into the core process of excitotoxicity and factors that affect neuronal vulnerability, we turn to a model system that offers simplified but conserved signaling cascades and strong research tools. We therefore study excitotoxicity in the nematode C. elegans, in which a strong track record of studies of cell death mechanisms and signaling cascades suggests that this genetically accessible model system can help illuminate critical and conserved cellular processes. Our model combines a deletion of glutamate transporter 3 (glt-3) in a sensitized background (nuIs5), resulting in glutamate-triggered necrotic cell death. Previously, other investigators showed the role of the evolutionary conserved Insulin/IGF Signaling pathway (IIS) in longevity and cell stress resistance. Recently, we were able to show that the IIS cascade also controls vulnerability of postsynaptic neurons to excitotoxicity, by regulating the nuclear/cytoplasmic localization of the neuroprotective transcription factor FOXO3/DAF-16. Active IIS signaling causes FOXO/DAF-16 to be sequestered in the cytoplasm, while IIS inhibition allows FOXO/DAF-16 to enter the nucleus and activate protective genes. To gain further insight into the ability of this signaling cascade to regulate neurodegeneration, we study factors that are upstream and downstream of the IIS cascade and may be involved in excitotoxicity. As a preliminary step, I confirmed the involvement of IIS pathway in excitotoxicity. I worked towards preparing an excitotoxicity strain that is permissible for RNAi effect in neurons, to facilitate the ability to screen for the effect of FOXO/DAF-16 candidate target genes on neuroprotection. I then examined potential upstream modulators of IIS, and focused on the relationship between the Cytohesin/GRP-1 protein complex (previously shown to control insulin-regulated metabolism in mammals) and IIS in excitotoxicity. I observed that mutations that are expected to decrease the complex\u27s activity and its potentiation of IIS signaling reduced susceptibility to excitotoxicity, while an over-activation of this complex increased neuronal vulnerability. These results support that the Cytohesin/GRP-1 complex regulates the ability of the IIS cascade to modulate excitotoxicity. As a preliminary step to examine a possible direct communication between glutamate receptors and Cytohesin/GRP-1 IIS complexes, I examined their cellular localization. I observed a rough co-localization of the Cytohesin/GRP-1 complex components PPK-1 and GRP-1 and the glutamate receptor subunit GLR-1. Put together, these observations suggest that the Cytohesin/GRP-1 complex modulates IIS cascade\u27s ability to regulate the susceptibility to excitotoxic neurodegeneration, and that glutamate might directly regulate this signaling cascade. We therefore provide novel insights into conserved signaling cascades that control neuronal sensitivity in nematode excitotoxicity. We hope that these new insights could inspire new research directions in the search for therapeutic interventions in stroke and brain ischemia
Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study
No full textObjective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious.Peer reviewe
R&D and LCA Across the Supply Chain: Choice of Unsaturated Polyester Resins for CC-GRP Pipe Systems
No full textAbstract
In today’s economy increased attention is given towards re-using of available resources and using of resources which are re-generable, to evaluate and reduce the impact on the environment. For the polymer industry, the development of alternative and renewable raw materials represents an essential task. The study evaluates the different choices of unsaturated polyester resins (UPR) for production of centrifugally-cast glass reinforced pipe (cc-GRP) systems. The environmental impacts of three types of resin were evaluated and compared. The resins are: UPR standard, UPR containing recycled PET material (rPET-UPR) and UPR containing bio-sourced material (BIO-UPR). The analysis focuses on comparing the variations in environmental indicators caused by resin selection for three increasingly complex product layers (Base plate of cc-GRP shaft, cc-GRP Shaft and 1km cc-GRP Pipe-system). The study equally provides an insight onto R&D and LCA collaboration across the supply-chain. One of the main challenges in LCA today is using specific data from the suppliers instead of generic data. The paper indicates how LCA tools and established R&D processes can be employed to transfer LCA calculations across the supply-chain. BIO-UPR and rPET-UPR are alternatives which are realistic in terms of costs and which ensure the required quality for the manufactured products. rPET-UPR can be used for production of complete pipe systems, with positive environmental indicators. Mechanical proprieties of BIO-UPR restrict its usability and use of this resin presents similarities with the debate regarding use of bio-diesel.</jats:p
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