Abstract Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number ...of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the ‘gold standard’ small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.
Highlights • Our study introduces a new algorithm for the prediction of imminent ischemia after subarachnoid hemorrhage based on quantitative EEG monitoring. • We developed an automated technique ...that does not require the presence of an EEG expert to preselect or analyze raw EEG data and is therefore suitable for everyday usage by ICU staff. • Our method indicated imminent ischemia earlier than established diagnostics such as transcranial Doppler sonography or imaging and could therefore trigger intervention early enough to prevent infarction.
Intracerebral hemorrhage (ICH) is one of the most detrimental sub-types of stroke and accounts for 10–15 % of all strokes Qureshi et al. (Lancet 373(9675):1632–1644,
2009
). ICH has an incidence of ...10–30 cases per 100,000 people/year which is increasing and expected to double by the year 2050 Qureshi et al. (N Engl J Med 344 (19):1450–1460,
2001
). Mortality rates still remain poor (30–50 %) and functional dependency after ICH is high (~75 %) van Asch et al. (Lancet Neurol 9 (2):167–176,
2010
). Up to now, all randomized controlled trials investigating treatment approaches in ICH have failed to document improvements on clinical endpoints Mayer et al. (N Engl J Med 358 (20):2127–2137,
2008
); Brouwers and Goldstein (Neurotherapeutics 9 (1):87–98,
2012
). Only a specialized treatment of severely injured patients at dedicated neuro intensive care units NICU has been shown to be beneficial Qureshi et al. (Lancet 373(9675):1632–1644,
2009
); Suarez et al. (Crit Care Med 32 (11):2311–2317,
2004
). Currently, ongoing trials are investigating aggressive blood pressure lowering, hemostatic therapies, different operative strategies, intraventricular thrombolysis as well as neuroprotective approaches, and brain edema therapies. This review will summarize advanced treatment strategies and novel approaches which are currently under investigation.
Radiation Induced DNA Double-Strand Breaks in Radiology Kuefner, M A; Brand, M; Engert, C ...
RöFo : Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebende Verfahren,
10/2015, Letnik:
187, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on ...physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations.
Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes. The number of radiation induced double-strand breaks correlates well with the radiation dose. Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level.
Germinal matrix hemorrhage (GMH) is a detrimental form of neonatal CNS injury. Following GMH-mediated eNOS inhibition, inflammation arises, contributing to GMH-induced brain injury. We investigated ...the beneficial effects of Serelaxin, a clinical tested recombinant Relaxin-2 protein, on brain injury after GMH in rats. We investigated whether effects of Serelaxin are mediated by its ability to activate the GMH-suppressed eNOS pathway resulting in attenuation of inflammatory marker overproduction. GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U). Seven day old Sprague-Dawley rat pups (P7) were used (n = 63). GMH animals were divided in vehicle or serelaxin treated (3 µg once, 30 µg once, 30 µg multiple, i.p., starting 30 after GMH and then daily). Sham operated animals were used. We monitored the developmental profile working memory and spatial function (T-maze and open field test respectively). At day 28, all rats underwent MRI-scans for assessment of changes in cortical thickness and white matter loss. Effects of Serelaxin on eNOS pathway activation and post-GMH inflammation were evaluated. We demonstrated that Serelaxin dose-dependently attenuated GMH-induced developmental delay, protected brain and improved cognitive functions of rats after GMH. That was associated with the decreased post-GMH inflammation, mediated at least partly by amelioration of GMH-induced eNOS inhibition.
Hemodialysis requires reliable recurrent access to the circulation. On a chronic basis, this has been best provided by the use of arteriovenous fistulae and arteriovenous grafts. In recent years, ...hemodialysis catheters have come to play an increasingly important role in the delivery of hemodialysis. The use of both temporary as well as cuffed hemodialysis catheters has emerged as a significant boon for both patients and practicing nephrologists. The complications, however, associated with each of these hemodialysis catheters, both in terms of anatomic, thrombotic, and infectious issues, have emerged as a major problem with their continued use. This significant morbidity and complication rate has forced many nephrologists to face a basic conundrum: they have come to hate having to deal with the problems inherent in catheter usage, but the enormous utility of these devices have forced physicians to accept the fact they cannot live without them in their current practice.
We used a comprehensive literature review to describe the types, use and dilemmas of hemodialysis catheters.
This article provides a comprehensive review of both the benefits inherent with the use of these hemodialysis catheters while cataloging their complications and offering some possible solutions.
Hemodialysis vascular access catheters are essential in the maintenance of hemodialysis vascular access. However, they have a significant infectious, thrombotic, anatomic complication rate that are detailed with proposed problem-solving guidelines.
Carnitine has an essential role in energy metabolism with possible neuroprotective effects. Very preterm (VPT, <32 gestation weeks) infants may be predisposed to carnitine deficiency during ...hospitalization. We studied the associations of carnitine intake and serum carnitine levels with growth and brain size at term equivalent age (TEA) in VPT infants. This prospective cohort study included 35 VTP infants admitted to Kuopio University Hospital, Finland. Daily nutrient intakes were registered at postnatal weeks (W) 1 and 5, and serum carnitine levels were determined at W1, W5, and TEA. The primary outcomes were weight, length, and head circumference Z-score change from birth to TEA, as well as brain size at TEA in magnetic resonance imaging. Carnitine intake at W1 and W5, obtained from enteral milk, correlated positively with serum carnitine levels. Both carnitine intake and serum levels at W1, W5, and TEA showed a positive correlation with weight, length, and head circumference Z-score change and with brain size at TEA. In linear models, independent positive associations of carnitine intake and serum carnitine levels with length and head circumference Z-score change and brain size at TEA were seen. In VPT infants, sufficient carnitine intake during hospitalization is necessary since it is associated with better postnatal growth and larger brain size at term age.
IV thrombolysis represents the most effective acute stroke therapy. However, it is almost exclusively performed in stroke centers and is not available in most community areas. The Telemedical Pilot ...Project for Integrative Stroke Care (TEMPiS) was started in February 2003. Twelve community hospitals with no or very limited stroke thrombolysis experience and two stroke centers were connected via a network providing online neurologic examination and transfer of neuroradiologic scans. Following recently published preliminary results on acute phase safety of telethrombolysis, the present study reports on its long-term functional outcome.
Modified Rankin Scale (mRS), Barthel Index (BI), and mortality rate were prospectively collected 3 and 6 months after IV thrombolysis in patients of community network hospitals (telemedical group) and the stroke centers. Values of 95/100 for the BI and 0/1 for the mRS were defined as a favorable outcome.
Over the first 22 months, 170 patients were treated with tPA in the telemedical hospitals and 132 in the stroke center hospitals. Mortality rates were 11.2% vs 11.5% at 3 months (p = 0.55) and 14.2% vs 13% at 6 months (p = 0.45). A good functional outcome after 6 months was found in 39.5% of the telemedical hospitals vs 30.9% of the stroke centers (p = 0.10) for the mRS and 47.1% vs 44.8% (p = 0.44) regarding the BI.
Mortality rates and functional outcomes for telemedicine-linked community hospitals and stroke centers were similar and comparable to the results from randomized trials.
Abstract
To tackle the upcoming renovation wave, this work evaluates renovation strategies with a life cycle GHG emissions perspective and includes time and sequencing in the decision-making process. ...A case study is used to conduct a full life cycle assessment of renovation strategies in line with the Swiss normative context. Improvements in the operational energy consumption are evaluated with an energy model using the software Lesosai and considering the normative limits from the SIA 380/1. GHG emissions are calculated using the Swiss KBOB data inventory and in line with the SIA 2032 methodology. The renovation measures are then examined individually with the carbon payback time indicator and strategies with cumulative emissions over time in contrast to carbon budgets. Results show that the sequence of the refurbishment steps can increase or decrease cumulative GHG emissions of ca. 30% over the lifetime of the building. Changing a fossil-fuel based heating system is the most impactful measure and must happen as soon as possible. Switching to decarbonized heating systems reduces the carbon effectiveness of subsequent renovation measures but poses the question of energy availability. Fully renovating a building but delaying the change of heating system by only 7 years can compromise the achievement of the carbon targets.
Ovarian reserve as a predictor of cumulative live birth Balachandren, N.; Salman, M.; Diu, N.L. ...
European journal of obstetrics & gynecology and reproductive biology,
September 2020, 2020-Sep, 2020-09-00, 20200901, Letnik:
252
Journal Article
Recenzirano
Develop an up to date prediction model using recent cycle data and key pre-treatment predictor variables to estimate a couple’s individualised probability of a cumulative live birth after one cycle ...of ovarian stimulation and transfer of all frozen embryos, before the first embryo transfer.
This was a retrospective cohort study. To estimate the cumulative live birth rate we only included couples who had used all embryos from their initial stimulation or achieved a live birth.
We constructed a logistic regression model using live birth as a dependent variable and age group, duration of infertility, primary vs. secondary infertility, insemination method, cause of infertility, Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH) and antral follicle count (AFC) as our independent variables and used a backward elimination method to create the best fitting regression models to predict the probability of a cumulative live birth (p < 0.05 for elimination).
There were 516 complete cycles of ovarian stimulation resulting in 357 livebirths giving a cumulative livebirth rate of 69.2 % (95 % CI 66.0–74.0). Women with a live birth had significantly lower median age (34 years IQR 31−37 vs. 36 years IQR 33–39, p = 0.01) and FSH (6.7 iu/L IQR 5.8−7.9 vs. 7.4 iu/L IQR 6.2−8.6 and a significantly higher median AMH (22.1 pmol/L IQR 12.1−30.9 vs. 10.5 pmol/L IQR 7.3−20.7, p = 0.01) and AFC (18 IQR 12−26 vs. 12 IQR 9−19, p = 0.01). The backward conditional logistic regression model retained age category, FSH category and AMH category as significant independent predictors. The area under the curve for this model was 0.68 (95 % CI 0.63 – 0.73).
Our prediction model estimates a couple’s individualised probability of achieving a live birth after their first complete cycle of IVF using all known pre-treatment predictors.
The study population were only those eligible for NHS funded IVF treatment which have strict ovarian reserve criteria. Exclusion of those with very low egg reserve is likely to influence the predictive capacity of out model. Furthermore, our model was developed using cycle data from one unit and thus its predictive capacity has not been assessed on an independent cohort of women. We therefore welcome external geographical validation of our model prior to its use in clinical practice.
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