C-reactive protein predicts further ischemic events in patients with transient ischemic attack or lacunar stroke

Patients who have experienced a first cerebral ischemic event are at increased risk of recurrent stroke. There is strong evidence that low-level inflammation as measured by high sensitivity C-reactive protein (hs-CRP) is a predictor of further ischemic events. Other mechanisms implicated in the pathogenesis of stroke may play a role in determining the risk of secondary events, including oxidative stress and the adaptive response to it and activation of neuroprotective pathways by hypoxia, for instance through induction of erythropoietin (EPO). This study investigated the association of the levels of CRP, peroxiredoxin 1 (PRDX1, an indicator of the physiological response to oxidative stress) and EPO (a neuroprotective factor produced in response to hypoxia) with the risk of a second ischemic event. Eighty patients with a diagnosis of lacunar stroke or transient ischemic attack (TIA) were included in the study and a blood sample was collected within 14 days from the initial event. Hs-CRP, PRDX1 and EPO were measured by ELISA. Further ischemic events were recorded with a mean follow-up of 42 months (min 24, max 64). Multivariate analysis showed that only CRP was an independent predictor of further events with an observed risk (OR) of 1.14 (P = 0.034, 95% CI 1.01-1.29). No association was observed with the levels of PRDX1 or EPO. A receiver operating curve (ROC) determined a cut-off CRP level of 3.25 μg/ml, with a 46% sensitivity and 81% specificity. Low-level inflammation as detected by hs-CRP is an independent predictor of recurrent cerebrovascular ischemic events

Human β-defensin-2 production from S. cerevisiae using the repressible MET17 promoter

BACKGROUND: Baker’s yeast Saccharomyces cerevisiae is a proven host for the commercial production of recombinant biopharmaceutical proteins. For the manufacture of heterologous proteins with activities deleterious to the host it can be desirable to minimise production during the growth phase and induce production late in the exponential phase. Protein expression by regulated promoter systems offers the possibility of improving productivity in this way by separating the recombinant protein production phase from the yeast growth phase. Commonly used inducible promoters do not always offer convenient solutions for industrial scale biopharmaceutical production with engineered yeast systems. RESULTS: Here we show improved secretion of the antimicrobial protein, human β-defensin-2, (hBD2), using the S. cerevisiae MET17 promoter by repressing expression during the growth phase. In shake flask culture, a higher final concentration of human β-defensin-2 was obtained using the repressible MET17 promoter system than when using the strong constitutive promoter from proteinase B (PRB1) in a yeast strain developed for high-level commercial production of recombinant proteins. Furthermore, this was achieved in under half the time using the MET17 promoter compared to the PRB1 promoter. Cell density, plasmid copy-number, transcript level and protein concentration in the culture supernatant were used to study the effects of different initial methionine concentrations in the culture media for the production of human β-defensin-2 secreted from S. cerevisiae. CONCLUSIONS: The repressible S. cerevisiae MET17 promoter was more efficient than a strong constitutive promoter for the production of human β-defensin-2 from S. cerevisiae in small-scale culture and offers advantages for the commercial production of this and other heterologous proteins which are deleterious to the host organism. Furthermore, the MET17 promoter activity can be modulated by methionine alone, which has a safety profile applicable to biopharmaceutical manufacturing

Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients

Purpose Sarcopenia is associated with poor outcomes, and evidence suggests an inverse relationship between skeletal muscle mass and cardiovascular risk. Sarcopenia has been studied after stroke, but its value as a risk factor for stroke has not been examined. This prospective cohort study measured sarcopenia in stroke/TIA patients at baseline to explore its role in predicting recurrent events. Method The Arterial Stiffness In lacunar Stroke and TIA (ASIST) study included 96 patients with TIA/lacunar stroke, of which 82 patients (mean age 71.2±10.8 years) had bioimpedance analysis to assess body composition. Skeletal Mass Index (SMI) was calculated and parameters of sarcopenia assessed using Davison (1) and Janssen (2) criteria. Recurrent cerebrovascular events were monitored over 5 years. Results Eighteen patients had recurrent events. On independent samples t test there were significantly more participants with sarcopenia in the recurrent events group (89% vs 56%, p<0.001) using Davison (1) criteria, as well as lower mean SMI, significantly more participants with diabetes and higher arterial stiffness. On binary logistic regression, the only significant predictors of recurrent events were SMI (p=0.036, hazard ratio=0.414, 95% confidence interval 0.195-0.948) and diabetes (p=0.004, hazard ratio=9.06, 95% confidence interval 2.009-40.860) when corrected for age, sex and cardiovascular risk factors. Using Janssen (2) criteria in the regression, severe sarcopenia was a significant predictor of recurrent events (p=0.028). There was a significant association between sarcopenia and recurrent events on Chi square based on Davison (p=0.02) and Janssen (p=0.034) definitions. Conclusions The presence of baseline sarcopenia in stroke and TIA patients is an independent predictor of recurrent events

Thule Inuit environmental impacts on Kangeq, southwest Greenland

The Leverhulme Trust is thanked for financial support for the project “Footsteps on the Edge of Thule” (Programme Grant F/00 152/Q), directed by Kevin Edwards (University of Aberdeen), Andy Dugmore, Eva Panagiotakopulu (both University of Edinburgh), and Ian Simpson (Stirling University). We are grateful to Andy McMullen, Kirsty Collinge and Ian Simpson for assistance with fieldwork and advice. Gordon Cook is thanked for the provision of radiocarbon dates. Jamie Bowie kindly assisted with the production of diagrams relating to palynological work. The maps and section were drawn by Anastasios Panagiotakopoulos, whose help is warmly acknowledged. Last but not least we are grateful for the helpful comments by the editor and three anonymous reviewers.Peer reviewedPostprin

Effects of Pre-Fire Vegetation on the Post-Fire Plant Community Response to Wildfire along a Successional Gradient in Western Juniper Woodlands

Western juniper was often historically restricted to fire refugia such as rocky outcrops but has since Euro-American settlement expanded into areas previously dominated by sagebrush steppe. Wildfires in developed woodlands have been rare. In 2007, the Tongue-Crutcher Wildland Fire burned 18,890 ha in southwestern Idaho along a woodland development gradient, providing unique research opportunities. To assess fire effects on vascular plants, field data were collected in 2012/2013 and 2019/2020. Species richness was uniform along the sere, while species diversity declined in late woodland stages attributed to juniper dominance. The greatest changes in species composition following fire occurred in later woodland development phases. Herbaceous vegetation increased following fire, but sagebrush cover was still lower in burned plots 12–13 years post-fire. Many stands dominated by juniper pre-fire became dominated by snowbrush ceanothus post-fire. Juniper seedlings were observed post-fire, indicating that juniper will reoccupy the area. Our research demonstrates resilience to fire and resistance to annual grasses particularly in early successional stages, which provides opportunities for fire use as a management tool on cool and moist ecological sites. Loss of old-growth juniper to wildfire underlines the importance of maintaining and provisioning for future development of some old growth on the landscape given century-long recovery times

Influence of Wildland Fire Along a Successional Gradient in Sagebrush Steppe and Western Juniper Woodlands

Western juniper (Juniperus occidentalis Hook. var. occidentalis) has been expanding into sagebrush (Artemisia L. spp.) steppe over the past 130 yr in Idaho, Oregon, and California. Fuel characteristics and expected fire behavior and effects change as sagebrush steppe transitions into juniper woodlands. Little is currently known about how wildfire influences burn severity and ecosystem response in steppe altered by woodland conversion. In 2007, the Tongue-Crutcher Wildland Fire burned 18 890 ha along a successional gradient ranging from sagebrush steppe to mature juniper woodlands, providing a unique opportunity to evaluate the effects of prefire vegetation on burn severity and ecosystem response across spatial scales. Plot-scale burn severity was evaluated with the composite burn index (CBI) in locations where prefire vegetation data were available, and landscape-scale burn severity was estimated via remotely sensed indices (differenced normalized burn ratio [dNBR] and relative differenced normalized burn ratio [RdNBR]). Strong positive relationships exist between CBI and remotely sensed burn severity indices in woodlands, whereas the relationships are weaker in steppe vegetation. Woodlands in late structural development phases, and sagebrush patches near developed woodlands, incurred higher burn severity than steppe and young woodlands. The results support the idea that a threshold exists for when juniper-encroached sagebrush steppe becomes difficult to restore. Implications for fire management in sagebrush/juniper ecosystems are discussed.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

A spatially explicit model to predict future landscape composition of aspen woodlands under various management scenarios

Quaking aspen (Populus tremuloides) is declining across the western United States. Aspen habitats are among the most diverse plant communities in this region and loss of these habitats can result in shifts in biodiversity, productivity, and hydrology across a range of spatial scales. Western aspen occurs on the majority of sites seral to conifer species, and long-term maintenance of these aspen woodlands requires periodic fire. Over the past century, fire intervals, extents, and intensities have been insufficient to regenerate aspen stands at historic rates; however the effects of various fire regimes and management scenarios on aspen vegetation dynamics at broad spatial and temporal scales are unexplored. Here we use field data, remotely sensed data, and fire atlas information to develop a spatially explicit landscape simulation model to assess the effects of current and historic wildfire regimes and prescribed burning programs on landscape vegetation composition across two mountain ranges in the Owyhee Plateau, Idaho. Model outputs depict the future structural makeup and species composition of the landscape at selected time steps under simulated management scenarios. We found that under current fire regimes and in the absence of management activities, loss of seral aspen stands will continue to occur over the next two centuries. However, a return to historic fire regimes (burning 12–14% of the modeled landscape per decade) would maintain the majority of aspen stands in early and mid seral woodland stages and minimizes the loss of aspen. A fire rotation of 70–80 years was estimated for the historic fire regime while the current fire regime resulted in a fire rotation of 340–450 years, underscoring the fact that fire is currently lacking in the system. Implementation of prescribed burning programs, treating aspen and young conifer woodlands according to historic fire occurrence probabilities, are predicted to prevent conifer dominance and loss of aspen stands

Regional Efficacy of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis (RRMS)

Natalizumab is an established treatment for highly active Relapsing-Remitting Multiple Sclerosis (RRMS). Two-year efficacy in the AFFIRM trial showed No Evidence of Disease Activity(NEDA) – no relapses, no disability progression, no new MRI lesions – in 37% of patients compared with 7% in the placebo group. NEDA is increasingly used as a treatment goal in RRMS.MethodologyWe performed a retrospective analysis of Natalizumab treatment in RRMS patients in our centre. We assessed the proportion of patients achieving NEDA in a typical clinical setting with at least 1 year treatment duration and analysed for predictors of response.ResultsMean age was 41.44 (13–62), 77% (51) of patients were female. 56 out of 66 patients had been on Natalizumab for &gt;1year and were analysed. 55.36% patients achieved NEDA at 1 year. No statistically significant predictors (age, gender, starting disability and relapse rate) of response were identified.DiscussionThe data confirms in a typical UK clinical setting good treatment response was achieved in highly active RRMS patients using Natalizumab. No additional factors were found which could predict treatment response suggesting within the limitations of power and length of this study that Natalizumab is effective in a broad range of highly active RRMS patients.</jats:sec

Time Series Aerial Photography Can Help Land Owners and Managers Understand Local Aspen Dynamics

Quaking aspen (Populus tremuloides) habitats contribute to species diversity, provide forage and shade for wildlife and livestock, and are highly valued by humans for their productivity and beauty. Aspen decline has been observed in the western United States over the past 50 years and has been mainly attributed to a decrease in fire frequency, caused by effective fire suppression. Changing fire regimes have allowed conifer species to expand into aspen stands. Another phenomenon, commonly referred to as “Sudden Aspen Decline” (SAD), has been observed within the past decade in the western mountains and in the Canadian aspen parklands. Mature aspen stems begin to die at rates beyond what is expected, which if aspen regeneration is limited, can eventually lead to the loss of the aspen roots and stands. Excessive browsing by livestock and wildlife can also inhibit aspen regeneration. The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform March 202