Eukaryotic Protein Kinases (ePKs) of the Helminth Parasite Schistosoma mansoni

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The <it>Schistosoma mansoni </it>genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the <it>S. mansoni </it>predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets.</p> <p>Results</p> <p>We have identified 252 ePKs, which corresponds to 1.9% of the <it>S. mansoni </it>predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that <it>S. mansoni </it>has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in <it>S. mansoni </it>or belong to an expanded family in this parasite. Only 16 <it>S. mansoni </it>ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite.</p> <p>Conclusions</p> <p>Our approach has improved the functional annotation of 40% of <it>S. mansoni </it>ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of <it>S. mansoni </it>in response to diverse environments during the parasite development, vector interaction, and host infection.</p

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Some Thoughts on Biography and the Historiography of the Twentieth-Century Arab World

The number of English-language biographies of Arab subjects is tiny compared to the number of English-language biographies of North American and European subjects. I argue that this discrepancy is due to three main factors: the preponderance of historians of Europe and North America in history departments in the English-speaking world; the limited crossover market for serious biographies of Arab subjects; and difficulties arising from access to, and the style of, the Arabic sources. A fragment from the life-story of Fawzi al-Qawuqji, an early-20th-century Arab nationalist and soldier, is introduced as a way of pointing to the challenges of using Arabic memoirs to craft a biographical narrative in English.Le nombre de biographies en langue anglaise portant sur des sujets arabes est minuscule comparativement aux biographies en anglais de sujets nord- américains ou européens. À mon sens, cet écart est attribuable à trois facteurs principaux : la prépondérance des historiens de l’Europe et de l’Amérique du Nord dans les départements d’histoire du monde anglophone; le marché réduit pour la publication de biographies sérieuses sur des sujets arabes; la complexité de la consultation et du style des sources arabes. Un fragment de la biographie de Fawzi al-Qawuqji, nationaliste et soldat arabe du début du XXe siècle, est présenté dans le but de faire ressortir la difficulté d’utiliser une autobiographie pour rédiger un exposé biographique en anglais

Micro-narrative and the Historiography of the Modern Middle East

Abstract Most recent scholarship on the early-20th-century Eastern Arab World (Mashriq) has been preoccupied with locating the words and actions of historical actors into one or more of three overarching and interconnected (post-colonial) themes: colonialism, nationalism, and modernity. As a result, historians have produced very few micro-narratives whose protagonists are individuals from the region and which take as their starting point the prosaic concerns of daily life. What explains this historiographical trend? The relative scarcity of micro-narratives is due to a number of factors, including challenges in using particular genres of Arabic source-materials, as well as the impact of Edward Said&apos;s Orientalism generally and post-colonial concerns about narrative as a mode of representation in particular. Two fragments from the life-story of an early-20th-century Arab soldier are introduced in order to show how these factors play out in the crafting of a micro-narrative. In the 32 years since its publication, Edward Said&apos;s Orientalism has reverberated in each of the disciplines that collectively constitute Middle East Studies, including history. The book had positive effects that those of us in the field know well. It forced us to take seriously the reality of the power relations produced and reinforced by British and French colonialism, and to detect the way in which those power relations are reflected in texts. Partly as a result of Said&apos;s work, most recent historians of the Middle East have produced scholarship that is strongly critical of the British and French colonial projects in the region. These are works that have exposed the power of colonialism to destroy not only lived lives but also imagined futures. Some historians have also shown how the independent states of the 20th-century Arab Middle East were largely continuations, rather than ruptures with, their immediate colonial pasts. And, in general, most recent historians of the Arab Middle East have drawn the lesson that they must steer clear of employing general oppositions -secular vs. religious, traditional vs. modern, Sunni vs. Shi&apos;ite -as explanations for historical events, when these essentializing binaries inevitably collapse under the weight of counter examples

Inter-species comparison of seed dormancy and germination of six annual Asteraceae weeds in an ecological context

To understand germination timing in an ecological context, the response to environmental events that affect seed dormancy is central, and has to be combined with knowledge of germination responses to different circumstances. In this study, seed dormancy, germination, and emergence phenology of six annual co-occurring weedy Asteraceae species were investigated. Three pre-treatments (warm and cold stratification, and dry storage) were tested as possible dormancy affecting environmental events. Seeds were also sown outdoors. Species-specific differences were revealed in analyses. To facilitate general descriptions of dormancy patterns and germination preferences separately, condensed responses to the different possible dormancy affecting treatments and relative germination in different environments were plotted, giving species-specific patterns. Most species exhibited decreased dormancy to two or three pre-treatments. Dormancy was most effectively reduced by cold stratification for three species (Guizotia scabra, Parthenium hysterophorus, Verbesina encelioides), by warm stratification for two (Bidens pilosa, Galinsoga parviflora) and by dry storage for one (Tagetes minuta). All species germinated more when provided with light than in continuous darkness. Temperature levels most suitable for germination varied from low (15/5-20/10°C) for Verbesina encelioides to high (25/15-30/20°C) for Bidens pilosa. It is concluded that, even though the species have different dormancy patterns and germination preferences that suggest different possible distribution ranges, the species achieve similar emergence timing in the field in environments with a pronounced dry period after dispersal and small annual temperature fluctuations.Original publication: Laila M. Karlsson, T. Tamado and Per Milberg, Inter-species comparison of seed dormancy and germination of six annual Asteraceae weeds in an ecological context, 2008, Seed Science Research, (18), 35-45. http://dx.doi.org/10.1017/S0960258508888496. Copyright: Cambridge University Press, http://journals.cambridge.org