Ethanol Extract of Blighia Sapida Stem Bark Show Remarkable Prophylactic Activity in Experimental Plasmodium berghei-Infected Mice.

This work explores the antiplasmodial potential of ethanol extract of Blighia sapida (Lin. Sapindaceae) in chloroquine (CQ)- resistant Plasmodium berghei (ANKA strain)–infected mice. Chloroquine-resistant (ANKA) strain of P berghei was inoculated intraperitoneally into Swiss albino mice. Mice were treated orally for 4 consecutive days, before and after inoculation (prophylactic, suppressive, and curative models) with graded doses of the plant extracts with Artemether-Lumefantrine (Coartem) as control. Prophylactically, the extract showed a remarkable activity in the chemosuppression of P berghei parasites (

Under-displaced normal faults: Strain accommodation along an early-stage rift-bounding fault in the Southern Malawi Rift

One of the fundamental problems in continental rift segmentation and propagation is how strain is accommodated along large rift-bounding faults (border faults) since the segmentation of propagating border faults control the expression of rift zones, syn-rift depo-centers, and long-term basin evolution. In the Southern Malawi Rift, where previous studies on the early-stage rifting only assessed border fault structure from surficial and topographic expression, we integrate surface and subsurface data to investigate border fault segmentation, linkage, and growth as proxies for strain accommodation along the Bilila-Mtakataka Fault (BMF) System. We used 30�m-resolution topographic relief maps, electrical resistivity tomography (ERT), and high-resolution aeromagnetic data to characterize the detailed fault geometry and provide a more robust estimate of along-fault displacement distribution. Our results reveal a discrepancy between sub-aerial segmentation of the BMF geometry (six segments), scarp height (five segments) reflecting the most recent episodes of fault offset, and cumulative throw (three composite segments) reflecting the long-term fault offset. We also observe that although the BMF exhibits continuity of sub-aerial scarps along its length, the throw distribution shows a higher estimate at the Northern-to-Central segment relay zone (423�m absolute, 364�m moving median) compared to the Central-to-Southern segment relay zone (371�m absolute, 297�m moving median). The ERT profiles across the relay zones suggest a shallower basement and a possible canyon-mouth alluvial fan stratigraphy at the Central-to-Southern segment relay zone, contrasting the deeper basement and 'simpler'� electrical stratigraphy at the Northern-to-Central relay. The results suggest a more complex long-term evolution of the BMF than was assumed in previous studies. A comparison of BMF's maximum displacement-vs-length with those of other Malawi Rift border faults and global normal fault populations suggest that although the BMF has possibly reached its maximum length, it remains largely under-displaced as its 580-837�m maximum displacement is significantly lower than that of faults of equivalent length. We suggest that the BMF may continue to accrue significant strain as tectonic extension progresses in the Southern Malawi Rift, thus posing a major seismic hazard in the region.Peer reviewedGeolog

The impact of donor policies in Europe: a steady increase, but not everywhere

<p>Abstract</p> <p>Background</p> <p>Transplantable organs are scarce everywhere. Therefore, countries have developed policies to support the efficient use of potential donors. Nevertheless, the shortage of organs remains. Were these policies in vain? The aim of this study is to assess the impact of donor policies on donor procurement in 10 Western European countries from 1995 to 2005.</p> <p>Method</p> <p>To assess the impact of the donor policies we studied the conversion of potential donors into effectuated donors. 80% of the donors died from CVAs or a (traffic) accident. We considered these mortality rates to be a good proxy for potential donors. Here we call the conversion of potential donors into actual donors 'the donor efficiency rate by proxy'.</p> <p>Results</p> <p>The mortality rates for CVA and (traffic) accidents have decreased in the countries under study. At the same time, in most countries the donor efficiency rates have steadily increased. The variance in donor efficiency rates between countries has also increased from 1995 to 2005. Four countries introduced a new consent system or changed their existing system, without (visible) long-term effects.</p> <p>Conclusion</p> <p>The overall increase in donor efficiency means that the efforts to improve donor policies have paid off. However, substantial differences between countries were found. The success of donor policies in terms of the number of absolute donors is blurred by the success of policies on traffic safety and CVA treatment. It remains unclear which specific policy measures are responsible for the increase in donor efficiency rates. This increase is not related to having a presumed consent system. Furthermore, an analysis of countries that introduced a new consent system or changed their system showed no effect on donor efficiency.</p

Effects of control interventions on Clostridium difficile infection in England: an observational study

Background: The control of Clostridium difficile infections is an international clinical challenge. The incidence of C difficile in England declined by roughly 80% after 2006, following the implementation of national control policies; we tested two hypotheses to investigate their role in this decline. First, if C difficile infection declines in England were driven by reductions in use of particular antibiotics, then incidence of C difficile infections caused by resistant isolates should decline faster than that caused by susceptible isolates across multiple genotypes. Second, if C difficile infection declines were driven by improvements in hospital infection control, then transmitted (secondary) cases should decline regardless of susceptibility. Methods: Regional (Oxfordshire and Leeds, UK) and national data for the incidence of C difficile infections and antimicrobial prescribing data (1998–2014) were combined with whole genome sequences from 4045 national and international C difficile isolates. Genotype (multilocus sequence type) and fluoroquinolone susceptibility were determined from whole genome sequences. The incidence of C difficile infections caused by fluoroquinolone-resistant and fluoroquinolone-susceptible isolates was estimated with negative-binomial regression, overall and per genotype. Selection and transmission were investigated with phylogenetic analyses. Findings: National fluoroquinolone and cephalosporin prescribing correlated highly with incidence of C difficile infections (cross-correlations >0·88), by contrast with total antibiotic prescribing (cross-correlations 0·2). Interpretation: Restricting fluoroquinolone prescribing appears to explain the decline in incidence of C difficile infections, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of C difficile infection control programmes

Calcineurin-Inhibitor Minimization in Liver Transplant Patients with Calcineurin-Inhibitor-Related Renal Dysfunction: A Meta-Analysis

BACKGROUND: Introduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction. METHODS: We included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up. RESULTS: GFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I(2) = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I(2) = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I(2) = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I(2) = 0%; survival: Z = 0.28, P = 0.78; I(2) = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I(2) = 0%). CONCLUSION: CNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen

Hypoxia Inducible Factor 1-Alpha (HIF-1 Alpha) Is Induced during Reperfusion after Renal Ischemia and Is Critical for Proximal Tubule Cell Survival

Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component

Need for recovery amongst emergency physicians in the UK and Ireland: A cross-sectional survey

OBJECTIVES: To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores. DESIGN: Cross-sectional electronic survey. SETTING: Emergency departments (EDs) (n=112) in the UK and Ireland. PARTICIPANTS: Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019. MAIN OUTCOME MEASURE: NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery. RESULTS: The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5-90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%-50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%-75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%-100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9). CONCLUSION: Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible

A review of combined advanced oxidation technologies for the removal of organic pollutants from water

Water pollution through natural and anthropogenic activities has become a global problem causing short-and long-term impact on human and ecosystems. Substantial quantity of individual or mixtures of organic pollutants enter the surface water via point and nonpoint sources and thus affect the quality of freshwater. These pollutants are known to be toxic and difficult to remove by mere biological treatment. To date, most researches on the removal of organic pollutants from wastewater were based on the exploitation of individual treatment process. This single-treatment technology has inherent challenges and shortcomings with respect to efficiency and economics. Thus, application of two advanced treatment technologies characterized with high efficiency with respect to removal of primary and disinfection by-products in wastewater is desirable. This review article focuses on the application of integrated technologies such as electrohydraulic discharge with heterogeneous photocatalysts or sonophotocatalysis to remove target pollutants. The information gathered from more than 100 published articles, mostly laboratories studies, shows that process integration effectively remove and degrade recalcitrant toxic contaminants in wastewater better than single-technology processing. This review recommends an improvement on this technology (integrated electrohydraulic discharge with heterogeneous photocatalysts) viz-a-vis cost reduction in order to make it accessible and available in the rural and semi-urban settlement. Further recommendation includes development of an economic model to establish the cost implications of the combined technology. Proper monitoring, enforcement of the existing environmental regulations, and upgrading of current wastewater treatment plants with additional treatment steps such as photocatalysis and ozonation will greatly assist in the removal of environmental toxicants