Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol.

Background: Six randomized trials have not detected a difference between intravenous alteplase plus endovascular thrombectomy and endovascular thrombectomy alone in stroke. Tenecteplase, a recombinant human tenecteplase tissue-type plasminogen activator, is a genetically modified variant of alteplase. It is unclear whether the outcomes are different if alteplase is replaced with tenecteplase.

Reach and effectiveness of a HEARTS hypertension pilot project in Guatemala.

The World Health Organization Global Hearts initiative (HEARTS) and technical package aim to improve the primary health care management of hypertension and other risk factors for cardiovascular disease at the population level. This study describes the first HEARTS implementation pilot project in Guatemala's Ministry of Health (MOH) primary health care system. This pilot began in April 2022 in six primary health care facilities in three rural indigenous municipalities.

Genetic differentiation and bottleneck effects in the malaria vectors and after an LLIN-based vector control program in Papua New Guinea.

Implementation of long-lasting insecticide-treated net (LLIN) programs to control human malaria transmission leads to substantial reductions in the abundance of mosquitoes, but the impact on the population genetic structure of the malaria vectors is poorly known, nor has it been investigated in Papua New Guinea, where malaria is highly endemic and where several species of have vector roles. Here, we applied Wright's -statistic, analysis of molecular variance, Bayesian structure analysis, and discriminant analysis of principle components to microsatellite genotype data to analyze the population genetic structure of between and within the northern and southern lowland plains and of within the northern plain of Papua New Guinea after such a program. Bottleneck effects in the two malaria vectors were analyzed using Luikart and Cornuet's tests of heterozygosity.

Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in .

The emergence of parasite resistance to current front-line antimalarial treatments poses a serious threat to global malaria control and highlights the necessity for the development of therapeutics with novel targets and mechanisms of action. Plasmepsins IX and X (PMIX/PMX) have been recognised as highly promising targets in due to their contribution to parasite's pathogenicity. Recent research has demonstrated that dual PMIX/PMX inhibition results in the impairment of multiple parasite's life cycle stages, which is an important feature in drug resistance prevention.

No evidence for direct thermal carryover effects on starvation tolerance in the obligate blood-feeder, .

Thermal stress during development can prime animals to cope better with similar conditions in later life. Alternatively, negative effects of thermal stress can persist across life stages and result in poorer quality adults (negative carryover effects). As mean temperatures increase due to climate change, evidence for such effects across diverse taxa is required.

Should all pregnant women take calcium supplements in Nepal? GRADE evidence to policy assessment.

Background: The WHO recommends oral calcium supplementation (1.5-2.0 g) in pregnant women to reduce the risk of pre-eclampsia living in areas with low dietary calcium intake.

Simultaneous Raman and infrared spectroscopy: a novel combination for studying bacterial infections at the single cell level.

Sepsis is a life-threatening clinical condition responsible for approximately 11 million deaths worldwide. Rapid and accurate identification of pathogenic bacteria and its antimicrobial susceptibility play a critical role in reducing the morbidity and mortality rates related to sepsis. Raman and infrared spectroscopies have great potential to be used as diagnostic tools for rapid and culture-free detection of bacterial infections.

Incorporating genetic selection into individual-based models of malaria and other infectious diseases.

Introduction: Control strategies for human infections are often investigated using individual-based models (IBMs) to quantify their impact in terms of mortality, morbidity and impact on transmission. Genetic selection can be incorporated into the IBMs to track the spread of mutations whose origin and spread are driven by the intervention and which subsequently undermine the control strategy; typical examples are mutations which encode drug resistance or diagnosis- or vaccine-escape phenotypes.

Methods And Results: We simulated the spread of malaria drug resistance using the IBM OpenMalaria to investigate how the finite sizes of IBMs require strategies to optimally incorporate genetic selection.

Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes.

The development of genetically modified (GM) mosquitoes and their subsequent field release offers innovative and cost-effective approaches to reduce mosquito-borne diseases, such as malaria. A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vector s.l.

Early on-demand drainage versus standard management among acute necrotizing pancreatitis patients complicated by persistent organ failure: The protocol for an open-label multi-center randomized controlled trial.

Introduction/aim: Pancreatic necrosis occurs in a quarter of patients with acute pancreatitis, many of whom form an acute necrotic collection (ANC). The current standard treatment is to defer percutaneous catheter drainage (PCD) until the latter becomes "walled off," which takes approximately four weeks. The majority of patients that develop persistent organ failure (POF), the primary determinant of mortality, do so within four weeks.

The effects of individual nonheritable variation on fitness estimation and coexistence.

Demographic theory and data have emphasized that nonheritable variation in individual frailty enables selection within cohorts, affecting the dynamics of a population while being invisible to its evolution. Here, we include the component of individual variation in longevity or viability which is nonheritable in simple bacterial growth models and explore its ecological and evolutionary impacts. First, we find that this variation produces consistent trends in longevity differences between bacterial genotypes when measured across stress gradients.

The tethered flight technique as a tool for studying life-history strategies associated with migration in insects.

1. Every year billions of insects engage in long-distance, seasonal mass migrations which have major consequences for agriculture, ecosystem services and insect-vectored diseases. Tracking this movement in the field is difficult, with mass migrations often occurring at high altitudes and over large spatial scales.

Geostatistical models using remotely-sensed data predict savanna tsetse decline across the interface between protected and unprotected areas in Serengeti, Tanzania.

Monitoring abundance is essential for vector management, but it is often only possible in a fraction of managed areas. For vector control programmes, sampling to estimate abundance is usually carried out at a local-scale (10s km), while interventions often extend across 100s km. Geostatistical models have been used to interpolate between points where data are available, but this still requires costly sampling across the entire area of interest.

Tracing the origin of the early wet-season in the Sahel.

In arid environments, the source of the malaria mosquito populations that re-establish soon after first rains remains a puzzle and alternative explanations have been proposed. Using genetic data, we evaluated whether the early rainy season (RS) population of is descended from the preceding late RS generation at the same locality, consistent with dry season (DS) dormancy (aestivation), or from migrants from distant locations. Distinct predictions derived from these two hypotheses were assessed, based on variation in 738 SNPs in eleven samples, including seven samples spanning 2 years in a Sahelian village.

Characterization of the Prophage Repertoire of African Typhimurium ST313 Reveals High Levels of Spontaneous Induction of Novel Phage BTP1.

In the past 30 years, bloodstream infections have become a significant health problem in sub-Saharan Africa and are responsible for the deaths of an estimated 390,000 people each year. The disease is predominantly caused by a recently described sequence type of Typhimurium: ST313, which has a distinctive set of prophage sequences. We have thoroughly characterized the ST313-associated prophages both genetically and experimentally.

One health - an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases.

Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions.

Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria.

Background: The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study, we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM.

Pathogenesis of cerebral malaria--inflammation and cytoadherence.

Despite decades of research on cerebral malaria (CM) there is still a paucity of knowledge about what actual causes CM and why certain people develop it. Although sequestration of P. falciparum infected red blood cells has been linked to pathology, it is still not clear if this is directly or solely responsible for this clinical syndrome.

Examining the tsetse teneral phenomenon and permissiveness to trypanosome infection.

Tsetse flies are the most important vectors of African trypanosomiasis but, surprisingly, are highly refractory to trypanosome parasite infection. In populations of wild caught flies, it is rare to find mature salivarian and mouthpart parasite infection rates exceeding 1 and 15%, respectively. This inherent refractoriness persists throughout the lifespan of the fly, although extreme starvation and suboptimal environmental conditions can cause a reversion to the susceptible phenotype.

Early detection of population declines: high power of genetic monitoring using effective population size estimators.

Early detection of population declines is essential to prevent extinctions and to ensure sustainable harvest. We evaluated the performance of two N e estimators to detect population declines: the two-sample temporal method and a one-sample method based on linkage disequilibrium (LD). We used simulated data representing a wide range of population sizes, sample sizes and number of loci.

The use of ultrasonography in obstetrics in developing countries.

Ultrasonography in pregnancy is one of the most important advances in antenatal and obstetric emergency care. The benefits of diagnostic ultrasound in a resource-poor setting are well known and undisputed. Routine ultrasound can provide real benefit to patients when it is included in antenatal care programmes designed to improve maternal and neonatal health, and it should become a standard procedure in developing countries.