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Malaria is a global health concern caused by infection with Plasmodium parasites. With rising insecticide and drug resistance, there is a critical need to develop novel control strategies, including strategies to block parasite sporogony in key mosquito vector species. MAPK signaling pathways regulated by extracellular signal-regulated kinases (ERKs) and the stress-activated protein kinases (SAPKs) c-Jun N-terminal kinases (JNKs) and p38 MAPKs are highly conserved across eukaryotes, including mosquito vectors of the human malaria parasite Plasmodium falciparum. Some of these pathways in mosquitoes have been investigated in detail, but the mechanisms of integration of parasite development and mosquito fitness by JNK signaling have not been elucidated. To this end, we engineered midgut-specific overexpression of MAPK phosphatase 4 (MKP4), which targets the SAPKs, and used two potent and specific JNK small molecule inhibitors (SMIs) to assess the effects of JNK signaling manipulations on Anopheles stephensi fecundity, lifespan, intermediary metabolism, and P. falciparum development. MKP4 overexpression and SMI treatment reduced the proportion of P. falciparum-infected mosquitoes and decreased oocyst loads relative to controls. SMI-treated mosquitoes exhibited no difference in lifespan compared to controls, whereas genetically manipulated mosquitoes exhibited extended longevity. Metabolomics analyses of SMI-treated mosquitoes revealed insights into putative resistance mechanisms and the physiology behind lifespan extension, suggesting for the first time that P. falciparum-induced JNK signaling reduces mosquito longevity and increases susceptibility to infection, in contrast to previously published reports, likely via a critical interplay between the invertebrate host and parasite for nutrients that play essential roles during sporogonic development.

In the current paper, we develop an approach to early science pedagogy that is based on insights about how complex adaptive systems function. Complexity approaches have an important advantage over traditional information-processing approaches: They anticipate the proverbial 'mind with a mind of its own' without having to postulate exclusively mental constructs. They also offer insights about key determinants of learning and effective pedagogy, again without postulating exclusively mental constructs. For complex adaptive systems, learning depends on the presence of sufficiently salient novelty (i.e., variability), and it depends on the presence of sufficiently salient repetitions or ordered patterns (i.e., stability). Science learning, therefore, requires science-relevant novelty and science-relevant patterns of order. Equipped with these insights, we address two challenges of early science pedagogy: (1) how to combine children's self-guided explorations with teachers' strategic interventions, and (2) how to minimize the chances of generating misconceptions about science. The answer lies in creating a learning context that maximizes science-relevant variability and science-relevant stability. If both aspects are abundantly available, a child's self-guided explorations are effective. Conversely, if either aspect is missing, efforts must be made to add them strategically to a child's experience. Adding science-relevant stability is particularly challenging, yet crucial to avoid science misconceptions.

Introduction: Problem‐solving skills (PSS) help to provide a systematic approach to dealing with and managing complex problems. The overall aim of this study was to assess the acceptability and feasibility of developing and adapting a prison‐based PSS workbook for adults within a medium‐ and low‐secure hospital. Method: We used the Medical Research Council framework in our participatory mixed methods study incorporating an adapted survey (to identify what types of problems people experience in secure hospitals), a series of three interactive workshops (to co‐produce two case study examples for a workbook) and we gathered feedback from patients and hospital staff on the acceptability and feasibility of the workbook. Data from the survey were used to inform the case study examples, and the feedback from patients and hospital staff was descriptively summarised and the results consolidated. Results: In total, 82 (51%) patients took part in the survey; 22 patients and 49 hospital staff provided feedback on the workbook. The survey results indicated that patients regularly experience problems while in the hospital. Patients reported problems relating to restrictions of freedom and boredom. The workshops produced two case studies for the workbooks, with mainly positive patient and staff feedback. More work is required to improve the visual representation of the characters in the case studies, the amount and content of the language and the mechanism of the intervention delivery. Conclusion: The adaptation process proved acceptable and feasible to both patients and staff. The co‐production methodology for the workbook and feedback from patients and staff was an effective way of iteratively refining the materials to ensure that they were both meaningful and acceptable to staff and patients. Subsequent work is required to develop the workbook and evaluate the feasibility of the intervention delivery, recruitment rates, uptake and adherence to the PSS using a randomised controlled trial. Patient or Public Contribution: At each stage of the project consultation with patients and/or hospital staff was involved. [ABSTRACT FROM AUTHOR]

Decisions about progress through an academic programme are made by Boards of Examiners, on the basis of students' course assessments. For most students such pass/fail grading decisions are straightforward. However, for those students whose results are borderline (either at a pass/fail boundary or boundaries between grades) the exercise of some discretion by university staff is required. In the interests of the transparency of the exercise of this discretion and to increase the chances that the "right" decision is made, we tested the validity of the second version of the Objective Borderline Method (OBM2) decision-making tool in a medical programme. Our results suggest that application of OBM2 provides valid data to help university staff make robust decisions about a student's progression through a programme, and with which to defend these decisions if that should be required.

ObjectivesSymptoms are compared among patients with coronary artery disease (CAD) admitted to the emergency department with or without acute coronary syndrome (ACS). Sex and age are also assessed.MethodsA secondary analysis from the PROMOTION (Patient Response tO Myocardial Infarction fOllowing a Teaching Intervention Offered by Nurses) trial, an multicenter randomized controlled trial, was conducted.ResultsOf 3522 patients with CAD, at 2 years, 565 (16%) presented to the emergency department, 234 (41%) with non-ACS and 331 (59%) with ACS. Shortness of breath (33% vs 25%, P = .028) or dizziness (11% vs 3%, P = .001) were more common in non-ACS. Chest pain (65% vs 77%, P = .002) or arm pain (9% vs 21%, P = .001) were more common in ACS. In men without ACS, dizziness was more common (11% vs 2%; P = .001). Men with ACS were more likely to have chest pain (78% vs 64%; P = .003); both men and women with ACS more often had arm pain (men, 19% vs 10% [P = .019]; women, 26% vs 13% [P = .023]). In multivariate analysis, patients with shortness of breath (odds ratio [OR], 0.617 [confidence interval [CI], 0.410-0.929]; P = .021) or dizziness (OR, .0311 [CI, 0.136-0.708]; P = .005) were more likely to have non-ACS. Patients with prior percutaneous coronary intervention (OR, 1.592 [CI, 1.087-2.332]; P = .017), chest pain (OR, 1.579 [CI, 1.051-2.375]; P = .028), or arm pain (OR, 1.751 [CI, 1.013-3.025]; P

BACKGROUND: Patient delay in seeking treatment for acute coronary syndrome symptoms remains a problem. Thus, it is vital to test interventions to improve this behavior, but at the same time it is essential that interventions not increase anxiety. PURPOSE: To determine the impact on anxiety and perceived control of an individual face-to-face education and counseling intervention designed to decrease patient delay in seeking treatment for acute coronary syndrome symptoms. METHODS: This was a multicenter randomized controlled trial of the intervention in which anxiety data were collected at baseline, 3-months and 12-months. A total of 3522 patients with confirmed coronary artery disease were enrolled; data from 2597 patients with anxiety data at all time points are included. The intervention was a 45 min education and counseling session, in which the social, cognitive and emotional responses to acute coronary syndrome symptoms were discussed as were barriers to early treatment seeking. Repeated measures analysis of covariance was used to compare anxiety and perceived control levels across time between the groups controlling for age, gender, ethnicity, education level, and comorbidities. RESULTS: There were significant differences in anxiety by group (p = 0.03). Anxiety level was stable in patients in the control group, but decreased across time in the intervention group. Perceived control increased across time in the intervention group and remained unchanged in the control group (p = 0.01). CONCLUSION: Interventions in which cardiac patients directly confront the possibility of an acute cardiac event do not cause anxiety if they provide patients with appropriate strategies for managing symptoms.

Little has been published on the demographic composition of the clinical and translational science research workforce within the Clinical and Translational Science Awards (CTSA) Program despite the well-documented need for greater diversity in the biomedical research workforce. Analyses of workforce demographic reveal that women and members of underrepresented groups remain persistently underrepresented in the CTSA hub and training components principal investigators. In contrast, in the CTSA Program career development and training programs, females have greater representation as participants, and non-Whites were better represented in training programs. [ABSTRACT FROM AUTHOR]

The 3-D structure of human lactoferrin was first solved in atomic detail in 1987. Since that time, a variety of proven and postulated activities have been added to the original annotation of lactoferrin as an iron-binding protein. Structural studies have also expanded to include iron-bound and iron-free (apo) forms, mutants, and the lactoferrins of different species. In this review, we take the current information on both structure and function and show that the 3-D structure provides a useful framework for understanding some activities and also points to productive research directions that could help elucidate other reported functions. Some functions relate to iron binding where the role of lactoferrin is to scavenge and retain iron across a wide pH range. We specifically focus on functions that depend on the surface structure of the molecule, identifying features that may determine the many other protective properties of this multifunctional protein. Key words: lactoferrin, protein structure, iron binding, protective functions, glycosylation. La structure tridimensionnelle de la lactoferri-ne humaine a ete d'abord resolue a l'echelle atomique en 1987. Depuis lors, une variete d'activites demontrees ou presumees ont ete ajoutees a la premiere indication que la lactoferrine etait une proteine de liaison du fer. Des etudes structurales se sont aussi developpees pour inclure les formes liee et non liee (apo) au fer, les mutants et les lactoferrines de differentes especes. Dans cet article de revue, nous compilons l'information actuelle portant tant sur la structure que la fonction de la lactoferrine, et nous montrons que la structure tridimensionnelle fournit un canevas utile pour comprendre certaines de ses activites et indique certaines directions productives de recherche qui pourraient nous aider a elucider d'autres fonctions connues. Certaines fonctions sont reliees a la liaison du fer ou le role de la lactoferrine est de desactiver et de retenir le fer a travers un large spectre de pH. Nous nous concentrons specialement sur les fonctions qui dependent de la structure de surface de la molecule, identifiant les caracteristiques qui peuvent determiner les nombreuses autres proprietes protectrices de cette proteine multifonctionnelle. Mots-cles : lactoferrine, structure proteique, liaison du fer, fonctions protectrices, glycosylation., Introduction It is just over 50 years since lactoferrin (Lf) was first isolated and characterized from both human and bovine milks (Johanson et al. 1960; Groves 1960; Montreuil et al. [...]