Explore the vast range of titles available.

Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education. The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction. We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models. A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI -0.17 to 0.39, I =74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I =88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence. Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients.

Traumatic brain injury (TBI) causes multiple cerebrovascular disruptions and oxidative stress. These pathological mechanisms are often accompanied by serious impairment of cerebral blood flow autoregulation and neuronal and glial degeneration. Background/Objectives: Multiple biochemical cascades are triggered by brain damage, resulting in reactive oxygen species production alongside blood loss and hypoxia. However, most currently available early antioxidant therapies lack capacity and hence sufficient efficacy against TBI. The aim of this study was to test a novel catalytic antioxidant nanoparticle to alleviate the damage occurring in blast TBI. Methods: TBI was elicited in an open blast rat model, in which the rats were exposed to the effects of an explosive blast. Key events of the post-traumatic chain in the brain parenchyma were studied using immunohistochemistry. The application of a newly developed biologically compatible catalytic superoxide dismutase mimetic carbon-based nanocluster, a poly-ethylene-glycol-functionalized hydrophilic carbon cluster (PEG-HCC), was tested post-blast to modulate the components of the TBI process. Results: The PEG-HCC was shown to significantly ameliorate neuronal loss in the brain cortex, the dentate gyrus, and hippocampus when administered shortly after the blast. There was also a significant increase in endothelial activity to repair blood–brain barrier damage as well as the modulation of microglial and astrocyte activity and an increase in inducible NO synthase in the cortex. Conclusions: We have demonstrated qualitatively and quantitatively that the previously demonstrated antioxidant properties of PEG-HCCs have a neuroprotective effect after traumatic brain injury following an explosive blast, acting at multiple levels of the pathological chain of events elicited by TBI.

Synthesizing evidence from randomized controlled trials of digital health education poses some challenges. These include a lack of clear categorization of digital health education in the literature; constantly evolving concepts, pedagogies, or theories; and a multitude of methods, features, technologies, or delivery settings. The Digital Health Education Collaboration was established to evaluate the evidence on digital education in health professions; inform policymakers, educators, and students; and ultimately, change the way in which these professionals learn and are taught. The aim of this paper is to present the overarching methodology that we use to synthesize evidence across our digital health education reviews and to discuss challenges related to the process. For our research, we followed Cochrane recommendations for the conduct of systematic reviews; all reviews are reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. This included assembling experts in various digital health education fields; identifying gaps in the evidence base; formulating focused research questions, aims, and outcome measures; choosing appropriate search terms and databases; defining inclusion and exclusion criteria; running the searches jointly with librarians and information specialists; managing abstracts; retrieving full-text versions of papers; extracting and storing large datasets, critically appraising the quality of studies; analyzing data; discussing findings; drawing meaningful conclusions; and drafting research papers. The approach used for synthesizing evidence from digital health education trials is commonly regarded as the most rigorous benchmark for conducting systematic reviews. Although we acknowledge the presence of certain biases ingrained in the process, we have clearly highlighted and minimized those biases by strictly adhering to scientific rigor, methodological integrity, and standard operating procedures. This paper will be a valuable asset for researchers and methodologists undertaking systematic reviews in digital health education.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-∞) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

Biobanks will have a crucial role in the identification of genes associated with disease — a prerequisite to designing adequate diagnostic and therapeutic tools. To maximize their impact and chances of success, collaboration at a global scale is highly desirable.

The three-dimensional structure of the DNA-binding domain (DBD) of the glucocorticoid receptor has been determined by nuclear magnetic resonance spectroscopy and distance geometry. The structure of a 71-residue protein fragment containing two \"zinc finger\" domains is based on a large set of proton-proton distances derived from nuclear Overhauser enhancement spectra, hydrogen bonds in previously identified secondary structure elements, and coordination of two zinc atoms by conserved cysteine residues. The DBD is found to consist of a globular body from which the finger regions extend. A model of the dimeric complex between the DBD and the glucocorticoid response element is proposed. The model is consistent with previous results indicating that specific amino acid residues of the DBD are involved in protein-DNA and protein-protein interactions.

Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education. The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction. We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models. A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI −0.17 to 0.39, I[sup.2]=74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I[sup.2]=88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence. Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients.