Differential microRNA expression in experimental cerebral and noncerebral malaria

MicroRNAs (miRNAs) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response to Plasmodium infection is unknown. We studied the expression of selected miRNAs following infection of CBA mice with Plasmodium berghei ANKA (PbA), which causes cerebral malaria (CM), or Plasmodium berghei K173 (PbK), which causes severe malaria but without cerebral complications, termed non-CM. The differential expression profiles of selected miRNAs (let-7i, miR-27a, miR-150, miR-126, miR-210, and miR-155) were analyzed in mouse brain and heart tissue by quantitative reverse transcription-PCR (qRT-PCR). We identified three miRNAs that were differentially expressed in the brain of PbA-infected CBA mice: let7i, miR-27a, and miR-150. In contrast, no miRNA changes were detected in the heart, an organ with no known pathology during acute malaria. To investigate the involvement of let-7i, miR-27a, and miR-150 in CM-resistant mice, we assessed the expression levels in gamma interferon knockout (IFN-γ-/-) mice on a C57BL/6 genetic background. The expression of let-7i, miR-27a, and miR-150 was unchanged in both wild-type (WT) and IFN-γ-/- mice following infection. Overexpression of these three miRNAs during PbA, but not PbK, infection in WT mice may be critical for the triggering of the neurological syndrome via regulation of their potential downstream targets. Our data suggest that in the CBA mouse at least, miRNA may have a regulatory role in the pathogenesis of severe malaria. © 2011, American Society for Microbiology

Mobile health use in low- and high-income countries: an overview of the peer-reviewed literature.

The evolution of mobile phone technology has introduced new possibilities to the field of medicine. Combining technological advances with medical expertise has led to the use of mobile phones in all healthcare areas including diagnostics, telemedicine, research, reference libraries and interventions. This article provides an overview of the peer-reviewed literature, published between 1 August 2006 and 1 August 2011, for the application of mobile/cell phones (from basic text-messaging systems to smartphones) in healthcare in both resource-poor and high-income countries. Smartphone use is paving the way in high-income countries, while basic text-messaging systems of standard mobile phones are proving to be of value in low- and middle-income countries. Ranging from infection outbreak reporting, anti-HIV therapy adherence to gait analysis, resuscitation training and radiological imaging, the current uses and future possibilities of mobile phone technology in healthcare are endless. Multiple mobile phone based applications are available for healthcare workers and healthcare consumers; however, the absolute majority lack an evidence base. Therefore, more rigorous research is required to ensure that healthcare is not flooded with non-evidence based applications and is maximized for patient benefit

Texture analysis-and support vector machine-assisted diffusional kurtosis imaging may allow in vivo gliomas grading and IDH-mutation status prediction:a preliminary study

We sought to investigate, whether texture analysis of diffusional kurtosis imaging (DKI) enhanced by support vector machine (SVM) analysis may provide biomarkers for gliomas staging and detection of the IDH mutation. First-order statistics and texture feature extraction were performed in 37 patients on both conventional (FLAIR) and mean diffusional kurtosis (MDK) images and recursive feature elimination (RFE) methodology based on SVM was employed to select the most discriminative diagnostic biomarkers. The first-order statistics demonstrated significantly lower MDK values in the IDH-mutant tumors. This resulted in 81.1% accuracy (sensitivity = 0.96, specificity = 0.45, AUC 0.59) for IDH mutation diagnosis. There were non-significant differences in average MDK and skewness among the different tumour grades. When texture analysis and SVM were utilized, the grading accuracy achieved by DKI biomarkers was 78.1% (sensitivity 0.77, specificity 0.79, AUC 0.79); the prediction accuracy for IDH mutation reached 83.8% (sensitivity 0.96, specificity 0.55, AUC 0.87). For the IDH mutation task, DKI outperformed significantly the FLAIR imaging. When using selected biomarkers after RFE, the prediction accuracy achieved 83.8% (sensitivity 0.92, specificity 0.64, AUC 0.88). These findings demonstrate the superiority of DKI enhanced by texture analysis and SVM, compared to conventional imaging, for gliomas staging and prediction of IDH mutational status

The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease

Working Memory Cells' Behavior May Be Explained by Cross-Regional Networks with Synaptic Facilitation

Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1) persistent fixed-frequency elevated rates above baseline, 2) elevated rates that decay throughout the tasks memory period, 3) rates that accelerate throughout the delay, and 4) patterns of inhibited firing (below baseline) analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

The circadian rhythm of corticosteroid-binding globulin has little impact on cortisol exposure after hydrocortisone dosing

CONTEXT: Optimisation of hydrocortisone replacement therapy is important to prevent under- and over dosing. Hydrocortisone pharmacokinetics is complex as circulating cortisol is protein bound mainly to corticosteroid-binding globulin (CBG) that has a circadian rhythm. OBJECTIVE: A detailed analysis of the CBG circadian rhythm and its impact on cortisol exposure after hydrocortisone administration. DESIGN AND METHODS: CBG was measured over 24 h in 14 healthy individuals and, employing a modelling and simulation approach using a semi-mechanistic hydrocortisone pharmacokinetic model, we evaluated the impact on cortisol exposure (area under concentration-time curve and maximum concentration of total cortisol) of hydrocortisone administration at different clock times and of the changing CBG concentrations. RESULTS: The circadian rhythm of CBG was well described with two cosine terms added to the baseline of CBG: baseline CBG was 21.8 μg/mL and inter-individual variability 11.9%; the amplitude for the 24 h and 12 h cosine functions were relatively small (24 h: 5.53%, 12 h: 2.87%) and highest and lowest CBG were measured at 18:00 and 02:00, respectively. In simulations, the lowest cortisol exposure was observed after administration of hydrocortisone at 23:00-02:00, whereas the highest was observed at 15:00-18:00. The differences between the highest and lowest exposure were minor (≤12.2%), also regarding the free cortisol concentration and free fraction (≤11.7%). CONCLUSIONS: CBG has a circadian rhythm but the difference in cortisol exposure is ≤12.2% between times of highest and lowest CBG concentrations; therefore hydrocortisone dose adjustment based on time of dosing to adjust for the CBG concentrations is unlikely to be of clinical benefit

Effect of an Injury Awareness Education Program on Risk-Taking Behaviors and Injuries in Juvenile Justice Offenders: A Retrospective Cohort Study

Background Risk-taking behavior is a leading cause of injury and death amongst young people. Methodology and Principal Findings This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences. Significance Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders

Algae as Protein Factories: Expression of a Human Antibody and the Respective Antigen in the Diatom Phaeodactylum tricornutum

Microalgae are thought to offer great potential as expression system for various industrial, therapeutic and diagnostic recombinant proteins as they combine high growth rates with all benefits of eukaryotic expression systems. Moreover, microalgae exhibit a phototrophic lifestyle like land plants, hence protein expression is fuelled by photosynthesis, which is CO2-neutral and involves only low production costs. So far, however, research on algal bioreactors for recombinant protein expression is very rare calling for further investigations in this highly promising field. In this study, we present data on the expression of a monoclonal human IgG antibody against the Hepatitis B surface protein and the respective antigen in the diatom Phaeodactylum tricornutum. Antibodies are fully-assembled and functional and accumulate to 8.7% of total soluble protein, which complies with 21 mg antibody per gram algal dry weight. The Hepatitis B surface protein is functional as well and is recognized by algae-produced and commercial antibodies

AIMD - A validated, simplified framework of interventions to promote and integrate evidence into health practices, systems, and policies

Background: Proliferation of terms describing the science of effectively promoting and supporting the use of research evidence in healthcare policy and practice has hampered understanding and development of the field. To address this, an international Terminology Working Group developed and published a simplified framework of interventions to promote and integrate evidence into health practices, systems, and policies. This paper presents results of validation work and a second international workgroup meeting, culminating in the updated AIMD framework [Aims, Ingredients, Mechanism, Delivery]. Methods: Framework validity was evaluated against terminology schemas (n = 51); primary studies (n = 37); and reporting guidelines (n = 10). Framework components were independently categorized as fully represented, partly represented, or absent by two researchers. Opportunities to refine the framework were systematically recorded. A meeting of the expanded international Terminology Working Group updated the framework by reviewing and deliberating upon validation findings and refinement proposals. Results: There was variation in representativeness of the components across the three types of literature, in particular for the component 'causal mechanisms'. Analysis of primary studies revealed that representativeness of this concept lowered from 92 to 68% if only explicit, rather than explicit and non-explicit references to causal mechanisms were included. All components were very well represented in reporting guidelines, however the level of description of these was lower than in other types of literature. Twelve opportunities were identified to improve the framework, 9 of which were operationalized at the meeting. The updated AIMD framework comprises four components: (1) Aims: what do you want your intervention to achieve and for whom? (2) Ingredients: what comprises the intervention? (3) Mechanisms: how do you propose the intervention will work? and (4) Delivery: how will you deliver the intervention? Conclusions: The draft simplified framework was validated with reference to a wide range of relevant literature and improvements have enhanced useability. The AIMD framework could aid in the promotion of evidence into practice, remove barriers to understanding how interventions work, enhance communication of interventions and support knowledge synthesis. Future work needs to focus on developing and testing resources and educational initiatives to optimize use of the AIMD framework in collaboration with relevant end-user groups