The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis performed a comprehensive search and critical review of the literature from 2001 to 2012 to update the 2002 ...best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101 were accepted as scientifically admissible. The methodological quality of the research literature on MTBI prognosis has not improved since the 2002 Task Force report. There are still many methodological concerns and knowledge gaps in the literature. Here we report and make recommendations on how to avoid methodological flaws found in prognostic studies of MTBI. Additionally, we discuss issues of MTBI definition and identify topic areas in need of further research to advance the understanding of prognosis after MTBI. Priority research areas include but are not limited to the use of confirmatory designs, studies of measurement validity, focus on the elderly, attention to litigation/compensation issues, the development of validated clinical prediction rules, the use of MTBI populations other than hospital admissions, continued research on the effects of repeated concussions, longer follow-up times with more measurement periods in longitudinal studies, an assessment of the differences between adults and children, and an account for reverse causality and differential recall bias. Well-conducted studies in these areas will aid our understanding of MTBI prognosis and assist clinicians in educating and treating their patients with MTBI.
Plants are foundational for global ecological and economic systems, but most plant proteins remain uncharacterized. Protein interaction networks often suggest protein functions and open new avenues ...to characterize genes and proteins. We therefore systematically determined protein complexes from 13 plant species of scientific and agricultural importance, greatly expanding the known repertoire of stable protein complexes in plants. By using co-fractionation mass spectrometry, we recovered known complexes, confirmed complexes predicted to occur in plants, and identified previously unknown interactions conserved over 1.1 billion years of green plant evolution. Several novel complexes are involved in vernalization and pathogen defense, traits critical for agriculture. We also observed plant analogs of animal complexes with distinct molecular assemblies, including a megadalton-scale tRNA multi-synthetase complex. The resulting map offers a cross-species view of conserved, stable protein assemblies shared across plant cells and provides a mechanistic, biochemical framework for interpreting plant genetics and mutant phenotypes.
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•A global snapshot of protein organization in plants from deep proteomics profiling•Biochemical fractionation reveals stable protein complexes conserved across plants•Many observed complexes have previously only been inferred in plants by gene content•Known molecular modules are elaborated in plants with novel subunits and organization
This massive plant proteomics project, using co-fractionation mass spectrometry to measure the amounts and associations of over two million proteins from 13 diverse plant species, reveals stable protein complexes shared across plant cells and provides a framework for interpreting plant genetics and mutant phenotypes.
In 1994, Robertson and Drummer formalised the responsibility analysis as an alternative to case-control studies in the study of road traffic crashes. Our objective was to assess whether published ...responsibility studies respected standards defining adequate case-control studies.
Using Web of Science, Scopus and Google Scholar, we identified responsibility studies indexed until October 2013, which cited Robertson and Drummer's paper. After reviewing titles, abstracts and reference lists, we selected original studies comparing responsible and non-responsible drivers, published in peer-reviewed journals or proceedings.
We applied a grid to judge the conformity of the responsibility assessment to the original definition, and whether methods addressing representativeness of selection, accuracy of measures of exposures, confounding variables, and power met standards defining adequate case-control studies.
Of 205 titles, we identified 20 papers. Methods of responsibility assessment were the original in three papers. Variations across studies concerned the number of mitigating factors included, or the use of questionnaires rather than police data (n=3). The ratio responsible/non-responsible drivers varied from 0.90 to 5.31, due to major variations in sampling methods, threshold selection, and data completeness. Selection or measurement issues were discussed in 13 papers, but seldom addressed in the design. A comparison of confounding factors in responsible and non-responsible drivers was presented in five papers.
Basic requirements of case-control studies are often not or not clearly met in responsibility studies. There is a need to revisit the method and to adapt existing publication standards to the way responsibility studies are reported.
•The importance of receptor discovery for extracellular nucleotide signaling is critiqued.•How downstream signaling changes leading from receptor activation to growth changes is discussed.•The ...potential functions of apyrase enzymes in turning off the eATP signal and in regulating growth are evaluated.•The new phylogenetic and structural analyses of plant apyrases are provided.•The relationship of apyrases and eATP signaling to biotic and abiotic stress responses is documented and discussed.
Animal and plant cells release nucleotides into their extracellular matrix when touched, wounded, and when their plasma membranes are stretched during delivery of secretory vesicles and growth. These released nucleotides then function as signaling agents that induce rapid increases in the concentration of cytosolic calcium, nitric oxide and superoxide. These, in turn, are transduced into downstream physiological changes. These changes in plants include changes in the growth of diverse tissues, in gravitropism, and in the opening and closing of stomates. The concentration of extracellular nucleotides is controlled by various phosphatases, prominent among which are apyrases EC 3.6.1.5 (nucleoside triphosphate diphosphohydrolases, NTPDases). This review provides phylogenetic and pHMM analyses of plant apyrases as well as analysis of predicted post-translational modifications for Arabidopsis apyrases. This review also summarizes and discusses recent advances in research on the roles of apyrases and extracellular nucleotides in controlling plant growth and development. These include new findings that document how apyrases and extracellular nucleotides control auxin transport, modulate stomatal aperture, and mediate biotic and abiotic stress responses, and on how apyrase suppression leads to growth inhibition.
Delayed implementation of effective road safety policies must be considered when quantifying the avoidable part of the fatal and nonfatal injuries burden. We sought to assess the avoidable part of ...disability-adjusted life years (DALYs) lost due to road traffic injuries related to delays in implementing road safety laws in low- and lower-middle-income countries.
We chose one country for each of the regions of the World Health Organization (WHO) and World Bank (WB) country income levels. We used freely available data sets (WHO, International Traffic Safety Data and Analysis Group, the WB). Delays in implementation were calculated until 2013, from the year mandatory use of safety belts by motor vehicle front seat occupants was first introduced worldwide. We used life expectancy tables and age groups as social values in the DALY calculation model. From the estimated total burden, avoidable DALYs were calculated using estimates of the effectiveness of seat belt laws on fatal and nonfatal injuries combined, as extracted from published international reviews of evidence.
From the reference year 1972, implementation delays varied from 27 years (Uzbekistan) to 41 years in Bolivia (no seat belt law as of 2013). During delays, total absolute numbers of DALYs lost due to road traffic injuries reached 8,462,099 in Nigeria, 7,203,570 in Morocco, 4,695,500 in Uzbekistan, 3,866,391 in Cambodia, 3,253,359 in Bolivia, and 3,128,721 in Sri Lanka. Using effectiveness estimates ranging from 3 to 20% reduction, the avoidable burden of road traffic injuries for car occupants was highest in Uzbekistan (avoidable part from 1.2 to 10.4%) and in Morocco (avoidable part from 1.5 to 12.3%). In countries where users of public transport and pedestrians were the most affected by the burden, the avoidable parts ranged from 0.5 to 4.4% (Nigeria) and from 0.5 to 3.4% (Bolivia). Burden of road traffic injuries mostly affected motorcyclists in Sri Lanka and Cambodia where the avoidable parts were less than 2% in both countries. In all selected countries, burden of traffic injuries mostly affected men (about 80%) as well as young people (15-34 years).
Despite limited data availability in low- and middle-income countries, the avoidable part of the burden related to delayed intervention is measurable. These results can be used to convince countries to avoid delaying the provision of better protection to road users.
The development of innovative antibacterial drugs against foodborne pathogens has led to an interest in novel materials such as nanomaterials. The unique features of nanomaterial qualify it for use ...as an antibacterial treatment. Noble metals and metal oxide nanoparticles, such as silver and magnetite nanoparticles, have been shown to be effective antibacterial medications against a range of microorganisms. In this work, Ag@Fe
3
O
4
-NPs were fabricated by using a wet chemical reduction and modified co-precipitation techniques. The antibacterial efficiency of the Ag/Fe
3
O
4
core shell nanoparticles was investigated by applying various techniques, such as the Kirby–Bauer Disk Diffusion test, minimum inhibitory concentration (MIC) and bactericidal concentration (MBC), Colony Forming Unit (CFU), and kill time assay. The toxicity mechanism of Ag@Fe
3
O
4
-NPs against
Salmonella typhimurium
and
Escherichia coli
was studied by apoptosis and reactive oxygen species (ROS) assays. The data revealed that a cubic core was surrounded by a silver shell, which indicated the regular morphology of silver magnetite core shell nanoparticles without any aggregation. Furthermore, Ag@Fe
3
O
4
-NPs is more toxic against
S. typhimurium
and
E. coli
than Ag-NPs and Fe
3
O
4
NPs. The MIC values for Ag/Fe
3
O
4
NPs against
S. typhimurium and E. coli
were 3.1 and 5.4 μg/ml, respectively, whereas the MIC values for Ag-NPs and MNPs against
S. typhimurium
and
E. coli
were 4.1 and 8.2 μg/ml for Ag-NPs and 6.9 and 10.3 μg/ml for MNPs. The results showed the ability of Ag@Fe
3
O
4
-NPs to induce apoptosis by generating ROS. Also, the ability of Ag@Fe
3
O
4
-NPs to liberate free Ag
+
and generate ROS
via
the Haber-Weiss cycle may be a plausible mechanism to explain the toxicity of Ag@Fe
3
O
4
-NPs - NPs.
Gravity directs the polarization of
Ceratopteris
fern spores. This process begins with the uptake of calcium through channels at the bottom of the spore, a step necessary for the gravity response. ...Data showing that extracellular ATP (eATP) regulates calcium channels led to the hypothesis that extracellular nucleotides could play a role in the gravity-directed polarization of
Ceratopteris
spores. In animal and plant cells ATP can be released from mechanosensitive channels. This report tests the hypothesis that the polarized release of ATP from spores could be activated by gravity, preferentially along the bottom of the spore, leading to an asymmetrical accumulation of eATP. In order to carry out this test, an ATP biosensor was used to measure the eATP at the bottom and top of germinating spores during gravity-directed polarization. The eATP along the bottom of the spore averaged 7-fold higher than the concentration at the top. All treatments that disrupted eATP signaling resulted in a statistically significant decrease in the gravity response. In order to investigate the source of ATP release, spores were treated with Brefeldin A (BFA) and gadolinium trichloride (GdCl
3
). These treatments resulted in a significant decrease in gravity-directed polarization. An ATP biosensor was also used to measure ATP release after treatment with both BFA and GdCl
3
. Both of these treatments caused a significant decrease in ATP measured around spores. These results support the hypothesis that ATP could be released from mechanosensitive channels and secretory vesicles during the gravity-directed polarization of Ceratopteris spores.
Germination of
spores is initiated by light and terminates 3-4 days later with the emergence of a rhizoid. Early studies documented that the photoreceptor for initiating this response is phytochrome. ...However, completion of germination requires additional light input. If no further light stimulus is given after phytochrome photoactivation, the spores do not germinate. Here we show that a crucial second light reaction is required, and its function is to activate and sustain photosynthesis. Even in the presence of light, blocking photosynthesis with DCMU after phytochrome photoactivation blocks germination. In addition, RT-PCR showed that transcripts for different phytochromes are expressed in spores in darkness, and the photoactivation of these phytochromes results in the increased transcription of messages encoding chlorophyll a/b binding proteins. The lack of chlorophyll-binding protein transcripts in unirradiated spores and their slow accumulation makes it unlikely that photosynthesis is required for the initial light reaction. This conclusion is supported by the observation that the transient presence of DCMU, only during the initial light reaction, had no effect on germination. Additionally, the ATP in
spores increased coincidentally with the length of light treatment during germination. Overall, these results support the conclusion that two distinct light reactions are required for the germination of
spores.
Screening is the early detection of a latent disorder by a test to allow early intervention with the aim of improving prognosis. Individual and population perspectives on screening are perceived as ...opposing interests of patients and the population. In this article, we try to reconcile these perspectives. The individual perspective is based on the clinical experience of a better prognosis at early stages and patients with missed opportunities. In the population perspective, screening is based on a population-oriented, evidence-based model and addresses the acceptability and possible negative effects, including for people without the disorder. Known possible obstacles to a positive effect of screening include a short latent stage, lead time, overdiagnosis, lack of acceptability, poor performance of tests, and misclassification of outcome. Randomized trials of screening are challenging and need an adaptation of standards such as the Consolidated Standards of Reporting Trials (CONSORT). Simulating the effects of screening can allow the consideration of complex screening strategies and other options to help avoid biases related to treatment improvement and prevention success. Reconciling both perspectives is possible by considering that hypotheses underlying the former are prerequisites for the latter. From an evidence-based medicine and policy perspective, we suggest that recommending screening or prescribing a test is unethical if all possible obstacles are not documented by providing the best available evidence.
suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid.
In the current work, we investigated the effect of sole GA ...combined with different agents such as doxorubicin (DOX) or probiotic bacteria (
) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue.
Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively.
GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.
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