Suicidal ingestion of organophosphorus (OP) or carbamate (CM) compounds challenges health care systems worldwide, particularly in Southeast Asia. The diagnosis and treatment of OP or CM poisoning is ...traditionally based on the clinical appearance of the typical cholinergic toxidrome, e.g. miosis, salivation and bradycardia. Yet, clinical signs might be inconclusive or even misleading. A current case report highlights the importance of enzymatic assays to provide rapid information and support clinicians in diagnosis and rational clinical decision making. Furthermore, the differentiation between OP and CM poisoning seems important, as an oxime therapy will most probably not provide benefit in CM poisoning, but—as every pharmaceutical product—it might result in adverse effects. The early identification of the causing agent and the amount taken up in the body are helpful in planning of the therapeutic regimen including experimental strategies, e.g. the use of human blood products to facilitate scavenging of the toxic agent. Furthermore, the analysis of biotransformation products and antidote levels provides additional insights into the pathophysiology of OP or CM poisoning. In conclusion, cholinesterase activities and modern analytical methods help to provide a more effective treatment and a thorough understanding of individual cases of OP or CM poisoning.
Understanding the factors that influence microbes' environmental distributions is important for determining drivers of microbial community composition. These include environmental variables like ...temperature and pH, and higher-dimensional variables like geographic distance and host species phylogeny. In microbial ecology, "specificity" is often described in the context of symbiotic or host parasitic interactions, but specificity can be more broadly used to describe the extent to which a species occupies a narrower range of an environmental variable than expected by chance. Using a standardization we describe here, Rao's (Theor Popul Biol, 1982. https://doi.org/10.1016/0040-5809(82)90004-1, Sankhya A, 2010. https://doi.org/10.1007/s13171-010-0016-3 ) Quadratic Entropy can be conveniently applied to calculate specificity of a feature, such as a species, to many different environmental variables.
We present our R package specificity for performing the above analyses, and apply it to four real-life microbial data sets to demonstrate its application. We found that many fungi within the leaves of native Hawaiian plants had strong specificity to rainfall and elevation, even though these variables showed minimal importance in a previous analysis of fungal beta-diversity. In Antarctic cryoconite holes, our tool revealed that many bacteria have specificity to co-occurring algal community composition. Similarly, in the human gut microbiome, many bacteria showed specificity to the composition of bile acids. Finally, our analysis of the Earth Microbiome Project data set showed that most bacteria show strong ontological specificity to sample type. Our software performed as expected on synthetic data as well.
specificity is well-suited to analysis of microbiome data, both in synthetic test cases, and across multiple environment types and experimental designs. The analysis and software we present here can reveal patterns in microbial taxa that may not be evident from a community-level perspective. These insights can also be visualized and interactively shared among researchers using specificity's companion package, specificity.shiny.
Somatic evolution selects cancer cell phenotypes that maximize survival and proliferation in dynamic environments. Although cancer cells are molecularly heterogeneous, we hypothesized convergent ...adaptive strategies to common host selection forces can be inferred from patterns of epigenetic and genetic evolutionary selection in similar tumors. We systematically investigated gene mutations and expression changes in lung adenocarcinomas with no common driver genes (
n
= 313). Although 13,461 genes were mutated in at least one sample, only 376 non-synonymous mutations evidenced positive evolutionary selection with conservation of 224 genes, while 1736 and 2430 genes exhibited ≥ two-fold increased and ≥ 50% decreased expression, respectively. Mutations under positive selection are more frequent in genes with significantly altered expression suggesting they often “hardwire” pre-existing epigenetically driven adaptations. Conserved genes averaged 16-fold higher expression in normal lung tissue compared to those with selected mutations demonstrating pathways necessary for both normal cell function and optimal cancer cell fitness. The convergent LUAD phenotype exhibits loss of differentiated functions and cell–cell interactions governing tissue organization. Conservation with increased expression is found in genes associated with cell cycle, DNA repair, p53 pathway, epigenetic modifiers, and glucose metabolism. No canonical driver gene pathways exhibit strong positive selection, but extensive down-regulation of membrane ion channels suggests decreased transmembrane potential may generate persistent proliferative signals. NCD LUADs perform niche construction generating a stiff, immunosuppressive microenvironment through selection of specific collagens and proteases. NCD LUADs evolve to a convergent phenotype through a network of interconnected genetic, epigenetic, and ecological pathways.
Germ cell tumors (GCT) are rare, frequently diagnosed in men aged 20–34 years old, and have a 95% 5-year relative survival rate. Metastasis from GCT has predictable spread to retroperitoneal lymph ...nodes. However, in cases of scrotal violation or tumor spillage, lymphatic drainage can be altered. Beyond the retroperitoneum, the most reported extra-nodal sites of metastases include the liver, lung, brain, and bone. Here we report a case of an unusual site of metastasis to the corpora cavernosa, as well as the complex reconstruction required to preserve sexual function.
Aberrant expression of stem cell-associated genes is a common feature in acute myeloid leukemia (AML) and is linked to leukemic self-renewal and therapy resistance. Using AF10-rearranged leukemia as ...a prototypical example of the recurrently activated "stemness" network in AML, we screened for chromatin regulators that sustain its expression. We deployed a CRISPR-Cas9 screen with a bespoke domain-focused library and identified several novel chromatin-modifying complexes as regulators of the TALE domain transcription factor MEIS1, a key leukemia stem cell (LSC)-associated gene. CRISPR droplet sequencing revealed that many of these MEIS1 regulators coordinately controlled the transcription of several AML oncogenes. In particular, we identified a novel role for the Tudor-domain-containing chromatin reader protein SGF29 in the transcription of AML oncogenes. Furthermore, SGF29 deletion impaired leukemogenesis in models representative of multiple AML subtypes in multiple AML subtype models. Our studies reveal a novel role for SGF29 as a nononcogenic dependency in AML and identify the SGF29 Tudor domain as an attractive target for drug discovery.
The growth, characteristics, and future of online CME Harris Jr, John M.; Sklar, Bernard M.; Amend, Robert W. ...
The Journal of continuing education in the health professions,
Winter 2010, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Introduction: Physician use of online continuing medical education (CME) is growing, but there are conflicting data on the uptake of online CME and few details on this market.
Methods: Analyses of 11 ...years of data from the Accreditation Council for Continuing Medical Education (ACCME) and a survey of 272 publicly available CME Web sites.
Results: The data suggest that online CME was 6.9%–8.8% of CME consumed in 2008. If previous exponential growth continues, online CME is likely to be 50% of all CME consumed within 7–10 years. Most (60%) online CME is produced by medical publishing and education companies. The online CME marketplace is consolidating, with 16% of surveyed sites providing 76% of available credits. Currently, 70% of online CME is offered at $10 or less per credit. Most online CME uses low‐technology educational approaches, such as pure text and repurposed live lectures.
Discussion: Online CME use is growing rapidly and is likely to be half of all CME consumed by practicing physicians within a few years. The pattern is consistent with Christensen's model of “disruptive innovation,” whereby an innovative technology eventually displaces an incumbent technology by first providing a relatively low‐quality, low‐cost product that meets the needs of unserved customers. The technologies being developed for online CME may facilitate broader changes in medical education as well.
Purpose
To evaluate the Risk Evaluation and Mitigation Strategies (REMS) for varenicline by assessing patients' understanding of the varenicline medication guide (MG) at pre‐specified time points: ...18 months, 3 years, and 7 years after the REMS approval.
Methods
Self‐administered surveys were mailed to people who received varenicline based on a pharmacy dispensing. Survey questions assessed understanding of potential risks outlined in the MG: neuropsychiatric symptoms, skin reactions, allergic reactions, and cardiovascular risks. Crude and weighted analyses were conducted.
Results
The response to the survey overall was between 18% and 19%. Among responders, approximately 90% recalled receiving the MG, and at least 80% read all or part of it. At least 88% correctly identified neuropsychiatric symptoms as potential medication effects, while 41% did so for skin reactions, 53% for allergic reactions, and 82% for cardiovascular risks. Patients who read the MG had a high proportion of correct responses to the risk comprehension questions.
Conclusions
A large majority of patients who were dispensed varenicline recalled receiving the MG and were able to correctly recall neuropsychiatric and cardiovascular risks in all 3 surveys. The varenicline MG may be an effective tool for patient education.
The dominant benthic primary producers in coral reef ecosystems are complex holobionts with diverse microbiomes and metabolomes. In this study, we characterize the tissue metabolomes and microbiomes ...of corals, macroalgae, and crustose coralline algae via an intensive, replicated synoptic survey of a single coral reef system (Waimea Bay, O'ahu, Hawaii) and use these results to define associations between microbial taxa and metabolites specific to different hosts. Our results quantify and constrain the degree of host specificity of tissue metabolomes and microbiomes at both phylum and genus level. Both microbiome and metabolomes were distinct between calcifiers (corals and CCA) and erect macroalgae. Moreover, our multi-omics investigations highlight common lipid-based immune response pathways across host organisms. In addition, we observed strong covariation among several specific microbial taxa and metabolite classes, suggesting new metabolic roles of symbiosis to further explore.
Substance use recovery homes represent the largest residential, community-based post-treatment option for those with substance use disorders in the United States. It is still unclear what unique ...factors predict relapse after residents leave such homes. This study presents results of a longitudinal study of 497 residents who departed from 42 Oxford House recovery houses. We hypothesized that the predictors of post-departure relapse would be a multi-item measure of latent recovery, length of stay, and reason for departure from the home (voluntary vs. involuntary). Predictor effects were estimated as part of a two-step model with two outcomes: (a) lack of follow-up data after departure from the house, and (b) the likelihood of relapse. Determinants of missing follow-up data included less education, less time in residence, and involuntary departure. Relapse was more likely for individuals who were younger, had involuntarily left the house, and had lower values on the latent recovery factor. The implications of these important factors related to relapse following departure from residential recovery home settings are discussed.
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