Intraosseous access in the resuscitation of trauma patients: a literature review.

PURPOSE: Intraosseous (IO) catheters continue to be recommended in trauma resuscitation. Their utility has recently been debated due to concerns regarding inadequate flow rates during blood transfusion, and the potential for haemolysis. The objective of this review was to examine the evidence for intraosseous catheters in trauma resuscitation, and to highlight areas for future research. METHODS: A PubMed and Embase search for articles published from January 1990 to August 2018 using the terms ("intra-osseous access" or "intraosseous access" or "IO access") AND trauma was performed. Original articles describing the use of an IO catheter in the resuscitation of one or more trauma patients were eligible. Animal, cadaveric studies and those involving healthy volunteers were excluded. RESULTS: Nine studies, comprising of 1218 trauma patients and 1432 device insertions, were included. The insertion success rate was 95% and the incidence of complications 0.9%. Flow-rate data and evidence of haemolysis were poorly reported. CONCLUSION: Intraosseous catheters have high insertion success rates and a low incidence of complications in trauma patients. Existing evidence suggests that IO transfusion is not associated with haemolysis, however, further studies in humans are needed. There is a paucity of flow rate data for blood transfusion via IO catheters in this population, although much anecdotal evidence advocating their use exists.

Poor Concordance of Floxed Sequence Recombination in Single Neural Stem Cells: Implications for Cell Autonomous Studies.

To manipulate target gene function in specific adult cell populations, tamoxifen (TAM)-dependent CreERT2 is widely used to drive inducible, site-specific recombination of loxP flanked sequences. In studies of cell autonomous target gene function, it is common practice to combine these CreERT2-lox systems with a ubiquitously expressed stop-floxed fluorescent reporter gene to identify single cells supposedly undergoing target gene recombination. Here, we studied the reliability of using Cre-induced recombination of one gene to predict recombination in another gene at the single-cell level in adult hippocampal neural stem and progenitor cells (NSPCs). Using both probabilistic predictions in a generic experimental paradigm, as well as a mouse model with two separate stop-floxed reporters plus a Nestin promoter-driven CreERT2, we found that, in individual cells, recombination of one gene was a poor predictor of recombination in another. This poor concordance in floxed sequence recombination across genes suggests that use of stop-floxed reporters to investigate cell autonomous gene function may not be universally reliable and could lead to false conclusions.

Survey of Ranavirus and Batrachochytrium dendrobatidis in Introduced Frogs in Hawaii, USA.

Ranaviruses and the fungus Batrachochytrium dendrobatidis are globally important agents of emerging infectious amphibian diseases. Amphibians on Oahu, the Hawaiian Island with the greatest potential for disease introduction through the movement of goods and people, have never been surveyed for ranaviruses or B. dendrobatidis. We surveyed all five species of frogs on Oahu, Hawaii, US for these pathogens. Of 325 individuals sampled from six sites, none were positive for ranavirus. However, we found B. dendrobatidis in a total of four individuals of three species, the cane toad (Bufo marinus), the American bullfrog (Rana catesbeiana), and the greenhouse frog (Eleutherodactylus planirostris), but not in the green and black poison dart frog (Dendrobates auratus) or the Japanese wrinkled frog (Rana rugosa). The apparent lack of ranavirus and low prevalence of B. dendrobatidis are noteworthy given how widespread these pathogens are in terms of both global distribution and host range. Surveillance should continue to document any changes in B. dendrobatidis prevalence or the arrival of ranaviruses in Hawaii.

Novel multi-target directed ligand-based strategies for reducing neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common causes of dementia. AD pathogenesis has been hypothesized to involve cholinergic deficits, amyloid-beta protein (Aß) deposition, tau protein hyperphosphorylation, and chronic neuroinflammation. Many single-target drugs have gone through the various stages of pre-clinical and clinical development in an effort to cure AD; however, the current clinically approved drugs have only limited effects on the disease progression. With the accumulation of unsuccessful clinical trials using single-target drugs, multi-target directed ligand (MTDL) drug development is becoming more common. MTDLs incorporate two or more pharmacophores into a single drug molecule. This approach can alleviate side effects and lead to a better pharmacokinetic profile of the MTDL compared to two or more separate drugs representing respective single pharmacophores. This review discusses cathepsin B (CatB), dual specificity phosphatase 2 (DUSP2), and monoglycerol lipase (MAGL) as targets for MTDLs aimed at slowing down the neuroinflammatory component of neurodegenerative diseases. CatB, DUSP2 and MAGL inhibitors show promising preclinical anti-inflammatory effects in vivo and in vitro. Incorporating pharmacophores that inhibit these targets into MTDLs represents a promising avenue towards effective suppression of neuroinflammation associated with AD.

Accents, Not Just Prosodic Boundaries, Influence Syntactic Attachment.

Traditionally, pitch accents are understood to relate to the information structure of a sentence and its discourse connections, while prosodic boundaries indicate groupings of words and affect how constituents attach into a syntactic structure. Here, we show that accents also affect syntactic attachment in multiple different syntactic structures. Three auditory questionnaires on ambiguous attachment sentences (such as Tom reported that Bill was bribed [last May]) find that accenting the higher or lower verb ( reported or bribed) increases the attachment of the final adverbial phrase as a modifier of the accented verb. A fourth experiment shows that accents on verbs or object nouns (in sentences like Jenny sketched a child [with crayons]) also increase the attachment of the final prepositional phrase to the accented head (sketched with crayons versus a child with crayons). Accent effects were small but consistent across sentences with different levels of bias and did not depend on prosodic boundaries. The results suggest that focused elements are important to the main assertion of the sentence and therefore draw the attachment of upcoming material (though the salience of attachment sites may also be important). The results also demonstrate that both prosodic phrasing and pitch accents can affect basic syntactic structure.

Form and function: Optional complementizers reduce causal inferences.

Many factors are known to influence the inference of the discourse coherence relationship between two sentences. Here, we examine the relationship between two conjoined embedded clauses in sentences like The professor noted that the student teacher did not look confident and (that) the students were poorly behaved. In two studies, we find that the presence of that before the second embedded clause in such sentences reduces the possibility of a forward causal relationship between the clauses, i.e., the inference that the student teacher's confidence was what affected student behavior. Three further studies tested the possibility of a backward causal relationship between clauses in the same structure, and found that the complementizer's presence aids that relationship, especially in a forced-choice paradigm. The empirical finding that a complementizer, a linguistic element associated primarily with structure rather than event-level semantics, can affect discourse coherence is novel and illustrates an interdependence between syntactic parsing and discourse parsing.