- An anti-barotrauma system for preventing barotrauma during hyperbaric oxygen therapy. [Journal Article]
- UHUndersea Hyperb Med 2018 Jan-Feb; 45(1):19-25
- In the present study, a tympanometry-based anti-barotrauma (ABT) device was designed using eardrum admittance measurements to develop an objective method of preventing barotrauma that occurs during h...
In the present study, a tympanometry-based anti-barotrauma (ABT) device was designed using eardrum admittance measurements to develop an objective method of preventing barotrauma that occurs during hyperbaric oxygen (HBO₂) therapy. The middle ear space requires active equalization, and barotrauma of these tissues during HBO₂therapy constitutes the most common treatment-associated injury. Decongestant nasal sprays and nasal steroids are used, but their efficacy is questionable to prevent middle ear barotrauma (MEB) during HBO₂ treatment. Accordingly, a tympanometry-based ABT device was designed using eardrum admittance measurements to develop an objective method for preventing MEB, which causes pain and injury, and represents one of the principal reasons for patients to stop treatment. This study was conducted to test a novel technology that can be used to measure transmembrane pressures, and provide chamber attendants with real-time feedback regarding the patient's equalization status prior to the onset of pain or injury. Eardrum admittance values were measured according to pressure changes inside a hyperbaric oxygen chamber while the system was fitted to the subject. When the pressure increased to above 200 daPa, eardrum admittance decreased to 16.255% of prepressurization levels. After pressure equalization was achieved, eardrum admittance recovered to 95.595% of prepressurization levels. A one-way repeated measures analysis of variance contrast test was performed on eardrum admittance before pressurization versus during pressurization, and before pressurization versus after pressure equalization. The analysis revealed significant differences at all points during pressurization (P⟨0.001), but no significant difference after pressure equalization was achieved. This ABT device can provide objective feedback reflecting eardrum condition to the patient and the chamber operator during HBO₂ therapy.
- Impaired set shifting is associated with previous falls in individuals with and without Parkinson's disease. [Journal Article]
- GPGait Posture 2018 Mar 06; 62:220-226
- CONCLUSIONS: Impaired set shifting is associated with previous falls in older adults with and without PD. Set shifting may be useful to include in fall risk assessments, particularly when global cognitive measures are within reference limits.
- Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin. [Journal Article]
- BBiomaterials 2018 Mar 12; 167:205-215
- Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug deliver...
Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from ∼5% to ∼79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy.
- Substrate stiffness modulates the multipotency of human neural crest derived ectomesenchymal stem cells via CD44 mediated PDGFR signaling. [Journal Article]
- BBiomaterials 2018 Mar 14; 167:153-167
- Mesenchymal stem cells (MSCs) have been isolated from various mesodermal and ectodermal tissues. While the phenotypic and functional heterogeneity of MSCs stemming from their developmental origins ha...
Mesenchymal stem cells (MSCs) have been isolated from various mesodermal and ectodermal tissues. While the phenotypic and functional heterogeneity of MSCs stemming from their developmental origins has been acknowledged, the genetic and environmental factors underpinning these differences are not well-understood. Here, we investigated whether substrate stiffness mediated mechanical cues can directly modulate the development of ectodermal MSCs (eMSCs) from a precursor human neural crest stem cell (NCSC) population. We showed that NCSC-derived eMSCs were transcriptionally and functionally distinct from mesodermal bone marrow MSCs. eMSCs derived on lower substrate stiffness specifically increased their expression of the MSC marker, CD44 in a Rho-ROCK signaling dependent manner, which resulted in a concomitant increase in the eMSCs' adipogenic and chondrogenic differentiation potential. This mechanically-induced effect can only be maintained for short-term upon switching back to a stiff substrate but can be sustained for longer-term when the eMSCs were exclusively maintained on soft substrates. We also discovered that CD44 expression modulated eMSC self-renewal and multipotency via the downregulation of downstream platelet-derived growth factor receptor beta (PDGFRβ) signaling. This is the first instance demonstrating that substrate stiffness not only influences the differentiation trajectories of MSCs but also their derivation from upstream progenitors, such as NCSCs.
- Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53-activating peptide for acute myeloid leukemia therapy. [Journal Article]
- BBiomaterials 2018 Mar 14; 167:132-142
- Roughly one third of all human cancers are attributable to the functional inhibition of the tumor suppressor protein p53 by its two negative regulators MDM2 and MDMX, making dual-specificity peptide ...
Roughly one third of all human cancers are attributable to the functional inhibition of the tumor suppressor protein p53 by its two negative regulators MDM2 and MDMX, making dual-specificity peptide antagonists of MDM2 and MDMX highly attractive drug candidates for anticancer therapy. Two pharmacological barriers, however, remain a major obstacle to the development of peptide therapeutics: susceptibility to proteolytic degradation in vivo and inability to traverse the cell membrane. Here we report the design of a fluorescent lanthanide oxyfluoride nanoparticle (LONp)-based multifunctional peptide drug delivery system for potential treatment of acute myeloid leukemia (AML) that commonly harbors wild type p53, high levels of MDM2 and/or MDMX, and an overexpressed cell surface receptor, CD33. We conjugated to LONp via metal-thiolate bonds a dodecameric peptide antagonist of both MDM2 and MDMX, termed PMI, and a CD33-targeted, humanized monoclonal antibody to allow for AML-specific intracellular delivery of a stabilized PMI. The resultant nanoparticle antiCD33-LONp-PMI, while nontoxic to normal cells, induced apoptosis of AML cell lines and primary leukemic cells isolated from AML patients by antagonizing MDM2 and/or MDMX to activate the p53 pathway. Fluorescent antiCD33-LONp-PMI also enabled real-time visualization of a series of apoptotic events in AML cells, proving a useful tool for possible disease tracking and treatment response monitoring. Our studies shed light on the development of antiCD33-LONp-PMI as a novel class of antitumor agents, which, if further validated, may help targeted molecular therapy of AML.
- Factors influencing noncompliance with bicycle passing distance laws. [Journal Article]
- AAAccid Anal Prev 2018 Mar 20; 115:137-142
- Many jurisdictions around the world have implemented laws to require a minimum distance when motor vehicles pass cyclists, but research into the factors influencing passing distances has produced inc...
Many jurisdictions around the world have implemented laws to require a minimum distance when motor vehicles pass cyclists, but research into the factors influencing passing distances has produced inconsistent results, indicating the need for future research. This study examined the factors influencing motorists' compliance with a legislated bicycle passing distance rule in Queensland, Australia. Unlike the earlier studies, which used volunteer riders to record passing events, this study used a naturalistic study design to record passing events where none of the motorists or the cyclists were aware of being studied. As a result, this study captured the 'true' driving and riding behaviours during passing events. The likelihood of non-compliance was greater on higher (70-80 km/h speed limits) and lower (40 km/h) speed roads than 60 km/h roads, at curved road sections, and on roads with narrower traffic lanes. Rider characteristics (age, gender, helmet status, type of clothing, type of bicycle, and individual or group riding) had no statistically significant association with compliance status. The findings indicate that efforts to improve cyclist safety during overtaking events should focus on non-rider related factors, such as roadway infrastructure characteristics.
- Metazoan MicroRNAs. [Review]
- CellCell 2018 Mar 22; 173(1):20-51
- MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression ...
MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression of most mRNAs. This article reviews advances in our understanding of the defining features of metazoan miRNAs and their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs are regulated, how they recognize and cause repression of their targets, and the biological functions of this repression, with a compilation of knockout phenotypes that shows that important biological functions have been identified for most of the broadly conserved miRNAs of mammals.
- Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR-expressing non-small cell lung cancer to EGFR TKIs. [Journal Article]
- MOMol Oncol 2018 Mar 23
- Cigarette smoking is one of the leading risks for lung cancer, and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor tyrosine kinase inhib...
Cigarette smoking is one of the leading risks for lung cancer, and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of EGFR TKIs. In this study, our data showed that chronic exposure to cigarette smoke extract (CSE) or tobacco smoke-derived carcinogen benzo[α]pyrene (B[α]P), but not NNK, reduced the sensitivity of wild-type EGFR-expressing non-small cell lung cancer (NSCLC) cells to EGFR TKIs. Treatment with TKIs almost abolished EGFR tyrosine kinase activity, but did not show an inhibitory effect on downstream Akt and ERK pathways in B[α]P-treated NSCLC cells. CSE and B[α]P transcriptionally upregulate c-MET and activate its downstream Akt pathway, which is not inhibited by EGFR TKIs. Silencing of c-MET reduces B[α]P-induced Akt activation. The CSE-treated NSCLC cells are sensitive to the c-MET inhibitor crizotinib. These findings suggest that cigarette smoke augments oncogene addiction to c-MET in NSCLC cells, and that MET inhibitors may show clinical benefits for lung cancer patients with a smoking history.
- The Effect of Match-Factors on the Running Performance of Elite Female Soccer Players. [Journal Article]
- JSJ Strength Cond Res 2018 Mar 22
- The purpose of this study was to examine the effects of match-factors on the match-running of elite female soccer players. Players from the same women's national team (n = 45) were monitored during 4...
The purpose of this study was to examine the effects of match-factors on the match-running of elite female soccer players. Players from the same women's national team (n = 45) were monitored during 47 international fixtures (files = 606) across four years (2012-2015) using 10-Hz global positioning system devices. A mixed model was used to analyse the effects of altitude, temperature, match-outcome, opposition ranking and congested schedules. At altitude (>500 m) a small increase in the number of accelerations (ES = 0.40) and a small decrease in total distance (ES = -0.54) was observed, whereas at higher temperatures there were decreases in all metrics (ES = -0.83 to -0.16). Playing a lower-ranked team in a draw resulted in a moderate increase in high-speed running (ES = 0.89), with small to moderate decreases in total distance and low-speed running noted in a loss or a win. Winning against higher-ranked opponents indicated moderately higher total distance and low-speed running (ES = 0.75), compared to a draw. Whilst the number of accelerations were higher in a draw against lower-ranked opponents, compared to a win and a loss (ES = 0.95 and 0.89 respectively). Practitioners should consider the effect of match-factors on match-running in elite female soccer.
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- The Imperative of Solving Nurses' Usability Problems With Health Information Technology. [Journal Article]
- JNJ Nurs Adm 2018; 48(4):191-196
- CONCLUSIONS: Nurses continue to endure significant health IT-usability issues that negatively impact patients, nurses, and healthcare organizations. Solutions include enhancing the voice of nursing at the national and local levels, creating a digital strategy for nursing, providing incentives to improve usability in health IT, and accelerating the understanding of nurses' work intended to inform and translate nurses' work into health IT design.