Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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Work-related injuries in the Australian education sector: A retrospective cohort study

IntroductionEducators are exposed to several work-related hazards. Evidence suggests musculoskeletal pain, psychological distress, and student-inflicted violence-related injuries are common. However, there is little evidence on the burden of workplace injury among Australian educators.AimTo compare incidence of injury claims and duration of compensated time off work between educators and non-educators, and associated factors.MethodsRetrospective cohort study of 1,559,676 Australian workers’ compensation claims, including 84,915 educator claims, lodged between July 2009 to June 2015, from the National Dataset for Compensation-based Statistics. Cases were included if aged 18+ years and working in the education sector less than 100 h per week. Negative binomial regression models estimated the relative risk of making a compensation claim and survival analyses calculated disability duration within educators by sex, age, injury type and mechanism, socioeconomic area, remoteness, and jurisdiction.ResultsCompared to non-educators, educators had lower rates of injury claims and shorter disability durations. However, educators had a higher rate of claims for mental health conditions and assault, with the highest risk being among those in special education and education aides. Among educators, injury claim rates were highest among special educators, education aides, and secondary educators.Discussion and ConclusionThough surveys indicate Australians in the education sector have higher incidences of work-related injuries, this study found lower incidence of injury claims and shorter disability durations than others. Educators’ injury-reporting and absenteeism behaviors may be constrained by ethical, social, and administrative attitudes. Educators had higher rates of claims for mental health and assault-related injury, particularly special educators, and education aides, which suggests a need for targeted prevention efforts.     

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.