Nanoformulation-by-design: an experimental and molecular dynamics study for polymer coated drug nanoparticles

The formulation of drug compounds into nanoparticles has many potential advantages in enhancing bioavailability and improving therapeutic efficacy. However, few drug molecules will assemble into stable, well-defined nanoparticulate structures. Amphiphilic polymer coatings are able to stabilise nanoparticles, imparting defined surface properties for many possible drug delivery applications. In the present article we explore, both experimentally and in silico, a potential methodology to coat drug nanoparticles with an amphiphilic co-polymer. Monomethoxy polyethylene glycol–polycaprolactone (mPEG-b-PCL) diblock copolymers with different mPEG lengths (M_w 350, 550, 750 and 2000), designed to give different levels of colloidal stability, were used to coat the surface of indomethacin nanoparticles. Polymer coating was achieved by a flow nanoprecipitation method that demonstrated excellent batch-to-batch reproducibility and resulted in nanoparticles with high drug loadings (up to 78%). At the same time, in order to understand this modified nanoprecipitation method at an atomistic level, large-scale all-atom molecular dynamics simulations were performed in parallel using the GROMOS53a6 forcefield parameters. It was observed that the mPEG-b-PCL chains act synergistically with the acetone molecules to dissolve the indomethacin nanoparticle while after the removal of the acetone molecules (mimicking the evaporation of the organic solvent) a polymer–drug nanoparticle was formed (yield 99%). This work could facilitate the development of more efficient methodologies for producing nanoparticles of hydrophobic drugs coated with amphiphilic polymers. The atomistic insight from the MD simulations in tandem with the data from the drug encapsulation experiments thus leads the way to a nanoformulation-by-design approach for therapeutic nanoparticles.

Experimental studies of drug–polymer nanoparticle formation combined with molecular dynamics simulations provide atomistic explanations for the high drug loadings obtained.     

Structural and Socio-cultural Barriers to Prenatal Care in a US Marshallese Community

Objectives Pacific Islanders are disproportionately burdened by poorer perinatal health outcomes with higher rates of pre-term births, low birth weight babies, infant mortality, and inadequate or no prenatal care. The aim of this study is to examine Marshallese mothers’ beliefs, perceptions, and experiences of prenatal care and to identify potential barriers. Methods Three focus groups were conducted with Marshallese mothers, who were 18 years or older, and living in Arkansas. Focus groups focused on mothers’ beliefs, perceptions, and experiences of prenatal care. A thematic qualitative analysis was conducted to identify salient themes within the data. Results The results demonstrated that negotiating health insurance, transportation, and language barriers were all major structural barriers that constrain prenatal care. The social–cultural barriers that emerged included a lack of understanding of the importance of seeking early and consistent prenatal care, as well as how to navigate the healthcare process. The more complicated challenges that emerged were the feelings of shame and embarrassment due to the perception of their age or being unmarried during pregnancy not being acceptable in American culture. Furthermore, the participants described perceived discrimination from prenatal care providers. Lastly, the participants described fear as a barrier to seeking out prenatal care. Conclusions for Practice This study identified both structural and socio-cultural barriers that can be incorporated into suggestions for policy makers to aid in alleviating maternal health disparities among Pacific Islander women. Further research is needed to address the Marshallese mothers’ perceived discrimination from maternal health care providers.     

Patterns of cell death and cell cycle profiles of cultured WEHI 13 var fibroblasts exposed to eluates of composite resins used for direct and indirect restorations

Previous studies have shown that in vitro exposure to single compounds released from composite resins may induce cell death. In the present study the effects of eluates from commercially available composite resins used for direct or indirect restorations were evaluated on the cell cycle progression and type of cell death of cultured WEHI 13 var fibroblasts. Cells exposed to eluates of the materials were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell death, for cell cycle profiles by flow cytometry, for caspase-3 biochemically and by immunocytochemistry, and for morphological changes by fluorescence microscopy with acridine orange. The direct composite resin eluates induced extensive apoptosis, followed by secondary necrosis. This was accompanied by cell enlargement, micromultinucleation, chromatin disintegration, cell cycle arrest at different phases, and caspase-3 activation. The composites for indirect restorations were much less cytotoxic at all biological end-points investigated. The findings suggest that composite resins used for direct and indirect dental restorations differ in their cytotoxic potential and their ability to affect basic cellular functions. This underlines the impact of improved polymerization with respect to their biologic behavior.     

Suggestions for overcoming the barriers to critical thinking in nursing

Nurses strive to provide the best quality of care to their patients in a stressful and constantly changing environment. Critical thinking (CT) could help nurses provide better quality of care to their patients. However, studies have shown that nurses either have low levels of CT or underutilize it during clinical practice. A possible explanation could be that nurses experience barriers during the development and/or utilization of CT. Since CT can be cultivated during university, nurse educators could utilize methods that improve CT. However, nurse educators do not sufficiently develop the CT of their students, since they usually rely on teacher-centered methods and not active learning methods. On the other hand, during clinical practice nurses cope with several barriers that inhibit their ability to use CT, such as: lack of teamwork, high levels of stress, time constraints, and understaffing. All these barriers decrease the utilization of CT and the quality of care that nurses provide. The present commentary suggests a simple strategy that could be used by educators and assist graduate nurses overcome the barriers to utilize CT during clinical practice. This strategy consists of three distinct components, namely: individual, interdisciplinary, and administrative. Each component could be used individually to improve the CT of nurses depending on the available resources and facilities. Nevertheless, educators by improving the CT of nurses could assist them in providing better quality of care.     

Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.     

Thermoelectric Performance of Mechanically Mixed BixSb2-xTe3—ABS Composites

In the current study, polymer-based composites, consisting of Acrylonitrile Butadiene Styrene (ABS) and Bismuth Antimony Telluride (Bi_xSb_2−xTe₃), were produced using mechanical mixing and hot pressing. These composites were investigated regarding their electrical resistivity and Seebeck coefficient, with respect to Bi doping and Bi_xSb_2-xTe₃ loading into the composite. Experimental results showed that their thermoelectric performance is comparable—or even superior, in some cases—to reported thermoelectric polymer composites that have been produced using other complex techniques. Consequently, mechanically mixed polymer-based thermoelectric materials could be an efficient method for low-cost and large-scale production of polymer composites for potential thermoelectric applications.