Effects of inadequate coverage on healthcare utilization: A regression discontinuity analysis

To examine the impact of inadequate health insurance coverage on physician utilization among older adults using a novel quasi-experimental design in the time period following the elimination of cost sharing for most preventative services under the US Affordable Care Act of 2010.The Medical Expenditure Panel Survey full year consolidated data files for the period 2010 to 2017 were used to construct a pooled cross-sectional dataset of adults aged 60 to 70. Regression discontinuity design was used to estimate the impact of transitioning between non-Medicare and Medicare plans on use of routine office-based physician visits and emergency room visits.For the overall population, gaining access to Medicare at age 65 is associated with a higher propensity to make routine office-based visits (2.94 percentage points [pp]; P < .01) and lower out-of-pocket costs (−23.86 pp; P < .01) Similarly, disenrollment from non-Medicare insurance plans at age 66 was associated with more routine office-based visits (3.01 pp; P < .01) and less out-of-pocket costs (−8.09 pp; P < .10). However, some minority groups reported no changes in visits and out-of-pocket costs or reported an increased propensity to make emergency department visits.Enrollment into Medicare from non-Medicare insurance plans was associated with increased use of routine office-based services and lower out-of-pocket costs. However, some subgroups reported no changes in routine visits or costs or an increased propensity to make emergency department visits. These findings suggest other nonfinancial, structural barriers may exist that limit patient''s ability to access routine services.     

Effect of novel alpha-conotoxins on nicotine-stimulated [3H]dopamine release from rat striatal synaptosomes

Nicotine's action on the midbrain dopaminergic neurons is mediated by nicotinic acetylcholine receptors (nAChRs) that are present on the cell bodies and the terminals of these neurons. Previously, it was suggested that one of the nAChR subtypes located on striatal dopaminergic terminals may be an alpha3beta2 subtype, based on partial inhibition of nicotine-stimulated [(3)H]dopamine release by alpha-conotoxin MII, a potent inhibitor of heterologously expressed alpha3beta2 nAChRs. More recent studies indicated that alpha-conotoxin MII also potently blocks alpha6-containing nAChRs. In the present study, we have examined the nAChR subtype(s) modulating [(3)H]dopamine release from striatal terminals by using novel alpha-conotoxins that have 37- to 78-fold higher selectivity for alpha6-versus alpha3-containing nAChRs. All of the peptides partially (20-35%) inhibit nicotine-stimulated [(3)H]dopamine release with IC(50) values consistent with those obtained with heterologously expressed rat alpha6-containing nicotinic acetylcholine receptors. These results, together with previous studies by others, further support the idea that alpha6-containing nicotinic receptors modulate nicotine-stimulated dopamine release from rat striatal synaptosomes.     

The Variable Region of Pneumococcal Pathogenicity Island 1 Is Responsible for Unusually High Virulence of a Serotype 1 Isolate

Streptococcus pneumoniae is the leading infectious cause of death in children in the world. However, the mechanisms that drive the progression from asymptomatic colonization to disease are poorly understood. Two virulence-associated genomic accessory regions (ARs) were deleted in a highly virulent serotype 1 clinical isolate (strain 4496) and examined for their contribution to pathogenesis. Deletion of a prophage encoding a platelet-binding protein (PblB) resulted in reduced adherence, biofilm formation, reduced initial infection within the lungs, and a reduction in the number of circulating platelets in infected mice. However, the region''s overall contribution to the survival of mice was not significant. In contrast, deletion of the variable region of pneumococcal pathogenicity island 1 (vPPI1) was also responsible for a reduction in adherence and biofilm formation but also reduced survival and invasion of the pleural cavity, blood, and lungs. While the 4496ΔPPI1 strain induced higher expression of the genes encoding interleukin-10 (IL-10) and CD11b in the lungs of challenged mice than the wild-type strain, very few other genes exhibited altered expression. Moreover, while the level of IL-10 protein was increased in the lungs of 4496ΔPPI1 mutant-infected mice compared to strain 4496-infected mice, the levels of gamma interferon (IFN-γ), CXCL10, CCL2, and CCL4 were not different in the two groups. However, the 4496ΔPPI1 mutant was found to be more susceptible than the wild type to phagocytic killing by a macrophage-like cell line. Therefore, our data suggest that vPPI1 may be a major contributing factor to the heightened virulence of certain serotype 1 strains, possibly by influencing resistance to phagocytic killing.     

Rotary jet-spun porous microfibers as scaffolds for stem cells delivery to central nervous system injury

Stem cell transplantation is a promising strategy to treat brain injuries. However, cell-based therapies are limited because poor local cell engraftment. Here, we present a polylactic acid (PLA) scaffold to support mesenchymal stem cells (MSCs) delivery in stroke. We isolated bone marrow MSCs from adult C57/Bl6 mice, cultured them on PLA polymeric rough microfibrous (PRM) scaffolds obtained by rotary jet spinning, and transplanted over the brains of adult C57/Bl6 mice, carrying thermocoagulation-induced cortical stroke. No inflammatory response to PRM was found. MSCs transplantation significantly reduced the area of the lesion and PRM delivery increased MSCs retention at the injury site. In addition, PRM upregulated α6-integrin and CXCL12 production, which may be the cause for greater cell retention at the lesion site and may provide additional benefit to MSCs transplantation procedures. We conclude that PRM scaffolds offer a promising new system to deliver stem cells to injured areas of the brain.