2,579 research outputs found
National income inequality predicts women's preferences for masculinized faces better than health does
This article is available open access through the publisher’s website at the link below. Copyright @ 2010 The Royal Society
Topical rosiglitazone is an effective anti-scarring agent in the cornea
Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas
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Emergency Department Clinicians’ Attitudes Toward Opioid Use Disorder and Emergency Department-initiated Buprenorphine Treatment: A Mixed-Methods Study
Introduction: Emergency department (ED) visits related to opioid use disorder (OUD) have increased nearly twofold over the last decade. Treatment with buprenorphine has been demonstrated to decrease opioid-related overdose deaths. In this study, we aimed to better understand ED clinicians’ attitudes toward the initiation of buprenorphine treatment in the ED.Methods: We performed a mixed-methods study consisting of a survey of 174 ED clinicians (attending physicians, residents, and physician assistants) and semi-structured interviews with 17 attending emergency physicians at a tertiary-care academic hospital.Results: A total of 93 ED clinicians (53% of those contacted) completed the survey. While 80% of respondents agreed that buprenorphine should be administered in the ED for patients requesting treatment, only 44% felt that they were prepared to discuss medication for addiction treatment. Compared to clinicians with fewer than five years of practice, those with greater experience were less likely to approve of ED-initiated buprenorphine. In our qualitative analysis, physicians had differing perspectives on the role that the ED should play in treating OUD. Most physicians felt that a buprenorphine-based intervention in the ED would be feasible with institutional support, including training opportunities, protocol support within the electronic health record, counseling and support staff, and a robust referral system for outpatient follow-up.Conclusion: ED clinicians’ perception of buprenorphine varied by years of practice and training level. Most ED clinicians did not feel prepared to initiate buprenorphine in the ED. Qualitative interviews identified several addressable barriers to ED-initiated buprenorphine
Concerted Motions Networking Pores and Distant Ferroxidase Centers Enable Bacterioferritin Function and Iron Traffic
X-ray crystallography, molecular dynamics (MD) simulations and biochemistry were utilized to investigate the effect of introducing hydrophobic interactions in the 4-fold (N148L and Q151L) and B-pores (D34F) of Pseudomonas aeruginosa bacterioferritin B (BfrB) on BfrB function. The structures show only local structural perturbations and confirm the anticipated hydrophobic interactions. Surprisingly, structures obtained after soaking crystals in Fe2+-containing crystallization solution revealed that although iron loads into the ferroxidase centers of the mutants, the side chains of ferroxidase ligands E51 and H130 do not reorganize to bind the iron ions, as is seen in the wt BfrB structures. Similar experiments with a double mutant (C89S/K96C) prepared to introduce changes outside the pores show competent ferroxidase centers that function akin to those in wt BfrB. MD simulations comparing wt BfrB with the D34F and N148L mutants show that the mutants exhibit significantly reduced flexibility, and reveal a network of concerted motions linking ferroxidase centers and 4-fold and B-pores, which are important for imparting ferroxidase centers in BfrB with the required flexibility to function efficiently. In agreement, the efficiency of Fe2+ oxidation and uptake of the 4-fold and B-pore mutants in solution is significantly compromised relative to wt or C89S/K96C BfrB. Finally, our structures show a large number of previously unknown iron binding sites in the interior cavity and B-pores of BfrB, which reveal in unprecedented detail conduits followed by iron and phosphate ions across the BfrB shell, as well as paths in the interior cavity that may facilitate nucleation of the iron phosphate mineral
DNA methylation modules in airway smooth muscle are associated with asthma severity
Abnormal DNA methylation patterns distinguish airway smooth muscle cell function in asthma and asthma severity
Participation of the Melanocortin-1 Receptor in the UV Control of Pigmentation
The cloning of the melanocortin-1 receptor (MC1R) gene from human melanocytes and the demonstration that these cells respond to the melanocortins α-melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) with increased proliferation and melanogenesis have renewed the interest in investigation the physiological role of these hormones in regulating human pigmentation. α-Melanocyte stimulating hormone and ACTH are both synthesized in the human epidermis, and their synthesis is upregulated by exposure to ultraviolet radiation (UVR). Activation of the MC1R by ligand binding results in stimulation of cAMP formation, which is a principal mechanism for inducing melanogenesis. The increase in cAMP is required for the pigmentary response of human melanocytes to UVR, and for allowing them to overcome the UVR-induced G1 arrest. Treatment of human melanocytes with α-MSH increases eumelanin synthesis, an effect that is expected to enhance photoprotection of the skin. Population studies have revealed more than 20 allelic variants of the MC1R gene. Some of these variants are overexpressed in individuals with skin type I or II, red hair, and poor tanning ability. Future studies will aim at further exploration of the role of these variants in MC1R function, and in determining constitutive human pigmentation, the response to sun exposure, and possibly the susceptibility to skin cancer
CHANG-ES XI: Circular Polarization in the Cores of Nearby Galaxies
We detect 5 galaxies in the CHANG-ES (Continuum Halos in Nearby Galaxies --
an EVLA Survey) sample that show circular polarization (CP) at L-band in our
high resolution data sets. Two of the galaxies (NGC~4388 and NGC~4845) show
strong Stokes \%, two (NGC~660 and NGC~3628) have
values of \%, and NGC~3079 is a marginal detection at \%. The two strongest galaxies also have the most luminous X-ray
cores and the strongest internal absorption in X-rays. We have expanded on our
previous Faraday conversion interpretation and analysis and provide analytical
expressions for the expected signal for a general case in which the cosmic
ray electron energy spectral index can take on any value. We provide examples
as to how such expressions could be used to estimate magnetic field strengths
and the lower energy cutoff for CR electrons. Four out of our detections are
{\it resolved}, showing unique structures, including a {\it jet} in NGC~4388
and a CP `conversion disk' in NGC~4845. The conversion disk is inclined to the
galactic disk but is perpendicular to a possible outflow direction. Such CP
structures have never before been seen in any galaxy to our knowledge. None of
the galaxy cores show linear polarization at L-band. Thus CP may provide a
unique probe of physical conditions deep into radio AGNs.Comment: 30 pages, 4 figures, accepted to MNRA
Vortex circulation patterns in planar microdisk arrays
We report a magnetic X-ray microscopy study of the pattern formation of circulation in arrays of magnetic vortices ordered in a hexagonal and a honeycomb lattice. In the honeycomb lattice, we observe at remanence an ordered phase of alternating circulations, whereas in the hexagonal lattice, small regions of alternating lines form. A variation in the edge-to-edge distance shows that the size of those regions scales with the magnetostatic interaction. Micromagnetic simulations reveal that the patterns result from the formation of flux closure states during the nucleation process
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