Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

Microscopic calculation of the pinning energy of a vortex in the inner crust of a neutron star

The structure of a vortex in the inner crust of a pulsar is calculated microscopically in the Wigner-Seitz cell approximation, simulating the conditions of the inner crust of a cold, non-accreting neutron star, in which a lattice of nuclei coexists with a sea of superfluid neutrons. The calculation is based on the axially deformed Hartree-Fock-Bogolyubov framework, using effective interactions. The present work extends and improves previous studies in four ways: i) it allows for the axial deformation of protons induced by the large deformation of neutrons due to the appearance of vortices; ii) it includes the effect of Coulomb exchange; iii) considers the possible effects of the screening of the pairing interaction; and iv) it improves the numerical treatment. We also demonstrate that the binding energy of the nucleus-vortex system can be used as a proxy to the pinning energy of a vortex and discuss in which conditions this applies. From our results, we can estimate the mesoscopic pinning forces per unit length acting on vortices. We obtain values ranging between $10^{14}$ to $10^{16}$ dyn/cm, consistent with previous findings.Comment: Paper submitted for publicatio

Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs

The Association Between Money and Opinion in Academic Emergency Medicine

Objectives: Financial conflicts of interest have come under increasing scrutiny in medicine, but their impact has not been quantified. Our objective was to use the results of a national survey of academic emergency medicine (EM) faculty to determine if an association between money and personal opinion exists.Methods: We conducted a web-based survey of EM faculty. Opinion questions were analyzed with regard to whether the respondent had either 1) received research grant money or 2) received money from industry as a speaker, consultant, or advisor. Responses were unweighted, and tests of differences in proportions were made using Chi-squared tests, with p<0.05 set for significance.Results: We received responses from 430 members; 98 (23%) received research grants from industry, while 145 (34%) reported fee-for-service money. Respondents with research money were more likely to be comfortable accepting gifts (40% vs. 29%) and acting as paid consultants (50% vs. 37%). They had a more favorable attitude with regard to societal interactions with industry and felt that industry-sponsored lectures could be fair and unbiased (52% vs. 29%). Faculty with fee-for-service money mirrored those with research money. They were also more likely to believe that industry-sponsored research produces fair and unbiased results (61% vs. 45%) and less likely to believe that honoraria biased speakers (49% vs. 69%).Conclusion: Accepting money for either service or research identified a distinct population defined by their opinions. Faculty engaged in industry-sponsored research benefitted socially (collaborations), academically (publications), and financially from the relationship. [West J Emerg Med. 2010; 11(2):126-132.

Supporting the massive scale-up of antiretroviral therapy: the evolution of PEPFAR-supported treatment facilities in South Africa, 2005-2009

<p>Abstract</p> <p>Background</p> <p>South Africa has an estimated 1.5 million persons in need of antiretroviral therapy (ART). In 2004, the South African government began collaborating with the United States President's Emergency Plan for AIDS Relief (PEPFAR) to increase access to ART. We determined how PEPFAR treatment support changed from 2005-2009.</p> <p>Methods</p> <p>In order to describe the change in number and type of PEPFAR-supported ART facilities, we analyzed routinely collected program-monitoring data from 2005-2009. The collected data included the number, type and province of facilities as well as the number of patients receiving ART at each facility.</p> <p>Results</p> <p>The number of PEPFAR-supported facilities providing ART increased from 184 facilities in 2005 to 1,469 facilities in 2009. From 2005-2009 the number of PEPFAR-supported government facilities increased 10.1 fold from 54 to 546 while the number of PEPFAR-supported NGO facilities (including general practitioner and NGO facilities) increased 6.2 fold from 114 to 708. In 2009 the total number of persons treated at PEPFAR-supported NGO facilities was 43,577 versus 501,089 persons at PEPFAR-supported government facilities. Overall, the median number of patients receiving ART per site increased from 81 in 2005 to 136 in 2009.</p> <p>Conclusions</p> <p>To mitigate the gap between those needing and those receiving ART, more facilities were supported. The proportion of government facilities supported and the median number of persons treated at these facilities increased. This shift could potentially be sustainable as government sites reach more individuals and receive government funding. These results demonstrate that PEPFAR was able to support a massive scale-up of ART services in a short period of time.</p

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center