Mutational study of the role of N-terminal amino acid residues in tetrachlorohydroquinone reductive dehalogenase from Sphingomonas sp. UG30

This research presents the first extensive mutational study of N-terminal amino acids necessary for activity of a bacterial Zeta class glutathione transferase (GST). Our studies on UG30 tetrachlorohydroquinone reductive dehalogenase (PcpC) revealed that, similar to other Zeta class GSTs, N-terminal Ser and Cys residues play critical roles in glutathione binding and their mutation results in functional and structural changes to PcpC. Mutation of the N-terminal Ser and Cys residues decreased the apparent temperature optimum (by 6-10 °C) and maximum (by 5 °C) of PcpC. Also, mutation of Ser12 and Ser15 resulted in structural changes that were accompanied by the emergence of substrate inhibition. Mutation of the N-terminal Cys residue adversely affected the rate of the enzymatic reaction, but not on the metabolites formed. This study adds to the knowledge that, despite low sequence homology for the Zeta GST protein family, differences in preferred electrophilic substrates, and the manner in which glutathione is utilized in catalysis, GSTs from prokaryotic and eukaryotic organisms rely upon the same critical amino acids for glutathione binding.     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.     

再发骨质疏松性椎体压缩骨折保守治疗患者出院后生存质量

目的：对比初次和再发骨质疏松性椎体压缩骨折(osteoporotic vertebral compression fractures,OVCFs)患者保 守治疗的生存质量,了解再次骨折对此类患者生存质量各方面的影响。方法：回顾性观察治疗OVCFs后出现再骨折 的患者30名(再骨折组)和同时期行保守治疗OVCFs后未发生再骨折的基本条件相似的患者30例(对照组),比较两组出 院后3个月时SF-36简明健康健康状况调查表的调查结果。结果：再骨折组治疗后的8个维度均不同程度较对照组变差 (均P<0.01)。结论：再骨折组患者的生存质量明显低于对照组,并且会进一步影响患者的心理预期、情绪和社会活动 的各个方面。     

Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors

Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision‐making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research. Copyright © 2014 John Wiley & Sons, Ltd.     

Influence of Socio-Demographic Characteristics on Eye Care Expenditure: Data from the Medical Expenditure Panel Survey 2007

ABSTRACT

Objective: To evaluate the association between sociodemographic factors and eye care expenditure and to assess the burden of ocular expenditure compared to total health care expenditure.

Methods: A retrospective analysis of ocular expenditure in participants of the 2007 Medical Expenditure Panel Survey. Data from 20,620 unique participants aged ≥18 years were evaluated for eye care expenditure by demographic characteristics.

Results: A total of 22% of the studied population had eye care expenditures in 2007. Demographic factors significantly associated with higher probability of having eye care expenditures included older age (65+ years 35%, 45–64 years 23%, <45 years 17%), female sex (female 26%, male 19%), higher educational attainment (greater than high school education 25%, less than high school education 17%), having insurance (private 24%, uninsured 13%), and visual impairment (mild 31%, none 22%). Older age, female sex, higher educational attainment, having insurance, and presence of visual impairment were also significantly associated with higher mean eye care expenditure. In those with eye care expenditure, the mean ratio between eye care and total medical expenditure was 24%, with uninsured patients spending 42% of their medical care expenditure on eye care.

Conclusions: Demographic factors are associated with both the probability of having ocular expenditure and the amount of expenditure. Of all factors examined, insurance status has the most potential for modification. Policy makers should consider these numbers when devising the terms by which eye care coverage will be provided under the Patient Protection and Affordable Care Act.     

Susceptibility of Carrion Crows to Experimental Infection with Lineage 1 and 2 West Nile Viruses

West Nile virus (WNV) outbreaks in North America have been characterized by substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a low incidence of bird deaths has been observed during WNV epidemic activity in Europe. To examine the susceptibility of the western European counterpart of American crows, we inoculated carrion crows (Corvus corone) with WNV strains isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with the highly virulent North American genotype strain (NY99). We also inoculated American crows with a selection of these strains to examine the strains’ virulence in a highly susceptible bird species. Infection with all strains, except WNV FIN, resulted in high rates of death and high-level viremia in both bird species and virus dissemination to several organs. These results suggest that carrion crows are highly susceptible to WNV and may potentially be useful as part of dead bird surveillance for early warning of WNV activity in Europe.     

Alcohol Acceptance, Preference, and Sensitivity in Mice. II. Quantitative Trait Loci Mapping Analysis Using BXD Recombinant Inbred Strains

Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (Rl) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e) , for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7) , and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.     

Comparison of health-related quality-of-life outcomes of men and women after coronary artery bypass surgery through 1 year: findings from the POST CABG Biobehavioral Study

Background

Women undergoing coronary artery bypass graft (CABG) surgery have a worse medical condition and fewer social and financial resources than men. Some studies have found that women recover less well than men after CABG, whereas others have found women's outcomes comparable to those of men. Past studies of health-related quality of life after CABG have too few women for adequate comparison with men and have not included patients whose data are not available at baseline (eg, emergency CABG), limiting generalizability.

Methods

A longitudinal study of symptoms and health-related quality of life was conducted among patients from four clinical centers enrolling both men (n = 405) and women (n = 269) in the Post CABG Biobehavioral Study in the United States and Canada.

Results

After 6 weeks from CABG (average 81 days), both men and women had less anxiety and symptoms related to depression than before surgery (P < .001). After 6 months (average 294 days), both men and women improved in physical and social functioning (P < .001). Although changes in scale scores were similar for men and women at each time point, women scored lower than men on these domains (P < .001, adjusted for baseline medical and sociodemographic differences) and had more symptoms related to depression through 1 year after CABG (P = .003).

Conclusions

Both male and female patients improve in physical, social, and emotional functioning after CABG, and recovery over time is similar in men and women. However, women's health-related quality-of-life scale scores remained less favorable than men's through 1 year after surgery.     

Synthesis and secretion of a high molecular weight form of nerve growth factor by skeletal muscle cells in culture.

Rat skeletal muscle cells and a cloned myogenic cell line synthesize and secrete in culture a molecule that is immunologically and biologically indistinguishable from the active form of nerve growth factor (NGF) from mouse submandibular gland. This protein can be detected in medium conditioned by muscle cells both before and after fusion and in the soluble fraction of muscle cell homogenates. Chromatographic data also reveal that the molecular properties of muscle cell NGF differ from those of the growth factor purified from mouse submandibular glands. Muscle cell NGF has a molecular weight between 140,000 and 160,000, whereas purified mouse gland NGF has a molecular weight of 26,000. The biologic function of muscle cell NGF is not known, although it could be that it plays some role relating to the association of nerves and muscle in vivo.