Induction of mosquitocidal activity in mice immunized with Anopheles gambiae midgut cDNA

Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undue mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.     

Differences in outcomes between the JoyBar control and standard wheelchair joystick control on two maneuverability tasks: a pilot study

Purpose: To determine if older adult, novice wheelchair users who drive a power wheelchair with a JoyBar control complete maneuverability tasks in less time and with less error than those who drive a power wheelchair with a standard joystick control.

Materials and methods: A parallel randomized controlled trial design conducted at a medical rehabilitation and research centre with ambulatory older adults aged 60 and above (n?=?27). The intervention was the JoyBar alternative wheelchair control. The primary outcome measure was total time to complete each of the two maneuverability tasks. The secondary outcome measure was total number of errors during each of the maneuverability tasks.

Results: An independent, two sampled t-test was conducted and revealed that the JoyBar group took a greater amount of time to complete both maneuverability tasks than the control group (p?p?Conclusions: Maneuverability of a powered wheelchair by novice wheelchair users was not improved through the use of the JoyBar when compared to a standard wheelchair joystick, as measured by rates of error and time to complete maneuverability tasks.

• Implications for rehabilitation

• Clients who are new to powered wheelchair use may perform maneuverability tasks faster, with equivalent accuracy, using a standard joystick versus the JoyBar.

• Clients who use a JoyBar may require adjustments to the programming of their wheelchair to ensure optimal performance.

• Additional training may be required to achieve proficiency in maneuverability tasks with a JoyBar versus a standard joystick.

     

Rapid creation of Arabidopsis doubled haploid lines for quantitative trait locus mapping

Quantitative trait loci (QTL) mapping is a powerful tool for investigating the genetic basis of natural variation. QTL can be mapped using a number of different population designs, but recombinant inbred lines (RILs) are among the most effective. Unfortunately, homozygous RIL populations are time consuming to construct, typically requiring at least six generations of selfing starting from a heterozygous F(1). Haploid plants produced from an F(1) combine the two parental genomes and have only one allele at every locus. Converting these sterile haploids into fertile diploids (termed "doubled haploids," DHs) produces immortal homozygous lines in only two steps. Here we describe a unique technique for rapidly creating recombinant doubled haploid populations in Arabidopsis thaliana: centromere-mediated genome elimination. We generated a population of 238 doubled haploid lines that combine two parental genomes and genotyped them by reduced representation Illumina sequencing. The recombination rate and parental allele frequencies in our population are similar to those found in existing RIL sets. We phenotyped this population for traits related to flowering time and for petiole length and successfully mapped QTL controlling each trait. Our work demonstrates that doubled haploid populations offer a rapid, easy alternative to RILs for Arabidopsis genetic analysis.     

Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study

Objective. To investigate the effect of tocilizumab on patient-reported outcomes (PROs) in RA patients with inadequate responses to TNF inhibitors (TNFis). Methods. In a Phase III randomized controlled trial, 489 patients received 4 or 8 mg/kg tocilizumab or placebo every 4 weeks plus MTX for 24 weeks. Mean changes from baseline over time and proportions of patients reporting improvements greater than or equal to minimum clinically important differences (MCIDs) in PROs were analyzed. Results. At week 24, 8?mg/kg resulted in significantly greater improvements vs placebo in pain, global assessment of disease activity (P?=?0.001), Health Assessment Questionnaire-Disability Index (HAQ-DI; P?相似文献   

Management of patients with hereditary hemorrhagic telangiectasia undergoing general anesthesia: a cohort from a single academic center’s experience

Purpose

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disease characterized by capillary malformation leading to multisite cutaneomucosal telangiectasias and multiorgan arteriovenous malformations, which can present challenges to anesthetic care. The primary aim of this report is to present a large cohort of patients with hereditary hemorrhagic telangiectasia undergoing general anesthesia at our institution in regard to comorbid conditions and complications of surgical and anesthetic management.

Methods

A computerized search from January 1, 2002 through December 31, 2011 of the Mayo Clinic medical records database was performed for patients with hereditary hemorrhagic telangiectasia who underwent general anesthesia. Medical records were reviewed. Eligibility criteria included patients with definite or suspected hereditary hemorrhagic telangiectasia based on the Curacao diagnostic criteria who underwent general anesthesia during the study period.

Results

We identified 74 patients with hereditary hemorrhagic telangiectasia who underwent 163 surgeries. The majority had pulmonary arteriovenous malformations (56.7 %) and iron deficiency anemia (64.7 %), and high levels of disease burden with a median American Society of Anesthesiologist Physical Status score of 3. Most surgeries were related to treating conditions associated with hereditary hemorrhagic telangiectasia, with the majority being procedures to the nasal mucosa for recurrent epistaxis (47.2 %). A sizeable proportion of procedures to the nasal mucosa required transfusion of blood (12/77). One case of epistaxis required 11 units of blood until it was successfully controlled. Another notable complication included migration of a coil to pulmonary arteriovenous malformations into the cerebral circulation.

Conclusion

Surgical patients with hereditary hemorrhagic telangiectasia often present with multiorgan involvement. The anesthesia provider needs to be aware of the high prevalence of pulmonary arteriovenous malformations, which may be asymptomatic but can lead to embolic complications. Hemorrhage from epistaxis can be severe, and relatively focal procedures to the nasal mucosa can require blood transfusions.     

Exposure to Fine Particulate Matter during Pregnancy and Risk of Preterm Birth among Women in New Jersey,Ohio, and Pennsylvania, 2000–2005

Background: Particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) has been variably associated with preterm birth (PTB).Objective: We classified PTB into four categories (20–27, 28–31, 32–34, and 35–36 weeks completed gestation) and estimated risk differences (RDs) for each category in association with a 1-μg/m³ increase in PM_2.5 exposure during each week of gestation.Methods: We assembled a cohort of singleton pregnancies that completed ≥ 20 weeks of gestation during 2000–2005 using live birth certificate data from three states (Pennsylvania, Ohio, and New Jersey) (n = 1,940,213; 8% PTB). We estimated mean PM_2.5 exposures for each week of gestation from monitor-corrected Community Multi-Scale Air Quality modeling data. RDs were estimated using modified Poisson linear regression and adjusted for maternal race/ethnicity, marital status, education, age, and ozone.Results: RD estimates varied by exposure window and outcome period. Average PM_2.5 exposure during the fourth week of gestation was positively associated with all PTB outcomes, although magnitude varied by PTB category [e.g., for a 1-μg/m³ increase, RD = 11.8 (95% CI: –6, 29.2); RD = 46 (95% CI: 23.2, 68.9); RD = 61.1 (95% CI: 22.6, 99.7); and RD = 28.5 (95% CI: –39, 95.7) for preterm births during 20–27, 28–31, 32–34, and 35–36 weeks, respectively]. Exposures during the week of birth and the 2 weeks before birth also were positively associated with all PTB categories.Conclusions: Exposures beginning around the time of implantation and near birth appeared to be more strongly associated with PTB than exposures during other time periods. Because particulate matter exposure is ubiquitous, evidence of effects of PM_2.5 exposure on PTB, even if small in magnitude, is cause for concern.Citation: Rappazzo KM, Daniels JL, Messer LC, Poole C, Lobdell DT. 2014. Exposure to fine particulate matter during pregnancy and risk of preterm birth among women in New Jersey, Ohio, and Pennsylvania, 2000–2005. Environ Health Perspect 122:992–997; http://dx.doi.org/10.1289/ehp.1307456     

Use of focus groups for the environmental health researcher

Qualitative research techniques, such as focus groups, are often underutilized by the environmental health researcher. Researchers can use the data from focus groups for study planning and implementation, as well as the interpretation of study results. Focus group data can also be used to understand community risk perceptions and potential barriers to co munity acceptance of programs and policies. This paper describes the value of focus groups for the environmental health researcher. Examples from the literature are inccorporated to demonstrate the effective use of focus groups in a variety of environmental health research settings. A brief review of data analysis approaches, including commercially available software, is provided. The authors encourage increased application of this and other qualitative research methods in environmental health research.