Influence of early or late dietary restriction on life span and immunological parameters in MRL/Mp-lpr/lpr mice.

Reduced food intake doubles and even triples the life span of (NZB X NZW)F1 (B/W) mice and greatly influences of food intake while keeping vitamin and mineral intake constant in mice of the MRL/Mp-lpr/lpr (MRL/l) strain. Restriction of food intake greatly prolongs life. This influence also was seen when dietary restriction was imposed later in life. Dietary restriction inhibited development of lymphoproliferative disease and greatly decreased the numbers of cells in thymus, lymph nodes, and spleen. It also delayed development of glomerulonephritis and maintained certain immunological responses. Proliferative responses to phytohemagglutinin, pokeweed mitogen, or allogeneic spleen cells were maintained in the mice fed a low-calorie diet from 6 wk. Imposing diet at 12 wk had a lesser influence than earlier restriction. These dietary influences did not depress formation of anti-DNA antibodies or circulating immunocomplexes. MRL/l mice show an apparently extremely low production of interleukin 2, and dietary restriction increased the capacity of lymph node cells but not spleen cells to produce this immunomodulator.     

Enhancing public involvement in assistive technology design research

Purpose: To appraise the application of accepted good practice guidance on public involvement in assistive technology research and to identify its impact on the research team, the public, device and trial design. Methods: Critical reflection and within-project evaluation were undertaken in a case study of the development of a functional electrical stimulation device. Individual and group interviews were undertaken with lay members of a 10 strong study user advisory group and also research team members. Results: Public involvement was seen positively by research team members, who reported a positive impact on device and study designs. The public identified positive impact on confidence, skills, self-esteem, enjoyment, contribution to improving the care of others and opportunities for further involvement in research. A negative impact concerned the challenge of engaging the public in dissemination after the study end. Conclusions: The public were able to impact significantly on the design of an assistive technology device which was made more fit for purpose. Research team attitudes to public involvement were more positive after having witnessed its potential first hand. Within-project evaluation underpins this case study which presents a much needed detailed account of public involvement in assistive technology design research to add to the existing weak evidence base.

• Implications for Rehabilitation

• The evidence base for impact of public involvement in rehabilitation technology design is in need of development.

• Public involvement in co-design of rehabilitation devices can lead to technologies that are fit for purpose.

• Rehabilitation researchers need to consider the merits of active public involvement in research.

     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Evaluation of the clinical usefulness of mycobacterial skin test antigens in adults with pulmonary mycobacterioses.

A double-blind, multicenter study was conducted to evaluate the usefulness of mycobacterial skin test antigens for the specific diagnosis of adult pulmonary mycobacterial disease. The skin test antigens used were PPD-T (M. bovis) and PPD-B (M. intracellulare), made bioequivalent to 5 TU PPD-S through bioassay in human subjects. Of the 192 adults (18 yr of age or older), those with disease caused by M. tuberculosis (MTB) had significantly larger reactions to PPD-T than did those with disease caused by nontuberculous mycobacteria (NTM) or those with negative culture results (NEG)(13.41 mm versus 4.87 and 4.96 mm, respectively, p less than 0.001). The mean induration to PPD-B in NTM was not different from that in MTB or NEG. Defining a "positive" to be greater than or equal to 10 mm induration and a size difference of greater than or equal to 3 mm between PPD-T and PPD-B, the sensitivity, specificity, and positive predictive value (PPV) for PPD-T in diagnosing MTB versus NTM was 29, 90, and 75%. Corresponding values for PPD-B and NTM disease were 70, 61, and 64%. Dual testing was less useful in distinguishing disease caused by any of the mycobacteria from NEG. Although the sensitivity of PPD-B, made bioequivalent to PPD-S, was high, the specificity and PPV were low. We conclude that this preparation of PPD-B is no more useful in distinguishing adult pulmonary disease caused by NTM than is PPD-T alone.     

Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations

When large asexual populations adapt, competition between simultaneously segregating mutations slows the rate of adaptation and restricts the set of mutations that eventually fix. This phenomenon of interference arises from competition between mutations of different strengths as well as competition between mutations that arise on different fitness backgrounds. Previous work has explored each of these effects in isolation, but the way they combine to influence the dynamics of adaptation remains largely unknown. Here, we describe a theoretical model to treat both aspects of interference in large populations. We calculate the rate of adaptation and the distribution of fixed mutational effects accumulated by the population. We focus particular attention on the case when the effects of beneficial mutations are exponentially distributed, as well as on a more general class of exponential-like distributions. In both cases, we show that the rate of adaptation and the influence of genetic background on the fixation of new mutants is equivalent to an effective model with a single selection coefficient and rescaled mutation rate, and we explicitly calculate these effective parameters. We find that the effective selection coefficient exactly coincides with the most common fixed mutational effect. This equivalence leads to an intuitive picture of the relative importance of different types of interference effects, which can shift dramatically as a function of the population size, mutation rate, and the underlying distribution of fitness effects.     

Effect of catheter ablation on progression of paroxysmal atrial fibrillation

Ablation and Progression of Atrial Fibrillation. Objective: The objective was to determine the effect of radiofrequency catheter ablation (RFA) on progression of paroxysmal atrial fibrillation (AF). Background: Progression to persistent AF may occur in up to 50% of patients with paroxysmal AF receiving pharmacological therapy. Hypertension, age, prior transient ischemic event, chronic obstructive pulmonary disease, and heart failure (HATCH score) have been identified as independent risk factors for progression of AF. Methods: RFA was performed in 504 patients (mean age: 58 ± 10 years) to eliminate paroxysmal AF. A repeat RFA procedure was performed in 193 patients (38%). Clinical variables predictive of outcome and their relation to progression of AF after RFA were assessed using multivariate analysis. Results: At a mean follow‐up of 27 ± 12 months after RFA, 434/504 patients (86%) were in sinus rhythm; 49/504 patients (9.5%) continued to have paroxysmal AF; and 14 (3%) were in atrial flutter. Among the 504 patients, 7 (1.5%) progressed to persistent AF. In patients with recurrent AF after RFA, paroxysmal AF progressed to persistent AF in 7/56 (13%, P < 0.001). The progression rate of AF was 0.6% per year after RFA (P < 0.001 compared to 9% per year reported in pharmacologically treated patients). Age >75 years, duration of AF >10 years and diabetes were independent predictors of progression to persistent AF. The HATCH score was not significantly different between patients with paroxysmal AF who did and did not progress to persistent AF (0.7 ± 0.8 vs 1.0 ± 0.5, P = 0.3). Conclusions: Compared to a historical control group of pharmacologically treated patients with paroxysmal AF, RFA appears to reduce the rate of progression of paroxysmal AF to persistent AF. Age, duration of AF, and diabetes are independent risk factors for progression to persistent AF after RFA. (J Cardiovasc Electrophysiol, Vol. 23, pp. 9‐14, January 2012)