Regeneration in vitro of the adult frog sciatic sensory axons

The adult frog sciatic nerve offers several advantages as an in vitro model to study nerve regeneration. The nerve with the attached dorsal root ganglia can easily be isolated and incubated in a culture medium for several days. If the nerve is subjected to a crush immediately after dissection there is a delay of 3.4 days after which the sensory axons start to regenerate into the distal nerve stump at a constant rate of about 1.1 mm · day−1 in serum-containing and 1.0 mm · day−1 in serum-free medium. Serum-free cultures may be used in future studies to examine the effect of various neurotrophic factors. The existence of an accurate method for examining the outgrowth distance, based on axonal transport of labelled proteins, contributes to the attractiveness of the model. A compartmental culture system permits separate exposure of the ganglia and the nerve to different agents. Taking advantage of this, pharmacological studies suggest that Schwann cells produce signals, dependent on newly transcribed RNA, which transform the preparation into a growth state. The present model system offers favourable conditions to learn more about the early events and also the subsequent steps of the regeneration process

Growth cones of regenerating adult sciatic sensory axons release axonally transported proteins

Labelled, rapidly transported axonal proteins were shown to be released frog adult frog sciatic sensory neurons, regenerating in vitro after a crush injury. The spatial distribution of the transported, released proteins could accurately be resolved by culturing the nerve on nitrocellulose paper, which trapped the released proteins. The release was located to the crush and to the entire outgrowth region. When regeneration was inhibited by adenosine, the release was limited to the crush site, implying that the release was linked to the growing axons. Other experiments suggested that the release emanated from growth cones. Furthermore, two-dimensional electrophoretical analysis of both fast axonally transported and of released proteins showed that the represented a selection of the transported protein species

Proposed Method for Probabilistic Energy Simulations for Multi-Family Dwellings

As regulations regarding energy use and emissions of CO2 equivalents in buildings become more stringent, the need for more accurate tools and improved methods for predicting these parameters in building performance simulations increases. In the first part of this project, a probabilistic method was developed and applied to the transient energy calculations and evaluated using a single-family dwelling case study. The method was used to successfully predict the variation of the energy use in 26 houses built in the same residential area and with identical building characteristics and services. This project continues the development and testing of the probabilistic method for energy calculations by applying it to a multi-family building. The complexity of the building model increases as the multi-family model consists of 52 zones, compared to the single-zone model used for the single-family dwelling. The multi-family model also includes additional parameters that are evaluated, such as the domestic hot water circulation losses. This paper presents the probabilistic method applied to the building performance simulations used to predict the energy use for the multi-family building and discusses the differences between the previous and new method used in this study

Regular, sustained-release morphine for chronic breathlessness : A multicentre, double-blind, randomised, placebo-controlled trial

Introduction Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness. Methods Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, â € as needed', immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0-100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms. Results Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference -0.15 mm (95% CI -4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation. Conclusion No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine. Trial registration number ACTRN12609000806268

The association of body mass index, weight gain and central obesity with activity-related breathlessness : The Swedish Cardiopulmonary Bioimage Study

Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes