Modification of the dystrophic phenotype after transient neonatal denervation: Role of MHC isoforms

While it recently has been demonstrated that it is possible to modify the phenotypic expression of murine dystrophy (dy/dy) (i.e., prevent myofiber loss) by subjecting the extensor digitorum longus (EDL) muscle of 14-day-old dy/dy mice to transient neonatal denervation (Moschella and Ontell, 1987), the mechanism responsible for this phenomenon has not been determined. Since it has been suggested that the effects of dystrophy vary according to fiber type, the fiber type frequency in 100-day-old normal (+/+) and dy/dy EDL muscles subjected to transient neonatal denervation has been determined by immunohistochemical analysis of their myosin heavy chain (MHC) composition. This frequency has been compared with that found in the EDL muscles of 14 -and 100-day-old unoperated +/+ and dy/dy mice, in order to determine whether the reinnervation of transiently denervated neonatal muscle results in a preponderance of fibers of the type that might be spared dystrophic deterioration. In unoperated dy/dy muscle there is a progressive decrease in the frequency and in the absolute number of fibers that express MHC_2B, with 100-day-old dy/dy muscles having ～32% of the number of myofibers fibers containing MHC_2B as is found in age-matched +/+ muscles. The number of fibers containing the other fast isoforms (MHC_2A and MHC_2X) is similar in +/+ and dy/dy muscles at this age, indicating that fibers with MHC_2B are most affected by the dystrophic process. Reinnervation following transient neonatal denervation of both the +/+ and the dy/dy EDL muscles results in a similar decrease (～62%) in the number of myofibers containing MHC_2B and an increase in myofibers containing the other fast MHC isoforms (MHC_2A and MHC_2X). The selective effect of dy/dy on fibers containing MHC_2B and the sparing of myofibers in transiently denervated dy/dy muscle (which contains a reduced frequency of fibers containing MHC_2B) are consistent with, although not direct proof of, the hypothesis that alterations in the fiber type may play a role in the failure of myofibers in transiently denervated dy/dy muscles to undergo dystrophic deterioration. Evidence is presented suggesting that neurons that supply myofibers containing MHC_2B may be at a selective disadvantage in their ability to reinnervate neonatally denervated muscles. © 1992 John Wiley & Sons, Inc.     

Lateral phase separation of phospholipids as a basis for increased permeability of membranes towards fluorescein and other chemical species

Summary Using mouse spleen cells, before and after treatment with glutaraldehyde or mild hyperthermia, we observe a strong correlation between permeability to fluorescein and susceptibility to staining with N-dansyl-l-lysine (irrespective of the cells' ability to exclude trypan blue). We observe the same correlation using liposomes prepared from phosphatidylcholine and varying amounts of cholesterol. We have recently introduced N-dansyl-l-lysine as a fluorescent membrane stain, or probe, whose uptake, we propose, is selective for phospholipid domains in membranes (G.M.K. Humphries & J.P. LovejoyBiophys. J. 42:307–310, 1983; G.M.K. Humphries & J.P. LovejoyJ. Membrane Biol. 77:115–122, 1984). The results presented here are consistent with the hypothesis that the presence or absence of phospholipid domains in membranes also modifies their permeability toward fluorescein, and suggests that permeability towards other chemical species may be similarly affected. On the basis of work using liposomes, we believe this to be the case for carboxy-fluorescein and for glucose.     

Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study

Aims

To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB) using intravascular ultrasound virtual histology (IVUS-VH) and fractional flow reserve (FFR).

Method and Results

This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5mm² to 13.2 ± 3.9mm², p <0.001; and 5.4 ± 1.2mm² to 6.5 ± 1.8mm², p <0.001, respectively). Although mean plaque area was unchanged (6.6 ± 2.6mm² to 6.6 ± 2.4mm², p = 0.269), percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002). The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up.

Conclusions

De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up.     

Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.     

Measuring the Quality of Life of Visually Impaired Children: First Stage Psychometric Evaluation of the Novel VQoL_CYP Instrument

Purpose

To report piloting and initial validation of the VQoL_CYP, a novel age-appropriate vision-related quality of life (VQoL) instrument for self-reporting by children with visual impairment (VI).

Methods

Participants were a random patient sample of children with VI aged 10–15 years. 69 patients, drawn from patient databases at Great Ormond Street Hospital and Moorfields Eye Hospital, United Kingdom, participated in piloting of the draft 47-item VQoL instrument, which enabled preliminary item reduction. Subsequent administration of the instrument, alongside functional vision (FV) and generic health-related quality of life (HRQoL) self-report measures, to 101 children with VI comprising a nationally representative sample enabled further item reduction and evaluation of psychometric properties using Rasch analysis. Construct validity was assessed through Pearson correlation coefficients.

Results

Item reduction through piloting (8 items removed for skewness and individual item response pattern) and validation (1 item removed for skewness and 3 for misfit in Rasch) produced a 35-item scale, with fit values within acceptable limits, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting in Rasch. The VQoL_CYP showed good construct validity, correlating strongly with HRQoL scores, moderately with FV scores but not with acuity.

Conclusions

Robust child-appropriate self-report VQoL measures for children with VI are necessary for understanding the broader impacts of living with a visual disability, distinguishing these from limited functioning per se. Future planned use in larger patient samples will allow further psychometric development of the VQoL_CYP as an adjunct to objective outcomes assessment.     

Will Passive Protection Save Congo Forests?

Central Africa’s tropical forests are among the world’s largest carbon reserves. Historically, they have experienced low rates of deforestation. Pressures to clear land are increasing due to development of infrastructure and livelihoods, foreign investment in agriculture, and shifting land use management, particularly in the Democratic Republic of Congo (DRC). The DRC contains the greatest area of intact African forests. These store approximately 22 billion tons of carbon in aboveground live biomass, yet only 10% are protected. Can the status quo of passive protection — forest management that is low or nonexistent — ensure the preservation of this forest and its carbon? We have developed the SimCongo model to simulate changes in land cover and land use based on theorized policy scenarios from 2010 to 2050. Three scenarios were examined: the first (Historical Trends) assumes passive forest protection; the next (Conservation) posits active protection of forests and activation of the national REDD+ action plan, and the last (Agricultural Development) assumes increased agricultural activities in forested land with concomitant increased deforestation. SimCongo is a cellular automata model based on Bayesian statistical methods tailored for the DRC, built with the Dinamica-EGO platform. The model is parameterized and validated with deforestation observations from the past and runs the scenarios from 2010 through 2050 with a yearly time step. We estimate the Historical Trends trajectory will result in average emissions of 139 million t CO₂ year^-1 by the 2040s, a 15% increase over current emissions. The Conservation scenario would result in 58% less clearing than Historical Trends and would conserve carbon-dense forest and woodland savanna areas. The Agricultural Development scenario leads to emissions of 212 million t CO₂ year^-1 by the 2040s. These scenarios are heuristic examples of policy’s influence on forest conservation and carbon storage. Our results suggest that 1) passive protection of the DRC’s forest and woodland savanna is insufficient to reduce deforestation; and 2): enactment of a REDD+ plan or similar conservation measure is needed to actively protect Congo forests, their unique ecology, and their important role in the global carbon cycle.