Dimeric Tubulin Modifies Mechanical Properties of Lipid Bilayer, as Probed Using Gramicidin A Channel.

Using the gramicidin A channel as a molecular probe, we show that tubulin binding to planar lipid membranes changes the channel kinetics-seen as an increase in the lifetime of the channel dimer-and thus points towards modification of the membrane's mechanical properties. The effect is more pronounced in the presence of non-lamellar lipids in the lipid mixture used for membrane formation. To interpret these findings, we propose that tubulin binding redistributes the lateral pressure of lipid packing along the membrane depth, making it closer to the profile expected for lamellar lipids.

Adaptive Physical Activity for Stroke: An Early-Stage Randomized Controlled Trial in the United States.

. As stroke survival improves, there is an increasing need for effective, low-cost programs to reduce deconditioning and improve mobility. .

The actions of volatile anesthetics: a new perspective.

This article reviews recent work in applying neutron and X-ray scattering towards the elucidation of the molecular mechanisms of volatile anesthetics. Experimental results on domain mixing in ternary lipid mixtures, and the influence of volatile anesthetics and hydrostatic pressure are placed in the contexts of ion-channel function and receptor trafficking at the postsynaptic density.

Neutron scattering in the biological sciences: progress and prospects.

The scattering of neutrons can be used to provide information on the structure and dynamics of biological systems on multiple length and time scales. Pursuant to a National Science Foundation-funded workshop in February 2018, recent developments in this field are reviewed here, as well as future prospects that can be expected given recent advances in sources, instrumentation and computational power and methods. Crystallography, solution scattering, dynamics, membranes, labeling and imaging are examined.

Lipid nanodomains change ion channel function.

Signaling proteins and neurotransmitter receptors often associate with saturated chain and cholesterol-rich domains of cell membranes, also known as lipid rafts. The saturated chains and high cholesterol environment in lipid rafts can modulate protein function, but evidence for such modulation of ion channel function in lipid rafts is lacking. Here, using raft-forming model membrane systems containing cholesterol, we show that lipid lateral phase separation at the nanoscale level directly affects the dissociation kinetics of the gramicidin dimer, a model ion channel.

Hydrostatic Pressure Promotes Domain Formation in Model Lipid Raft Membranes.

Neutron diffraction measurements demonstrate that hydrostatic pressure promotes liquid-ordered (Lo) domain formation in lipid membranes prepared as both oriented multilayers and unilamellar vesicles made of a canonical ternary lipid mixture for which demixing transitions have been extensively studied. The results demonstrate an unusually large dependence of the mixing transition on hydrostatic pressure. Additionally, data at 28 °C show that the magnitude of increase in Lo caused by 10 MPa pressure is much the same as the decrease in Lo produced by twice minimum alveolar concentrations (MAC) of general anesthetics such as halothane, nitrous oxide, and xenon.

Community-based exercise for chronic disease management: an Italian design for the United States?

Although only a small proportion of older adults in the United States engage in recommended amounts of physical exercise, the health benefits of exercise for this population and the potential for lowering health care costs are substantial. However, access to regular exercise programs for the frail elderly and individuals with disabilities remains limited. In the context of health reform and emerging opportunities in developing integrated systems of care, the experience in Tuscany in implementing a community-based program of exercise for the elderly should be of interest.

Community-based exercise for upper limb paresis: a controlled trial with telerehabilitation.

Background: Arm paresis remains a major impairment after stroke despite the best conventional rehabilitation. Randomized, controlled trials of intensive exercise programs have demonstrated improvements in arm function for patients with chronic stroke. However, the gains achieved have been relatively modest for the large investments in patient and therapist time.

Xenon and other volatile anesthetics change domain structure in model lipid raft membranes.

Inhalation anesthetics have been in clinical use for over 160 years, but the molecular mechanisms of action continue to be investigated. Direct interactions with ion channels received much attention after it was found that anesthetics do not change the structure of homogeneous model membranes. However, it was recently found that halothane, a prototypical anesthetic, changes domain structure of a binary lipid membrane.

Halothane changes the domain structure of a binary lipid membrane.

X-ray and neutron diffraction studies of a binary lipid membrane demonstrate that halothane at physiological concentrations produces a pronounced redistribution of lipids between domains of different lipid types identified by different lamellar d-spacings and isotope composition. In contrast, dichlorohexafluorocyclobutane (F6), a halogenated nonanesthetic, does not produce such significant effects. These findings demonstrate a specific effect of inhalational anesthetics on mixing phase equilibria of a lipid mixture.

Commentary: beyond educational initiatives: how can we change health care to improve the health of persons with disabilities?

Minihan and colleagues discuss necessary elements of an educational program to instruct generalist physicians in the care of individuals with disabilities. To support these physicians adequately in practice will require significant adaptations of health care financing, recognition of the unique medical needs of persons with disabilities, and efficient utilization of experienced clinical resources. The author outlines what remains to be addressed in the pursuit of better health for patients with disabilities as the U.

Coverage policy for neurorehabilitation: an international perspective.

Background: Coverage policy ultimately determines the delivery of services. This article summarizes the authors' effort to ascertain the extent of publically available information on coverage for neurorehabilitation services internationally.

Objective: Present available data on neurorehabilitation coverage and examine the needs for further research in this area.

Methodological issues in monitoring health services and outcomes for stroke survivors: a case study.

Background: Obtaining comprehensive health outcomes and health services utilization data on stroke patients has been difficult. This research grew out of a memorandum of understanding between the NIH and the ISS (its Italian equivalent) to foster collaborative research on rehabilitation.

Objective: The purpose of this study was to pilot a methodology using administrative data to monitor and improve health outcomes for stroke survivors in Tuscany.

Lipid-dependent effects of halothane on gramicidin channel kinetics: a new role for lipid packing stress.

We find that the sensitivity of gramicidin A channels to the anesthetic halothane is highly lipid dependent. Specifically, exposure of membranes made of lamellar DOPC to halothane in concentrations close to clinically relevant reduces channel lifetimes by 1 order of magnitude. At the same time, gramicidin channels in membranes of nonlamellar DOPE are affected little, if at all, by halothane.

Community-based adaptive physical activity program for chronic stroke: feasibility, safety, and efficacy of the Empoli model.

Objective: To determine whether Adaptive Physical Activity (APA-stroke), a community-based exercise program for participants with hemiparetic stroke, improves function in the community.

Methods: Nonrandomized controlled study in Tuscany, Italy, of participants with mild to moderate hemiparesis at least 9 months after stroke. Forty-nine participants in a geographic health authority (Empoli) were offered APA-stroke (40 completed the study).

Adaptive physical activity improves mobility function and quality of life in chronic hemiparesis.

This study investigated the effects of an adaptive physical activity (APA) program on mobility function and quality of life (QOL) in chronic stroke patients. Twenty subjects with chronic hemiparesis completed a 2-month, combined group, class-home exercise regimen that emphasized mobility training. APA improved Berg Balance Scale scores (35 +/- 2 vs 45 +/- 2, p = 0.

Voltage gating of VDAC is regulated by nonlamellar lipids of mitochondrial membranes.

Evidence is accumulating that lipids play important roles in permeabilization of the mitochondria outer membrane (MOM) at the early stage of apoptosis. Lamellar phosphatidylcholine (PC) and nonlamellar phosphatidylethanolamine (PE) lipids are the major membrane components of the MOM. Cardiolipin (CL), the characteristic lipid from the mitochondrial inner membrane, is another nonlamellar lipid recently shown to play a role in MOM permeabilization.

Stroke rehabilitation in Switzerland versus the United States: a preliminary comparison.

This article compares the structure and process of rehabilitation for stroke patients at 2 internationally recognized rehabilitation hospitals, Klinik Valens ("Valens") in Switzerland and the William Donald Schaeffer Rehabilitation Hospital at Kernan ("Kernan") in the United States. Although the patient mix, structure, and process of rehabilitation were similar in many regards, there were some important differences. Most notably, on average, patients at the U.

Rules for rehabilitation: an agenda for research.

Rehabilitation services have grown tremendously in the United States over the past 2 decades. Rules originally designed to guide Medicare reimbursement policies have had substantial effects in shaping the design of clinical services. This article traces the development of the most significant federal rules regarding rehabilitation, outlines the existing empirical evidence to support these rules, and discusses an agenda for research to improve the evidence for future policy development.

Timing, intensity, and duration of rehabilitation for hip fracture and stroke: report of a workshop at the National Center for Medical Rehabilitation Research.

This article summarizes the proceedings of an NIH workshop on timing, intensity, and duration of rehabilitation for acute stroke and hip fracture. Participants concentrated on methodological issues facing investigators and suggested priorities for future research in this area.