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Self-propagating beta-sheet-rich protein aggregates are implicated in a wide range of protein-misfolding phenomena, including amyloid diseases and prion-based inheritance. Two properties have emerged as common features of amyloids. Amyloid formation is ubiquitous: many unrelated proteins form such aggregates and even a single polypeptide can misfold into multiple forms--a process that is thought to underlie prion strain variation. Despite this promiscuity, amyloid propagation can be highly sequence specific: amyloid fibres often fail to catalyse the aggregation of other amyloidogenic proteins. In prions, this specificity leads to barriers that limit transmission between species. Using the yeast prion [PSI+], we show in vitro that point mutations in Sup35p, the protein determinant of [PSI+], alter the range of 'infectious' conformations, which in turn changes amyloid seeding specificity. We generate a new transmission barrier in vivo by using these mutations to specifically disfavour subsets of prion strains. The ability of mutations to alter the conformations of amyloid states without preventing amyloid formation altogether provides a general mechanism for the generation of prion transmission barriers and may help to explain how mutations alter toxicity in conformational diseases.

The Agency for Health Care Policy and Research has had a turbulent history. Created with little opposition in 1989, it narrowly escaped being eliminated in 1995, only to be reauthorized (with a new mandate and name--the Agency for Healthcare Research and Quality, or AHRQ) with overwhelming support in 1999. In focusing on budgetary history, this paper sheds light on why health services research (HSR) has difficulty obtaining funding from a government that is willing to spend vast sums on basic biomedical research. The paper argues that three strategies--bureaucratic, marketing, and constituency building--that advocates adopted in the late 1980s made HSR more visible and consequential and were responsible for AHCPR's budgetary successes as well as its near-demise.

This article compares the use and cost of home-care services among traditional Medicaid recipients with acquired immunodeficiency syndrome (AIDS) and among participants in a statewide Human Immunodeficiency Virus (HIV)/AIDS-specific home and community-based Medicaid waiver program in New Jersey, using Medicaid claims and AIDS surveillance data. Waiver program participation appears to mitigate racial and risk group differences in the probability of home-care use. However, the program's successes are confined to its enrollees of which subgroups of the AIDS population are underrepresented. Our findings suggest the need to expand access to home-care programs to racial minorities and injection drug users (IDUs) with HIV/AIDS.

A microprocessor based TENS device is developed which utilizes a spatial procedure in the administration of electrical fields to actively interfere with pain signals reaching the brain. This unusual design also has the advantage of requiring the frequency characteristics of the electrical waveform produced to be optimally tuned to the mechanical impedance properties of the skin/tissue. Hence a much more efficient procedure for the transfer of electrical energy from the TENS device to the human tissue is provided. Data are presented involving patients from the Dayton VA Medical Center in Ohio, USA being tested with this new microprocessor system compared to the treatment obtained via a traditional stimulator.

Background: Previous studies have found that hospitals at which more procedures, such as coronary-artery bypass grafting (CABG) and other vascular surgery, are performed have lower rates of mortality related to these procedures than hospitals where fewer such procedures are performed., Methods: We examined the relation between the number of percutaneous transluminal coronary angioplasty (PTCA) procedures performed at hospitals (volume) and short-term mortality in a population of 217,836 Medicare beneficiaries 65 years of age or older who underwent angioplasty in the United States from 1987 through 1990., Results: The unadjusted in-hospital mortality among patients who underwent PTCA increased from 2.5 percent among the 10 percent of patients treated in hospitals with the highest volume of such procedures to 3.9 percent among the 10 percent of patients treated in hospitals with the lowest volume. The rate of bypass surgery after PTCA also increased, from 2.8 percent among patients in the highest-volume hospitals to 5.3 percent among those in the lowest-volume hospitals. Higher rates of mortality and CABG persisted in all the groups of patients treated in hospitals that performed fewer than 100 angioplasty procedures per year in Medicare beneficiaries; this volume in Medicare beneficiaries can be extrapolated to an overall annual volume of 200 to 400 angioplasty procedures. In a logistic-regression model, the volume of PTCA procedures at a hospital was found to be a highly significant predictor of in-hospital mortality (P < 0.001). These results suggest that if the hospitals with the lowest volume had achieved the experience and technical results of the highest-volume hospitals, 381 fewer patients would have undergone CABG and there would have been 300 fewer in-hospital deaths in the population we studied., Conclusions: Hospitals that perform more PTCA procedures have lower short-term mortality rates after the procedure. These data provide evidence in support of the regionalization of angioplasty services.

The purpose of this study was to determine and compare acute hemodynamic responses of spinal cord injured (SCI) quadriplegics (quads), and paraplegics (paras) during a graded-intensity knee extension (KE) exercise test utilizing functional neuromuscular stimulation (FNS) of paralyzed quadriceps muscles. Seven quads and seven paras (N = 14) performed a series of 4-minute stages of bilateral alternating FNS-KE exercise (approximately zero to 70 degree range of motion at the knee and 6 KE/min/leg) at ankle loads of 0, 5, 10, and 15 kg/leg. Physiologic responses were determined with open-circuit spirometry, impedance cardiography, and auscultation. Comparing rest with peak FNS-KE for both groups combined, FNS-KE exercise elicited significant (p less than 0.05) increases in oxygen uptake (130 percent), pulmonary ventilation (120 percent), respiratory exchange ratio (37 percent), arteriovenous oxygen difference (57 percent), cardiac output (32 percent), stroke volume (41 percent), mean arterial pressure (18 percent), and rate-pressure product (23 percent). Heart rate increased significantly by 11 percent from the 5- to the 15-kg/leg stages. Physiologic responses of quads and paras were very similar, except for lower (p less than 0.05) arterial pressures, rate-pressure product, and peripheral vascular resistance in quads. This graded FNS-KE exercise up to the 15-kg/leg load induced relatively small but appropriate increases in aerobic metabolism and cardiopulmonary responses that appear to be safe and easily tolerated by quads and paras. Arterial pressure needs to be monitored carefully in quads to prevent excessive hypertension or hypotension. Although FNS-KE exercise has been shown to elicit peripheral adaptations to improve muscle strength and endurance, it is probably not an effective central cardiovascular training tool for all but the least fit SCI individuals. This information is important for understanding the effects of FNS use during more complex activities such as cycling and ambulation.

This study was conducted to evaluate a newly designed functional neuromuscular stimulation (FNS)-induced knee extension (KE) exercise system that incorporates the most desired features of previously described systems by determining the musculoskeletal responses of spinal cord injured (SCI) individuals to training. A specially designed chair and electrical stimulator were fabricated for FNS-induced KE resistance exercise. Surface electrodes were placed over motor points of the quadriceps muscles, and KE was alternated between legs at an average rate of 6 KE/min/leg. KE testing protocols were developed for pre- and post-training evaluations of performance, and 12 SCI subjects exercise-trained up to three times per week for 36 sessions using a progressive resistance load at ankle level. Pre- and post-training evaluation data were statistically compared using a 0.05 level for significance. Quadriceps muscle performance (strength x repetitions) improved for both legs in all subjects as indicated by significant increases in load resistance and repetitions over the 36-session training period (right leg mean = 1156.0 versus 1624.8 kg.reps, left leg mean = 1127.3 versus 1721.1 kg.reps). In addition, knee range of motion significantly increased (right leg mean = 134 versus 146 degrees, left leg mean = 133 versus 144 degrees). Thigh skinfold, thigh girth, body weight and bone density were not significantly changed. The lack of decrease in bone density in some subjects suggests that the training may retard the rate of bone loss which typically occurs with SCI. No injuries or problems were encountered during testing and training.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to test a hypothesis concerning the origin of the stereotype of the stuttering personality. According to this hypothesis the stereotype is formed by inference from beliefs about the internal variables that accompany disfluencies resembling stuttering on occasions when they occur in normally fluent speakers. This hypothesis leads to the prediction that ratings of the personality of the typical adult male stutterer will be similar to ratings of the internal state of a normally fluent speaker during a transitory spell of disfluent speech. This prediction was tested by obtaining ratings of each of these targets, using the 25 bipolar rating scales employed in previous research on this topic, from two groups each of 40 students. As predicted, the mean ratings of each target were highly correlated across the scales. These results imply that the stereotype of the stuttering personality, although mainly negative, may be derived not from motivational factors, but from judgments made under uncertainty.

The purpose of this project was to develop instrumentation and protocols in which electrical stimulation is used to induce exercise in paralyzed quadriceps muscles strength and endurance evaluation and conditioning. A computer-controlled electrical stimulation system, using surface electrodes, automatically regulates the bouts of leg extension exercise. Load weights attached just above the ankles can be progressively increased over a number of training sessions in such a manner that a measure of the fitness of the legs can be obtained. With three exercise sessions per week for 9 weeks, the strength and endurance of the quadriceps muscles of two paraplegic and four quadriplegic subjects were gradually and safely increased. During exercise at a means load weight of 5.4 kg, means heart rate did not rise above rest, whereas systolic blood pressure increased about 20 mm Hg, and skin temperature above the active muscles increased about 1.75 degrees C. Such exercise conditioning appears to be safe and may provide important health benefits, including improved fitness of the muscles and bones, better circulation in the paralyzed limbs, and enhanced self-image. Conditioned electrically stimulated paralyzed leg muscles may be used for locomotion in conjunction with special vehicles.

Functional electrical stimulation has been used to restore some degree of controllable movement to paralyzed muscle. The purpose of this study was to demonstrate the feasibility of using electrically stimulated paralyzed leg muscles to propel a wheelchair-type vehicle. For this, a conventional manual wheelchair was modified by the addition of a drive system which permits forward propulsion by reciprocating movements of the legs. A battery-powered electrical stimulator using surface electrodes over the quadriceps muscles controls locomotive characteristics. This vehicle has been successfully operated by paraplegic and quadriplegic test subjects. Advantages of using paralyzed leg muscles for locomotion may include improvement in locomotive capability, circulation in the lower extremities, cardiovascular and respiratory fitness, strength and size of the exercised muscles and bones, and self-image.