Components and Indicators of Frailty Measures: A Literature Review.

BACKGROUND: Frailty is a debilitating condition in older adults that is associated with increased risks for adverse outcomes. However, the issue of quantifying frailty remains elusive. There is a lack of consistency in the frailty components and the corresponding indicators used to quantify these components. OBJECTIVE: 1) to describe the components of frailty and examine the existing measures of frailty; and 2) to identify current gaps in knowledge of frailty measures. METHODS: The PubMed, CINAHL, and Web of Science databases were searched. Each study was reviewed to determine its fit with inclusion/exclusion criteria. RESULTS: A total of 49 studies were identified and comprised the sample. Each study described one unique measure of frailty. The frailty components and corresponding indicators within three domains (physical, psychological, and social) were described. The most frequently reported components of frailty were mobility and balance, nutrition, and cognitive function. Fifteen of 49 frailty measures included components across all three domains. Current frailty measures were critiqued and important areas for future study are identified. CONCLUSIONS: The frailty components and corresponding indicators vary considerably across different frailty measures. Future studies are needed to address inconsistences in frailty measures and models.

Russian health care workers' knowledge of tuberculosis and infection control.

BACKGROUND: Lack of knowledge may contribute to a higher risk of nosocomial tuberculosis (TB) among Russian TB health care workers (HCWs). DESIGN: Community-based participatory study. Russian TB HCWs at five TB facilities (n = 96) were surveyed to assess knowledge specific to TB and infection control. RESULTS: Overall scores were low. Analysis of variance showed a significant difference in knowledge by job category. Physicians scored significantly higher than nurses, laboratory staff and support staff. Nurses and laboratory technicians scored significantly higher than support staff. The biggest area of knowledge deficit was in infection control. CONCLUSION: Knowledge level of TB among HCWs could influence the prevalence of nosocomial TB infection.

High-intensity inspiratory muscle training in patients with chronic obstructive pulmonary disease and severely reduced function.

PURPOSE: This study examined the effects of inspiratory muscle training (IMT) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea. METHODS: This was a randomized single-blind clinical trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men, 9 women) with severe to very severe airflow obstruction and severely limited functional performance were assigned randomly to an IMT group (n = 12) or an educational control group (n = 15). The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques. Training was initiated with inspiratory pressure loads equal to 30% of maximal inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax. Dependent variables were measured before and after 4 months of IMT: inspiratory muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/- 5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength, respiratory muscle endurance, and respiratory symptoms during daily activities and respiratory exertion.

Can relative spermatozoal galactosyltransferase activity be predictive of dairy bull fertility?

The best and poorest bovine semen samples used commercially for artificial insemination in dairy cattle typically differ in pregnancy rates by 20 to 25% but are within a range that pregnancy rates cannot be predicted consistently by commonly used laboratory assays. Sperm motility and morphology are the characteristics most often evaluated. Laboratory assays that measure other functional traits of sperm may be useful as supplemental assays to increase the reliability of predicting fertility. One such functional trait is the ability of sperm to bind to the zona pellucida, a process mediated by complementary receptors on each gamete. On mouse sperm, beta1,4-galactosyltransferase acts as a receptor for the zona pellucida. Beta1,4-galactosyltransferase is expressed on sperm from many mammals, including bovine sperm, and is a candidate for a zona pellucida receptor. The ability of sperm to bind to the zona pellucida may be related to the amount of beta1,4-galactosyltransferase present on sperm. The aim of this work was to determine if bull sperm beta1,4-galactosyltransferase activity was related to fertility. Beta1,4-galactosyltransferase enzyme assays were performed on sperm from 24 bulls whose fertility was estimated by nonreturn rate and on sperm from a second group of seven bulls whose fertility was ranked by in vivo competitive fertilization. Beta1,4-galactosyltransferase activity varied between individual bulls but was not correlated to fertility as estimated by nonreturn rate or by competitive fertilization. These results demonstrate that beta1,4-galactosyltransferase activity on sperm varies between animals, but that beta1,4-galactosyltransferase activity alone is not an accurate indicator of fertility in dairy bulls.

Purification, characterization, cDNA cloning and expression of a novel ketoreductase from Zygosaccharomyces rouxii.

A novel ketoreductase isolated from Zygosaccharomyces rouxii catalyzes the asymmetric reduction of selected ketone substrates of commercial importance. The 37.8-kDa ketoreductase was purified more than 300-fold to > 95% homogeneity from whole cells with a 30% activity yield. The ketoreductase functions as a monomer with an apparent Km for 3,4-methylenedioxyphenyl acetone of 2.9 mM and a Km for NADPH of 23.5 microM. The enzyme is able to effectively reduce alpha-ketolactones, alpha-ketolactams, and diketones. Inhibition is observed in the presence of diethyl pyrocarbonate, suggesting that a histidine is crucial for catalysis. The 1.0-kb ketoreductase gene was cloned and sequenced from a Z. rouxii cDNA library using a degenerate primer to the N-terminal sequence of the purified protein. Furthermore, it was expressed in both Escherichia coli and Pichia pastoris and shown to be active. Substrate specificity, lack of a catalytic metal, and extent of protein sequence identity to known reductases suggests that the enzyme falls into the carbonyl reductase enzyme class.

Chronic effects of the novel glucocorticosteroid RPR 106541 administered to beagle dogs by inhalation.

The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (air and placebo controls), 10, 100, or 1,000 microg/kg/d for 26 weeks. A solution-based aerosol formulation was administered to mature dogs (approximately 10 months at initiation) from a pressurized metered dose inhaler at 0 (air and placebo controls), 10, 50, and 150 microg/kg/d for 52 weeks. Clinical evidence of glucocorticosteroid-induced immunosuppression was observed by weeks 20-26 following relatively high dose exposures (100 microg/kg/d and 1,000 microg/kg/d) in young dogs receiving the dry powder formulation for 26 weeks. Classic glucocorticosteroid effects were observed, including adrenocortical atrophy, reduced bone mass with retention of epiphyseal growth plates in long bones, prominence of stromal adipose tissue in bone marrow, and atrophy of lymphoid tissues. Inhalation administration of RPR 106541 to sexually mature dogs facilitated more definitive characterization of endocrine affects of RPR 106541 as compared with administration in younger, sexually immature animals. Significant effects in female reproductive organs included absence of corpora lutea in association with atresia of vesicular follicles within the ovaries, endometrial hyperplasia, and lobular development of mammary tissue. Discordant development of mammary tissue, accumulation of secretory material within hyperplastic endometrial glands, and hypertrophy of uterine lining epithelium in absence of ovulation were consistent with a secondary progestin effect by a potent glucocorticosteroid.

Effect of hyperbaric oxygen on neutrophil CD18 expression.

Previous work has shown that treatment with hyperbaric oxygen significantly reduces neutrophil adhesion to postcapillary venules in a rat microcirculation model of ischemia-reperfusion injury. The mechanism of this process is unknown. The purpose of this study was to evaluate the effect of hyperbaric oxygen on neutrophil CD18 adhesion sites by flow cytometry in an animal model of ischemia-reperfusion injury. The gracilis muscle flap was raised in three groups of male Wistar rats: (1) a sham group (n = 25), (2) a group that underwent 4 hours of ischemia (n = 25), and (3) a group that underwent 4 hours of ischemia and received hyperbaric oxygen (100% 02, 2.5 atmospheres absolute, during the last 90 minutes of ischemia) (n = 25). Samples from one subgroup of each group (n = 5) were divided into two portions, and one portion was stimulated with phorbol-12 myristate 13-acetate (PMA). Samples from another subgroup of each group (n = 5) were treated in the same manner, and a flap flush was added at the end of reperfusion to determine the number of CD18 adhesion sites on adherent neutrophils remaining in the flap. Venous blood was drawn 10 minutes after the operation, at 5 minutes of reperfusion, and at 90 minutes of reperfusion. Hematocrit and white blood cell count were measured. Samples were analyzed by flow cytometry, and the antibody binding capacity was assessed using microbead standards and linear regression (antibody binding capacity was expressed as the mean number of sites per cell +/- SEM). Microbeads were used to align the flow cytometer and to provide external and internal standards. Ischemia-reperfusion injury increased the expression of CD18 by neutrophils (p < 0.05). Expression of CD18 was not decreased by hyperbaric oxygen treatment. Stimulation with PMA increased the expression of CD18 in all groups (p < 0.01). These results suggest that ischemia-reperfusion injury does increase the expression of CD18 by neutrophils. Hyperbaric oxygen, as administered in this experiment, did not prevent the increase in CD18 expression.

Direct measurement of islet amyloid polypeptide fibrillogenesis by mass spectrometry.

A novel method for monitoring fibrillogenesis is developed and applied to the amyloidogenic peptide, islet amyloid polypeptide (IAPP). The approach, based on electrospray ionization mass spectrometry, is complementary to existing assays of fibril formation as it monitors directly the population of precursor rather than product molecules. We are able to monitor fiber formation in two modes: a quenched mode in which fibril formation is halted by dilution into denaturant and a real time mode in which fibril formation is conducted within the capillary of the electrospray source. Central to the method is the observation that fibrillar IAPP does not compromise the ionization of monomeric IAPP. Furthermore, under mild ionization conditions, fibrillar IAPP does not dissociate and contribute to the monomeric signal. Critically, we introduce an internal standard, rat IAPP, for analysis on the mass spectrometer. This standard is sufficiently similar in sequence in that it ionizes identically to human IAPP. Furthermore, the sequence is sufficiently different in that it does not form fibrils and is distinguishable on the basis of mass. Applied to IAPP fibrillogenesis, our technique reveals that precursor consumption in seeded reactions obeys first-order kinetics. Furthermore, a consistent level of monomer persists in both seeded and unseeded experiments after the fibril formation is complete. Given the inherent stability of fibrils, we expect this approach to be applicable to other amyloid systems.

The reproductive and developmental toxicity of the antifungal drug Nyotran (liposomal nystatin) in rats and rabbits.

Nyotran is a liposomally encapsulated i.v. formulation of the antifungal polyene nystatin. This drug was evaluated in a series of reproductive toxicity studies, according to the guidelines outlined by the International Conference on Harmonization (ICH). A fertility and early embryonic development study (SEG I) and a prenatal and postnatal development (SEG III) study were conducted in rats, and embryo-fetal development (SEG II) studies were conducted in rats and rabbits. Nyotran was administered iv in all studies. In SEG I and SEG III, rats were administered daily doses of 0.5, 1.5, or 3.0 mg/kg Nyotran. In both studies, parental mortality and toxicity in the 3.0 mg/kg dose group necessitated the lowering of the high dose to 2.0 mg/kg/day. Parental toxicity, in the form of decreased body weights, decreased food consumption, and piloerection were also observed at the 1.5 mg/kg/day dose level in the SEG I and SEG III studies. Despite the parentally toxic doses in the SEG I study, there was no effect of Nyotran on F0 male or female fertility or early embryonic development of F1 offspring. In the SEG III study, lactational body weights of the F1 generation were decreased at all Nyotran dose levels. There was no effect on pre-wean developmental landmarks, but post-wean development was affected by Nyotran administration at all dosage levels. Preputional separation was delayed in the 1.5 and 3.0/2.0 mg/kg/day F1 offspring, auditory startle function was decreased in F1 females at all dose levels, and motor activity was decreased in male F1 offspring at all dose levels. However, there were no treatment-related effects on the subsequent mating of the F1 generation and resulting F2 offspring. In SEG II studies, rats and rabbits were also administered 0.5, 1.5, or 3.0 mg/kg/day of Nyotran during gestation. The high dose in these SEG II studies was not lowered, as the maternal animals were able to tolerate the shorter duration of dosing. Maternal effects in rabbits were observed only in the high-dose group and were limited to decreased food consumption and decreased absolute and relative liver weight. Decreased food consumption in high-dose dams and clinical weight loss in some animals at the mid- and high-dose levels evidenced maternal toxicity in rats. Nyotran did not have any effect on Caesarian section parameters in either rats or rabbits and no effect on the incidence of fetal malformations in rabbits. A statistically significant increase in mild hydrocephaly, observed in 4 rat fetuses, was seen at the highest dose level of 3.0 mg/kg/day. The biological significance and relationship to Nyotran treatment of this finding is not clear. This finding may represent a change in the background incidence or a change in the pattern of responsiveness of this strain of rat fetus to the test chemical. Toxicokinetic data were also collected in the SEG II rabbit and rat studies for comparison to human exposures. In both species, systemic exposure to the nystatin at effective antifungal concentrations was demonstrated. The systemic exposures in rats and rabbits were, however, considerably less than have been reported in humans administered clinical doses of 2 or 4 mg/kg/day Nyotran. Thus, humans tolerate higher dosages and systemic exposures of Nyotran relative to rats and rabbits and there is no margin of safety in either dosage level or systemic exposure to drug. Given this lack of a margin of safety and the effects on postnatal development in F1 rats, caution should be exercised when using this drug in females of childbearing potential.

Reliability of submaximal exercise tests in patients with COPD. Chronic obstructive pulmonary disease.

UNLABELLED: Submaximal constant work rate exercise tests are often used to measure the efficacy of an exercise intervention, but the reliability of these tests in patients with chronic obstructive pulmonary disease (COPD) has not been established. PURPOSE: To examine the reproducibility of submaximal exercise responses of COPD patients compared with those of healthy elderly subjects. METHODS: Sixteen COPD patients and 15 healthy subjects performed four weekly submaximal exercise tests against two different constant work rates: 20 W and 50% of the peak work rate (PWR). Spirometry was performed before each exercise test. COPD patients and healthy subjects were: age 69 +/- 5 and 65 +/- 5 yr, body mass index 26.4 +/- 3.9 and 26.7 +/- 3.0 kg x m(-2), respectively. RESULTS: Both groups had no change in minute ventilation (V(E)), oxygen uptake (VO2), breathlessness (RPB), and leg fatigue (RPLF) for either work rate over repeated measures (P > 0.05). At 50% PWR test-retest reliability coefficients for V(E) and VO2 ranged from r = 0.88 to r = 0.96 for COPD patients and from r = 0.72 to r = 0.97 for healthy subjects; for RPB and RPLF test-retest reliability ranged from r = 0.76 to r = 0.89 for COPD patients and from r = 0.70 to r = 0.91 for healthy subjects. Intrasubject mean absolute differences for repeated measures of V(E), VO2, RPB, or RPLF were low and there were no group differences (P > 0.05). Percent error for V(E) and VO2 ranged from 6 +/- 3 to 9 +/- 7%, and for RPB and RPLF ranged from 19 +/- 18 to 68 +/- 65% for both groups at each work rate. CONCLUSIONS: Submaximal exercise responses were reliable over a 1-month period, and measures of the physiological and psychophysical responses of COPD patients were as reliable as those of healthy subjects.

Toxicologic and carcinogenic effects of the type IV phosphodiesterase inhibitor RP 73401 on the nasal olfactory tissue in rats.

RP 73401, a type IV phosphodiesterase inhibitor, caused toxic effects in the nasal olfactory region of Sprague-Dawley rats when administered by either oral or inhalation exposure. A single oral administration of RP 73401 (at a dose of > or = 50 mg/kg) or 5-day inhalation exposure (1 hr/day) at a dose of approximately 1.0 mg/kg per day caused degeneration and sloughing of the olfactory surface epithelium. Degeneration and loss of Bowman's glands were noted in the underlying lamina propria and submucosa. Electron microscopy of these lesions demonstrated that sustentacular cells and the epithelial cells lining Bowman's glands were the primary target cells in the olfactory mucosa. The earliest ultrastructural changes detected in these cells were dilatation and vesiculation of the endoplasmic reticulum, suggesting that metabolic activation is important for the toxic effects. In repeated-dose studies, 13 wk of oral dosing at 2.0 or 6.0 mg/kg per day resulted in subtle disorganization of the olfactory epithelium, whereas basal cell hyperplasia in the olfactory epithelium was identified in a 6-month inhalation study at a dose of 1.0 mg/kg per day. A 2-yr inhalation carcinogenicity study resulted in tumors of the nasal olfactory region in rats treated at 0.5 and 1.0 mg/kg per day. Most tumors were classified as olfactory neuroblastomas, and immunohistochemistry on selected tumors was consistent with their being of neuroectodermal origin. Of the species studied (rat, mouse, and dog), the olfactory toxicity of RP 73401 was confined to the rat, and the toxicity was likely related to metabolic activation by olfactory epithelial cells rather than the phosphodiesterase activity of the compound.

Cycle ergometer and inspiratory muscle training in chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD) the intensity of aerobic training is limited by dyspnea. Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea. We examined effects of home-based inspiratory muscle training (IMT) and cycle ergometry training (CET) in 53 patients with moderate to severe COPD (FEV(1)% pred, 50 +/- 17 [mean +/- SD]). Patients were randomly assigned to 4 mo of training in one of four groups: IMT, CET, CET + IMT, or health education (ED). Patients were encouraged to train to the limits of their dyspnea. Inspiratory muscle strength and endurance increased in IMT and CET + IMT groups compared with CET and ED groups (p < 0. 01). Peak oxygen uptake increased and heart rate, minute ventilation, dyspnea, and leg fatigue decreased at submaximal work rates in the CET and CET + IMT groups compared with the IMT and ED groups (p < 0. 01). There were no differences between the CET and CET + IMT groups. Home-based CET produced a physiological training effect and reduced exercise-related symptoms while IMT increased respiratory muscle strength and endurance. The combination of CET and IMT did not produce additional benefits in exercise performance and exercise-related symptoms. This is the first study to demonstrate a physiological training effect with home-based exercise training.

Simple histochemical stain for acrosomes on sperm from several species.

The acrosome reaction is an exocytotic process that enables a sperm to penetrate the zona pellucida and fertilize an egg. The process involves the fenestration and vesiculation of the sperm plasma membrane and outer acrosomal membrane releasing the acro somal contents. Many different methods have been devel oped to detect the acrosomal status of sperm. These techniques are sometimes complicated, costly, and can be used on only a few species. The aim of this study was to develop an efficient and inexpensive method to assess the acrosomal status of sperm from a variety of species. We prepared and fixed sperm from humans, cattle, swine, rabbits, guinea pigs, and mice and stained them with Coomassie G250. The acrosomes were stained intensely blue in color. Following capacitation, some sperm were incubated for 1 hr with 10 microM calcium ionophore A23187 to induce the acrosome reaction. They were also stained with Coomassie G-250. Ionophore-treated sperm lacked Coomassie staining over the acrosomal region. Differential interference contrast (DIC), bright field microscopy or Pisum sativum agglutinin staining confirmed that the acrosomes of sperm from these species were reacted in response to calcium ionophore treatment and the acrosome reaction frequencies matched results with Coomassie staining. These results demonstrate that the acrosomal status of mammalian sperm from several species can be determined easily and reliably using this simple Coomassie Blue G-250 staining method.

Test-retest reliability of symptom-limited cycle ergometer tests in patients with chronic obstructive pulmonary disease.

BACKGROUND: Symptom-limited exercise tests are widely used to evaluate the effects of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), but the reliability of these tests is not well established in COPD patients. OBJECTIVES: We compared test-retest reliability of two repeated symptom-limited exercise tests between COPD patients and healthy elderly subjects and between male and female patients. METHOD: Fifty-six COPD patients (40 men, 16 women) and 16 healthy subjects (6 men, 10 women) performed two symptom-limited exercise tests approximately 2 weeks apart. Measures of oxygen uptake (VO2), minute ventilation (VE), heart rate, and ratings of breathlessness and leg fatigue were obtained at peak exercise at each symptom-limited exercise test. RESULTS: Repeated measures of peak exercise responses were stable for patients and healthy subjects and for male and female patients. Although mean percent error (absolute difference/mean) for peak exercise responses was low, some individuals' values exceeded 10%. There was no difference in the percent error between COPD patients and healthy subjects or between men and women with COPD. Test-retest reliability was lower for breathlessness ratings than for other peak exercise responses for all groups. CONCLUSIONS: Repeated symptom-limited exercise tests are reliable in COPD patients and healthy subjects. However, some individuals are less reliable, and these patients may require more than one exercise test to establish reliable performance.

Discontinuous incremental threshold loading test: measure of respiratory muscle endurance in patients with COPD.

STUDY OBJECTIVE: To assess the discontinuous incremental threshold loading (DC-ITL) test as a measure of respiratory muscle endurance for patients with COPD in terms of perceived breathing difficulty, reliability, and validity. DESIGN: The DC-ITL test was repeated three times at weekly intervals under identical test conditions. SETTING: Clinical research laboratory. PATIENTS: Forty-eight patients with moderate to severe COPD. MEASUREMENTS AND RESULTS: Rating of perceived breathing difficulty (RPBD) was measured at the end of each stage of the DC-ITL test with a Borg category-ratio scale. The maximal inspiratory pressure (PImax) was measured before and after the DC-ITL test. Breathing patterns were measured during the DC-ITL test. The mean (+/-SD) for RPBD at the maximal load was 6.3 (3.1), 6.6 (2.8), and 6.7 (2.7) for visits one, two, and three, respectively (not significant). The mean relative maximal load for the DC-ITL test (peak mouth pressure as a percent of PImax) at the last completed stage was 59+/-23%, 62+/-20%, and 63+/-19% for visits one, two, and three, respectively (not significant). Test-retest reliability was r1,2=0.82 and r2,3=0.69 for relative maximal load and r1,2=0.90 and r2,3=0.90 for absolute maximal load (peak mouth pressure). Tidal volume decreased (p < 0.01) and respiratory rate increased (p < 0.01) from the next-to-the-last to the last completed stage. PImax decreased after the DC-ITL test (p < 0.01). CONCLUSIONS: Moderate breathing difficulty was experienced during the DC-ITL test. The test was reliable and the results of this study support its validity as a measure of respiratory muscle endurance.

Reliability and validity of the functional performance inventory in patients with moderate to severe chronic obstructive pulmonary disease.

The Functional Performance inventory (FPI) is a new instrument designed to measure functional status in terms of activities that people perform on a daily basis. Psychometric characteristics were examined by a survey of 45 men and 27 women with chronic obstructive pulmonary disease (COPD). Internal consistency reliability was high and no ceiling and floor effects were observed for the Total FPI. Concurrent validity was demonstrated by correlations with the Total Sickness Impact Profile (r = -.59). Construct validity was supported by correlations with the Medical Outcomes Study Short Form-36, Physical Functioning (r = .69), the Physical Activity Scale for the Elderly (r = .62) and American Thoracic Society-Division of Lung Disease Breathlessness scale (r = -.62). The Total FPI is a reliable and valid measure of functional performance in persons with COPD.

Chronic obstructive pulmonary disease: strategies to improve functional status.

People with chronic obstructive pulmonary disease (COPD) experience deterioration in functional status, therefore improving functional status is a major goal of treatment. We reviewed interventions to improve functional status in people with COPD published from 1980 through September 1996. Randomized controlled clinical trials were reviewed to document outcomes in terms of functional capacity and functional performance for the following interventions: pharmacologic therapy including theophylline, inhaled bronchodilators, steroids, antianxiolytics and antidepressants; general exercise strategies including exercise training, exercise and comprehensive pulmonary rehabilitation, and upper extremity training; inspiratory muscle therapy including inspiratory muscle training and inspiratory muscle rest; nutritional therapy; oxygen therapy; and specialized nursing care. Improvements for functional capacity were documented in terms of strength of the inspiratory muscles and upper extremities, walking tests, and peak oxygen uptake. Most interventions were targeted to enhance functional capacity, and few were aimed at enhancing functional performance. Further research is needed to examine the relationship between functional capacity and functional performance and to design and test interventions to improve functional performance.

Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine.

The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.

Sperm from a variety of mammalian species express beta1,4-galactosyltransferase on their surface.

In mice, initial gamete recognition is mediated by the binding of sperm surface beta1,4-galactosyltransferase (GalTase) to a glycoprotein of the zona pellucida, ZP3. When sperm bind to the zona pellucida, ZP3 induces the acrosome reaction by aggregating GalTase. The acrosome reaction releases acrosomal enzymes allowing sperm to pass through the zona pellucida, bind to the egg membrane, and activate development. In addition to GalTase, there is evidence that other sperm proteins may also bind ZP3. Although fertilization in the mouse is morphologically similar to fertilization in most other mammalian species, the degree of parallelism at the molecular level is not well defined. Less information is available about the molecular details of fertilization in other species. The aim of this work was to determine whether sperm from other mammalian species express GalTase on their surface. We performed GalTase enzyme assays on sperm from six species, and all six expressed GalTase on their surface. The amounts of GalTase varied between species. Guinea pig, mouse, and rat sperm had higher levels of GalTase than bovine, porcine, and rabbit sperm. GalTase was localized by immunofluorescence on live and fixed sperm to the anterior portion of the sperm head in all species examined. This is the expected location for a receptor that binds the zona pellucida. Biotinylation of sperm surface proteins confirmed that GalTase detected by immunofluorescence and enzyme assay was expressed on the sperm surface. These results demonstrate that various mammalian species express GalTase on their surface and that it is found in the proper location to bind to the zona pellucida.