Improvement in body composition following a supervised exercise-training program of adult patients with cystic fibrosis.

OBJECTIVES: Maintenance of optimal nutritional status is a crucial issue for cystic fibrosis (CF) patients. Here, we evaluate the effects of an 8-week exercise training (ET) program on body composition in CF patients. METHODS: This prospective pilot observational study was conducted in adult CF subjects in stable condition following their annual check-up. The ET program consisted of three sessions per week and included aerobic training (≥30min), muscle strengthening, circuit training, and relaxation. Exercise tolerance (6-minute walk test, 6MWT), pulmonary function, quadriceps isometric strength, and body composition (bioelectrical impedance analysis of fat-free mass [FFM], fat mass, and body cell mass) were analyzed before and immediately after the ET program. A control group of CF patients who preferred not to participate in the ET program received the same evaluations. RESULTS: A total of 43 CF patients were enrolled and offered the ET program; 28 accepted (aged 28±5 years, forced expiratory volume in 1s [FEV1] 48.8±19% predicted) and 15 declined the ET program but agreed to be part of the control group (matched for age and CF severity: 30.8±9 years, FEV1 51.8±16.5%). Pulmonary function was unchanged at the end of the ET program, but significant improvements were observed in 6MWT distance (from 520±96m to 562±105m, P<0.001) and muscle strength (331±141N to 379±168N, P<0.001). Although mean body mass index did not change, the ET group showed significantly increased FFM (43.85±8kg to 44.5±9.2kg, P=0.03) and a trend towards increased body cell mass (21.4±6 to 22.1±6.6kg, P=0.06). All other parameters were unchanged by ET. There were no significant correlations between the increase in FFM and the improvements in either 6MWT distance or muscle strength. The CF control group exhibited no significant changes in any parameters between evaluations. CONCLUSIONS: ET significantly improved FFM, but not body mass index, in CF patients. The results illustrate the superiority of bioimpedancemetry for assessing changes in body composition and reveal the importance of ET for improving not only exercise tolerance but also nutritional status in these patients.

Patient preferences for healthcare delivery through community pharmacy settings in the USA: A discrete choice study.

WHAT IS KNOWN AND OBJECTIVE: In order to improve public health, it is necessary to facilitate patients' easy access to affordable high-quality primary health care, and one enhanced approach to do so may be to provide primary healthcare services in the community pharmacy setting. Discrete choice experiments to evaluate patient demand for services in pharmacy are relatively limited and have been hampered by a focus on only a few service alternatives, most focusing on changes in more traditional pharmacy services. The study aim was to gauge patient preferences explicitly for primary healthcare services that could be delivered through community pharmacy settings in the USA, using a very large sample to accommodate multiple service delivery options. METHODS: An online survey was administered to a total of 9202 adult patients from the general population. A subsequent online survey was administered to 50 payer reimbursement decision-makers. The patient survey included a discrete choice experiment (DCE) which showed competing scenarios describing primary care service offerings. The respondents chose which scenario would be most likely to induce them to switch from their current pharmacy, and an optimal patient primary care service model was derived. The likelihood this model would be reimbursed was then determined in the payer survey. RESULTS AND DISCUSSION: The final optimal service configuration that would maximize patient preference included the pharmacy: offering appointments to see a healthcare provider in the pharmacy, having access to their full medical record, provide point-of-care diagnostic testing, offer health preventive screening, provide limited physical examinations such as measuring vital signs, and drug prescribing in the pharmacy. The optimal model had the pharmacist as the provider; however, little change in demand was evident if the provider was a nurse-practitioner or physician's assistant. The demand for this optimal model was 2-fold higher (25.5%; 95% Bayesian precision interval (BPI) 23.5%-27.0%) than for a base pharmacy offering minimal primary care services (12.6%; 95% BPI 12.2%-13.2%), and was highest among Hispanic (30.6%; 95% BPI: 25.7%-34.3%) and African American patients (30.7%; 95% BPI: 27.1%-35.2%). In the second reimbursement decision-maker survey, the majority (66%) indicated their organization would be likely to reimburse the services described in the optimal patient model if provided in the pharmacy setting. WHAT IS NEW AND CONCLUSION: This United States national study provides empirical support for a model of providing primary care services through community pharmacy settings that would increase access, with the potential to improve the public health.

A Frailty Index Based On Deficit Accumulation Quantifies Mortality Risk in Humans and in Mice.

Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index. Here we show the results of extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 [1.04-1.05] in humans; 1.15 [1.12-1.18] in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.

Effect of citrulline on muscle functions during moderate dietary restriction in healthy adult rats.

Low calorie diets are designed to reduce body weight and fat mass, but they also lead to a detrimental loss of lean body mass, which is an important problem for overweight people trying to lose weight. In this context, a specific dietary intervention that preserves muscle mass in people following a slimming regime would be of great benefit. Leucine (LEU) and Citrulline (CIT) are known to stimulate muscle protein synthesis (MPS) in post-prandial and post-absorptive state, respectively. This makes them interesting bioactive components to test in the context of dietary restriction. We tested the concept of combining LEU and CIT in adult female rats. We postulated that the sequential administration of LEU (mixed in chow) and CIT (given in drinking water before a rest period) could be beneficial for preservation of muscle function during food restriction. Sixty female rats (22 weeks old) were randomized into six groups: one group fed ad libitum with a standard diet (C) and five food-restricted groups (60 % of spontaneous intake for 2 weeks) receiving a standard diet (R group), a CIT-supplemented diet (0.2 or 1 g/kg/day, CIT0.2 group and CIT1 group, respectively), a LEU-supplemented diet (1.0 g/kg/day) or a CIT + LEU-supplemented diet (CIT + LEU 1.0 g/kg/day each). At the end of the experiment, body composition, muscle contractile properties and muscle protein synthesis (MPS) rate were studied in the tibialis anterior muscle. Dietary restriction tended to decrease MPS (R: 2.5 ± 0.2 vs. C: 3.4 ± 0.4 %/day, p = 0.06) and decrease muscle strength (R: 3,045 ± 663 vs. C: 5,650 ± 661 A.U., p = 0.03). Only CIT administration (1 g/kg) was able to restore MPS (CIT1: 3.4 ± 0.3 vs. R: 2.5 ± 0.2 %/day, p = 0.05) and increase muscle maximum tetanic force (CIT1: 441 ± 15 vs. R: 392 ± 22 g, p = 0.05) and muscle strength (CIT1: 4,259 ± 478 vs. R: 3,045 ± 663 A.U., p = 0.05). LEU had no effect and CIT + LEU supplementation had few effects, limited to adipose mass and fatigue force. The results of this study highlight the ability of CIT alone to preserve muscle function during dietary restriction. Surprisingly, LEU antagonized some effects of CIT. The mechanisms involved in this antagonistic effect warrant further study.

Size-mediated response to public cues of predation risk in a tropical stream fish.

In order to investigate any size-dependent differences between behavioural patterns, wild-caught Hart's rivulus Rivulus hartii of varying sizes were exposed to chemical alarm cues extracted from the skin of conspecifics or heterospecific Poecilia reticulata, or a tank water control, in a series of laboratory trials. In response to conspecific alarm cues, R. hartii subjects of the range of body sizes tested exhibited consistent, size-independent antipredator behaviours that were characterized by decreased locomotory activity and foraging levels and increased refuging behaviour. Conversely, focal R. hartii demonstrated significant size-dependent trends in response to heterospecific alarm cues, with smaller individuals exhibiting antipredator responses and larger individuals shifting their behaviour to increased levels of activity consistent with a foraging, or predatory, response. These results show that the behavioural responses of individual R. hartii to publicly available chemical alarm cues from heterospecifics are mediated by the size of the receiver.

Social familiarity and shoal formation in juvenile fishes.

The potential influence of social familiarity in shoal-choice decisions was investigated in two sympatric species of north temperate fishes, juvenile banded killifish Fundulus diaphanus and juvenile bluegill sunfish Lepomis macrochirus. Groups of socially familiar and unfamiliar conspecifics were formed in the laboratory using wild-caught fishes. Juvenile F. diaphanus demonstrated a strong preference for familiar conspecific shoalmates, whereas juvenile L. macrochirus exhibited no preference for either unfamiliar or familiar conspecific shoalmates. The differential influence of familiarity on shoalmate choice in juveniles of these two species could be due to their different ecologies, local population densities and life histories.

Glatiramer acetate in combination with minocycline in patients with relapsing--remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial.

Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing-remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study by determining the total number of T1 gadolinium-enhanced lesions at months 8 and 9 in patients who were starting glatiramer acetate and had at least one T1 gadolinium-enhanced lesion on screening magnetic resonance imaging. Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study. Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63% (mean 1.47 versus 2.95; p = 0.08), the total number of new and enlarging T2 lesions by 65% (mean 1.84 versus 5.14; p = 0.06), and the total T2 disease burden (p = 0.10). A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging. The risk of relapse tended to be lower in the combination group (0.19 versus 0.41; p = NS). Treatment was safe and well tolerated. We conclude that efficacy endpoints showed a consistent trend favoring combination treatment. As minocycline is a relatively safe oral therapy, further study of this combination is warranted in relapsing-remitting multiple sclerosis.

HLA-B27 rats develop osteopaenia through increased bone resorption without any change in bone formation.

Osteopaenia is a common complication of inflammatory bowel diseases (IBD). However, the mechanisms of bone loss are still the subject of debate. The aims of this study were to investigate bone loss in HLA-B27 transgenic rats, a spontaneous model of colitis and to compare the results provided by the usual markers of bone remodelling and by direct measurement of bone protein synthesis. Systemic inflammation was evaluated in HLA-B27 rats and control rats from 18 to 27 months of age. Then bone mineral density, femoral failure load, biochemical markers of bone remodelling and protein synthesis in tibial epiphysis were measured. Bone mineral density was lower in HLA-B27 rats than in controls. Plasma osteocalcin, a marker of bone formation, and fractional protein synthesis rate in tibial epiphysis did not differ between the two groups of rats. In contrast, urinary excretion of deoxypyridinoline, a marker of bone resorption, was significantly increased in HLA-B27 rats. The present results indicate that bone fragility occurs in HLA-B27 rats and mainly results from an increase in bone resorption. Systemic inflammation may be the major cause of the disruption in bone remodelling homeostasis observed in this experimental model of human IBD.

Head capsule width as an instar indicator for larvae of the cranberry fruitworm (Lepidoptera: Pyralidae) in southeastern New Brunswick.

The objective of this study was to determine the number of instars of the cranberry fruitworm Acrobasis vaccinii Riley in southeastern New Brunswick based on the distribution of head capsule widths from field and laboratory observations. In 2000, head capsules from field samples were measured across their widest point, and the results were plotted against observed frequencies. The data from field samples suggested that A. vaccinii exhibited five instars in 2000. In 2001, larvae were reared in the laboratory until the final molt, and head capsules were counted and measured. The results were also plotted against observed frequencies. None of the laboratory specimens exhibited more than five instars, supporting the results of the previous year. Various factors are invoked to explain the difference between these results and those of a previous study conducted 50 yr earlier and 200 km away, in which six instars and larger head capsules were reported.

Brook charr alevins alter timing of nest emergence in response to chemical cues from fish predators.

Brook charr (Salvelinus fontinalis) lay their eggs in gravel nests called redds. The nests are not defended for extended periods and the eggs and young may be subject to predation from predators that travel through the substrate into the redd. In this study we tested whether long-term exposure of brook charr eggs to chemical cues from predatory sculpins (Cottus cognatus) resulted in an adaptive shift in the timing of emergence of charr alevins from artificial redds. We reared brook charr eggs in the presence of chemical cues from sculpins fed brook charr eggs, sculpins fed brine shrimp, and a well water control. Significantly more alevins emerged during the first week of the emergence period when exposed to chemical cues from sculpins fed eggs than from cues from sculpins fed brine shrimp or from well water. Alevins that emerged sooner were smaller and possessed larger yolk sacs than alevins that emerged later in the emergence period. Our results suggest that alevins that emerge sooner may escape predation in the redd, but may pay a cost in being under-developed upon emergence into the open water of the stream or lake.

[Can one die of sorrow?]. / Peut-on mourir de chagrin?

The authors report the case of a 49 year old woman who, on two occasions four years apart, presented with cardiogenic shock following the same type of intense emotional stress. Acute left ventricular systolic dysfunction in the initial phase regressed completely with drugs. A diagnostic investigation excluded atheromatous coronary artery disease, myocarditis and pheochromocytoma. Two hypotheses remained: prolonged coronary spasm causing myocardial stunning or acute catecholaminergic cardiomyopathy secondary to the stress.

[Cure of superacute eosinophilic myocarditis treated by temporary circulatory assistance]. / Guérison d'une myocardite suraiguë à éosinophiles traitée par assistance circulatoire temporaire.

The authors report the case of a 31 year old woman, admitted as an emergency for acute myopericarditis, in cardiogenic shock. Echocardiography showed severe left ventricular dysfunction associated with concentric biventricular hypertrophy with increased echogenicity of the myocardial walls. Poor response to treatment with intravenous inotropic drugs led to referral for biventricular circulatory assistance with a Biomedicus pump, which was withdrawn on the 9th day after recovery of normal left ventricular function. Myocardial biopsies showed massive interstitial inflammation with a predominance of eosinophilic cells suggesting a hypersensitivity reaction. Steroid therapy was prescribed when the results of biopsy were known and stopped after 6 months. This case emphasises the value of echocardiography and myocardial biopsy in diagnosis and treatment of acute myocarditis with cardiogenic shock.

Fish shoal composition: mechanisms and constraints.

Observations were made on three fish species (banded killifish (Fundulus diaphanus), golden shiner (Notemigonus crysoleucas) and white sucker (Catostomus commersoni)) in a temperate lake (New Brunswick, Canada) in order to investigate the relationship between shoal choice behaviour of individual fishes and shoal composition. Encounters between shoals were observed to take place every 1.1 min per shoal and an encounter lasted 3.7 s on average. The duration of shoal encounters was influenced by shoal size but not by differences between shoals in either body length or species. Conversely, the outcome of shoal encounters (i.e. ences between shoals in either body length or species. Conversely, the outcome of shoal encounters (i.e. whether or not an individual changes shoal) was influenced by body length and species differences but not by shoal size. Together, these results suggest that encounter duration itself is unlikely to have an important influence on encounter outcome. The collection of ten entire fish shoals showed that they were assorted by species and body length. A simulation model demonstrated that individual shoal choice behaviour alone could account for the generation and maintenance of the observed levels of size assortedness of shoals without invoking the existence of other sorting mechanisms such as differential swimming speeds. However, the generation of species assortedness was not predicted by the model. Furthermore, our data suggest that fish density acts as a constraint on shoal choice, influencing both shoal size and composition. This work has implications for studies on information transfer and reciprocal altruism within populations.

Common degradative pathways of morpholine, thiomorpholine, and piperidine by Mycobacterium aurum MO1: evidence from (1)H-nuclear magnetic resonance and ionspray mass spectrometry performed directly on the incubation medium.

In order to see if the biodegradative pathways for morpholine and thiomorpholine during degradation by Mycobacterium aurum MO1 could be generalized to other heterocyclic compounds, the degradation of piperidine by this strain was investigated by performing (1)H-nuclear magnetic resonance directly with the incubation medium. Ionspray mass spectrometry, performed without purification of the samples, was also used to confirm the structure of some metabolites during morpholine and thiomorpholine degradation. The results obtained with these two techniques suggested a general pathway for degradation of nitrogen heterocyclic compounds by M. aurum MO1. The first step of the degradative pathway is cleavage of the C---N bond; this leads formation of an intermediary amino acid, which is followed by deamination and oxidation of this amino acid into a diacid. Except in the case of thiodiglycolate obtained from thiomorpholine degradation, the dicarboxylates are completely mineralized by the bacterial cells. A comparison with previously published data showed that this pathway could be a general pathway for degradation by other strains of members of the genus Mycobacterium.

Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns.

Lead poisoning induces hematological, gastrointestinal and neurological dysfunctions. One of the potential mechanisms is the inhibition of calcium-pump (Ca-pump), a transport protein. We investigated the effects of an environmental low lead exposure on Ca-pump activity in 247 mothers and their newborns. Maternal and cord blood, and newborn and mother hair, were sampled at delivery. Geometric means for mother and cord blood lead (Pb-B), and for mother and newborn hair lead (Pb-H), were 6.3 and 4.8 microg/dl, and 1.7 and 1.1 microg/g. Means for mother and cord basal Ca-pump activities were 2,442 and 2,675 nM/mg/hr. Mother enzymatic activity was negatively related to her Pb-B and Pb-H and to the cord Pb-B and newborn Pb-H levels. Newborn enzymatic activity was negatively related to his Pb-H level only. Adjustment for gestational age, child's sex, mother's age at delivery, alcohol, coffee and tea consumption, and smoking habits during pregnancy did not modify these relationships. Our findings support the hypothesis that lead toxicity could be in part mediated by a reduction of Ca-pump activity. This effect could be observed at low environmental exposure, in mothers and newborns.