Pleiotropic effects of statins: do they matter?

Treatment with the 3-hydroxy-3-methylglutaryl coenyzme A reductase inhibitors (or statins) reduces the risk for cardiovascular events across a broad spectrum of patient profiles, as evidenced by both primary prevention and secondary prevention trials. Improved survival by way of reduced deaths from coronary heart disease was also reported with these agents, which are primarily indicated for substantial reduction in LDL-cholesterol levels. However, the statins are extremely complex drugs and exhibit a wide variety of vascular effects that may or may not be dependent on their lipid-modifying properties. These so-called pleiotropic effects include alterations of endothelial function, inflammation, coagulation, and plaque stability. The relative contribution of the nonlipid effects of statin therapy to the well-documented clinical benefits is currently under intense investigation.     

Fertility intentions and subsequent fertility behaviour in Matlab: do fertility intentions matter?

This study examines the extent of the interrelationship between future fertility intention and subsequent fertility behaviour in rural Bangladesh using longitudinal data. It confirms that fertility intention is an important predictor of subsequent fertility behaviour for rural Bangladeshi women. Women wanting no more children are over three times less likely to have a child during a 5-year follow-up than those wanting more children. A multivariate model using logistic regression shows that fertility intention is a useful indicator for fertility behaviour, when background and life-cycle variables are controlled. The different patterns of fertility intentions by socioeconomic and demographic subgroups suggest that different programme strategies should be designed for specific target groups.     

Trade-offs and the evolution of virulence of microparasites: do details matter?

Models of the within-host dynamics of parasites have been used to consider the evolution of microparasites causing acute infections in vertebrate hosts. In this paper, we use these models to examine how the level of virulence to which a parasite evolves, depends on factors such as the relationship between parasite density and its rate of transmission from infected hosts, and the mechanism of parasite-induced pathogenesis. We show that changes in the terms describing transmissibility and pathogenesis may lead to dramatic differences in the level of virulence to which a parasite evolves. This suggests that no single factor is likely to be responsible for the differences in virulence of different parasites, and that understanding of the evolution of virulence of parasites will require a detailed quantitative understanding of the interaction between the parasite and its host.     

Covariates of child mortality in Mali: does the health-seeking behaviour of the mother matter?

This paper uses data from the 1995/96 Mali DHS survey to examine the importance of a wide range of socioeconomic, behavioural and biodemographic factors in the determination of child mortality in Mali, with a special focus on maternal education and behaviour. The central hypothesis of the study is that advances in maternal education would contribute little to child survival in settings such as Mali's urban and rural communities where progress in educational attainment is not matched with improvements in other aspects of socioeconomic development such as economic growth, job creation, financial security and public health and medical resources. Units of analysis are children born in the past 5 years to DHS respondents (women aged 15-45) who were married at the time of the survey. The Cox proportional hazards regression technique has been used to estimate the net effects of variables included as covariates. The findings indicate that the health-seeking behaviour of the mother matters more than maternal education in explaining the observed differences in infant and child mortality in Mali's urban and rural areas.     

Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia?

The high affinity of antipsychotic drugs for the dopamine D2 receptor focused attention onto the role of these receptors in the genesis of psychoses and the pathology of schizophrenia. However, psychotic symptoms are only one aspect of the complex symptom profile associated with schizophrenia. Therefore, research continues into other neurochemical systems and their potential roles in key features associated with schizophrenia. Modulating the cholinergic system in attempts to treat schizophrenia predates specific neurochemical hypotheses of the disorder. Cholinergic modulation has progressed from the use of coma therapy, through the use of anti-cholinergic drugs to control side-effects of older (typical) antipsychotic medications, to the development of drugs designed to specifically activate selected muscarinic receptors. This review presents data implicating a decrease in muscarinic receptors, particularly the M1 receptor, in the pathology of schizophrenia and explores the potential physiological consequences of such a change, drawing on data available from muscarinic receptor knockout mice as well as clinical and pre-clinical pharmacology. The body of evidence presented suggests that deficits in muscarinic receptors are associated with some forms of schizophrenia and that targeting these receptors could prove to be of therapeutic benefit to patients with the disorder.     

Validity and reliability of a self-reported measure of medication adherence in patients with Type 2 diabetes mellitus in Singapore

Diabet. Med. 29, e338-e344 (2012) ABSTRACT: Aims A reliable and valid measure is essential for the assessment of medication adherence. Until now, no patient-reported medication adherence measure has been validated in Singapore. The aim of this study was to validate a modified 4-item Morisky-Green-Levine Medication Adherence Scale in patients with Type?2 diabetes in Singapore. Methods A cross-sectional survey was conducted in a sample of outpatients with Type?2 diabetes in Singapore from September to December in 2009. Respondents completed either an English or Chinese version of the modified 4-item Morisky-Green-Levine Medication Adherence Scale. The scale scores ranged from 0 to 4, with higher scores indicating better medication adherence. Reliability was assessed using Cronbach's alpha. Content validity was assessed by expert review. Construct validity was examined using factor analysis and hypothesis testing. Results Of the 294 respondents who completed the modified Morisky-Green-Levine Medication Adherence Scale, 13.3, 21.4, 35.7 and 29.6% had a score of 0-1, 2, 3 and 4, respectively. The internal consistency of the scale was moderate (Cronbach's alpha?=?0.62). Principal component analysis showed that the four items loaded onto one factor (eigenvalue?=?1.95). Respondents with higher scores were older (P?相似文献   

The timing of hibernation in Tasmanian echidnas: why do they do it when they do?

We investigated the patterns of hibernation and arousals in seven free-ranging echidnas Tachyglossus aculeatus setosus (two male, five female) in Tasmania using implanted temperature data loggers. All echidnas showed a ‘classical’ pattern of mammalian hibernation, with bouts of deep torpor interrupted by periodic arousals to euthermia (mean duration 1.04±0.05 (n=146). Torpor bout length increased as body temperature fell during the hibernation season, and became more variable as temperature rose again. Hibernation started in late summer (February 28±5 days, n=6) and males aroused just before the winter solstice (June 15±3 days, n=3), females that subsequently produced young aroused 40 days later (July 25±3, n=4) while females that did not produce young hibernated for a further two months (arousal Sept 27±5, n=7). We suggest that hibernation in Tasmanian echidnas can be divided into two phases, the first phase, marked by declining minimum body temperatures as ambient temperature falls, appears to be obligatory for all animals, while the second phase is ‘optional’ and is utilised to varying amounts by females. We suggest that early arousal and breeding is the favoured option for females in good condition, and that the ability to completely omit breeding in some years, and hibernate through to spring is an adaptation to an uncertain climate.     

Mechanosensitive channels: what can they do and how do they do it?

While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.     

Nurse practitioners in accident and emergency departments: what do they do?

OBJECTIVE--To determine the distribution and scope of nurse practitioner schemes in accident and emergency departments in England and Wales; to describe the caseloads of doctors and nurse practitioners on two representative days; and to estimate the number of patients managed by nurse practitioners in the year to 31 March 1991. DESIGN--A postal survey of accident and emergency departments and a content analysis of case notes of new patients attending a representative sample of accident and emergency departments on two days. SETTING--All accident and emergency departments in England and Wales. PARTICIPANTS--Survey: 560 nurses in charge of accident and emergency departments. Census: case notes of 5814 patients in 37 accident and emergency departments. MAIN OUTCOME MEASURES--Survey: number of accident and emergency departments with nurse practitioner schemes. Census: demographic and clinical characteristics of new patients attending and whether nurse practitioner or doctor made diagnoses and ordered investigations, treatments, referrals, discharges. RESULTS--513 replies (92%) from 465 surveyed functioning accident and emergency departments and 48 departments recently closed. 27 (6%) departments used designated nurse practitioners and 159 (34%) "unofficial" nurse practitioners. Only 530 (9%) of the 5814 patients in the census were managed entirely or mainly by nurse practitioners, with higher proportions in ophthalmic departments (nearly 30%) and minor casualty departments (over 40%) than in major departments (3%). Most patients managed by nurse practitioners (86%) had minor trauma. In the year ending 31 March 1991 an estimated 390,000 (95% confidence interval 260,000 to 520,000) patients out of a total of 12.5 million (3.1%, 2.1% to 4.1%) were clinically managed by a nurse practitioner. CONCLUSIONS--Designated nurse practitioner schemes are rare. The volume and range of nurse practitioner work in major general accident and emergency departments is small compared with those in specialised and minor accident and emergency departments.     

State of the Art: Why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?

Background

Pollens are important triggers for allergic asthma and seasonal rhinitis, and proteases released by major allergenic pollens can injure airway epithelial cells in vitro. Disruption of mucosal epithelial integrity by proteases released by inhaled pollens could promote allergic sensitisation.

Methods

Pollen diffusates from Kentucky blue grass (Poa pratensis), rye grass (Lolium perenne) and Bermuda grass (Cynodon dactylon) were assessed for peptidase activity using a fluorogenic substrate, as well as by gelatin zymography. Following one- or two-dimensional gel electrophoresis, Coomassie-stained individual bands/spots were excised, subjected to tryptic digestion and analysed by mass spectrometry, either MALDI reflectron TOF or microcapillary liquid chromatography MS-MS. Database searches were used to identify allergens and other plant proteins in pollen diffusates.

Results

All pollen diffusates tested exhibited peptidase activity. Gelatin zymography revealed high M_r proteolytic activity at ~ 95,000 in all diffusates and additional proteolytic bands in rye and Bermuda grass diffusates, which appeared to be serine proteases on the basis of inhibition studies. A proteolytic band at M_r ~ 35,000 in Bermuda grass diffusate, which corresponded to an intense band detected by Western blotting using a monoclonal antibody to the timothy grass (Phleum pratense) group 1 allergen Phl p 1, was identified by mass spectrometric analysis as the group 1 allergen Cyn d 1. Two-dimensional analysis similarly demonstrated proteolytic activity corresponding to protein spots identified as Cyn d 1.

Conclusion

One- and two-dimensional electrophoretic separation, combined with analysis by mass spectrometry, is useful for rapid determination of the identities of pollen proteins. A component of the proteolytic activity in Bermuda grass diffusate is likely to be related to the allergen Cyn d 1.     

Elderly patients in a general surgical unit: do they block beds?

In a prospective study of patients aged 65 years and over admitted to a general surgical unit only one patient in 10 remained in hospital for more than a month and fewer than one patient in a hundred became a "bed-blocker." While the over-65s had mean and median durations of stay which were longer than those of younger patients, in almost all cases a prolonged stay in hospital resulted from postoperative morbidity and was not related to social or administrative factors. Only a reduction in the incidence of postoperative morbidity could achieve a significant saving in the number of bed-days occupied by elderly people.     

Fledging success of little auks in the high Arctic: do provisioning rates and the quality of foraging grounds matter?

Long-lived birds often face a dilemma between self-maintenance and reproduction. In order to maximize fitness, some seabird parents alternate short trips to collect food for offspring with long trips for self-feeding (bimodal foraging strategy). In this study, we examined whether temporal and spatial variation in the quality of foraging grounds affect provisioning and fledging success of a long-lived, bimodal forager, the little auk (Alle alle), the most abundant seabird species in the Arctic ecosystem. We predicted that an increase in sea surface temperature (SST), with an associated decrease in the preferred Arctic zooplankton prey, would increase foraging trip durations, decrease chick provisioning rates and decrease chick fledging success. Chick provisioning and survival were observed during three consecutive years (2008–2010) at two colonies with variable foraging conditions in Spitsbergen: Isfjorden and Magdalenefjorden. We found that a change in SST (range 1.6–5.4 °C) did not influence trip durations or provisioning rates. SST was, however, negatively correlated with the number of prey items delivered to a chick. Furthermore, provisioning rates did not influence chick’s probability to fledge; instead, SST was also negatively correlated with fledging probability. This was likely related to the prey availability and quality in the little auk’s foraging grounds. Our findings suggest that predicted warmer climate in the Arctic will negatively influence the ability of parents to provide their chicks, and consequently, the fledging prospects of little auk chicks.