Is excessive daytime sleepiness a separate manifestation in Parkinson's disease?

BACKGROUND: Excessive daytime sleepiness (EDS) is common in Parkinson's disease (PD), but its role and relation to other PD features is less well understood. OBJECTIVE: To investigate potential predictors of EDS in PD and to explore how EDS relates to other motor and non-motor PD features. METHODS: 118 consecutive persons with PD (54% men; mean age, 64) were assessed regarding EDS using the Epworth Sleepiness Scale (ESS) and a range of motor and non-motor symptoms. Variables significantly associated with ESS scores in bivariate analyses were used in multiple regression analyses with ESS scores as the dependent variable. Principal component analysis (PCA) was conducted to explore the interrelationships between ESS scores and other motor and non-motor PD aspects. RESULTS: Among 114 persons with complete ESS data, significant independent associations were found between ESS scores and axial/postural/gait impairment, depressive symptoms, and pain (R2, 0.199). ESS scores did not load significantly together with any other PD features in the PCA. CONCLUSIONS: Only a limited proportion of the variation in EDS could be accounted for by other symptoms, and EDS did not cluster together with any other PD features in PCAs. This suggests that EDS is a separate manifestation differing from, for example, poor sleep quality and fatigue.

The role of pleiotropy and linkage in genes affecting a sexual ornament and bone allocation in the chicken.

Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits.

The occupational contribution to severe exacerbation of asthma.

The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1-2.6) and high (RR 3.6, 95% CI 2.2-5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02-3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2-5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9-5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role.

Ethical dilemmas and ethical competence in the daily work of research nurses.

In spite of the growing interest in nursing ethics, few studies have focused on ethical dilemmas experienced by nurses working with clinical studies as 'research nurses'. The aim of the present study was to describe and explore ethical dilemmas that Swedish research nurses experience in their day-to-day work. In a qualitative study a purposeful sample of six research nurses from five wards of differing disciplines in four Swedish hospitals was interviewed. The analysis displayed several examples of ethical dilemmas, primarily tensions between the nurses' obligations to the study and to the patients involved. A guiding moral principle for the nurses was patient-centeredness, where the interest of research must not override the interest of the patient. In situations where tensions between research and patient interests occurred, and doctors and nurses disagreed upon the judgement, the nurses sometimes chose to follow the doctors' advice, and thus acted against their own moral judgment. Such situations seemed to create feelings of moral distress among the nurses. They described their profession as being 'invisible' and as lacking opportunities for ethical competence building. The conclusion is that research nurses frequently experience severe and difficult ethical dilemmas in their daily work. They need to be acknowledged as a particular profession in the health care organisation and encouraged to develop their specific ethical competence.

CREBBP and WDR 24 Identified as Candidate Genes for Quantitative Variation in Red-Brown Plumage Colouration in the Chicken.

Plumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signalling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilising a domestic × wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red-brown colouration in chickens. By treating colour as a quantitative rather than qualitative trait, we have identified both QTL and genes of small effect. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.

Knowledge of human papillomavirus and attitudes to vaccination among Swedish high school students.

The aim of the study was to investigate knowledge of and attitudes to sexually transmitted infection (STI) and STI prevention with special focus on human papillomavirus (HPV) and the new vaccine against HPV, among 16-year-old high school students in a Swedish context. A study-specific questionnaire was distributed to 572 first year high school students from five different high schools in a medium-sized town in Sweden. The students lacked knowledge of HPV and its association with cervical cancer. Similarly, their knowledge of the new vaccine was limited. Their attitude to condom use when having sex with a new partner was positive, but decreased if oral contraceptives were used and if they were vaccinated against an STI. The main source of information was the school, followed by youth clinics and the media. The results highlight the clinical importance for school nurses and personnel at youth clinics to inform adolescents about HPV and its association with cancer.

Exploring research participants' perceptions of cardiovascular risk information-Room for improvement and empowerment.

OBJECTIVE: The objective of this study was to explore research participants' (adults, age 50-65) perceptions of receiving cardiovascular risk information. METHODS: Five focus group interviews (N = 31) were performed with research participants aged 50-65 who participated in the Swedish CArdioPulmonary BioImage Study (SCAPIS). The interviews were analyzed using qualitative content analysis. RESULTS: The categories; the complexity of cardiovascular risk; insufficient presentation of test result; emotional responses; and health examinations provides confirmation, emerged. The test results were written in medical terms and lacked recommendations for further action which made it difficult for lay people to understand and use, and for some, also caused unnecessary worry. CONCLUSION: There was inadequate guidance concerning the implications of the test results, especially for participants without clinical findings. In order to allow research participants to obtain better cognitive and behavioral control, improvements are needed with regard to how personal risk information is communicated in research projects connected to health services. PRACTICAL IMPLICATIONS: The participants largely relied on physical signs when assessing their own cardiovascular risk. Health examinations are crucial for helping to add nuance to individuals' risk perceptions. For personal health information to have any real value for individuals, it must be designed from a user perspective.

The effect of ketamine on intraspinal acetylcholine release: involvement of spinal nicotinic receptors.

The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine release. Microdialysis probes were placed intraspinally in male rats, and acetylcholine was quantified with HPLC. Anaesthesia was switched from isoflurane (1.3%) to ketamine (150 mg/kg h), which resulted in a 500% increased acetylcholine release. The increase was attenuated during nicotinic receptor blockade (50 microM mecamylamine). The nicotinic receptor agonist epibatidine (175 microM) produced a ten-fold higher relative increase of acetylcholine release during isoflurane anaesthesia compared to ketamine anaesthesia (270% to 27%). Intraspinal administration of ketamine and norketamine both increased the acetylcholine release in high concentrations (100 microM to 10 mM). The results indicate that spinal nicotinic receptors are important for the ketamine-induced acetylcholine release, and that the effect is partly mediated at the spinal level.

Swedish healthcare providers' perceptions of preconception expanded carrier screening (ECS)-a qualitative study.

Reproductive autonomy, medicalization, and discrimination against disabled and parental responsibility are the main ongoing ethical debates concerning reproductive genetic screening. To examine Swedish healthcare professionals' views on preconception expanded carrier screening (ECS), a qualitative study involving academic and clinical institutions in Sweden was conducted in September 2014 to February 2015. Eleven healthcare professionals including clinicians, geneticists, a midwife, and a genetic counselor were interviewed in depth using a semi-structured interview guide. The questionnaire was constructed after reviewing the main literature and meetings with relevant healthcare providers. The interviews were recorded, transcribed verbatim, and content analyzed for categories and subcategories. Participants nurtured many ethical and non-ethical concerns regarding preconception ECS. Among the ethical concerns were the potential for discrimination, medicalization, concerns with prioritization of healthcare resources, and effects on reproductive freedom. The effects of implementation of preconception ECS, its stakeholders, regulations, and motivation are some of non-ethical concerns. These concerns, if not addressed, may affect the uptake and usage of carrier screening within Swedish healthcare system. As this is a qualitative study with a small non-random sample size, the findings cannot be generalized. The participants had little to no working experience with expanded screening panels. Moreover, the interviews were conducted in English, a second language for the participants, which might have limited the expression of their views. However, the authors claim that the findings may be pertinent to similar settings in other Scandinavian countries.

Evidence for several gamma-carboxyglutamic acid-containing proteins in dentin.

With anion-exchange chromatography, the gamma-carboxyglutamic acid (Gla)-containing proteins of rat dentin were separated into four closely related fractions (gamma 1-gamma 4). Edman degradation of gamma 2 gave two NH2-terminal sequences with a minor sequence beginning five residues shorter than the major one. Gel electrophoresis of gamma 2 yielded one major and one minor protein band. Fraction gamma 3 gave one band on gel electrophoresis and a single NH2-terminal sequence. The composition of gamma 4 suggested that, compared to gamma 2 and gamma 3, a portion of the COOH-terminal was missing. Thus some of the heterogeneity of rat dentin Gla-containing proteins can be explained by shortened ends.

Preparation and evaluation of (68)Ga-DOTA-hEGF for visualization of EGFR expression in malignant tumors.

UNLABELLED: Detection of epidermal growth factor receptor (EGFR) overexpression in many carcinomas provides important diagnostic information, which can influence patient management. The use of PET may enable such detection in vivo by a noninvasive procedure with high sensitivity. The aim of this study was to develop a method for preparation of a positron-emitting tracer based on a natural ligand to EGFR, the recombinant human epidermal growth factor (hEGF), and to perform a preclinical evaluation of the tracer. METHODS: DOTA-hEGF (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was prepared by coupling of a N-sulfosuccinimide ester of DOTA to hEGF. The conjugate was labeled with a generator-produced positron-emitting nuclide, (68)Ga (half-life = 68 min), using microwave heating. Binding specificity, affinity, internalization, and retention of (68)Ga-DOTA-hEGF was studied in 2 EGFR-expressing cell lines, U343 glioma cells and A431 cervical carcinoma cells. Biodistribution and microPET visualization studies were performed in BALB/c nu/nu mice bearing A431 carcinoma xenografts. RESULTS: A 1-min-long microwave-assisted labeling provided radioactivity incorporation of 77% +/- 4%. Both cell lines demonstrated receptor-specific uptake of the conjugate, rapid internalization of the tracer, and good retention of radioactivity. Binding to both cell lines occurred with high affinity, approximately 2 nmol/L. The biodistribution study demonstrated accumulation of radioactivity in xenografts and in EGFR-expressing organs. The microPET imaging study enabled visualization of tumors and demonstrated quick--within 5 min--localization of radioactivity in tumors. CONCLUSION: (68)Ga-DOTA-hEGF has potential for imaging EGFR overexpression in tumors.

Involvement of spinal GABA receptors in the regulation of intraspinal acetylcholine release.

It has been shown that analgesics such as morphine, lidocaine and clonidine increase the release of spinal acetylcholine. Acetylcholine may therefore play an important role in the regulation of spinal pain threshold. Since behavioral as well as in vitro studies have shown a clear involvement of GABA (gamma-amino butyric acid) receptors in the regulation of spinal nociceptive mechanisms, the present study focused on the role of GABA receptors for spinal acetylcholine release control. GABA receptor agonists and antagonists were infused via a spinal microdialysis probe and acetylcholine release was measured. The GABA(A) receptor agonist muscimol decreased acetylcholine release and the antagonist bicuculline increased acetylcholine release. The GABA(B) receptor agonist baclofen decreased acetylcholine release whereas the antagonist saclofen did not change acetylcholine release. The results suggest that both GABA receptor subtypes have an inhibitory role on spinal dorsal horn acetylcholine release and that the GABA(A) receptors are tonically regulating acetylcholine release.

Involvement of spinal serotonin receptors in the regulation of intraspinal acetylcholine release.

Stimulation of spinal serotonin (5-HT) receptors results in analgesia and release of acetylcholine. We investigated the involvement of 5-HT1, 5-HT2, and 5-HT3 receptor subtypes in the regulation of spinal acetylcholine release. A spinal microdialysis probe was placed dorsally at about the C5 level in anaesthetized rats. The selective serotonin reuptake inhibitor citalopram was found to increase acetylcholine release when infused via the microdialysis probe. Several doses of the 5-HT receptor agonists 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT, 5-HT1A), 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one dihydrochloride (CP93129, 5-HT1B), alpha-methyl-5-hydroxytryptamine maleate (m5-HT, 5-HT2), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 5-HT2C), and 1-(m-chlorophenyl)-biguanide (5-HT3) were subsequently infused via the microdialysis probe. Only 8-OH-DPAT, CP93129, and m5-HT increased acetylcholine release dose dependently. The 5-HT1A receptor selective antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide hydrochloride and the 5-HT2A receptor selective antagonist ketanserin tartrate inhibited the 8-OH-DPAT and the m5-HT induced acetylcholine release. The results suggest that 5-HT1A and the 5-HT2A receptors are involved in the regulation of acetylcholine release in the spinal cord.

Potential of [11C]DASB for measuring endogenous serotonin with PET: binding studies.

The serotonin transporter radioligand [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, or [11C]DASB, was examined in order to assess its potential for measuring fluctuations in endogenous serotonin concentrations with positron emission tomography. Binding characteristics of [11C]DASB and the propensity for serotonin to displace the tracer were explored in rat brain homogenates. Experiments showed that serotonin displaced [11C]DASB in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15 mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that serotonin may compete with [11C]DASB for transporter binding.

Occupational exposures associated with severe exacerbation of asthma.

BACKGROUND: The exacerbation of asthma by workplace conditions is common, but little is known about which agents pose a risk. OBJECTIVE: We used data from an existing survey of adults with asthma to identify occupational exposures associated with severe exacerbation of asthma. DESIGN: Questionnaires were completed by 557 working adults with asthma. Severe exacerbation of asthma in the past 12 months was defined as asthma-related hospitalization, or reports of both unplanned asthma care and treatment with a short course of oral corticosteroids. Occupational exposures for the same time period were assessed using an asthma-specific job exposure matrix. We modeled severe exacerbation to yield prevalence ratios (PRs) for exposures while controlling for potential confounders. RESULTS: A total of 164 participants (29%) were positive for severe exacerbation, and 227 (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs were observed for several specific agents, notably the irritant subcategories of environmental tobacco smoke (PR 1.84, 95%CI 1.34-2.51) among all participants, inorganic dusts (PR 2.53, 95%CI 1.37-4.67) among men, and the low molecular weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08-3.60) among women. CONCLUSION: Among working adults with asthma, severe exacerbation was associated with several occupational agents.

On the ultrastructural organization of the microfilament system and the possible role of profilactin.

This paper summarizes results of studies on human glia cells concerning the ultrastructural relationships in the microfilament system and the possible role of the profilactin complex. It presents electron micrographs of the leading lamella of cells grown on solid substratum, visualizing the organization of the microfilament system in this highly motile part of the cell at high resolution and at what appears to be a high level of preservation. These results are linked to observations made in our laboratory of the biochemical basis for the dramatic rearrangements occurring in platelets in response to thrombin stimulation. Taken together these results lead to a relatively detailed model for the mechanism of cell motility.

The long-term effects of 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) on copulatory and exploratory behaviour in male rats.

The long-term effects of low doses of the 5-HT1A-agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied to assess differences in the development of subsensitivity in 8-OH-DPAT-induced behavioural responses. Male rats received 33 or 100 micrograms/kg per day s.c. for 8 or 15 days. The chronic treatment did not alter the facilitatory effects of 8-OH-DPAT on male copulatory behaviour. In contrast, the effects on exploratory activity and the induction of flat body posture observed after the acute treatment were attenuated by prolonged administration of 8-OH-DPAT. The results presented indicate that gonadal hormones are involved in 5-HT receptor regulatory mechanisms.

Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats.

The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced by systemically administered lidocaine is mediated through an action on muscarinic and nicotinic receptors.

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats.

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg/kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin, but not by paracetamol.

Effects of lysine-vasopressin in an exploratory behaviour test situation.

Changes in the exploratory behaviour pattern in rats were studied over a period of eight weeks. Certain characteristics emerged during repeated exposure to the same environment. The activity of "investigating" behaviour increased, while rearing activity decreased. We suggest that these changes reflect habituation by the animal to the test situation. Administration of lysine-vasopressin (LVP; 5.0 micrograms/kg SC) resulted in some alterations of the exploratory behaviour pattern, but no other behaviours than those observed without drug treatment were seen. The administration of LVP resulted in a higher performance of "investigating" behaviour. Since the change in the exploratory behaviour pattern after LVP administration was similar to that during repeated exposure to the test situation, we conclude that the LVP treatment influenced processes of habituation.