Optical biosensor differentiates signaling of endogenous PAR<Subscript>1</Subscript> and PAR<Subscript>2</Subscript> in A431 cells

Background  

Protease activated receptors (PARs) consist of a family of four G protein-coupled receptors. Many types of cells express several PARs, whose physiological significance is mostly unknown.     

The impact of operative approach on outcome of surgery for gastro-oesophageal tumours

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.     

Effect of retirement on alcohol consumption: longitudinal evidence from the French Gazel cohort study

Background

Little is known about the effect of retirement on alcohol consumption. The objectives were to examine changes in alcohol consumption following retirement, and whether these patterns differ by gender and socioeconomic status.

Methods and Findings

We assessed alcohol consumption annually from 5 years before to 5 years after retirement among 10,023 men and 2,361 women of the French Gazel study. Data were analyzed separately for men and women, using repeated-measures logistic regression analysis with generalized estimating equations. Five years prior to retirement, the prevalence of heavy drinking was about 16% among men, and not patterned by socioeconomic status. Among women, this prevalence was 19.5% in managers, 14.7% in intermediate occupations, and 12.8% in clerical workers. Around retirement, the estimated prevalence of heavy drinking increased in both sexes. In men, this increase was 3.1 percentage points for managers, 3.2 in intermediate occupations, 4.6 in clerical workers, and 1.3 in manual workers. In women, this increase was 6.6 percentage points among managers, 4.3 in intermediate occupations, and 3.3 among clerical workers. In men the increase around retirement was followed by a decrease over the following four years, not significant among manual workers; among women such a decrease was also observed in the non-managerial occupations. It is difficult to assess the extent to which the results observed in this cohort would hold for other working populations, other conditions of employment, or in other cultural settings. A plausible explanation for the increase in heavy drinking around retirement could be that increased leisure time after retirement provides more opportunities for drinking, and not having to work during the day after may decrease constraints on drinking.

Conclusions

Our findings of increased consumption around retirement suggest that information about negative effects of alcohol consumption should be included in pre-retirement planning programs.     

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Methods/Design

A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.

Discussion

The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.

Trial registration

Dutch Trial Register, NTR1447.

     

The social, economic, and environmental contributions of Pan African Sanctuary Alliance primate sanctuaries in Africa

Over the last few decades, primate sanctuaries have become more numerous, particularly in Africa. Sanctuaries play an obvious and vital role in the battle against the illegal trade in wildlife and provide opportunities for local people to learn about the importance of protecting habitat and laws governing wildlife trade. Given the multi-disciplinary role of sanctuaries, the Pan African Sanctuary Alliance provides mechanisms to exchange best practices and establishes links to other conservation partners. In April 2011, the managers of the 22 Pan African Sanctuary Alliance members were surveyed in order to collect detailed information on the conservation activities of each sanctuary. The majority of the 22 sanctuaries conducted both on- and off-site education activities, engaging more than 429,000 people in education activities per year. Sanctuaries reported that they provided employment for over 550 local community members across Africa, as well as resources for community education and infrastructure, with an economic impact over $3 million per year. Sanctuaries were also involved in activities that promote law enforcement and believed that the activities they supported have led to better protection of primate habitats. The results of the survey demonstrate that sanctuaries have moved towards supporting and implementing community development activities aimed at poverty reduction, while conducting conservation activities. While Pan African Sanctuary Alliance sanctuaries were initially established to provide care and housing for orphaned, confiscated and displaced primates, this paper demonstrates how sanctuaries have combined ex-situ with in-situ initiatives to support social, economic, and environmental progress in primate range countries in Africa.     

Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]

Background  

Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I.     

Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene.

The amplification refractory mutation system (ARMS) is a simple, rapid and reliable method for the detection of any mutation involving single base changes or small deletions. We have applied ARMS methodology to the detection of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Single ARMS tests have been developed for 11 CFTR mutations found in the northwest of England. ARMS reactions for the most common mutations have been multiplexed to give a test which will detect the presence of the delta F508, G551D, G542X, and 621 + 1G----T mutations in a DNA sample. The multiplex test has been validated by the analysis of over 500 previously genotyped samples and has been found to be completely accurate. The rapid detection of the most common mutations has enabled early molecular confirmation of suspected cystic fibrosis in neonates, rapid typing of cystic fibrosis patients and their relatives, and testing of sperm and egg donors.     

The Joint Effect of Sleep Duration and Disturbed Sleep on Cause-Specific Mortality: Results from the Whitehall II Cohort Study

Background

Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study.

Methods

We included 9,098 men and women free of pre-existing disease from the Whitehall II study, UK. Sleep measures were self-reported at baseline (1985–1988). Participants were followed until 2010 in a nationwide death register for total and cause-specific (cardiovascular disease, cancer and other) mortality.

Results

There were 804 deaths over a mean 22 year follow-up period. In men, short sleep (≤6 hrs/night) and disturbed sleep were not independently associated with CVD mortality, but there was an indication of higher risk among men who experienced both (HR = 1.57; 95% CI: 0.96–2.58). In women, short sleep and disturbed sleep were independently associated with CVD mortality, and women with both short and disturbed sleep experienced a much higher risk of CVD mortality (3.19; 1.52–6.72) compared to those who slept 7–8 hours with no sleep disturbances; equivalent to approximately 90 additional deaths per 100,000 person years. Sleep was not associated with death due to cancer or other causes.

Conclusion

Both short sleep and disturbed sleep are independent risk factors for CVD mortality in women and future studies on sleep may benefit from assessing disturbed sleep in addition to sleep duration in order to capture health-relevant features of inadequate sleep.