Vitamin D and UV exposure in construction workers-a randomized control trial using text messaging to promote positive behaviours.

BACKGROUND: The aim of this study was to determine whether a text messaging intervention (supported by a smartphone application) would be effective in the promotion of sun-safe behaviours. Both excessive and insufficient exposure to ultra-violet (UV) radiation were considered. METHODS: A randomized control crossover trial was conducted. 112 participants from nine sites in the United Kingdom contributed to the study. There were three intervention waves, two in winter (Vitamin D-focussed) and one in summer (UV exposure-focussed). Stages of Change, Standard Erythemal (UV) Dose and assayed blood samples (Vitamin D) were employed to evaluate the effectiveness throughout the 21-day data collection periods. RESULTS: The intervention was effective in promoting positive progression in Stages of Change for Vitamin D; and this in turn was predictive of increased Vitamin D levels in participants. More limited positive findings were found with respect to UV exposure. Overall, for those in the Intervention, Vitamin D levels were significantly predicted to increase during both of the winter data collection waves. CONCLUSIONS: Interventions of this type are recommended to promote healthy Vitamin-D levels in construction workers.

Feasibility and acceptability of introducing routine antenatal contraceptive counselling and provision of contraception after delivery: the APPLES pilot evaluation.

OBJECTIVE: To determine the feasibility and acceptability of routine antenatal contraceptive counselling and contraception provision including long-acting reversible contraception (LARC) postpartum. DESIGN: Health service research evaluation. SETTING: Community antenatal clinics and hospital maternity settings in National Health Service, Scotland UK. POPULATION: Women booked for antenatal care. METHODS: Contraceptive counselling with a community midwife (22 weeks' gestation) and provision of contraception (with facilitated access to LARC methods) prior to discharge from maternity hospital. Evaluation consisted of (i) self administered questionnaire (32-34 weeks) of women's views of antenatal contraceptive counselling, (ii) database review of contraceptive methods provided at discharge, and (iii) focus groups with midwives and obstetricians. MAIN OUTCOME MEASURES: Women's views on antenatal contraceptive counselling. Secondary outcomes included (i) uptake of LARC methods and (ii) barriers and facilitators to providing antenatal counselling and contraception. RESULTS: There were 1369 women in the cohort. Questionnaires were distributed to 1064 women (78%) and completed by 794 (75%). In all, 78% of respondents (n = 621) discussed contraception antenatally with a community midwife and 74% (n = 461) found this helpful. Although 43% of respondents (n = 341) were planning to use LARC, only 9% of the cohort (118 of 1369) received LARC prior to discharge. Community midwives indicated that antenatal contraceptive counselling was now embedded in their role, but hospital staff indicated that workloads impacted upon ability to provide contraception for women. CONCLUSIONS: Antenatal contraceptive counselling, delivered by community midwives, is feasible and highly acceptable to women. However, providing contraception and LARC for women before they are discharged home remains a challenge. TWEETABLE ABSTRACT: Giving contraceptive advice antenatally is feasible and acceptable.

Can local muscles augment stability in the hip? A narrative literature review.

Hip pain and dysfunction are increasingly recognised as important causes of morbidity in younger and older adults. Pathology compromising the passive stability of the hip joint, including acetabular labral injury, may lead to increased femoral head translation, greater joint contact pressures and ultimately degenerative hip disease. Activation of hip muscles may play an important role in augmenting the stability in the normal and the passively unstable hip. Research at other joints suggests that the local, rather than global, muscles are well suited to provide subtle joint compression, limiting translation, with minimal metabolic cost. Based on the known characteristics of local muscles and the limited research available on hip muscles, it is proposed that the local hip muscles; quadratus femoris, gluteus minimus, gemelli, obturator internus and externus, iliocapsularis and the deep fibres of iliopsoas, may be primary stabilisers of the hip joint. Interventions aimed at restoring isolated neuromuscular function of the primary hip stabilisers may be considered when treating people with passive hip instability prior to commencing global muscle rehabilitation. Finally, further research is needed to investigate the potential association between function of the hip muscles (including muscles likely to have a role in stabilising the hip) and hip pathology affecting hip stability such as acetabular labral lesions.

Hepatitis B prevalence in Denmark - an estimate based on nationwide registers and a national screening programme, as on 31 December 2007.

The prevalence of chronic hepatitis B virus (HBV) infection in Denmark is not clear. The primary aim of this study was to estimate the prevalence of chronic HBV infection in Denmark. The capture­recapture method was used to estimate the total population diagnosed with chronic HBV infection in Denmark using four nationwide registers. The population with undiagnosed chronic HBV infection was estimated by incorporating data from a two-year nationwide HBsAg screening programme in pregnant women. We identified 4,466 individuals with chronic HBV infection in the four registers until the end of 2007, and the capture­recapture estimate of the total population diagnosed with chronic hepatitis B was 7,112 (95% confidence interval (CI): 6,953­10,747). Only 17% of the identified patients attended recommended clinical care according to national guidelines. Including undiagnosed patients, the current population alive with HBV infection was 10,668 (95% CI: 10,224­16,164), corresponding to a prevalence of 0.24% (95% CI: 0.23­0.37%) in the Danish population older than 15 years. The estimated prevalence of chronic HBV infection among adults in Denmark was lower than reported from other northern European countries. Only half of the infected population had been diagnosed, and a minority attended specialised clinical care.

Successful management of bleeding complications in patients supported with extracorporeal membrane oxygenation with primary respiratory failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure in patients with severe respiratory insufficiency failing conventional support. Bleeding complications are common due to the necessity for anticoagulation and circuit-related factors. METHODS: A retrospective review was conducted in patients requiring ECMO for respiratory failure from 7/2010 to 6/2011 to identify episodes of major bleeding, bleeding management and outcomes. RESULTS: Twenty-one patients were supported with ECMO during the study although five experienced massive bleeding related to chest tube insertion, jejunal arterio-venous malformations, distal perfusion cannula dislodgement and ventricular rupture. Patients required aggressive resuscitation or endoscopic or operative intervention, totaling 28 procedures. There were no instances of dehiscence, infection or sepsis related to interventions. Anticoagulation was stopped six hours before and restarted 24 hours after major interventions, with no thrombotic or neurologic complications. All patients weaned off ECMO were discharged. CONCLUSIONS: ECMO bleeding complications can be managed successfully via surgical and endoscopic approaches in this high-risk population.

Description and analysis of 12 years of surveillance for Creutzfeldt-Jakob disease in Denmark, 1997 to 2008.

Prospective surveillance of Creutzfeldt­Jakob disease (CJD) was initiated in Denmark in 1997, following the observation of variant CJD in the United Kingdom. Demographic, clinical and diagnostic information was collected for each patient with clinical suspicion of CJD. Here we describe the methods for surveillance and the observed outcomes between 1 January 1997 and 31 December 2008. A total of 83 patients were classified as sporadic CJD, 47 were definite diagnoses, 34 probable and two possible. This resulted in a mean incidence of 1.26 patients with probable and definite sporadic CJD per million inhabitants. Two sporadic CJD patients were found to have a genetic variant of unknown significance: Thr201Ser and Glu200Asp. One patient was diagnosed with Gerstmann-Sträussler-Scheinker syndrome. No patients were classified as having variant, iatrogenic or familial CJD. The Danish surveillance system, like those in other countries, has a multidisciplinary approach, which is labour-intensive and time-consuming but ensures the most complete set of information possible. With this approach we think that patients with variant CJD would have been detected had they occurred in Denmark. Certain aspects of CJD surveillance need further discussion at European level and beyond, in order to find a balance between efficiency of the systems and accuracy of surveillance data.

Interferon gamma signaling alters the function of T helper type 1 cells.

One mechanism regulating the ability of different subsets of T helper (Th) cells to respond to cytokines is the differential expression of cytokine receptors. For example, Th2 cells express both chains of the interferon gamma receptor (IFN-gammaR), whereas Th1 cells do not express the second chain of the IFN-gammaR (IFN-gammaR2) and are therefore unresponsive to IFN-gamma. To determine whether the regulation of IFN-gammaR2 expression, and therefore IFN-gamma responsiveness, is important for the differentiation of naive CD4(+) T cells into Th1 cells or for Th1 effector function, we generated mice in which transgenic (TG) expression of IFN-gammaR2 is controlled by the CD2 promoter and enhancer. CD4(+) T cells from IFN-gammaR2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice also display several defects in Th1-dependent immunity in vivo, including attenuated delayed-type hypersensitivity responses and decreased antigen-specific IFN-gamma production. In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates. Together, these data suggest that the sustained expression of IFN-gammaR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-gamma-unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.

Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function.

There are conflicting views on whether collagen X is a purely structural molecule, or regulates bone mineralization during endochondral ossification. Mutations in the human collagen alpha1 (X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen alpha1 (X) gene (Col10a1) null mutants were previously reported to show no obvious phenotypic change. We have generated collagen X deficient mice, which shows that deficiency does have phenotypic consequences which partly resemble SMCD, such as abnormal trabecular bone architecture. In particular, the mutant mice develop coxa vara, a phenotypic change common in human SMCD. Other consequences of the mutation are reduction in thickness of growth plate resting zone and articular cartilage, altered bone content, and atypical distribution of matrix components within growth plate cartilage. We propose that collagen X plays a role in the normal distribution of matrix vesicles and proteoglycans within the growth plate matrix. Collagen X deficiency impacts on the supporting properties of the growth plate and the mineralization process, resulting in abnormal trabecular bone. This hypothesis would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD.

Dialkylglycine decarboxylase structure: bifunctional active site and alkali metal sites.

The structure of the bifunctional, pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase was determined to 2.1-angstrom resolution. Model building suggests that a single cleavage site catalyzes both decarboxylation and transamination by maximizing stereoelectronic advantages and providing electrostatic and general base catalysis. The enzyme contains two binding sites for alkali metal ions. One is located near the active site and accounts for the dependence of activity on potassium ions. The other is located at the carboxyl terminus of an alpha helix. These sites help show how proteins can specifically bind alkali metals and how these ions can exert functional effects.

Altered hip and trunk muscle function in individuals with patellofemoral pain.

OBJECTIVE: The purpose of this study was to investigate the role of hip muscles in patellofemoral pain (PFP), specifically by investigating neuromotor control, strength and range of motion of the hip muscles. DESIGN: Cross-sectional. SETTING: University laboratory. PATIENTS: Ten participants diagnosed with PFP and 27 asymptomatic controls were recruited, using standard inclusion and exclusion criteria. MAIN OUTCOME MEASURES: Electromyographic activity of the vasti and anterior gluteus medius (GM) were recorded using surface electrodes and posterior GM using fine wire electrodes while the participant completed a stair-stepping task. Hip strength and trunk side flexion strength was assessed using a hand-held dynamometer and hip range of motion with an inclinometer. Pain and disability measures were recorded for the PFP participants. RESULTS: When individuals with PFP completed the stair-stepping task there was a delay in activation of both anterior and posterior GM (p<0.02) and an alteration in vasti control (p = 0.001). In addition, trunk side flexion strength was significantly less (29%) in individuals with PFP (p = 0.03). CONCLUSION: This study provides evidence that trunk side flexion strength and neuromotor control of the GM are affected in people with PFP. This study also confirms the presence of a delayed vastus medialis obliquus relative to vastus lateralis, providing further evidence underpinning the importance of retraining the vasti function in patients with PFP.

HIV and risk behaviour among men who have sex with men in Denmark--the 2006 Sex Life Survey.

Behavioural surveys among men who have sex with men (MSM) are important for HIV surveillance. The Danish 2006 Sex Life Survey was carried out as a self administered questionnaire, which was distributed at gay venues and bars and posted on the internet. The questionnaire was completed by 3,141 MSM. We describe the methods, the respondent group and the results of the 2006 Sex Life Survey, and discuss it implications. The main finding of this survey is that 33% of the respondents have practised unsafe sex, defined as unprotected anal intercourse with one or more partners of different or unknown HIV status. In the three previous Sex Life Surveys of 2000, 2001 and 2002, this figure was between 26% and 28%.

Brunfelsia spp (yesterday, today, tomorrow) toxicity in four dogs.

Four dogs were treated for acute toxicity following ingestion of the popular garden shrub 'Yesterday, today, tomorrow' (Brunfelsia spp). Clinical signs included vomiting, diarrhoea, muscle tremors, anxiousness, opisthotonus and seizures. All dogs recovered following treatment with any or all of general anaesthetic, gastric lavage, enema, diazepam, phenobarbitone or propofol sedation. Brunfelsia spp toxicity should be considered in young, previously healthy dogs presenting with gastrointestinal signs that rapidly progress to muscle tremors and seizures. Examination of faeces was required for diagnosis in all cases. Owners should also be questioned thoroughly about their dogs' access to such plants.

Asialo GM1(+) CD8(+) T cells play a critical role in costimulation blockade-resistant allograft rejection.

Simultaneous blockade of the CD40 and CD28 costimulatory pathways is an effective treatment strategy to promote allograft acceptance but does not lead to indefinite allograft survival. The immune mechanisms responsible for costimulation-independent rejection are not defined. Here we have studied the rejection responses of murine C57BL/6 recipients, which we show to be relatively resistant to inhibition by combined CD40/CD28 blockade. We demonstrate that asialo GM1(+) CD8(+) cells play a critical role in this costimulation blockade-resistant rejection. These results provide new insights into the costimulatory requirements for T-cell subsets and demonstrate for the first time that combined blockade of the CD40 and CD28 pathways does not adequately inhibit CD8-mediated skin allograft rejection. Furthermore, we provide evidence that asialo GM1 is a potentially important therapeutic target for CD8-dependent immune responses.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer.

PURPOSE: Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. METHODS: In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. RESULTS: Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). CONCLUSIONS: Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial.

Patellar taping does not change the amplitude of electromyographic activity of the vasti in a stair stepping task.

OBJECTIVES: To investigate the effect of patellar taping on the amplitude of electromyographic activity (EMG) of vasti activation in subjects with and without patellofemoral pain (PFP). METHODS: Ten participants with PFP and 12 asymptomatic controls were recruited to the study. The study was designed as a randomised crossover trial. Participants completed a stair stepping task. Three experimental conditions were assessed: no tape, therapeutic medially directed tape, and placebo vertically directed tape. The main outcome measure was the EMG amplitude of the vastus medialis obliquus and vastus lateralis during the concentric phase of stair stepping. RESULTS: The application of medially directed therapeutic tape significantly decreased pain in subjects with PFP. However, application of tape over the patella (therapeutic or placebo) did not alter the amplitude of vasti EMG when either the PFP or control participants completed the concentric stair stepping task. CONCLUSION: The results of this study indicate that the positive clinical effects of medially directed therapeutic tape are not due to changes in EMG amplitude of the vasti muscle. Thus other effects such as changes in timing of contraction of the vasti are more likely candidates for the mechanism of efficacy.

The structure of OmpF porin in a tetragonal crystal form.

BACKGROUND: OmpF porin is a trimeric integral membrane protein responsible for the passive transport of small hydrophilic molecules, such as nutrients and waste products, across the outer membrane of Escherichia coli. Very few membrane proteins have been crystallized in three dimensions, yet this stable protein can be obtained in several crystal forms. Comparison of the structures of the same membrane protein in two different packing environments is of major interest, because it allows us to explore the integrity of the structure outside the natural membrane environment. RESULTS: The structure of OmpF porin in a tetragonal crystal form with two trimers per asymmetric unit has been determined at 3.2 A resolution and compared with that obtained previously in a trigonal crystal form. The lattice contacts involve only polar atoms, whereas extensive hydrophobic protein-protein interactions were found in the trigonal lattice. The trimer structure is virtually identical in both. CONCLUSIONS: Our comparison reveals that the overall structure of OmpF is not influenced by crystal lattice constraints and, thus, presumably bears close resemblance to the in vivo structure. The tetragonal crystal structure has provided the starting model for the phasing of neutron diffraction data obtained from this crystal form, as described in an accompanying article.

New storage procedure for human tumor biopsies prior to estrogen receptor measurement.

Breast tumor biopsies required for steroid receptor determination are normally frozen in liquid nitrogen and stored until assay. However, some limitations of this type of storage exist. To try to both eliminate the need for liquid nitrogen and as part of a study of serial assays on a single tumor biopsy, alternative storage media were investigated. This study shows that storage of breast tumor biopsies at -20 degrees in sucrose buffer made 50% in glycerol prevented the tissues from freezing, yet retained the specific estrogen receptor content both quantitatively and in terms of molecular form (8S:4S ratio). Receptor was stable for up to 100 days, and individual samples could be successfully reassayed throughout this period. Forty-four biopsies from 40 patients were halved, and one section from each was stored in liquid nitrogen, while the other was stored in sucrose:glycerol. Overall, the correlation of receptor content between the two storage methods was good. Using a clinical cutoff value of 20 fmol/mg cytosol protein, only one sample of the 44 would have been classified differently after storage in the two media. Progesterone receptor in biopsies stored in sucrose:glycerol also appears to be stable for at least a limited period.

Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol.

P2 myelin protein (P2) and cellular retinol binding protein (CRBP) are members of a family of cellular lipophilic transport proteins. P2 has been refined at a resolution of 2.7 A, and CRBP has been solved by molecular replacement and refined to a resolution of 2.1 A. The members of this family form a compact three-dimensional structure built up from ten antiparallel strands that fold to form an orthogonal barrel containing the ligand. In P2, the carboxylate group of an oleic acid ligand interacts with the side-chains of two arginine (106 and 126), and one tyrosine (128) residues. The ligand adopts a U-shaped conformation. In CRBP, the all-trans-retinol has a planar conformation with its alcohol group hydrogen bonding to the side-chain of glutamine 108 (equivalent to residue 106 in P2). The local interactions of glutamine 108 explain CRBP's preference for binding retinol rather than retinal. The side-chain of lysine 40 makes a close contact with the isoprene tail of the retinol.

Electrostatic properties of two porin channels from Escherichia coli.

The electrostatic interactions in the channels of OmpF and PhoE porins from Escherichia coli were analysed on the basis of a macroscopic multi-dielectric model of the protein-membrane complex derived from the respective porin X-ray structures. The membrane was represented as layers of distinct dielectric constants corresponding to the aliphatic core and the polar head groups of the lipids. The pKa values of the titratable groups and the electrostatic field in the region of the channel were calculated by the finite difference technique. In spite of the differences in sequences and charge constellations, the calculated electrostatic properties of the two porins are similar in several aspects: (1) unusual titration behaviour (pKa below 7) was found for some groups of the cluster of basic residues at the constriction of the pore; (2) a number of acidic groups buried between the internal loop and the barrel wall are stabilized in their protonated forms at neutral pH; (3) there is a strong transverse electrostatic field in the channel characterized by a screw-like form. The strength of the field is greatest at the region of the constriction zone. This would facilitate the diffusion of solutes with a large dipole moment such as free amino acids. Differences between the electrostatic fields of OmpF and PhoE are mainly confined to that end of the pore that faces the cell exterior in vivo. In OmpF the electrostatic potential is close to zero in this region of the channel, whereas a positive potential was found in PhoE. It was shown that the experimentally observed difference in ion selectivity of the two porins can largely be attributed to this distinct electrostatic property.

Crystallization and preliminary crystallographic data of the Fab fragment of an anti-phenylalanine hydroxylase monoclonal antibody.

Two crystal habits, one rod shaped and the other square prismatic, of the Fab fragment of a monoclonal anti-phenylalanine hydroxylase antibody have been grown using the method of vapour phase diffusion against polyethylene glycol 6000. The square prisms diffract to better than 2.8 A, belong to the space group P1 and have unit cell parameters a = 41.8 A, b = 50.3 A, c = 114.7 A, alpha = 97.6 degrees, beta = 91.7 degrees, gamma = 91.0 degrees, while the rod-shaped crystals belong to the space group P212121, have unit cell parameters a = 105.6 A, b = 119.8 A, c = 82.2 A and diffract to 3.5 A resolution.