Perceived annoyance and asthmatic symptoms in relation to vehicle exhaust levels outside home: a cross-sectional study

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Exhaust emissions from vehicles is a well known problem with both epidemiological and experimental studies showing increasing adverse health effects with elevating levels. Many of the studies concerning vehicle exhausts and health are focused on health outcomes where the proportion attributed to exhaust is low, while there is less information on early and more frequent subjective indicators of adverse effects. Methods: The primary aim of this study was to study perceived annoyance in relation to vehicle exhaust concentrations using modelled levels of nitrogen dioxide outside the home as an indicator with high spatial resolution. Almost 2800 persons in a random sample from three Swedish cities (Umea, Uppsala and Gothenburg) responded to our questionnaire. Questions were asked to determine the degree of annoyance related to vehicle exhausts and also the prevalence of irritating and asthmatic symptoms. Exposure was described for each participants home address by meteorological dispersion models with a 50 meter resolution. Results: We found a significant increase of peoples ' self-assessed annoyance with rising levels of NO2. The odds of being very annoyed by vehicle exhausts increased by 14 % per 1 µg/m3 increas

HCMV Targets the Metabolic Stress Response through Activation of AMPK Whose Activity Is Important for Viral Replication

Human Cytomegalovirus (HCMV) infection induces several metabolic activities that have been found to be important for viral replication. The cellular AMP-activated protein kinase (AMPK) is a metabolic stress response kinase that regulates both energy-producing catabolic processes and energy-consuming anabolic processes. Here we explore the role AMPK plays in generating an environment conducive to HCMV replication. We find that HCMV infection induces AMPK activity, resulting in the phosphorylation and increased abundance of several targets downstream of activated AMPK. Pharmacological and RNA-based inhibition of AMPK blocked the glycolytic activation induced by HCMV-infection, but had little impact on the glycolytic pathway of uninfected cells. Furthermore, inhibition of AMPK severely attenuated HCMV replication suggesting that AMPK is an important cellular factor for HCMV replication. Inhibition of AMPK attenuated early and late gene expression as well as viral DNA synthesis, but had no detectable impact on immediate-early gene expression, suggesting that AMPK activity is important at the immediate early to early transition of viral gene expression. Lastly, we find that inhibition of the Ca2+-calmodulin-dependent kinase kinase (CaMKK), a kinase known to activate AMPK, blocks HCMV-mediated AMPK activation. The combined data suggest a model in which HCMV activates AMPK through CaMKK, and depends on their activation for high titer replication, likely through induction of a metabolic environment conducive to viral replication

Arctigenin Efficiently Enhanced Sedentary Mice Treadmill Endurance

Physical inactivity is considered as one of the potential risk factors for the development of type 2 diabetes and other metabolic diseases, while endurance exercise training could enhance fat oxidation that is associated with insulin sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an energy sensor plays pivotal roles in the regulation of energy homeostasis, and its activation could improve glucose uptake, promote mitochondrial biogenesis and increase glycolysis. Recent research has even suggested that AMPK activation contributed to endurance enhancement without exercise. Here we report that the natural product arctigenin from the traditional herb Arctium lappa L. (Compositae) strongly increased AMPK phosphorylation and subsequently up-regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice treadmill based in vivo assay further indicated that administration of arctigenin improved efficiently mice endurance as reflected by the increased fatigue time and distance, and potently enhanced mitochondrial biogenesis and fatty acid oxidation (FAO) related genes expression in muscle tissues. Our results thus suggested that arctigenin might be used as a potential lead compound for the discovery of the agents with mimic exercise training effects to treat metabolic diseases

Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.

Background Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease.Methods We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT).Results In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer.Conclusions We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Using Intervention Mapping to develop an occupational advice intervention to aid return to work following hip and knee replacement in the United Kingdom

Background There are increasing numbers of total hip replacements (THR) and total knee replacements (TKR) being performed in patients of working age. Providing patients undergoing TKR and THR with return to work advice might facilitate return to work. The aim of this paper is to report on the process used to systematically develop an occupational advice intervention to be delivered in hospital for those undergoing arthroplasty. Methods The six-step Intervention Mapping (IM) approach to development, implementation and evaluation of a theory and evidence-based interventions was followed. This paper reports on the development of the intervention covered by steps 1 to 4 of the IM process. Steps 1-3 gathered data on current practice and barriers to change using a mixed methods approach (cohort study of patients undergoing THR or TKR, stakeholder interviews, survey of practice, evidence synthesis) and provided a theoretical framework for intervention development. Step 4 used information from steps 1-3 in combination with a Delphi consensus process to develop the intervention and the associated tools and materials to facilitate its delivery. Results The final intervention identified included a number of core principles including: early patient identification; delivery of key information to patients and their employers; assessment and support by a member of the orthopaedic team; procedures for escalation based on patient need; mechanisms to support communication; and training and support for the clinical teams delivering care. A total of 13 patient and 20 staff performance objectives as delivery requirements, supported by a range of tools, roles and training resources. The intervention addressed outcomes based at the individual and interpersonal levels of the ecological model. Conclusions Following the IM approach resulted in a structured and justified occupational intervention for delivery in secondary care for patients undergoing total hip and knee replacement. The feasibility of the intervention will subsequently be tested alongside further investigation to establish its effectiveness and cost-effectiveness. Key Words Intervention Mapping Return to Work Occupational advice Arthroplasty Hip Kne

Community-based intervention to promote breast cancer awareness and screening: The Korean experience

<p>Abstract</p> <p>Background</p> <p>There are many differences in culture, community identity, community participation, and ownership between communities in Western and Asian countries; thus, it is difficult to adopt the results of community intervention studies from Western countries. In this study, we conducted a multicity, multicomponent community intervention trial to correct breast cancer myths and promote screening mammography for women living in an urban community in Korea.</p> <p>Methods</p> <p>A 6-month, 2-city community intervention trial was conducted. In the intervention city, 480 women were surveyed at baseline and 7 months later to evaluate the effects of the intervention program. Strategies implemented in the intervention city included community outreach and clinic and pharmacy-based in-reach strategies.</p> <p>Results</p> <p>This study showed a 20.4-percentage-point decrease in myths about the link between cancer and breast size, a 19.2-percentage-point decrease in myths concerning mammography costs, and a 14.1-percentage-point increase in intention to undergo screening mammography. We also saw a 23.4-percentage-point increase in the proportion of women at the action stage of the transtheoretical model in the intervention city. In the comparison city, smaller decreases and increases were observed.</p> <p>Conclusions</p> <p>Our study showed the value of an intervention study aimed at reducing belief in breast cancer myths in an urban community in Korea. The invention also made women more likely to undergo mammography in future.</p