Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter

<p>Abstract</p> <p>Background</p> <p>The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members.</p> <p>Results</p> <p>MMTV-like envelope (<it>env</it>) and long terminal repeat (<it>LTR</it>) sequences containing the MMTV superantigen gene (<it>sag</it>) were detected in the malignant tissues of all three family members. The amplified <it>env </it>gene sequences were 98.0%–99.6% homologous to the MMTV <it>env </it>sequences found in the GR, C3H, and BR6 mouse strains. The amplified <it>LTR </it>sequences containing <it>sag </it>sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.</p> <p>Conclusion</p> <p>The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice.</p

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work

Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

Tumor progression: In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in, among other things, that it often occurs in the absence of the original carcinogenic stimulus. Mechanism of immunostimulation: Relatively low titers of specific immune reactants are known to stimulate, but cell-to-cell or cell-to-matrix interactions appear to be major inhibitors of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell or cell-to-matrix communication by a sub-lethal immune-reaction. Discussion: While the above hypothesis remains unproven, some evidence suggests that immunity may have a major facilitating effect on tumor growth especially at the time of malignant transformation. There is even some evidence suggesting that transformation in vivo may seldom occur in the absence of immunostimulation of the premalignant lesion. Positive selection by the immune reaction may be the reason that tumors are immunogenic

Assessing the causal association of glycine with risk of cardio-metabolic diseases

Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance

An exploratory mixed methods study of the acceptability and effectiveness of mindfulness -based cognitive therapy for patients with active depression and anxiety in primary care

BACKGROUND: Mindfulness Based Cognitive Therapy (MBCT) is an 8-week course developed for patients with relapsing depression that integrates mindfulness meditation practices and cognitive theory. Previous studies have demonstrated that non-depressed participants with a history of relapsing depression are protected from relapse by participating in the course. This exploratory study examined the acceptability and effectiveness of MBCT for patients in primary care with active symptoms of depression and anxiety METHODS: 13 patients with recurrent depression or recurrent depression and anxiety were recruited to take part in the study. Semi-structured qualitative interviews were conducted three months after completing the MBCT programme. A framework approach was used to analyse the data. Beck depression inventories (BDI-II) and Beck anxiety inventories (BAI) provided quantitative data and were administered before and three months after the intervention. RESULTS: The qualitative data indicated that mindfulness training was both acceptable and beneficial to the majority of patients. For many of the participants, being in a group was an important normalising and validating experience. However most of the group believed the course was too short and thought that some form of follow up was essential. More than half the patients continued to apply mindfulness techniques three months after the course had ended. A minority of patients continued to experience significant levels of psychological distress, particularly anxiety. Statistically significant reductions in mean depression and anxiety scores were observed; the mean pre-course depression score was 35.7 and post-course score was 17.8 (p = 0.001). A similar reduction was noted for anxiety with a mean pre-course anxiety score of 32.0 and mean post course score of 20.5 (p = 0.039). Overall 8/11 (72%) patients showed improvements in BDI and 7/11 (63%) patients showed improvements in BAI. In general the results of the qualitative analysis agreed well with the quantitative changes in depression and anxiety reported. CONCLUSION: The results of this exploratory mixed methods study suggest that mindfulness based cognitive therapy may have a role to play in treating active depression and anxiety in primary care

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site

Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer–Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures6. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon–oxygen bonds and generate carbon–carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl–diphosphine ligand, that activates and cleaves the strong carbon–oxygen bond of carbon monoxide, enacts carbon–carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl–diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site

Unwanted incidents during transition of geriatric patients from hospital to home: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Geriatric patients recently discharged from hospital experience increased chance of unplanned readmissions and admission to nursing homes. Several studies have shown that medication-related discrepancies are common. Few studies report unwanted incidents by other factors than medications. In 2002 an ambulatory team (AT) was established within the Department of Geriatrics, St. Olavs University Hospital HF, Trondheim, Norway. The AT monitored the transition of the patients from hospital to home and four weeks after discharge in order to reveal unwanted incidents.</p> <p>The aim of the present study was to describe unwanted incidents registered by the AT among patients discharged from a geriatric evaluation and management unit (GEMU) by character, frequency and stage in the transitional process. Only unwanted incidents with a severity making contact with the primary health care (PHC) necessary were registered.</p> <p>Methods</p> <p>A prospective observational study with patients treated in the GEMU and followed by the AT was performed. Current practice included comprehensive geriatric assessment and management including discharge planning in the GEMU and collaboration with the primary health care on appointments on assistance to be provided after discharge from hospital. Unwanted incidents severe enough to induce contact with the primary health care were registered during the transitional phase and after discharge.</p> <p>Results</p> <p>118 patients (65% female), with mean age 83.2 ± 6.4 years participated. Median Barthel Index at discharge was 18 (interquartile range 16-19) and median Mini Mental Status Examination 24 (interquartile range 21-26). A total of 146 unwanted incidents were registered in 70 (59%) of the patients. Most frequent were unwanted incidents related to drug prescription regime (32%), exchange of information in and between the GEMU and the primary health care (25%) and service or help provided from the PHC (17%).</p> <p>Conclusions</p> <p>Despite a seemingly well-organised system for transition of patients from the GEMU to their homes, one or more unwanted incidents occurred in most patients during discharge or four weeks post discharge. The study has revealed areas of importance for improving transitional care of geriatric patients.</p

Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study

IntroductionCancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.MethodsIndividuals diagnosed in 2007-08 and age 15-39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.Results525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p  &lt;  0.01), Hispanics and non-Hispanic blacks (p  &lt;  0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.DiscussionDespite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.Implications for cancer survivorsAchieving a reasonable response rate in this population is possible, but requires extensive resources

Randomised controlled trial of thermostatic mixer valves in reducing bath hot tap water temperature in families with young children in social housing: A protocol

<p>Abstract</p> <p>Background</p> <p>Each year in the UK 2000 children attend emergency departments and 500 are admitted to hospital following a bath water scald. The long term effects can include disability, disfigurement or psychological harm and repeated skin grafts may be required as the child grows. The costs of treating a severe scald are estimated at 250,000 GBP. Children living in the most deprived wards are at greatest risk of thermal injuries; hospital admission rates are three times that for children living in the least deprived wards.</p> <p>Domestic hot water, which is usually stored at around 60 degrees Celsius, can result in a second-degree burn after 3 seconds and a third-degree burn after 5 seconds. Educational strategies to encourage testing of tap water temperature and reduction of hot water thermostat settings have largely proved unsuccessful. Legislation in the USA mandating pre-setting hot water heater thermostats at 49 degrees Celsius was effective in reducing scald injuries, suggesting passive measures may have a greater impact. Thermostatic mixer valves (TMVs), recently developed for the domestic market, fitted across the hot and cold water supply pipes of the bath, allow delivery of water set at a fixed temperature from the hot bath tap. These valves therefore offer the potential to reduce scald injuries.</p> <p>Design/Methods</p> <p>A pragmatic, randomised controlled trial to assess the effectiveness of TMVs in reducing bath hot tap water temperatures in the homes of families with young children in rented social housing. Two parallel arms include an intervention group and a control group where the intervention will be deferred.</p> <p>The intervention will consist of fitting a TMV (set at 44 degrees Celsius) by a qualified plumber and provision of educational materials. The control arm will not receive a TMV or the educational materials for the study duration but will be offered the intervention after collection of follow-up data 12 months post randomisation.</p> <p>The primary outcome measure will be the bath hot tap water temperature. Fifteen families per arm are required to detect a reduction in the mean bath hot tap water temperature from 60.4 degrees Celsius (SD 9.1) in the control group to 46 degrees Celsius in the intervention group, with 90% power and a 5% significance level (2 sided). Secondary outcome measures including acceptability will require a sample size of 120 participants.</p> <p>Discussion</p> <p>Whilst TMVs have the potential to reduce scald injuries, to date there have been no randomised controlled trials assessing their effectiveness, acceptability and cost effectiveness.</p> <p>Trial Registration</p> <p>ISRCTN21179067</p