Cloning and functional analysis of tipE, a novel membrane protein that enhances drosophila para sodium channel function

AbstractVoltage-dependent sodium channels are involved in the initiation and propagation of action potentials in many excitable cells. Here we report that tipE, a gene defined by a temperature-sensitive paralytic mutation in Drosophila, encodes a novel integral membrane protein that dramatically stimulates functional expression in Xenopus oocytes of the Drosophila sodium channel α subunit encoded by the paralytic (para) locus. Using a heat shock promoter to control tipE+ gene expression in transgenic flies, we demonstrate that tipE+ gene expression is required during pupal development to rescue adult paralysis. In addition, we demonstrate a role or the tipE gene product in adults

Responding to symptoms suggestive of lung cancer: a qualitative interview study.

BACKGROUND: Late diagnosis of lung cancer can impact on survival rates. Patients delay seeking help for a number of reasons. This study explored symptom appraisal and help-seeking decisions among patients referred to specialist respiratory services with symptoms suggestive of lung cancer. METHODS: In-depth qualitative interviews with patients as soon as possible after referral, ideally before diagnosis and mainly within 10 weeks, explored factors impacting on their pathways prior to referral. Framework analysis, underpinned by the Model of Pathways to Treatment, was used to explore the data with particular focus on patients' beliefs and experiences, disease factors and healthcare professional influences. RESULTS: 35 patients were interviewed (aged 41-88 years, 15 women, 17 with lung cancer). All described similar presenting symptoms and triggers to seek help. Appraisal of symptoms was influenced by whether they had a lung comorbidity; seriousness of symptoms was interpreted within the context of previous illness experiences. Help-seeking was triggered when: symptoms failed to respond as expected; there was an increased awareness of symptoms of lung cancer; the public nature of a cough meant others were able to endorse help-seeking. Almost half visited the general practitioner (GP) two or more times before referral; during this period they reinterpreted initial symptoms and appraised new symptoms. The meaning given to symptoms changed over time and many became increasingly concerned they may have lung cancer. The GP played a role in ensuring timely further help-seeking but often there was little guidance on how to monitor symptoms or when to reconsult. CONCLUSIONS: Patients diagnosed with and without lung cancer had similar symptom pathways. Findings provide guidance for lung cancer awareness campaigns on the importance of social networks in endorsing patient help-seeking. The importance of appropriate advice, monitoring and safety-netting procedures by GPs for people presenting with symptoms suggestive of lung cancer is also highlighted.This report presents independent research funded by the National Institute for Health Research Programme Grants for Applied Research programme (RP-PG-0608-10045).This is the final version. It was first published by BMJ Group at http://bmjopenrespres.bmj.com/content/1/1/e00006

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

BackgroundSentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance.MethodsA total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept.ResultsA total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept.Conclusion[(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD

Social Media Friends From Afterschool are Associated With Positive Youth Development in Digital Settings

Positive youth development has been extensively documented in contexts such as the family, school, and afterschool. Emerging theory and research indicate that digital contexts such as social media may also be venues through which young people develop skills and attributes associated with the 5 Cs model of positive youth development and thriving. This research attempted to understand if and how middle school youth’s in-person and online networks connect, and if they do connect, do these connections relate to engaging in beliefs and behaviors associated with PYD. Results suggest that in this sample, middle school youth include peers from afterschool in their online networks, and those who have friends from afterschool and school engaged in PYD- related social media behaviors at higher rates than those who were not connected to in-person networks. No association was found between the amount of time spent in after-school contexts and any of the positive or problematic social media outcomes in this study. Implications for youth development professionals considering the influence of social media on youth, and next steps for research on after-school activities and social media use of middle school youth are discussed

Unlocking the role of a genital herpesvirus, otarine herpesvirus 1, in California sea lion cervical cancer

This research was funded by the Geoffrey Hughes Research Fellowship and The Marine Mammal Center.Urogenital carcinoma in California sea lions (Zalophus californianus) is the most common cancer of marine mammals. Primary tumors occur in the cervix, vagina, penis, or prepuce and aggressively metastasize resulting in death. This cancer has been strongly associated with a sexually transmitted herpesvirus, otarine herpesvirus 1 (OtHV1), but the virus has been detected in genital tracts of sea lions without cancer and a causative link has not been established. To determine if OtHV1 has a role in causing urogenital carcinoma we sequenced the viral genome, quantified viral load from cervical tissue from sea lions with (n = 95) and without (n = 163) urogenital carcinoma, and measured viral mRNA expression using in situ mRNA hybridization (Basescope®) to quantify and identify the location of OtHV1 mRNA expression. Of the 95 sea lions diagnosed with urogenital carcinoma, 100% were qPCR positive for OtHV1, and 36% of the sea lions with a normal cervix were positive for the virus. The non-cancer OtHV1 positive cases had significantly lower viral loads in their cervix compared to the cervices from sea lions with urogenital carcinoma. The OtHV1 genome had several genes similar to the known oncogenes, and RNA in situ hybridization demonstrated high OtHV1 mRNA expression within the carcinoma lesions but not in normal cervical epithelium. The high viral loads, high mRNA expression of OtHV1 in the cervical tumors, and the presence of suspected OtHV1 oncogenes support the hypothesis that OtHV1 plays a significant role in the development of sea lion urogenital carcinoma.Publisher PDFPeer reviewe

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study

Objective: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. Design: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. Participants and setting: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. Results: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48–84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a ‘tipping point’. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. Conclusions: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer