Three steps to open access.

A short guide to open access compliance

Guide to adding publications to PURE.

A step by step guide for GCU researchers on how to add publications to PURE

Three steps to open access.

A short guide to open access compliance

Rapid eradication of colon carcinoma by Clostridium perfringens Enterotoxin suicidal gene therapy

Background Bacterial toxins have evolved to an effective therapeutic option for cancer therapy. The Clostridium perfringens enterotoxin (CPE) is a pore- forming toxin with selective cytotoxicity. The transmembrane tight junction proteins claudin-3 and -4 are known high affinity CPE receptors. Their expression is highly upregulated in human cancers, including breast, ovarian and colon carcinoma. CPE binding to claudins triggers membrane pore complex formation, which leads to rapid cell death. Previous studies demonstrated the anti-tumoral effect of treatment with recombinant CPE-protein. Our approach aimed at evaluation of a selective and targeted cancer gene therapy of claudin-3- and/or claudin-4- expressing colon carcinoma in vitro and in vivo by using translation optimized CPE expressing vector. Methods In this study the recombinant CPE and a translation optimized CPE expressing vector (optCPE) was used for targeted gene therapy of claudin-3 and/or -4 overexpressing colon cancer cell lines. All experiments were performed in the human SW480, SW620, HCT116, CaCo-2 and HT-29 colon cancer and the isogenic Sk-Mel5 and Sk-Mel5 Cldn-3-YFP melanoma cell lines. Claudin expression analysis was done at protein and mRNA level, which was confirmed by immunohistochemistry. The CPE induced cytotoxicity was analyzed by the MTT cytotoxicity assay. In addition patient derived colon carcinoma xenografts (PDX) were characterized and used for the intratumoral in vivo gene transfer of the optCPE expressing vector in PDX bearing nude mice. Results Claudin-3 and -4 overexpressing colon carcinoma lines showed high sensitivity towards both recCPE application and optCPE gene transfer. The positive correlation between CPE cytotoxicity and level of claudin expression was demonstrated. Transfection of optCPE led to targeted, rapid cytotoxic effects such as membrane disruption and necrosis in claudin overexpressing cells. The intratumoral optCPE in vivo gene transfer led to tumor growth inhibition in colon carcinoma PDX bearing mice in association with massive necrosis due to the intratumoral optCPE expression. Conclusions This novel approach demonstrates that optCPE gene transfer represents a promising and efficient therapeutic option for a targeted suicide gene therapy of claudin-3 and/or claudin-4 overexpressing colon carcinomas, leading to rapid and effective tumor cell killing in vitro and in vivo

Men's Psychotherapy Use, Male Role Norms, and Male-Typical Depression Symptoms: Examining 716 Men and Women Experiencing Psychological Distress

Men as compared to women are half as often affected by depressive and anxiety disorders and seek significantly less help for mental health issues than women. Adherence to traditional male role norms (AtTMRN) may hinder men from describing prototypical depression symptoms and from seeking psychotherapy. The current study compared whether AtTMRN, gender role identity, or the experience of prototypical or male-typical externalizing mental health symptoms were associated with psychotherapy use in men and women. In an anonymous online survey, 716 participants (37% men) reporting to currently experience psychological distress were examined. Information was obtained on psychotherapy use, depression and anxiety symptoms, gender role identity, and traditional male role norms. Although experiencing similar levels of depression, men compared to women showed a reduction in psychotherapy use by 29%. Masculine role identity was directly associated with reduced psychotherapy use in men (β = -0.41, p = 0.029), whereas AtTMRN was not (men: β = -0.04, p = 0.818; women: β = -0.25, p = 0.064). Higher externalizing depression symptomatology (β = -0.68, p = 0.005), but not prototypical depression symptomatology (β = -0.02, p = 0.499), was associated with reduced psychotherapy use in men but not women (p > 0.05). Interactions revealed that men, but not women, with high AtTMRN use psychotherapy only when exhibiting elevated symptom levels. The results corroborate previous reports showing reduced psychotherapy use in men as compared to women and identify elevated masculine role identity and male-typical externalizing depression symptomatology as direct factors associated with reduced psychotherapy use in psychologically distressed men. AtTMRN interacts with mental health symptoms to predict psychotherapy use, indicating that men with high AtTMRN only use psychotherapy when exhibiting high symptomatology

Male depression risk, psychological distress, and psychotherapy uptake: Validation of the German version of the male depression risk scale

Background Screening for depressive disorders in men may be complicated by traditional male role norms. The Male Depression Risk Scale (MDRS) was developed to aid screening for depression in men adhering to traditional male role norms and to facilitate identification of depression in men in general and to promote treatment uptake. Aims Validation of a German version of the MDRS and examination of its potential to predict clinical characteristics. Methods In an anonymous online survey comprising of 1605 participants (male: N = 671; 42%), information was obtained on psychological distress, diagnosed psychological disorders, psychotherapy and psychopharmacological treatment. Additional measures included a German version of the MDRS as further mental-health-related constructs. Results The German version of the MDRS showed good validity and reliability. The previously identified 6-factor structure could be replicated for the German version. Compared to the Patient Health Questionnaire 9, the MDRS showed similar detection performance in identifying men who self-reported psychological distress, psychological disorders, depression, psychotherapy usage, or usage of psychopharmacological therapy. Conclusions The German version of the MDRS shows good psychometric validity and represents a valid screening instrument for the identification of psychological distress specifically in men

Effects of ceftiofur treatment on the susceptibility of commensal porcine E.coli – comparison between treated and untreated animals housed in the same stable

Background Healthy farm animals have been found to act as a reservoir of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli). Therefore, the objective of the study was to determine the input of antimicrobial active ceftiofur metabolites in the stable via faeces and urine after intramuscular administration of the drug to pigs and the elucidation of the Escherichia coli ESBL resistance pattern of treated and untreated pigs housed in the same barn during therapy. Methods For determination of the minimal inhibitory concentration (MIC) the method of microdilutionaccording to the recommended procedure of the Clinical and Laboratory Standards Institute was used. Inaddition to that, a qualitative determination was performed by agar dilution. Unsusceptible E. coli speciesselected via agar dilution with cefotaxime were confirmed by MALDI-TOF and ESBL encoding genes wereidentified by PCR. The amounts of ceftiofur measured as desfuroylceftiofur (DFC) in the different probes (plasma, urine, faeces and dust) were analysed by UPLC-MS/MS. Results In a first experiment two groups of pigs (6 animals per group) were housed in the same barn in two separated boxes. One group (group B) were treated with ceftiofur according to the licence (3 mg/kg administered intramuscularly (i.m.) on three consecutive days, day 1–3). During a second treatment period (day 29–31) an increased rate of ESBL resistant E. coli was detectable in these treated pigs and in the air of the stable. Moreover, the second group of animals (group A) formerly untreated but housed for the whole period in the same stable as the treated animals revealed increased resistance rates during their first treatment (day 45–47) with ceftiofur. In order to investigate the environmental input of ceftiofur during therapy and to simulate oral uptake of ceftiofur residues from the air of the stable a second set of experiments were performed. Pigs (6 animals) were treated with an interval of 2 weeks for 3 days with different doses of ceftiofur (3 mg/kg, 1 mg/kg and 0.3 mg/kg i.m.) as well as with 3 mg/kg per os) and the renal and biliary excretion of ceftiofur as its active metabolite were measured in comparison to the plasma levels. In addition to that, probes of the sedimentation dust and the air of the stable were analysed for drug residues. Conclusion The present study shows that treatment of several animals in a stable with ceftiofur influences the resistance pattern of intestinal Escherichia coli of the treated as well as untreated animals housed in the same stable. During therapy with the drug which was administered by injection according to the licence we detected nameable amounts of ceftiofur and its active metabolites in the dust and air of the stable

A new era of wide-field submillimetre imaging: on-sky performance of SCUBA-2

SCUBA-2 is the largest submillimetre wide-field bolometric camera ever built. This 43 square arc-minute field-of-view instrument operates at two wavelengths (850 and 450 microns) and has been installed on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. SCUBA-2 has been successfully commissioned and operational for general science since October 2011. This paper presents an overview of the on-sky performance of the instrument during and since commissioning in mid-2011. The on-sky noise characteristics and NEPs of the 450 and 850 micron arrays, with average yields of approximately 3400 bolometers at each wavelength, will be shown. The observing modes of the instrument and the on-sky calibration techniques are described. The culmination of these efforts has resulted in a scientifically powerful mapping camera with sensitivities that allow a square degree of sky to be mapped to 10 mJy/beam rms at 850 micron in 2 hours and 60 mJy/beam rms at 450 micron in 5 hours in the best weather.Comment: 18 pages, 15 figures.SPIE Conference series 8452, Millimetre, Submillimetre and Far-infrared Detectors and Instrumentation for Astronomy VI 201

Status loss due to COVID-19, traditional masculinity, and their association with recent suicide attempts and suicidal ideation

The COVID-19 pandemic is causing extensive job loss leading to a loss of social status in many men. Endorsement of traditional masculinity ideology may render some men particularly sensitive to status loss and thereby to an increased risk for suicidality. In this anonymous online survey conducted in German-speaking European countries, 490 men completed questionnaires regarding loss of social status due to the COVID-19 pandemic, past-month and lifetime suicide attempt and suicidal ideation. Furthermore, endorsement of traditional masculinity ideology and prototypical and male-typical externalizing depression symptoms were measured. Out of a total of 490 men, 14.7% of men reported experiencing status loss due to the pandemic. These men were more than four times as likely to have attempted suicide in the past month (OR = 4.48, 95% CI [1.72, 11.67]) and more than twice as likely to report suicidal ideation during the past 2 weeks (OR = 2.47, 95% CI [1.42, 4.28]), than men not reporting status loss. Status loss, but not endorsement of traditional masculinity ideology, was associated with suicide outcomes. However, when male-typical externalizing depression symptoms and prototypical depression symptoms were included in the models, they exhibited the only direct associations with suicide outcomes (e.g., for past-month suicide attempt: male-typical externalizing depression symptoms OR = 2.18, 95% CI [1.31, 3.62], prototypical depression symptoms OR = 2.41, 95% CI [1.13, 5.12]). A significant interaction between status loss and endorsement of traditional masculinity ideology further suggests an enhancing moderating effect of traditional masculinity on the relationship between status loss and past-month suicide attempts (OR = 3.27, 95% CI [1.16, 9.27]). Status loss due to the COVID-19 pandemic emerges as risk factor for suicide in men. Men who experience status loss due to the COVID-19 pandemic while concomitantly exhibiting strong endorsement of traditional masculinity ideology have an additional increased risk of suicide

A Methodology for the Classification and Characterisation of Industrial Demand-Side Integration Measures

In the context of the ongoing climate change and increasingly strict climate goals of the European Green Deal, industry faces a growing challenge to decrease its high demand for electrical energy and its greenhouse gas emissions. Demand-Side Integration measures have a great potential to reduce the greenhouse gas emissions of the industrial sector. However, there is still no definition and consistent characterising terms for Industrial Demand-Side Integration. The lack of clarity in concepts and definitions may impose hurdles in the transfer of results and methodologies from research activities and thus, in the implementation of measures in the industry. Furthermore, the economic value of implementing these measures is often unclear but of high relevance to industrial consumers. This paper proposes a comprehensive Industrial Demand-Side Integration definition and a methodology to classify and characterise its measures. The methodology is aimed at helping industrial consumers decide which measures can be implemented in their specific setting and how these measures can be monetised. The methodology is validated by applying it to eight relevant use cases in the ETA Research Factory