Metastatic melanoma positively influences pregnancy outcome in a mouse model: could a deadly tumor support embryo life?

The incidence of melanoma is increasing worldwide. It is one of the leading cancers in pregnancy and the most common malignancy to metastasize to placenta and fetus. There are no publications about experimental models of melanoma and pregnancy. We propose a new experimental murine model to study the effects of melanoma on pregnancy and its metastatic process. We tested several doses of melanoma cells until we arrived at the optimal dose, which produced tumor growth and allowed animal survival to the end of pregnancy. Two control groups were used: control (C) and stress control (SC) and three different routes of inoculation: intravenous (IV), intraperitoneal (IP) and subcutaneous (SC). All the fetuses and placentas were examined macroscopically and microscopically. The results suggest that melanoma is a risk factor for intrauterine growth restriction but does not affect placental weight. When inoculated by the SC route, the tumor grew only in the site of implantation. The IP route produced peritoneal tumoral growth and also ovarian and uterine metastases in 60% of the cases. The IV route produced pulmonary tumors. No placental or fetal metastases were obtained, regardless of the inoculation route. The injection of melanoma cells by any route did not increase the rate of fetal resorptions. Surprisingly, animals in the IV groups had no resorptions and a significantly higher number of fetuses. This finding may indicate that tumoral factors released in the host organism to favor tumor survival may also have a pro-gestational action and consequently improve the reproductive performance of these animals.

Excess androgen during perinatal life alters steroid receptor expression, apoptosis, and cell proliferation in the uteri of the offspring

Exposure to environmental chemicals may contribute to reproductive disorders, especially when it occurs in critical periods of development. The female reproductive system can be a target for androgens derived from environmental contaminants or pathological conditions. The purpose of this study was to assess the long-term effects of androgens on uterine tissue after maternal exposure limited to the time of gestation and lactation. Pregnant Wistar rats were treated with testosterone propionate (TP) at 0.05. mg/kg, 0.1. mg/kg, 0.2. mg/kg or corn oil (vehicle), s.c., from gestational day 12 until the end of lactation. The results show changes in the pattern of expression of receptors for estrogen, progesterone, and androgen at all doses tested, and decreases in both apoptosis and cell proliferation indices at 0.1 and 0.2. mg/kg. We conclude that early TP exposure, under these experimental conditions, causes changes in cellular and molecular parameters that are essential for normal uterine function in the adult. © 2013 Elsevier Inc.

Signs, translation, and life in the Bakhtin circle and in Welby's significs

“Significs” is provisionally defined by Welby (1911: vii) as the study of the nature of significance in all its forms and relationships, of its workings in all spheres of human life and knowledge. Considering “significs” as a movement highlighting significance, Welby explores the action of signs in life; and more than the Saussurean sign composed of signifier and signified, the sign as understood by Welby refers to meaning as generated through signs in motion. This notion of “significs” empowers the study of signs when it considers the sign not in terms of the Saussurean structural representation of the union of the concept and acoustic image, but as (responsive and responsible) sign action in the world, in life. This also means to take into account the “extra-linguistic referent” (translinguistic and transdiscursive character of significs), history (space-time), subjectivity, the architecture of values connected to language, their communicative function. We believe that a dialogue can be established between Welby’s vision of significs and the notion of ideological sign proposed by Vološinov in Marxism and the Philosophy of Language, expanding the notions of “meaning” and “sense.”

Auditory steady-state response in the first six months of life

Objective: To characterize the thresholds of the auditory steady-state response that relates to term newborns and infants. Design: The study was cross-sectional using auditory steadystate response assessment, and the real-ear-to-dial difference was measured in the external auditory canal. Study Sample: The study group included 60 newborns and infants between the age of 0 and 6 months. Results: A statistically significant difference was found in the carrier frequency variable for auditory steady-state response thresholds but not in comparison to ages. Furthermore, there is an association between auditory steady-state response thresholds and the real-ear-to-dial difference. Conclusion: The same threshold can be used as a normality reference for this age range, with distinct values for the different carrier frequencies. The influence of external auditory canal amplification should be taken into account.

Induktion von Pro-Autophagie-Signalen durch einen extra- oder intrazellulären Alpha-Toxin-Angriff

Autophagie ist ein konservierter, kataboler Mechanismus in allen eukaryoten Zellen. Unter anderem wird ihm eine wichtige Rolle als zellautonomer Abwehrmechanismus gegen Mikroorganismen zugeschrieben; von manchen Infektionserregern wird er jedoch unterlaufen oder sogar genutzt. Der stärkste Auslöser der Autophagie ist ein Mangel an Nährstoffen, insbesondere Aminosäuren. Über die Deaktivierung der Kinase mTORC1 und die Phosphorylierung des eukaryoten Translationsinitiationsfaktors eIF2α hemmt die Nährstoffknappheit die Proteinbiosynthese und aktiviert gleichzeitig Autophagie. Wie Mikroorganismen, insbesondere Bakterien, Autophagie auslösen oder manipulieren, ist derzeit Gegenstand intensiver Forschung. Modifikationen an Mikroben oder Phagosomen und Adapterproteine, die diese Veränderungen und Komponenten des Autophagieapparates erkennen, scheinen jedenfalls bei der selektiven Erkennung durch die Autophagie-Maschinerie wichtig zu sein. rnIn der vorliegenden Dissertationsarbeit wird die Rolle des membranporenbildenden α-Toxins von Staphylococcus aureus für die Induktion von Autophagie beleuchtet. Zum einen erwies sich die Akkumulation von (EGFP)-LC3(II), einem Marker der Autophagosomen, um intrazelluläre S. aureus als abhängig von α-Toxin. Zweitens, genügt extrazellulär appliziertes α-Toxin um (EGFP)-LC3(II)-positive Endosomen zu induzieren. Während der Angriff aus dem extrazellulären Raum jedoch binnen kurzer Zeit eine fokale Kumulation von phosphoryliertem eIF2α an der Plasmamembran induziert, die an der Internalisierung des Toxins beteiligt ist, findet sich am phagosomalen Kompartiment keine Toxin-abhängige Anhäufung von p-eIF2α oder proximalen Autophagieregulatoren. Dies impliziert, dass Toxin-Angriff auf die Plasmamembran, nicht aber auf das Phagosom, zu einer Reaktion führt, wie sie bei massivem Nährstoffmangel zu beobachten ist. Obwohl keine α-Toxin-abhängige Kumulation von p-eIF2α bei einem Angriff aus dem Phagosom erfolgt, findet sich um α-Toxin-produzierende Bakterien eine massive Kumulation von LC3 und Adapterprotein p62/Sequestosome1. Dies deutet daraufhin, dass der Ort des Angriffs - Plasmamembran oder Phagosom – für den Autophagie-induzierenden Mechanismus wichtig sein könnte. Der unterschiedliche Effekt auf die zellulären Ionenkonzentrationen, den ein Angriff auf die Plasmamembran oder auf ein Phagosom auslösen würde, bietet hierfür eine mögliche Erklärung. Die Aktivierung der Autophagie über Adapterproteine könnte dann als back-up Mechanismus fungieren, der auch dann greift, wenn eine Invasion ohne Schädigung der Plasmamembran erfolgt. Ein cross-talk der beiden Induktionswege ist angesichts der Bedeutung von p62 für die selektive und die Hunger-assoziierte Autophagie gut möglich; sezerniertes Toxin könnte durch die Aktivierung der basalen Autophagie Adapter-basierte Mechanismen verstärken.

Effetti di un sistema innovativo di confezionamento e conservazione sulla qualita dell'olio extra vergine di oliva

Questo lavoro di tesi è stato finalizzato allo studio dell’applicabilità e dell’efficacia di una modalità di confezionamento dell’olio extra vergine di oliva (EVO) in grado di raggiungere due obiettivi: - il prolungamento della shelf-life dell’olio d’oliva grazie ad un’azione protettiva del packaging dalla radiazione luminosa; - l’ottenimento di un’estetica accattivante che consenta al consumatore di apprezzare colore e livello del prodotto contenuto. È stata, quindi, testata l’efficacia di un film protettivo trasparente, termoretraibile, stampabile e con effetto barriera contro le radiazioni UV applicato su bottiglie in vetro trasparente, confrontando i risultati ottenuti con quelli raccolti per campioni conservati in bottiglie in vetro scuro e trasparente. Per la realizzazione di questo studio sono stati utilizzati due EVO monovarietali e per ognuno di questi sono state confrontate tre tipologie di confezionamento: vetro scuro, vetro trasparente rivestito con pellicola, vetro trasparente. Per simulare un processo di “invecchiamento accelerato” le bottiglie sono state poste in un termostato (20 °C) all’interno del quale sono state istallate delle lampade in grado di illuminare le bottiglie in continuo e i campioni erano monitorati ad intervalli regolari (5, 10 e 15 settimane). Le determinazioni analitiche svolte (titrimetriche, spettrofotometriche, cromatografiche e sensoriali) hanno riguardato i principali parametri quali-quantitativi correlati allo stato idrolitico (acidità libera, digliceridi) ed ossidativo (numero di perossidi) degli oli d’oliva, nonché relativi alle molecole antiossidanti (contenuto in fenoli totali e tocoferoli) ed agli attributi sensoriali. I risultati ottenuti da queste prove esplorative hanno evidenziato come l’applicazione di sleeve additivate con anti-UV su bottiglie in vetro trasparente possa costituire una valida modalità di confezionamento dell’olio EVO, anche se saranno necessarie ulteriori conferme ed approfondimenti.

Life cycle assessment of trayless dining

Universities in the United States are applying more sustainable approaches to their dining service operations. "The increase in social consciousness and environmental stewardship on college campuses has spurred an array of new and innovative sustainability programs"(ARAMARK Higher Education 2008). University residence dining is typically cafeteria style, with students using trays to carry food. Studies report that food served without trays substantially reduces food waste and water and electrical consumption associated with washing trays. Commonly, these reported results are estimates and not measurements taken under actual operating conditions. This study utilizes measurements recorded under actual dining service conditions in student residence halls at Michigan Technological University to develop the following: 1) operational-specific data on the issues and potential savings associated with a conversion to trayless dining and 2) life cycle assessment (LCA) cost and environmental impact analyses comparing dining with and without trays. For the LCA, the entire life cycle of the system is considered, from the manufacturing to the usage and disposal phases. The study shows that trayless dining reduces food waste because diners carry less food. The total savings for the diner shifts when not using trays for the standard academic year (205 days), with an average number of 700 diners, is 7,032 pounds of food waste from the pre-rinse area (33% reduction) and 3,157 pounds of food waste from the pan washing area (39% reduction). In addition, for each day of the study, the diners consumed more food during the trayless portion of the experiment. One possible explanation for the increased food consumption during this short duration study could be that the diners found it more convenient to eat the extra food on their plate rather than carrying it back for disposal. The trayless dining experiment shows a reduction in dishwasher water, steam, and electrical consumption for each day of the study. The average reduction of dishwasher water, steam, and electrical consumption over the duration of the study were 10.7%, 9.5%, and 6.4% respectively. Trayless dining implementation would result in a decrease of 4,305 gallons of consumption and wastewater discharge, 2.87 mm BTU of steam consumption, and 158 kWh of electrical consumption for the dinner shift over the academic year. Results of the LCA indicate a total savings of $190.4 when trays are not used during the dinner shift. Trayless dining requires zero CO2 eq and cumulative energy demand in the manufacturing stage, reductions of 1005 kg CO2 eq and 861 MJ eq in the usage phase, and reductions of 6458 kg CO2 eq and 1821 MJ eq in the end of the life cycle.

Feasibility and acceptance of electronic quality of life assessment in general practice: an implementation study

Background Patients' health related quality of life (HRQoL) has rarely been systematically monitored in general practice. Electronic tools and practice training might facilitate the routine application of HRQoL questionnaires. Thorough piloting of innovative procedures is strongly recommended before the conduction of large-scale studies. Therefore, we aimed to assess i) the feasibility and acceptance of HRQoL assessment using tablet computers in general practice, ii) the perceived practical utility of HRQoL results and iii) to identify possible barriers hindering wider application of this approach. Methods Two HRQoL questionnaires (St. George's Respiratory Questionnaire SGRQ and EORTC QLQ-C30) were electronically presented on portable tablet computers. Wireless network (WLAN) integration into practice computer systems of 14 German general practices with varying infrastructure allowed automatic data exchange and the generation of a printout or a PDF file. General practitioners (GPs) and practice assistants were trained in a 1-hour course, after which they could invite patients with chronic diseases to fill in the electronic questionnaire during their waiting time. We surveyed patients, practice assistants and GPs regarding their acceptance of this tool in semi-structured telephone interviews. The number of assessments, HRQoL results and interview responses were analysed using quantitative and qualitative methods. Results Over the course of 1 year, 523 patients filled in the electronic questionnaires (1–5 times; 664 total assessments). On average, results showed specific HRQoL impairments, e.g. with respect to fatigue, pain and sleep disturbances. The number of electronic assessments varied substantially between practices. A total of 280 patients, 27 practice assistants and 17 GPs participated in the telephone interviews. Almost all GPs (16/17 = 94%; 95% CI = 73–99%), most practice assistants (19/27 = 70%; 95% CI = 50–86%) and the majority of patients (240/280 = 86%; 95% CI = 82–91%) indicated that they would welcome the use of electronic HRQoL questionnaires in the future. GPs mentioned availability of local health services (e.g. supportive, physiotherapy) (mean: 9.4 ± 1.0 SD; scale: 1 – 10), sufficient extra time (8.9 ± 1.5) and easy interpretation of HRQoL results (8.6 ± 1.6) as the most important prerequisites for their use. They believed HRQoL assessment facilitated both communication and follow up of patients' conditions. Practice assistants emphasised that this process demonstrated an extra commitment to patient centred care; patients viewed it as a tool, which contributed to the physicians' understanding of their personal condition and circumstances. Conclusion This pilot study indicates that electronic HRQoL assessment is technically feasible in general practices. It can provide clinically significant information, which can either be used in the consultation for routine care, or for research purposes. While GPs, practice assistants and patients were generally positive about the electronic procedure, several barriers (e.g. practices' lack of time and routine in HRQoL assessment) need to be overcome to enable broader application of electronic questionnaires in every day medical practice.

„Extra locos sepulturae“ – Review about finds of newborns inside Roman settlements in present-day Switzerland

Finds of remains of newborns inside Roman settlements are a widespread phenomenon in the Imperium Romanum, including presentday Switzerland. Since the publication of the last review article (Berger 1993) numerous new finds have been made. Therefore it seems important to summarize archaeological and anthropological parameters again, and to re-assess them collectively. During a literature review a total of 262 cases were collected. Similarities as well as differences in the funerary practices become evident. A combination of inhumation, single deposit/grave, and absence of grave goods is the least common denominator in the funerary treatment of individuals who died around the time of birth. However, methods of classical physical anthropology are limited. Histological and biochemical methods are promising and may allow further statements in the future, e.g. with regard to the differentiation between live and still births. In order to evaluate possible correlations between archaeological and anthropological parameters, findings from settlements and cemeteries that are documented in situ as well as a sustainable theoretical framework are required.

Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice

BACKGROUND Intrauterine growth restriction (IUGR) occurs in up to 10% of pregnancies and is considered as a major risk to develop various diseases in adulthood, such as cardiovascular diseases, insulin resistance, hypertension or end stage kidney disease. Several IUGR models have been developed in order to understand the biological processes linked to fetal growth retardation, most of them being rat or mouse models and nutritional models. In order to reproduce altered placental flow, surgical models have also been developed, and among them bilateral uterine ligation has been frequently used. Nevertheless, this model has never been developed in the mouse, although murine tools display multiple advantages for biological research. The aim of this work was therefore to develop a mouse model of bilateral uterine ligation as a surgical model of IUGR. RESULTS In this report, we describe the set up and experimental data obtained from three different protocols (P1, P2, P3) of bilateral uterine vessel ligation in the mouse. Ligation was either performed at the cervical end of each uterine horn (P1) or at the central part of each uterine horn (P2 and P3). Time of surgery was E16 (P1), E17 (P2) or E16.5 (P3). Mortality, maternal weight and abortion parameters were recorded, as well as placentas weights, fetal resorption, viability, fetal weight and size. Results showed that P1 in test animals led to IUGR but was also accompanied with high mortality rate of mothers (50%), low viability of fetuses (8%) and high resorption rate (25%). P2 and P3 improved most of these parameters (decreased mortality and improved pregnancy outcomes; improved fetal viability to 90% and 27%, respectively) nevertheless P2 was not associated to IUGR contrary to P3. Thus P3 experimental conditions enable IUGR with better pregnancy and fetuses outcomes parameters that allow its use in experimental studies. CONCLUSIONS Our results show that bilateral uterine artery ligation according to the protocol we have developed and validated can be used as a surgical mouse model of IUGR.

The utilitarian and hedonic outcomes of music information seeking in everyday life

This qualitative study focuses on what contributes to making a music information-seeking experience satisfying in the context of everyday life. Data were collected through in-depth interviews conducted with 15 younger adults (18 to 29 years old). The analysis revealed that satisfaction could depend on both hedonic (i.e., experiencing pleasure) and utilitarian outcomes. It was found that two types of utilitarian outcomes contributed to satisfaction: (1) the acquisition of music, and (2) the acquisition of information about music. Information about music was gathered to (1) enrich the listening experience, (2) increase one's music knowledge, and/or (3) optimize future acquisition. This study contributes to a better understanding of music information-seeking behavior in recreational contexts. It also has implications for music information retrieval systems design: results suggest that these systems should be engaging, include a wealth of extra-musical information, allow users to navigate among music items, and encourage serendipitous encountering of music.

The utilitarian and hedonic outcomes of music information seeking in everyday life

This qualitative study focuses on what contributes to making a music information-seeking experience satisfying in the context of everyday life. Data were collected through in-depth interviews conducted with 15 younger adults (18 to 29 years old). The analysis revealed that satisfaction could depend on both hedonic (i.e., experiencing pleasure) and utilitarian outcomes. It was found that two types of utilitarian outcomes contributed to satisfaction: (1) the acquisition of music, and (2) the acquisition of information about music. Information about music was gathered to (1) enrich the listening experience, (2) increase one's music knowledge, and/or (3) optimize future acquisition. This study contributes to a better understanding of music information-seeking behavior in recreational contexts. It also has implications for music information retrieval systems design: results suggest that these systems should be engaging, include a wealth of extra-musical information, allow users to navigate among music items, and encourage serendipitous encountering of music.

The life of Alexander Nowell, dean of St. Paul's,

Extra illustrated.