Chemotherapy-Induced Late Transgenerational Effects in Mice

To our knowledge, there is no report on long-term reproductive and developmental side effects in the offspring of mothers treated with a widely used chemotherapeutic drug such as doxorubicin (DXR), and neither is there information on transmission of any detrimental effects to several filial generations. Therefore, the purpose of the present paper was to examine the long-term effects of a single intraperitoneal injection of DXR on the reproductive and behavioral performance of adult female mice and their progeny. C57BL/6 female mice (generation zero; G0) were treated with either a single intraperitoneal injection of DXR (G0-DXR) or saline (G0-CON). Data were collected on multiple reproductive parameters and behavioral analysis for anxiety, despair and depression. In addition, the reproductive capacity and health of the subsequent six generations were evaluated. G0-DXR females developed despair-like behaviors; delivery complications; decreased primordial follicle pool; and early lost of reproductive capacity. Surprisingly, the DXR-induced effects in oocytes were transmitted transgenerationally; the most striking effects being observed in G4 and G6, constituting: increased rates of neonatal death; physical malformations; chromosomal abnormalities (particularly deletions on chromosome 10); and death of mothers due to delivery complications. None of these effects were seen in control females of the same generations. Long-term effects of DXR in female mice and their offspring can be attributed to genetic alterations or cell-killing events in oocytes or, presumably, to toxicosis in non-ovarian tissues. Results from the rodent model emphasize the need for retrospective and long-term prospective studies of survivors of cancer treatment and their offspring

A class of solvable Lie algebras and their Casimir Invariants

A nilpotent Lie algebra n_{n,1} with an (n-1) dimensional Abelian ideal is studied. All indecomposable solvable Lie algebras with n_{n,1} as their nilradical are obtained. Their dimension is at most n+2. The generalized Casimir invariants of n_{n,1} and of its solvable extensions are calculated. For n=4 these algebras figure in the Petrov classification of Einstein spaces. For larger values of n they can be used in a more general classification of Riemannian manifolds.Comment: 16 page

Evaluation of a self-management programme for congestive heart failure patients: design of a randomised controlled trial

BACKGROUND: Congestive heart failure (CHF) has a substantial impact on care utilisation and quality of life. It is crucial for patients to cope with CHF adequately, if they are to live an acceptable life. Self-management may play an important role in this regard. Previous studies have shown the effectiveness of the 'Chronic Disease Self-Management Program' (CDSMP), a group-based cognitive behavioural programme for patients with various chronic conditions. However, the programme's effectiveness has not yet been studied specifically among CHF patients. This paper presents the design of a randomised controlled trial to evaluate the effects of the CDSMP on psychosocial attributes, health behaviour, quality of life, and health care utilisation of CHF patients. METHODS/DESIGN: The programme is being evaluated in a two-group randomised controlled trial. Patients were eligible if they had been diagnosed with CHF and experienced slight to marked limitation of physical activity. They were selected from the Heart Failure and/or Cardiology Outpatient Clinics of six hospitals. Eligible patients underwent a baseline assessment and were subsequently allocated to the intervention or control group. Patients allocated to the intervention group were invited to attend the self-management programme consisting of six weekly sessions, led by a CHF nurse specialist and a CHF patient. Those allocated to the control group received care as usual. Follow-up measurements are being carried out immediately after the intervention period, and six and twelve months after the start of the intervention. An effect evaluation and a process evaluation are being conducted. The primary outcomes of the effect evaluation are self-efficacy expectancies, perceived control, and cognitive symptom management. The secondary outcome measures are smoking and drinking behaviour, Body Mass Index (BMI), physical activity level, self-care behaviour, health-related quality of life, perceived autonomy, symptoms of anxiety and depression, and health care utilisation. The programme's feasibility is assessed by measuring compliance with the protocol, patients' attendance and adherence, and the opinions about the programme. DISCUSSION: A total number of 318 patients were included in the trial. At present, follow-up data are being collected. The results of the trial become clear after completion of the data collection in January 2007. TRIAL REGISTRATION: Trialregister () ISRCTN88363287

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

The Interaction of Hypotaurine and Other Sulfinates with Reactive Oxygen and Nitrogen Species:A Survey of Reaction Mechanisms

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants. In the last decade, many experiments have been performed to understand whether peroxynitrite, nitrogen dioxide and carbonate radical anion could be included in the biologically relevant reactive species capable of oxidizing sulfinates. Thanks to this work, it has been possible to highlight two possible reaction mechanisms (direct and indirect reaction) of sulfinates with reactive oxygen and nitrogen species.The sulfinates oxidation, mediated by peroxynitrite, is an example of both reaction mechanisms: through a two-electron-direct-reaction with peroxynitrite or through a one-electron-indirect-transfer reaction. In the indirect mechanism, the peroxynitrite homolysis releases hydroxyl and nitrogen dioxide radical and in addition the degradation of short-lived adduct formed by peroxynitrite and CO2 can generate carbonate radical anion. The reaction of hypotaurine and cysteine sulfinic acid with peroxynitrite-derived radicals is accompanied by extensive oxygen uptake with the generation of transient intermediates, which can begin a reaction by an oxygen-dependent mechanism with the sulfonates, taurine, and cysteic acid as final products. Due to pulse radiolysis studies, it has been shown that transient sulfonyl radicals (RSO2(•)) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years

A Prospective Randomized Trial of Either Famotidine or Pantoprazole for the Prevention of Bleeding after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) has been reported to have a higher bleeding rate than conventional methods. However, there are few reports on whether a proton pump inhibitor or a histamine2-receptor antagonist is the more effective treatment for preventing bleeding after ESD. In a prospective trial, patients undergoing ESD due to gastric adenoma or adenocarcinoma were randomly assigned to pantoprazole or famotidine. Both drugs were given intravenously for the first 2 days, thereafter by mouth. Eighty-five in the pantoprazole group and 79 in the famotidine group were included for analysis. Primary outcome measure was the delayed bleeding rate. Clinical characteristics were not different between the two groups. The delayed bleeding rate was significantly lower in the pantoprazole group compared with the famotidine group (3.5% vs. 12.7%, p=0.031). On multivariate analysis, the preventive use of pantoprazole (relative hazard: 0.220, 95% CI: 0.051- 0.827, p=0.026) and the specimen size (≥34 mm, relative hazard: 4.178, 95% CI: 1.229-14.197, p=0.022) were two independent factors predictive of delayed bleeding. There were no significant differences in en bloc and complete resection rate between the two groups. In conclusion, pantoprazole is more effective than famotidine for the prevention of delayed bleeding after ESD

Survival Benefits of Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy in Locally Advanced Chemoresistant Cervical Cancer

The aim of this study was to analyze long-term survivals in patients with stage IB to IIA cervical cancer treated by neoadjuvant chemotherapy setting. Between February 1989 and January 1998, 94 women with previously untreated stage IB to IIA carcinoma of the uterine cervix who received cisplatin based neoadjuvant chemotherapy were enrolled in this study. All of patients with chemoresponse (complete response, n=15; partial response, n=47) and 16 patients with chemoresistance received radical surgery (RS group). The other 16 patients with chemoresistance received radiotherapy for definite treatment (RT group). In the RS group, the 10 yr survival estimation in patients with bulky tumors (diameter ≥4 cm, n=26) was similar to that with non-bulky tumors (83.3% vs. 89.3%, p=NS). In selected patients with chemoresistance, those treated by radiotherapy (n=16) showed significantly poorer survivals than those treated by radical surgery (n=16) [10 yr survival rates of RT (25%) vs. RS (76.4%), p=0.0111]. Our results support that a possible therapeutic benefit of neoadjuvant chemotherapy plus radical surgery is only in patients with bulky stage IB to IIA cervical cancer. In cases of chemoresistance, radical surgery might be a better definite treatment option

Business model innovation and transition to a sustainable food system: A case study in the Lisbon metropolitan area

The food systems’ transition towards a sustainable involves structural changes, namely the emphasis on local production, short supply chains, and the preference for organic products. The shift in the agri-food system is taking place through the creation of entirely new businesses and individual farms moving towards organic production. In both cases, the enterprises use a combination of well-established agricultural knowledge and techniques, new scientific knowledge on productive methods and new technological platforms for commercialization. These mixed sources permit the creation of innovative business models (BMs). They exemplify how traditional industries can absorb/generate innovation at technological and organizational levels, and become part of the new knowledge-based era. The study has three objectives: to analyse the emerging agri-food businesses in the Lisbon Metropolitan Area (LMA); to characterize innovative sustainable BMs within the transition dynamics; to reflect on the challenges that the characteristics of the food system pose for the emergence of these BMs. The study is part of an interdisciplinary project on Spatial Planning for Change (SPLACH). The analysis addresses the food system transition in a specific territory, namely the LMA. The paper presents results of the research conducted, focusing on the case of an organic food initiative, Quinta do Oeste.info:eu-repo/semantics/acceptedVersio

High-efficiency exfoliation of large-area mono-layer graphene oxide with controlled dimension

In this work, we introduce a novel and facile method of exfoliating large-area, single-layer graphene oxide using a shearing stress. The shearing stress reactor consists of two concentric cylinders, where the inner cylinder rotates at controlled speed while the outer cylinder is kept stationary. We found that the formation of Taylor vortex flow with shearing stress can effectively exfoliate the graphite oxide, resulting in large-area single- or few-layer graphene oxide (GO) platelets with high yields (>90%) within 60 min of reaction time. Moreover, the lateral size of exfoliated GO sheets was readily tunable by simply controlling the rotational speed of the reactor and reaction time. Our approach for high-efficiency exfoliation of GO with controlled dimension may find its utility in numerous industrial applications including energy storage, conducting composite, electronic device, and supporting frameworks of catalyst