Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment

Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impact

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes.

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

How to describe species richness patterns for bryophyte conservation?

A large amount of data for inconspicuous taxa is stored in natural history collections; however, this information is often neglected for biodiversity patterns studies. Here, we evaluate the performance of direct interpolation of museum collections data, equivalent to the traditional approach used in bryophyte conservation planning, and stacked species distribution models (S-SDMs) to produce reliable reconstructions of species richness patterns, given that differences between these methods have been insufficiently evaluated for inconspicuous taxa. Our objective was to contrast if species distribution models produce better inferences of diversity richness than simply selecting areas with the higher species numbers. As model species, we selected Iberian species of the genus Grimmia (Bryophyta), and we used four well-collected areas to compare and validate the following models: 1) four Maxent richness models, each generated without the data from one of the four areas, and a reference model created using all of the data and 2) four richness models obtained through direct spatial interpolation, each generated without the data from one area, and a reference model created with all of the data. The correlations between the partial and reference Maxent models were higher in all cases (0.45 to 0.99), whereas the correlations between the spatial interpolation models were negative and weak (-0.3 to -0.06). Our results demonstrate for the first time that S-SDMs offer a useful tool for identifying detailed richness patterns for inconspicuous taxa such as bryophytes and improving incomplete distributions by assessing the potential richness of under-surveyed areas, filling major gaps in the available data. In addition, the proposed strategy would enhance the value of the vast number of specimens housed in biological collections.

Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression.

An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ.

Characterizing the vulnerability of frequent emergency department users by applying a conceptual framework: a controlled, cross-sectional study.

BACKGROUND: Frequent emergency department (ED) users meet several of the criteria of vulnerability, but this needs to be further examined taking into consideration all vulnerability's different dimensions. This study aimed to characterize frequent ED users and to define risk factors of frequent ED use within a universal health care coverage system, applying a conceptual framework of vulnerability. METHODS: A controlled, cross-sectional study comparing frequent ED users to a control group of non-frequent users was conducted at the Lausanne University Hospital, Switzerland. Frequent users were defined as patients with five or more visits to the ED in the previous 12 months. The two groups were compared using validated scales for each one of the five dimensions of an innovative conceptual framework: socio-demographic characteristics; somatic, mental, and risk-behavior indicators; and use of health care services. Independent t-tests, Wilcoxon rank-sum tests, Pearson's Chi-squared test and Fisher's exact test were used for the comparison. To examine the -related to vulnerability- risk factors for being a frequent ED user, univariate and multivariate logistic regression models were used. RESULTS: We compared 226 frequent users and 173 controls. Frequent users had more vulnerabilities in all five dimensions of the conceptual framework. They were younger, and more often immigrants from low/middle-income countries or unemployed, had more somatic and psychiatric comorbidities, were more often tobacco users, and had more primary care physician (PCP) visits. The most significant frequent ED use risk factors were a history of more than three hospital admissions in the previous 12 months (adj OR:23.2, 95%CI = 9.1-59.2), the absence of a PCP (adj OR:8.4, 95%CI = 2.1-32.7), living less than 5 km from an ED (adj OR:4.4, 95%CI = 2.1-9.0), and household income lower than USD 2,800/month (adj OR:4.3, 95%CI = 2.0-9.2). CONCLUSIONS: Frequent ED users within a universal health coverage system form a highly vulnerable population, when taking into account all five dimensions of a conceptual framework of vulnerability. The predictive factors identified could be useful in the early detection of future frequent users, in order to address their specific needs and decrease vulnerability, a key priority for health care policy makers. Application of the conceptual framework in future research is warranted.

Screening of mental health and substance users in frequent users of a general Swiss emergency department.

BACKGROUND: The objectives of this study were to determine the proportions of psychiatric and substance use disorders suffered by emergency departments' (EDs') frequent users compared to the mainstream ED population, to evaluate how effectively these disorders were diagnosed in both groups of patients by ED physicians, and to determine if these disorders were predictive of a frequent use of ED services. METHODS: This study is a cross-sectional study with concurrent and retrospective data collection. Between November 2009 and June 2010, patients' mental health and substance use disorders were identified prospectively in face-to-face research interviews using a screening questionnaire (i.e. researcher screening). These data were compared to the data obtained from a retrospective medical chart review performed in August 2011, searching for mental health and substance use disorders diagnosed by ED physicians and recorded in the patients' ED medical files (i.e. ED physician diagnosis). The sample consisted of 399 eligible adult patients (≥18 years old) admitted to the urban, general ED of a University Hospital. Among them, 389 patients completed the researcher screening. Two hundred and twenty frequent users defined by >4 ED visits in the previous twelve months were included and compared to 169 patients with ≤4 ED visits in the same period (control group). RESULTS: Researcher screening showed that ED frequent users were more likely than members of the control group to have an anxiety, depressive disorder, post-traumatic stress disorder (PTSD), or suffer from alcohol, illicit drug abuse/addiction. Reviewing the ED physician diagnosis, we found that the proportions of mental health and substance use disorders diagnosed by ED physicians were low both among ED frequent users and in the control group. Using multiple logistic regression analyses to predict frequent ED use, we found that ED patients who screened positive for psychiatric disorders only and those who screened positive for both psychiatric and substance use disorders were more likely to be ED frequent users compared to ED patients with no disorder. CONCLUSIONS: This study found high proportions of screened mental health and/or substance use disorders in ED frequent users, but it showed low rates of detection of such disorders in day-to-day ED activities which can be a cause for concern. Active screening for these disorders in this population, followed by an intervention and/or a referral for treatment by a case-management team may constitute a relevant intervention for integration into a general ED setting.