Mapping the habitat refugia of Isidella elongata under climate change and trawling impacts to preserve Vulnerable Marine Ecosystems in the Mediterranean.

The bamboo-coral Isidella elongata is a key habitat-forming species in the deep Mediterranean Sea. This alcyonacean is listed as an indicator of Vulnerable Marine Ecosystems (VMEs) and as Critically Endangered due to bottom trawling impacts. In this work, a modeling approach was used to predict and map the habitat suitability of I. elongata in the Mediterranean Sea under current environmental conditions. Occurrence data were modeled as a function of environmental parameters. Using climate change scenarios and fishing effort data, the risk of climate change and fisheries impacts on habitat suitability were estimated, and climate refugia were identified. A drastic loss of habitat is predicted, and climate change scenarios suggest a loss of 60% of suitable habitats by 2100. In the central Mediterranean, climate refugia overlapped with active fishing grounds. This study represents the first attempt to identify hot spots for the protection of soft bottom Vulnerable Marine Ecosystems for the entire Mediterranean Sea, and highlights areas most at risk from trawling. This work is relevant to the objectives of the EU Marine Strategy Framework and Maritime Spatial Planning Directives, the Biodiversity Strategy for 2030 regarding priority areas for conservation.

Investigating wound healing characteristics of gingival and skin keratinocytes in organotypic cultures.

OBJECTIVES: The gingiva heals at an accelerated rate with reduced scarring when compared to skin. Potential well-studied factors include immune cell number, angiogenesis disparities and fibroblast gene expression. Differential keratinocyte gene expression, however, remains relatively understudied. This study explored the contrasting healing efficiencies of gingival and skin keratinocytes, alongside their differential gene expression patterns. METHODS: 3D organotypic culture models of human gingiva and skin were developed using temporarily immortalised primary keratinocytes. Models were wounded for visualisation of re-epithelialisation and analysis of keratinocyte migration to close the wound gap. Concurrently, differentially expressed genes between primary gingival and skin keratinocytes were identified, validated, and functionally assessed. RESULTS: Characterisation of the 3D cultures of gingiva and skin showed differentiation markers that recapitulated organisation of the corresponding in vivo tissue. Upon wounding, gingival models displayed a significantly higher efficiency in re-epithelialisation and stratification versus skin, repopulating the wound gap within 24 hours. This difference was likely due to distinct patterns of migration, with gingival cells demonstrating a form of sheet migration, in contrast to skin, where the leading edge was typically 1-2 cells thick. A candidate approach was used to identify several genes that were differentially expressed between gingival and skin keratinocytes. Knockdown of PITX1 resulted in reduced migration capacity of gingival cells. CONCLUSION: Gingival keratinocytes retain in vivo superior wound healing capabilities in in vitro 2D and 3D environments. Intrinsic gene expression differences could result in gingival cells being 'primed' for healing and play a role in faster wound resolution. CLINICAL SIGNIFICANCE STATEMENT: The successful development of organotypic models, that recapitulate re-epithelialisation, will underpin further studies to analyse the oral response to wound stimuli, and potential therapeutic interventions, in an in vitro environment.

Programmes of measures of the marine strategy framework directive: Are they contributing to achieving good environmental status in the Mediterranean?

The Marine Strategy Framework Directive (MSFD) is the piece of legislation with which the EU aims to achieve Good Environmental Status (GES) of its seas. This Directive requires Member States (MSs) to set up and implement Programmes of Measures (PoMs) to achieve this goal. This paper presents a catalogue as well as the analysis of the 535 measures proposed by the eight Mediterranean EU MSs to combat pollution and non-indigenous species and contribute to the GES of the Mediterranean Sea. The results reiterate the need for better coherence and coordination between MSs, also with non-EU countries in the preparation of the next iteration of PoMs. Only 5% of the measures applied have an effect beyond MSs´ marine waters jurisdiction, and a fifth of them lack linkages with any ecosystem component. The results point to gaps, while desired goals and recommendations will help policy makers to implement the and conceptualise measures.

Using socio-demographic and early clinical features in general practice to identify people with lung cancer earlier.

INTRODUCTION: In the UK, most people with lung cancer are diagnosed at a late stage when curative treatment is not possible. To aid earlier detection, the socio-demographic and early clinical features predictive of lung cancer need to be identified. METHODS: We studied 12,074 cases of lung cancer and 120,731 controls in a large general practice database. Logistic regression analyses were used to identify the socio-demographic and clinical features associated with cancer up to 2 years before diagnosis. A risk prediction model was developed using variables that were independently associated with lung cancer up to 4 months before diagnosis. The model performance was assessed in an independent dataset of 1,826,293 patients from the same database. Discrimination was assessed by means of a receiver operating characteristic (ROC) curve. RESULTS: Clinical and socio-demographic features that were independently associated with lung cancer were patients' age, sex, socioeconomic status and smoking history. From 4 to 12 months before diagnosis, the frequency of consultations and symptom records of cough, haemoptysis, dyspnoea, weight loss, lower respiratory tract infections, non-specific chest infections, chest pain, hoarseness, upper respiratory tract infections and chronic obstructive pulmonary disease were also independently predictive of lung cancer. On validation, the model performed well with an area under the ROC curve of 0.88. CONCLUSIONS: This new model performed substantially better than the current National Institute for Health and Clinical Excellence referral guidelines and all comparable models. It has the potential to predict lung cancer cases sufficiently early to make detection at a curable stage more likely by allowing general practitioners to better risk stratify their patients. A clinical trial is needed to quantify the absolute benefits to patients and the cost effectiveness of this model in practice.

The distribution of lung cancer across sectors of society in the United Kingdom: a study using national primary care data.

BACKGROUND: There is pressing need to diagnose lung cancer earlier in the United Kingdom (UK) and it is likely that research using computerised general practice records will help this process. Linkage of these records to area-level geo-demographic classifications may also facilitate case ascertainment for public health programmes, however, there have as yet been no extensive studies of data validity for such purposes. METHODS: To first address the need for validation, we assessed the completeness and representativeness of lung cancer data from The Health Improvement Network (THIN) national primary care database by comparing incidence and survival between 2000 and 2009 with the UK National Cancer Registry and the National Lung Cancer Audit Database. Secondly, we explored the potential of a geo-demographic social marketing tool to facilitate disease ascertainment by using Experian's Mosaic Public Sector ™ classification, to identify detailed profiles of the sectors of society where lung cancer incidence was highest. RESULTS: Overall incidence of lung cancer (41.4/100, 000 person-years, 95% confidence interval 40.6-42.1) and median survival (232 days) were similar to other national data; The incidence rate in THIN from 2003-2006 was found to be just over 93% of the national cancer registry rate. Incidence increased considerably with area-level deprivation measured by the Townsend Index and was highest in the North-West of England (65.1/100, 000 person-years). Wider variations in incidence were however identified using Mosaic classifications with the highest incidence in Mosaic Public Sector ™types 'Cared-for pensioners, ' 'Old people in flats' and 'Dignified dependency' (191.7, 174.2 and 117.1 per 100, 000 person-years respectively). CONCLUSIONS: Routine electronic data in THIN are a valid source of lung cancer information. Mosaic ™ identified greater incidence differentials than standard area-level measures and as such could be used as a tool for public health programmes to ascertain future cases more effectively.

Test-retest reliability of a battery of field-based health-related fitness measures for adolescents.

The main aim of this study was to determine the test-retest reliability of existing tests of health-related fitness. Participants (mean age 14.8 years, s = 0.4) were 42 boys and 26 girls who completed the study assessments on two occasions separated by one week. The following tests were conducted: bioelectrical impedance analysis (BIA) to calculate percent body fat, leg dynamometer, 90° push-up, 7-stage sit-up, and wall squat tests. Intra-class correlation (ICC), paired samples t-tests, and typical error expressed as a coefficient of variation were calculated. The mean percent body fat intra-class correlation coefficient was similar for boys (ICC = 0.95) and girls (ICC = 0.93), but the mean coefficient of variation was considerably higher for boys than girls (22.2% vs. 12.2%). The boys' coefficients of variation for the tests of muscular fitness ranged from 9.0% for the leg dynamometer test to 26.5% for the timed wall squat test. The girls' coefficients of variation ranged from 17.1% for the sit-up test to 21.4% for the push-up test. Although the BIA machine produced reliable estimates of percent body fat, the tests of muscular fitness resulted in high systematic error, suggesting that these measures may require an extensive familiarization phase before the results can be considered reliable.

Quorum sensing in Cyanobacteria: N-octanoyl-homoserine lactone release and response, by the epilithic colonial cyanobacterium Gloeothece PCC6909.

Quorum sensing involving acyl homoserine lactones (AHLs) is a density-dependent form of intercellular communication that occurs in many different members of the group Proteobacteria. However, to date, there have been few investigations of its occurrence in cyanobacteria. Here, using both a bioreporter Agrobacterium tumefaciens NTL4 (PZLR4) and mass spectrometry, we provide evidence of N-octanoyl homoserine lactone (C8-AHL) production in axenic cultures of the cyanobacterium Gloeothece PCC6909 and its sheathless mutant PCC6909/1. Accumulation of C8-AHL in the culture medium of laboratory cultures of Gloeothece followed a pattern characteristic of the phenomenon of autoinduction, a common feature of functional AHL-based quorum-sensing systems. Analysis by two-dimensional gel electrophoresis showed that, in response to treatment with C8-AHL, early growth-stage cells of PCC6909/1 showed changes in expression of 43 proteins compared with untreated cells. Among the 15 proteins that showed more than a twofold change in expression were RuBisCo, glutamate synthase, chorismate synthase, a member of the LysR family of transcriptional regulators (all upregulated), and enolase and aldolase, both of which were downregulated. The significance of such changes in response to C8-AHL is discussed in relation to carbohydrate and amino-acid metabolism and involvement of Gloeothece in biofilms.

A comprehensive analysis of adverse obstetric and pediatric complications in women with asthma.

RATIONALE: Previous studies have raised concern that women with asthma have increased risks of adverse obstetric and pediatric complications, but these have generally been underpowered. OBJECTIVES: To quantify risks of major adverse pregnancy outcomes and obstetric complications in women with and without asthma. METHODS: We extracted information on 281,019 pregnancies from the Health Improvement Network database between 1988 and 2004. We analyzed the data using logistic regression. MEASUREMENTS AND MAIN RESULTS: In 37,585 pregnancies of women with asthma compared with 243,434 pregnancies of women without asthma, risks of stillbirth and therapeutic abortion were similar; however, the risk of miscarriage was slightly higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.06-1.13). Risks of most obstetric complications (placental abruption, placental insufficiency, placenta previa, preeclampsia, hypertension, gestational diabetes, thyroid disorders in pregnancy, and assisted delivery) were not higher in pregnancies of women with asthma compared with those without asthma, with the exception of increases in antepartum (OR, 1.20; 95% CI, 1.08-1.34) or postpartum (OR, 1.38; 95% CI, 1.21-1.57) hemorrhage, anemia (OR, 1.06; 95% CI, 1.01-1.12), depression (OR, 1.52; 95% CI, 1.36-1.69), and caesarean section (OR, 1.11; 95% CI, 1.07-1.16). Risks of miscarriage, depression, and caesarean section increased moderately in women with more severe asthma and previous asthma exacerbations. CONCLUSIONS: We found some increased risks in women with asthma that need to be considered in the future; however, our results indicate that women with asthma have similar reproductive risks compared with women without asthma in the general population for most of the range of outcomes studied.

Plant proteome analysis by mass spectrometry: principles, problems, pitfalls and recent developments.

The genome of several species has now been elucidated; these genomes indicate the proteomic potential of the cell. While identification of genomes has been, and continues to be, a technically and intellectually demanding process, the identification of the proteome contains inherently greater difficulties. The proteome of each living cell is dynamic, altering in response to the individual cell's metabolic state and reception of intracellular and extracellular signal molecules, and many of the proteins which are expressed will be post-translationally altered. Thus if the purpose of the proteome analysis is to aid the understanding of protein function and interaction, then it is identification of the proteins in their final state which is required: for this mass spectrometric identification of individual proteins, indicating site and nature of modifications, is essential. Here we review the principles of the methodologies involved in such analyses, give some indication of current achievements in plant proteomics, and indicate imminent and prospective technical developments.

Malignancy and mortality in people with coeliac disease: population based cohort study.

OBJECTIVE: To quantify the risks of malignancy and mortality in people with coeliac disease compared with the general population. DESIGN: Population based cohort study. SETTING: General practice research database. PARTICIPANTS: 4732 people with coeliac disease and 23,620 matched controls. MAIN OUTCOME MEASURES: Hazard ratios for malignancy and mortality. RESULTS: Of the 4732 people with coeliac disease, 134 (2.8%) had at least one malignancy and 237 (5.0%) died. The overall hazard ratios were: for any malignancy 1.29 (95% confidence interval 1.06 to 1.55), for mortality 1.31 (1.13 to 1.51), for gastrointestinal cancer 1.85 (1.22 to 2.81), for breast cancer 0.35 (0.17 to 0.72), for lung cancer 0.34 (0.13 to 0.95), and for lymphoproliferative disease 4.80 (2.71 to 8.50). The increased risk was primarily in the first year after diagnosis, with the risk for only lymphoproliferative disease remaining significantly raised thereafter. After excluding events in the year after diagnosis, the hazard ratio for malignancy was 1.10 (0.87 to 1.39) and for mortality was 1.17 (0.98 to 1.38), giving absolute excess rates of 6 and 17 per 10,000 person years, respectively. CONCLUSIONS: People with coeliac disease have modest increases in overall risks of malignancy and mortality. Most of this excess risk occurs in the year of follow up after diagnosis. People with coeliac disease also have a noticeably reduced risk of breast cancer. The mechanism of this merits further attention as it may provide insights into the cause of this common malignancy.

Inhaled corticosteroids and hip fracture: a population-based case-control study.

There is accumulating evidence that the use of inhaled corticosteroids is associated with a dose-related reduction in bone mineral density. Whether this translates to an increase in fracture is unclear. We have used the General Practice Research Database to perform a case-control analysis, including 16,341 cases of hip fracture (mean age of 79 years, 79% female, median period prescribing data 2.7 years) and 29,889 control subjects, individually matched by age, sex, and general practice. Data for all prescriptions for corticosteroids and for potential confounders, including other drug use and comorbid illnesses, were extracted, and the impact of inhaled corticosteroid exposure was analyzed using conditional logistic regression. The risk of hip fracture was associated with exposure to inhaled corticosteroids with an odds ratio of 1.26 (95% confidence interval, 1.17 to 1.36). This odds ratio was reduced after adjusting the model for annual courses of oral corticosteroids, the only confounder of note (OR 1.19; 95% CI, 1.10 to 1.28). There was a dose-response relationship between inhaled corticosteroid use and hip fracture even after adjusting for the annual number of courses of oral corticosteroids (p trend = 0.007). In older subjects, the recent use of inhaled corticosteroids is associated with a dose-related increase in hip fracture.