Spatial cost-benefit analysis of blue restoration and factors driving net benefits globally.

This is the final version. Available from Wiley via the DOI in this record. Marine coastal ecosystems, commonly referred to as blue ecosystems, provide valuable services to society but are under increasing threat worldwide due to a variety of drivers, including eutrophication, development, land-use change, land reclamation, and climate change. Ecological restoration is sometimes necessary to facilitate recovery in coastal ecosystems. Blue restoration (i.e., in marine coastal systems) is a developing field, and projects to date have been small scale and expensive, leading to the perception that restoration may not be economically viable. We conducted a global cost-benefit analysis to determine the net benefits of restoring coral reef, mangrove, saltmarsh, and seagrass ecosystems, where the benefit is defined as the monetary value of ecosystem services. We estimated costs from published restoration case studies and used an adjusted-value-transfer method to assign benefit values to these case studies. Benefit values were estimated as the monetary value provided by ecosystem services of the restored habitats. Benefits outweighed costs (i.e., there were positive net benefits) for restoration of all blue ecosystems. Mean benefit:cost ratios for ecosystem restoration were eight to 10 times higher than prior studies of coral reef and seagrass restoration, most likely due to the more recent lower cost estimates we used. Among ecosystems, saltmarsh had the greatest net benefits followed by mangrove; coral reef and seagrass ecosystems had lower net benefits. In general, restoration in nations with middle incomes had higher (eight times higher in coral reefs and 40 times higher in mangroves) net benefits than those with high incomes. Within an ecosystem type, net benefit varied with restoration technique (coral reef and saltmarsh), ecosystem service produced (mangrove and saltmarsh), and project duration (seagrass). These results challenge the perceptions of the low economic viability of blue restoration and should encourage further targeted investment in this field

Feasibility of Photofrin II as a radiosensitizing agent in solid tumors - Preliminary results

Background: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. Material and Methods: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. Results: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of > 45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. Conclusion: The early follow-up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent

Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake

Glucocorticoids increase adipocyte proliferation and differentiation, a process underpinned by the local reactivation of inactive cortisone to active cortisol within adipocytes catalyzed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been shown to inhibit 11β-HSD1 in murine adipocytes; however, rodent adrenals do not produce DHEA physiologically. Here, we aimed to determine the effects and underlying mechanisms of the potential antiglucocorticoid action of DHEA and its sulfate ester DHEAS in human preadipocytes. Utilizing a human subcutaneous preadipocyte cell line, Chub-S7, we examined the metabolism and effects of DHEA in human adipocytes, including adipocyte proliferation, differentiation, 11β-HSD1 expression, and activity and glucose uptake. DHEA, but not DHEAS, significantly inhibited preadipocyte proliferation via cell cycle arrest in the G1 phase independent of sex steroid and glucocorticoid receptor activation. 11β-HSD1 oxoreductase activity in differentiated adipocytes was inhibited by DHEA. DHEA coincubated with cortisone significantly inhibited preadipocyte differentiation, which was assessed by the expression of markers of early (LPL) and terminal (G3PDH) adipocyte differentiation. Coincubation with cortisol, negating the requirement for 11β-HSD1 oxoreductase activity, diminished the inhibitory effect of DHEA. Further consistent with glucocorticoidopposing effects of DHEA, insulin-independent glucose uptake was significantly enhanced by DHEA treatment. DHEA increases basal glucose uptake and inhibits human preadipocyte proliferation and differentiation, thereby exerting an antiglucocorticoid action. DHEA inhibition of the amplification of glucocorticoid action mediated by 11β-HSD1 contributes to the inhibitory effect of DHEA on human preadipocyte differentiation

Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells

Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells. Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in MCF-7 (drug-sensitive) and MDA-MB-231 (drug-insensitive) cells. Furthermore, when we transiently silenced Bcl-2, both cisplatin and paclitaxel induced apoptosis more than parental cells. Dose dependent induction of apoptosis by drugs was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin was significant on both cell lines, the effect of paclitaxel was much less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in MDA-MB-231 cells pretreated with HA14-1, caspases and Bcl-2 family proteins were studied. The apoptotic effect of cisplatin with or without HA14-1 pre-treatment is shown to be caspase-dependent. Among pro-apoptotic Bcl-2 proteins, Bax and Puma were found to be up-regulated whereas Bcl-2 and Bcl-x(L) were down-regulated when cells were pretreated with HA14-1 followed by paclitaxel or cisplatin. Enforced Bcl-2 expression in MDA-MB-231 cells abrogated the sensitizing effect of HA14-1 in cisplatin induced apoptosis. These results suggest that the potentiating effect of HA14-1 is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs

The Outcome of Phagocytic Cell Division with Infectious Cargo Depends on Single Phagosome Formation

Given that macrophages can proliferate and that certain microbes survive inside phagocytic cells, the question arises as to the post-mitotic distribution of microbial cargo. Using macrophage-like cells we evaluated the post-mitotic distribution of intracellular Cryptococcus yeasts and polystyrene beads by comparing experimental data to a stochastic model. For beads, the post-mitotic distribution was that expected from chance alone. However, for yeast cells the post-mitotic distribution was unequal, implying preferential sorting to one daughter cell. This mechanism for unequal distribution was phagosomal fusion, which effectively reduced the intracellular particle number. Hence, post-mitotic intracellular particle distribution is stochastic, unless microbial and/or host factors promote unequal distribution into daughter cells. In our system unequal cargo distribution appeared to benefit the microbe by promoting host cell exocytosis. Post-mitotic infectious cargo distribution is a new parameter to consider in the study of intracellular pathogens since it could potentially define the outcome of phagocytic-microbial interactions

A systematic approach to performing a comprehensive transesophageal echocardiogram. A call to order

<p>Abstract</p> <p>Background</p> <p>While the order for a clinical transthoracic examination is fairly standardized, there is considerable variability between laboratories and even among physicians in the same laboratory with regard to the order for transesophageal echocardiograms (TEE). A systematic approach is desirable for more efficient use of physician and patient time, avoidance of inadvertent omission of important views, and to facilitate study review.</p> <p>Methods</p> <p>We propose a standardized approach to TEE data acquisition in which cardiac structures are systematically identified and characterized at sequential positions and imaging planes to facilitate organized, efficient and comprehensive assessment.</p> <p>Results</p> <p>Our approach to TEE study begins in the mid-esophagus with the imaging plane at 0°. Based on the specific indication for the TEE, a cardiac structure (e.g., mitral valve, left atrial appendage, or interatrial septum) is chosen as the primary focal point for a comprehensive, multiplane analysis. This structure is assessed in 20° – 30° increments as the imaging plane is advanced from 0° to 165°. Using the aortic valve as a reference point, pertinent cardiac structures are then assessed as the imaging plane is reduced to 135°, to 90°, to 40 – 60° and then back to 0°. The probe is then advanced into the stomach to obtain transgastric images at 0°, 90°, and 120°. Finally, the thoracic aorta and pulmonary artery are assessed as the probe is withdrawn from the body. Using this method, an organized and comprehensive TEE can be performed in 10 – 15 minutes.</p> <p>Conclusion</p> <p>A standardized and systematic TEE approach is described for efficient and comprehensive TEE study.</p

Cross-sectional associations between personality traits and device-based measures of step count and sedentary behaviour in older age: the Lothian Birth Cohort 1936

Background: While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age. Methods: We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2. Results: None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps &gt;.07). Conclusions: We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.</p

Purinergic receptors are part of a signalling system for proliferation and differentiation in distinct cell lineages in human anagen hair follicles

We investigated the expression of P2X5, P2X7, P2Y1 and P2Y2 receptor subtypes in adult human anagen hair follicles and in relation to markers of proliferation [proliferating cell nuclear antigen (PCNA) and Ki-67], keratinocyte differentiation (involucrin) and apoptosis (anticaspase-3). Using immunohistochemistry, we showed that P2X5, P2Y1 and P2Y2 receptors were expressed in spatially distinct zones of the anagen hair follicle: P2Y1 receptors in the outer root sheath and bulb, P2X5 receptors in the inner and outer root sheaths and medulla and P2Y2 receptors in living cells at the edge of the cortex/medulla. P2X7 receptors were not expressed. Colocalisation experiments suggested different functional roles for these receptors: P2Y1 receptors were associated with bulb and outer root sheath keratinocyte proliferation, P2X5 receptors were associated with differentiation of cells of the medulla and inner root sheaths and P2Y2 receptors were associated with early differentiated cells in the cortex/medulla that contribute to the formation of the hair shaft. The therapeutic potential of purinergic agonists and antagonists for controlling hair growth is discussed

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Change in depressive symptoms over higher education and professional establishment - a longitudinal investigation in a national cohort of Swedish nursing students

<p>Abstract</p> <p>Background</p> <p>There are indications of a high prevalence of psychological distress among students in higher education and also that distress increases over the course of study. However, not all studies on student distress controlled for sociodemographic differences and few followed development of distress over an extended period through professional establishment. We investigated if there is an independent effect of time in education and the first two years in the profession on depressive symptoms and mapped change over the period in a national cohort of students.</p> <p>Methods</p> <p>Data came from LANE, a nation-wide longitudinal panel survey of Swedish nursing students (N = 1700) who responded to annual questionnaires over five years from 2002 to 2007. Depressive symptoms were measured by the Major Depression Inventory and change over time analysed in a linear mixed effects model for repeated measures.</p> <p>Results</p> <p>There was a significant change in level of depressive symptoms over time: an increase from the first to later years in education and a decrease to levels similar to baseline after graduation and a year in the profession. The change in symptoms remained significant after adjustment for sociodemographic factors (p < 0.01). Symptom levels differed due to age, gender, household composition and prior nurse assistant training but change over time was similar in all groups. The correlation among the repeated measures, representing within individual correlation over time, varied between 0.44-0.60.</p> <p>Conclusions</p> <p>The findings indicate an independent but transitional effect of time in education and professional establishment on depressive symptoms. We think heightened distress over education abates as the graduate accommodates to the profession. Nevertheless, within education, the differences in depressive symptoms associated to demographic factors can help identify student groups more vulnerable to distress. Also, as individual differences in distress seem to persist over time, perhaps students highly distressed in the beginning of education can be helped by awareness among educators of the elevated levels of distress in late education.</p