Chronic exposure to fluoxetine (Prozac) causes developmental delays in Rana pipiens larvae

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are among the many pharmaceuticals detected in aquatic ecosystems. Although the acute effects of SSRIs on select organisms have been reported, little is understood about the chronic effects of these drugs on amphibians, which are particularly sensitive to environmental pollutants. Serotonin plays important roles in many physiological functions, including a wide array of developmental processes. Exposure to SSRIs during development may cause developmental complications in a variety of organisms, but little is known about the degree of exposure necessary to cause deleterious effects. Here, we sought to gain a better understanding of the effects of SSRIs on amphibian development by use of a combined laboratory and outdoor mesocosm study. Tadpoles in a laboratory setting were exposed to a low (0.029 µg/L) and a high (0.29 µg/L) concentration of the common SSRI fluoxetine from stages 21 and 22 through completion of metamorphosis. Tadpoles in outdoor mesocosms were exposed to fluoxetine concentrations ranging from 0.1 to 0.3 µg/L. Exposed tadpoles in the laboratory showed delayed development compared with controls when stage was assessed throughout the experiment. Control tadpoles also gained weight faster than treatment tadpoles, which may be explained by reduced food intake. Mesocosm tadpoles exhibited similar trends, but no significant differences were detected. These results indicate that ecologically relevant levels of fluoxetine may cause developmental delays in amphibians. Environ. Toxicol. Chem. 2010;29:2845–2850. © 2010 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78304/1/345_ftp.pd

CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent KATP channel closure.

Hallmarks of mature β cells are restricted proliferation and a highly energetic secretory state. Paradoxically, cyclin-dependent kinase 2 (CDK2) is synthesized throughout adulthood, its cytosolic localization raising the likelihood of cell cycle-independent functions. In the absence of any changes in β cell mass, maturity, or proliferation, genetic deletion of Cdk2 in adult β cells enhanced insulin secretion from isolated islets and improved glucose tolerance in vivo. At the single β cell level, CDK2 restricts insulin secretion by increasing KATP conductance, raising the set point for membrane depolarization in response to activation of the phosphoenolpyruvate (PEP) cycle with mitochondrial fuels. In parallel with reduced β cell recruitment, CDK2 restricts oxidative glucose metabolism while promoting glucose-dependent amplification of insulin secretion. This study provides evidence of essential, non-canonical functions of CDK2 in the secretory pathways of quiescent β cells

Patterns of abundance across geographical ranges as a predictor for responses to climate change:Evidence from UK rocky shores

Aim: Understanding patterns in the abundance of species across thermal ranges can give useful insights into the potential impacts of climate change. The abundant-centre hypothesis suggests that species will reach peak abundance at the centre of their thermal range where conditions are optimal, but evidence in support of this hypothesis is mixed and limited in geographical and taxonomic scope. We tested the applicability of the abundant-centre hypothesis across a range of intertidal organisms using a large, citizen science-generated data set. Location: UK. Methods: Species' abundance records were matched with their location within their thermal range. Patterns in abundance distribution for individual species, and across aggregated species abundances, were analysed using Kruskal–Wallis tests and quantile general additive models. Results: Individually, invertebrate species showed increasing abundances in the cooler half of the thermal range and decreasing abundances in the warmer half of the thermal range. The overall shape for aggregated invertebrate species abundances reflected a broad peak, with a cool-skewed maximum abundance. Algal species showed little evidence for an abundant-centre distribution individually, but overall the aggregated species abundances suggested a hump-backed abundance distribution. Main Conclusions: Our study follows others in showing mixed support for the abundant-centre hypothesis at an individual species level, but demonstrates an increased predictability in species responses when an aggregated overall response is considered

Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model

Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia. It was proposed that this was due to siglec-F-dependent apoptosis, triggered via engagement with ligands that are upregulated on bronchial epithelium. Our aim was to further investigate the functions of siglec-F by comparing two commonly used models of ovalbumin-induced airway inflammation that differ in the dose and route of administration of ovalbumin. In confirmation of published results, siglec-F-deficient mice had enhanced lung tissue eosinophilia in response to intranasal ovalbumin delivered every other day. However, following aerosolised ovalbumin delivered daily, there was no influence of siglec-F deficiency on lung eosinophilia. Expression of siglec-F ligands in lung tissues was similar in both models of allergen induced inflammation. These data demonstrate that siglec-F-dependent regulation of eosinophilia is subtle and depends critically on the model used. The findings also indicate that mechanisms other than ligand-induced apoptosis may be important in siglec-F-dependent suppression of eosinophilia

A National Survey of Musculoskeletal Impairment in Rwanda: Prevalence, Causes and Service Implications

BACKGROUND: Accurate information on the prevalence and causes of musculoskeletal impairment (MSI) is lacking in low income countries. We present a new survey methodology that is based on sound epidemiological principles and is linked to the World Health Organisation's International Classification of Functioning. METHODS: Clusters were selected with probability proportionate to size. Households were selected within clusters through compact segment sampling. 105 clusters of 80 people (all ages) were included. All participants were screened for MSI by a physiotherapist and medical assistant. Possible cases plus a random sample of 10% of non-MSI cases were examined further to ascertain diagnosis, aetiology, quality of life, and treatment needs. FINDINGS: 6757 of 8368 enumerated individuals (80.8%) were screened. There were 352 cases, giving an overall prevalence for MSI of 5.2%. (95% CI 4.5-5.9) The prevalence of MSI increased with age and was similar in men and women. Extrapolating these estimates, there are approximately 488,000 MSI diagnoses in Rwanda. Only 8.2% of MSI cases were severe, while the majority were moderate (43.7%) or mild (46.3%). Diagnostic categories comprised 11.5% congenital, 31.3% trauma, 3.8% infection, 9.0% neurological, and 44.4% non-traumatic non infective acquired. The most common individual diagnoses were joint disease (13.3%), angular limb deformity (9.7%) and fracture mal- and non-union (7.2%). 96% of all cases required further treatment. INTERPRETATION: This survey demonstrates a large burden of MSI in Rwanda, which is mostly untreated. The survey methodology will be useful in other low income countries, to assist with planning services and monitoring trends

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling

Announcing The Lancet Global Health Commission on Global Eye Health

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Does Cataract Surgery Alleviate Poverty? Evidence from a Multi-Centre Intervention Study Conducted in Kenya, the Philippines and Bangladesh

BACKGROUND: Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. METHODOLOGY/PRINCIPAL FINDINGS: A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh:$16 vs $24 p = 0.004, Philippines:$24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh:$23 vs $23 p = 0.20, Philippines:$45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. CONCLUSIONS/SIGNIFICANCE: This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Online dietary intake estimation : The food4me food frequency questionnaire

Copyright ©Hannah Forster, Rosalind Fallaize, Caroline Gallagher, Clare B O’Donovan, Clara Woolhead, Marianne C Walsh, Anna L Macready, Julie A Lovegrove, John C Mathers, Michael J Gibney, Lorraine Brennan, Eileen R Gibney. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.06.2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.Dietary assessment methods are important tools for nutrition research. Online dietary assessment tools have the potential to become invaluable methods of assessing dietary intake because, compared with traditional methods, they have many advantages including the automatic storage of input data and the immediate generation of nutritional outputs. Objective: The aim of this study was to develop an online food frequency questionnaire (FFQ) for dietary data collection in the Food4Me study and to compare this with the validated European Prospective Investigation of Cancer (EPIC) Norfolk printed FFQ. Methods: The Food4Me FFQ used in this analysis was developed to consist of 157 food items. Standardized color photographs were incorporated in the development of the Food4Me FFQ to facilitate accurate quantification of the portion size of each food item. Participants were recruited in two centers (Dublin, Ireland and Reading, United Kingdom) and each received the online Food4Me FFQ and the printed EPIC-Norfolk FFQ in random order. Participants completed the Food4Me FFQ online and, for most food items, participants were requested to choose their usual serving size among seven possibilities from a range of portion size pictures. The level of agreement between the two methods was evaluated for both nutrient and food group intakes using the Bland and Altman method and classification into quartiles of daily intake. Correlations were calculated for nutrient and food group intakes. Results: A total of 113 participants were recruited with a mean age of 30 (SD 10) years (40.7% male, 46/113; 59.3%, 67/113 female). Cross-classification into exact plus adjacent quartiles ranged from 77% to 97% at the nutrient level and 77% to 99% at the food group level. Agreement at the nutrient level was highest for alcohol (97%) and lowest for percent energy from polyunsaturated fatty acids (77%). Crude unadjusted correlations for nutrients ranged between .43 and .86. Agreement at the food group level was highest for other fruits (eg, apples, pears, oranges) and lowest for cakes, pastries, and buns. For food groups, correlations ranged between .41 and .90. Conclusions: The results demonstrate that the online Food4Me FFQ has good agreement with the validated printed EPIC-Norfolk FFQ for assessing both nutrient and food group intakes, rendering it a useful tool for ranking individuals based on nutrient and food group intakes.Peer reviewedFinal Published versio