Testing Bergmann's rule in marine copepods

Macroecological relationships provide insights into rules that govern ecological systems. Bergmann's rule posits that members of the same clade are larger at colder temperatures. Whether temperature drives this relationship is debated because several other potential drivers covary with temperature. We conducted a near-global comparative analysis on marine copepods (97 830 samples, 388 taxa) to test Bergmann's rule, considering other potential drivers. Supporting Bergmann's rule, we found temperature better predicted size than did latitude or oxygen, with body size decreasing by 43.9% across the temperature range (-1.7 to 30ºC). Body size also decreased by 26.9% across the range in food availability. Our results provide strong support for Bergman's rule in copepods, but emphasises the importance of other drivers in modifying this pattern. As the world warms, smaller copepod species are likely to emerge as ‘winners', potentially reducing rates of fisheries production and carbon sequestration

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

A successfully thrombolysed acute inferior myocardial infarction due to type A aortic dissection with lethal consequences: the importance of early cardiac echocardiography

Thrombolysis, a standard therapy for ST elevation myocardial infarction (STEMI) in non-PCI-capable hospitals, may be catastrophic for patients with aortic dissection leading to further expansion, rupture and uncontrolled bleeding. Stanford type A aortic dissection, rarely may mimic myocardial infarction. We report a case of a patient with an inferior STEMI thrombolysed with tenecteplase and followed by clinical and electrocardiographic evidence of successful reperfusion, which was found later to be a lethal acute aortic dissection. Prognostic implications of early diagnosis applying transthoracic echocardiography (TTE) are described

Preventive drugs in the last year of life of older adults with cancer: Is there room for deprescribing?

BACKGROUND: The continuation of preventive drugs among older patients with advanced cancer has come under scrutiny because these drugs are unlikely to achieve their clinical benefit during the patients' remaining lifespan. METHODS: A nationwide cohort study of older adults (those aged ≥65 years) with solid tumors who died between 2007 and 2013 was performed in Sweden, using routinely collected data with record linkage. The authors calculated the monthly use and cost of preventive drugs throughout the last year before the patients' death. RESULTS: Among 151,201 older persons who died with cancer (mean age, 81.3 years [standard deviation, 8.1 years]), the average number of drugs increased from 6.9 to 10.1 over the course of the last year before death. Preventive drugs frequently were continued until the final month of life, including antihypertensives, platelet aggregation inhibitors, anticoagulants, statins, and oral antidiabetics. Median drug costs amounted to $1482 (interquartile range [IQR],$700-$2896]) per person, including$213 (IQR, $77-$490) for preventive therapies. Compared with older adults who died with lung cancer (median drug cost, $205; IQR,$61-$523), costs for preventive drugs were higher among older adults who died with pancreatic cancer (adjusted median difference,$13; 95% confidence interval, $5-$22) or gynecological cancers (adjusted median difference, $27; 95$18-$36). There was no decrease noted with regard to the cost of preventive drugs throughout the last year of life. CONCLUSIONS: Preventive drugs commonly are prescribed during the last year of life among older adults with cancer, and often are continued until the final weeks before death. Adequate deprescribing strategies are warranted to reduce the burden of drugs with limited clinical benefit near the end of life

Regulation of Progranulin Expression in Human Microglia and Proteolysis of Progranulin by Matrix Metalloproteinase-12 (MMP-12)

Background: The essential role of progranulin (PGRN) as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia. Goal: In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12), as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI), in human CNS cells. Methods: Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC), Th1 cytokines (IL-1/IFNc), or Th2 cytokines (IL-4, IL-13). Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined. Results: Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNc, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

BACKGROUND: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5- year overall survival rate is similar to 50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. METHODS: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. RESULTS: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1-4.6; P = 0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2-27.4; P = 0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2- 6.5; P = 0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance. CONCLUSION: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC. British Journal of Cancer (2010) 102, 1778-1785. doi: 10.1038/sj.bjc.6605707 www.bjcancer.com Published online 25 May 2010 (C) 2010 Cancer Research U

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort

BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development