Effects of photoperiod and temperature on recent growth rates of sprat larvae in the Baltic Sea

Growth rate has been shown to effect survival and recruitment of marine fishes. How growth rates in the field are affected by larval development and environmental variability is poorly understood. Recent growth rates of sprat larvae, a key species in the Baltic Marine ecosystem, were determined by converting RNA/DNA ratios determined from individual larvae into recent growth based on a laboratory calibrated RNA/DNA temperature growth model. Several factors (larval size, temperature and photoperiod) that may contribute to the observed variability in recent growth sampled in the spawning seasons 2002 through 2004 were analyzed with a variety of models. Best fit was found for the Generalized Additive Models (GAMs). Larval size (dry weight), photoperiod and temperature terms explained 29 % and 36 % of the variability observed in recent growth of sprat larvae in the Baltic Sea, respectively

Case complexity scores in congenital heart surgery: A comparative study of the Aristotle Basic Complexity score and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) system

ObjectiveThe Aristotle Basic Complexity score and the Risk Adjustment in Congenital Heart Surgery system were developed by consensus to compare outcomes of congenital cardiac surgery. We compared the predictive value of the 2 systems.MethodsOf all index congenital cardiac operations at our institution from 1982 to 2004 (n = 13,675), we were able to assign an Aristotle Basic Complexity score, a Risk Adjustment in Congenital Heart Surgery score, and both scores to 13,138 (96%), 11,533 (84%), and 11,438 (84%) operations, respectively. Models of in-hospital mortality and length of stay were generated for Aristotle Basic Complexity and Risk Adjustment in Congenital Heart Surgery using an identical data set in which both Aristotle Basic Complexity and Risk Adjustment in Congenital Heart Surgery scores were assigned. The likelihood ratio test for nested models and paired concordance statistics were used.ResultsAfter adjustment for year of operation, the odds ratios for Aristotle Basic Complexity score 3 versus 6, 9 versus 6, 12 versus 6, and 15 versus 6 were 0.29, 2.22, 7.62, and 26.54 (P < .0001). Similarly, odds ratios for Risk Adjustment in Congenital Heart Surgery categories 1 versus 2, 3 versus 2, 4 versus 2, and 5/6 versus 2 were 0.23, 1.98, 5.80, and 20.71 (P < .0001). Risk Adjustment in Congenital Heart Surgery added significant predictive value over Aristotle Basic Complexity (likelihood ratio χ2 = 162, P < .0001), whereas Aristotle Basic Complexity contributed much less predictive value over Risk Adjustment in Congenital Heart Surgery (likelihood ratio χ2 = 13.4, P = .009). Neither system fully adjusted for the child’s age. The Risk Adjustment in Congenital Heart Surgery scores were more concordant with length of stay compared with Aristotle Basic Complexity scores (P < .0001).ConclusionsThe predictive value of Risk Adjustment in Congenital Heart Surgery is higher than that of Aristotle Basic Complexity. The use of Aristotle Basic Complexity or Risk Adjustment in Congenital Heart Surgery as risk stratification and trending tools to monitor outcomes over time and to guide risk-adjusted comparisons may be valuable

Conventional and sutureless techniques for management of the pulmonary veins: Evolution of indications from postrepair pulmonary vein stenosis to primary pulmonary vein anomalies

ObjectiveWe have previously reported a limited but favorable experience with a novel sutureless technique for surgical management of postoperative pulmonary vein stenosis occurring after repair of total anomalous pulmonary venous drainage. Because this technique requires integrity of the retrocardiac space for hemostasis, extension of the technique to the primary repair of pulmonary vein anomalies requires evaluation. This analysis reviews our experience with the sutureless technique in patients with postrepair pulmonary vein stenosis, as well as our extension of the technique into primary repair of pulmonary vein anomalies.MethodsRetrospective univariable-multivariable analysis of all pulmonary vein stenosis procedures and sutureless pulmonary vein procedures over a 20-year period was performed. Cox proportional hazards modeling was used to identify variables associated with freedom from reoperation or death.ResultsSixty patients underwent 73 procedures, with pulmonary vein stenosis present in 65 procedures. The sutureless technique was used in 40 procedures. Freedom from reoperation or death at 5 years after the initial procedure was 49%. Unadjusted freedom from reoperation or death was greater with the sutureless technique for patients with postrepair pulmonary vein stenosis (P = .04). By using multivariable analysis, a higher pulmonary vein stenosis score was associated with greater risk of reoperation or death. After adjustment, the sutureless repair was associated with a nonsignificant trend toward greater freedom from reoperation or death (P = .12). Despite the absence of retrocardiac adhesions, operative mortality was not increased with the sutureless technique (P = .64). Techniques to control bleeding (intrapleural hilar reapproximation) and improve exposure (inferior vena cava division) were identified.ConclusionThe sutureless technique for postrepair pulmonary vein stenosis is associated with encouraging midterm results. Extension of the indications for the technique to primary repair appears safe with the development of simple intraoperative maneuvers

Chemistry And Behavioral Studies Identify Chiral Cyclopropanes As Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting An Antidepressant Profile

Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing α4β2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at α4β2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other α4β2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression. © 2011 American Chemical Society

Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action

We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37 with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10–60 mg/kg) decreased immobility time in the mouse forced swim test

Biochemical indices and life traits of loggerhead turtles (Caretta caretta) from Cape Verde Islands

The loggerhead turtle (Caretta caretta) is an endangered marine reptile for whom assessing population health requires knowledge of demographic parameters such as individual growth rate. In Cape Verde, as within several populations, adult female loggerhead sea turtles show a size-related behavioral and trophic dichotomy. While smaller females are associated with oceanic habitats, larger females tend to feed in neritic habitats, which is reflected in their physiological condition and in their offspring. The ratio of RNA/DNA provides a measure of cellular protein synthesis capacity, which varies depending on changes in environmental conditions such as temperature and food availability. The purpose of this study was to evaluate the combined use of morphometric data and biochemical indices as predictors of the physiological condition of the females of distinct sizes and hatchlings during their nesting season and how temperature may influence the physiological condition on the offspring. Here we employed biochemical indices based on nucleic acid derived indices (standardized RNA/DNA ratio-sRD, RNA concentration and DNA concentration) in skin tissue as a potential predictor of recent growth rate in nesting females and hatchling loggerhead turtles. Our major findings were that the physiological condition of all nesting females (sRD) decreased during the nesting season, but that females associated with neritic habitats had a higher physiological condition than females associated with oceanic habitats. In addition, the amount of time required for a hatchling to right itself was negatively correlated with its physiological condition (sRD) and shaded nests produced hatchlings with lower sRD. Overall, our results showed that nucleic acid concentrations and ratios of RNA to DNA are an important tool as potential biomarkers of recent growth in marine turtles. Hence, as biochemical indices of instantaneous growth are likely temperature-, size- and age-dependent, the utility and validation of these indices on marine turtles stocks deserves further study.The authors thank the Cape Verde Ministry of Environment (General Direction for the Environment), INDP (National Fisheries Institution), the Canary Islands Government (D.G. Africa and D.G. Research and Universities), ICCM (Canarian Institution for Marine Sciences), the Andalusian Government (Andalusian Environmental Office) and AEGINA PROJECT (INTERREG IIIB) for funding and hosting them during this study. The authors also thank the European Regional Development Fund (ERDF) through the COMPETE - Operational Competitiveness Programme, and national funds through FCT - PEst-C/MAR/LA0015/2011 for supporting the biochemical analysis

Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design

We found that spadin, a natural peptide derived from sortilin, blocks the mouse TREK-1 channel and might be an efficient and fast-acting antidepressant

Genetic Background and Sex: Impact on Generalizability of Research Findings in Pharmacology Studies

Animal models consisting of inbred laboratory rodent strains have been a powerful tool for decades, helping to unravel the underpinnings of biological problems and employed to evaluate potential therapeutic treatments in drug discovery. While inbred strains demonstrate relatively reliable and predictable responses, using a single inbred strain alone or as a background to a mutation is analogous to running a clinical trial in a single individual and their identical twins. Indeed, complex etiologies drive the most common human diseases, and a single inbred strain that is a surrogate of a single genome, or data generated from a single sex, is not representative of the genetically diverse patient populations. Further, pharmacological and toxicology data generated in otherwise healthy animals may not translate to disease states where physiology, metabolism, and general health are compromised. The purpose of this chapter is to provide guidance for improving generalizability of preclinical studies by providing insight into necessary considerations for introducing systematic variation within the study design, such as genetic diversity, the use of both sexes, and selection of appropriate age and disease model. The outcome of implementing these considerations should be that reproducibility and generalizability of significant results are significantly enhanced leading to improved clinical translation