Effect of ploidy on salinity and temperature tolerance in early life stages of the Eastern oyster (\u3ci\u3eCrassostrea virginica\u3c/i\u3e)

The U.S. Gulf of Mexico contains the largest remaining wild oyster fishery in the world, but populations have declined in recent decades. A growing interest in off-bottom aquaculture that relies on triploid eastern oysters (Crassostrea virginica) has emerged in the Gulf region, yet these faster growing oysters suffer high mortality as adults during low salinity (\u3c5) events in warmer summer months. The combined effects of low salinity and high temperature stress on early life stages of triploid oysters are unknown. Early life stages are particularly crucial to understand because triploid oysters do not occur naturally and must be reared in hatchery settings, requiring appropriate water conditions to yield the greatest survival and growth. Thus, we tested the effects of different temperatures (28 ºC and 32 ºC) and salinities (5, 10, and 15) on diploid and triploid oysters at three critical production stages: veliger, pediveliger, and spat. Veliger survival was significantly lower for triploids relative to diploid oysters at all experimental conditions, but triploid veligers had faster growth than diploids at 32 ºC and salinity of 15. Pediveliger settlement was not affected by ploidy type and was reduced only at high temperature (32 ºC) and the lowest salinity (5). Diploid spat showed highest survival at 28 ºC and 15 salinity, while triploids survived best at 32 ºC and 15 salinity. Triploid spat attained greater shell height compared to diploids in our 6- day exposures, but growth decreased for both ploidies at lower salinities. At the salinity and temperature levels examined, diploid early life stages performed best at 28 ºC and 15 salinity, whereas triploids were more successful at 32 ºC and 15 salinity. A broader understanding of the combined effects of environmental stressors will improve the success of hatchery production yields and the resulting economic and environmental benefits of the oyster industry

Effectiveness of Switching Smoking-Cessation Medications Following Relapse

Introduction—Nicotine dependence is a chronic disorder often characterized by multiple failed quit attempts (QAs). Yet, little is known about the sequence of methods used across multiple QAs or how this may impact future ability to abstain from smoking. This prospective cohort study examines the effectiveness of switching smoking-cessation medications (SCMs) across multiple QAs. Methods—Adult smokers (aged ≥ 18 years) participating in International Tobacco Control surveys in the United Kingdom, U.S., Canada, and Australia (N=795) who: (1) completed two consecutive surveys between 2006 and 2011; (2) initiated a QA at least 1 month before each survey; and (3) provided data for the primary predictor (SCM use during most recent QA), outcome (1-month point prevalence abstinence), and relevant covariates. Analyses were conducted in 2016. Results—Five SCM user classifications were identified: (1) non-users (43.5%); (2) early users (SCM used for initial, but not subsequent QA; 11.4%); (3) later users (SCM used for subsequent, but not initial QA; 18.4%); (4) repeaters (same SCM used for both QAs; 10.7%); and (5) switchers (different SCM used for each QA; 14.2%). Abstinence rates were lower for non-users (15.9%, OR=0.48, p=0.002), early users (16.6%, OR=0.27, p=0.03), and repeaters (12.4%, OR=0.36, p=0.004) relative to switchers (28.5%). Conclusions—Findings suggest smokers will be more successful if they use a SCM in QAs and vary the SCM they use across time. That smokers can increase their odds of quitting by switching SCMs is an important message that could be communicated to smokers

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

ObjectiveTo determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.MethodsWe report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.ResultsOf 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.ConclusionSpecific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials

Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the \u27pediatric Status Epilepticus Research Group\u27 (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE

Near or far: the effect of spatial distance and vocabulary knowledge on word learning

The current study investigated the role of spatial distance in word learning. Two-year-old children saw three novel objects named while the objects were either in close proximity to each other or spatially separated. Children were then tested on their retention for the name-object associations. Keeping the objects spatially separated from each other during naming was associated with increased retention for children with larger vocabularies. Children with a lower vocabulary size demonstrated better retention if they saw objects in close proximity to each other during naming. This demonstrates that keeping a clear view of objects during naming improves word learning for children who have already learned many words, but keeping objects within close proximal range is better for children at earlier stages of vocabulary acquisition. The effect of distance is therefore not equal across varying vocabulary sizes. The influences of visual crowding, cognitive load, and vocabulary size on word learning are discussed

Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet.

AIMS: Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity. METHODS AND RESULTS: The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure, and function was assessed in 8-week-old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001); maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002) increased absolute heart weight; maternal obesity (P = 0.01) and offspring obesity (P = 0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these genes were not affected by offspring diet; maternal obesity (P = 0.02); and offspring obesity (P = 0.05) caused hypertension and effects were additive. CONCLUSIONS: Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes, and remodelling of cardiac structure. These data highlight that the perinatal period is just as important as adult-onset obesity in predicting CVD risk. Therefore, early developmental periods are key intervention windows to reduce the prevalence of CVD.This work was supported by the Medical Research Council (MRC_MC_UU_12012/4), the British Heart Foundation (FS/12/64/30001 to E.L., PG/14/20/ 30769 and RG/17/12/33167) and São Paulo Research Foundation (2017/03525-8 to J.A.F.)

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.

Background and purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy