Correction: Rating early child development outcome measurement tools for routine health programme use.

The authors would like to correct the funding statement. Currently it reads as 'Funding: This supplement has been made possible by funding support from the Bernard van Leer Foundation. Saving Brains impact and process evaluation funded by Grand Challenges Canada.' This funding statement is correct for all the other papers in the series but for this specific paper a key funder (Children's Investment Fund Foundation) was not listed, and Grand Challenges Canada should not be listed. The correct funding statement should be as follows: 'Funding: This supplement has been made possible by funding support from the Bernard van Leer Foundation (funding costs of publication and launch) and the Children's Investment Foundation Fund (partial funding of author time (DB) and (JC) and funding for EN-SMILING study)

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Characterizing Community-Based Mental Health Services for Children with Autism Spectrum Disorders and Disruptive Behavior Problems

This study describes the characteristics of children with autism spectrum disorders (ASD) with disruptive behavior problems served in community-based mental health clinics, characterizes psychotherapy process and outcome, and examines differences between children with ASD and a non-ASD comparison group. Results indicate that children with ASD served in this setting are high functioning and diagnostically complex. Certain research-based behavioral and cognitive behavioral psychotherapeutic strategies were observed frequently, while parent training strategies and active teaching strategies were observed less frequently. The intensity or thoroughness with which strategies were pursued was relatively low. Outcome analyses indicate improvement in child symptoms and family functioning. Treatment delivery and outcome were similar for children with and without ASD. These findings represent the first detailed observational data characterizing community-based mental health services for children with ASD

Thermal Variability Increases the Impact of Autumnal Warming and Drives Metabolic Depression in an Overwintering Butterfly

Increases in thermal variability elevate metabolic rate due to Jensen's inequality, and increased metabolic rate decreases the fitness of dormant ectotherms by increasing consumption of stored energy reserves. Theory predicts that ectotherms should respond to increased thermal variability by lowering the thermal sensitivity of metabolism, which will reduce the impact of the warm portion of thermal variability. We examined the thermal sensitivity of metabolic rate of overwintering Erynnis propertius (Lepidoptera: Hesperiidae) larvae from a stable or variable environment reared in the laboratory in a reciprocal common garden design, and used these data to model energy use during the winters of 1973–2010 using meteorological data to predict the energetic outcomes of metabolic compensation and phenological shifts. Larvae that experienced variable temperatures had decreased thermal sensitivity of metabolic rate, and were larger than those reared at stable temperatures, which could partially compensate for the increased energetic demands. Even with depressed thermal sensitivity, the variable environment was more energy-demanding than the stable, with the majority of this demand occurring in autumn. Autumn phenology changes thus had disproportionate influence on energy consumption in variable environments, and variable-reared larvae were most susceptible to overwinter energy drain. Therefore the energetic impacts of the timing of entry into winter dormancy will strongly influence ectotherm fitness in northern temperate environments. We conclude that thermal variability drives the expression of metabolic suppression in this species; that phenological shifts will have a greater impact on ectotherms in variable thermal environments; and that E. propertius will be more sensitive to shifts in phenology in autumn than in spring. This suggests that increases in overwinter thermal variability and/or extended, warm autumns, will negatively impact all non-feeding dormant ectotherms which lack the ability to suppress their overwinter metabolic thermal sensitivity

Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis

Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ.In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein‐mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways.In this study we demonstrated that levels of the thyroid hormone 3,3’,5‐triodo‐L‐thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFβ signalling.In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration

Brain-Derived Neurotrophic Factor Ameliorates Brain Stem Cardiovascular Dysregulation during Experimental Temporal Lobe Status Epilepticus

Background: Status epilepticus (SE) is an acute, prolonged epileptic crisis with a mortality rate of 20–30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM), a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF) via an antioxidant action. Methodology/Principal Findings: In a clinically relevant experimental model of temporal lobe SE (TLSE) using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47 phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB), angiotensin AT1 receptor subtype (AT1R), nitric oxide synthase II (NOS II) or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol), a specific antagonist of NADPH oxidase (apocynin) or an AT1R antagonist (losartan) blunted significantly the augmented superoxide anion or phosphorylated p47 phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdn

A cross-sectional study of US rural adults’ consumption of fruits and vegetables: do they consume at least five servings daily?

<p>Abstract</p> <p>Background</p> <p>Rural residents are increasingly identified as being at greater risk for health disparities. These inequities may be related to health behaviors such as adequate fruits and vegetable consumption. There is little national-level population-based research about the prevalence of fruit and vegetable consumption by US rural population adults. The objective of this study was to examine the prevalence differences between US rural and non-rural adults in consuming at least five daily servings of combined fruits and vegetables.</p> <p>Methods</p> <p>Cross-sectional analysis of weighted 2009 Behavioral Risk Factor Surveillance Survey (BRFSS) data using bivariate and multivariate techniques. 52,259,789 US adults were identified as consuming at least five daily servings of fruits and vegetables of which 8,983,840 were identified as living in rural locales.</p> <p>Results</p> <p>Bivariate analysis revealed that in comparison to non-rural US adults, rural adults were less likely to consume five or more daily servings of fruits and vegetables (OR = 1.161, 95% CI 1.160-1.162). Logistic regression analysis revealed that US rural adults consuming at least five daily servings of fruits and vegetables were more likely to be female, non-Caucasian, married or living with a partner, living in a household without children, living in a household whose annual income was > $35,000, and getting at least moderate physical activity. They were also more likely to have a BMI of <30, have a personal physician, have had a routine medical exam in the past 12 months, self-defined their health as good to excellent and to have deferred medical care because of cost. When comparing the prevalence differences between rural and non-rural US adults within a state, 37 States had a lower prevalence of rural adults consuming at least five daily servings of fruits and vegetables and 11 States a higher prevalence of the same.</p> <p>Conclusions</p> <p>This enhanced understanding of fruit and vegetable consumption should prove useful to those seeking to lessen the disparity or inequity between rural and non-rural adults. Additionally, those responsible for health-related planning could benefit from the knowledge of how their state ranks in comparison to others vis-à-vis the consumption of fruits and vegetables by rural adults---a population increasingly being identified as one at risk for health disparities.</p