A three-dimensional co-culture system to investigate macrophage-dependent tumor cell invasion

Acknowledgments: This work was supported by funding from the Cancer Council of Western Australia. ARD is a holder of an Australian Postgraduate Award from the University of Western Australia. The authors acknowledge the facilities, and the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Governments. We also thank Dr. Richard Stanley for the kind gift of CSF-1 and Gilead Sciences for providing GS-1101.Peer reviewedPublisher PD

A Randomized Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder.

Objective: Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as measured by the Mullen Scales of Early Learning (MSEL) among those with comorbid autism spectrum disorder (ASD) in post hoc analysis, prompting the authors to probe whether sertraline is also indicated in nonsyndromic ASD. Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 58 children with ASD aged 24 to 72 months. Results: 179 subjects were screened for eligibility, and 58 were randomized to sertraline (32) or placebo (26). Eight subjects from the sertraline arm and five from the placebo arm discontinued. Intent-to-treat analysis showed no significant difference from placebo on the primary outcomes (MSEL expressive language raw score and age equivalent combined score) or secondary outcomes. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events possibly related to study treatment occurred. Conclusion: This randomized controlled trial of sertraline treatment showed no benefit with respect to primary or secondary outcome measures. For the 6-month period, treatment in young children with ASD appears safe, although the long-term side effects of low-dose sertraline in early childhood are unknown. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02385799

Assessment of training and technical assistance needs of Colorectal Cancer Control Program Grantees in the U.S.

Background Practitioners often require training and technical assistance to build their capacity to select, adapt, and implement evidence-based interventions (EBIs). The CDC Colorectal Cancer Control Program (CRCCP) aims to promote CRC screening to increase population-level screening. This study identified the training and technical assistance (TA) needs and preferences for training related to the implementation of EBIs among CRCCP grantees. Methods Twenty-nine CRCCP grantees completed an online survey about their screening activities, training and technical assistance in 2012. They rated desire for training on various evidence-based strategies to increase cancer screening, evidence-based competencies, and program management topics. They also reported preferences for training formats and facilitators and barriers to trainings. Results Many CRCCP grantees expressed the need for training with regards to specific EBIs, especially system-level and provider-directed EBIs to promote CRC screening. Grantees rated these EBIs as more difficult to implement than client-oriented EBIs. Grantees also reported a moderate need for training regarding finding EBIs, assessing organizational capacity, implementing selected EBIs, and conducting process and outcome evaluations. Other desired training topics reported with higher frequency were partnership development and data collection/evaluation. Grantees preferred training formats that were interactive such as on-site trainings, webinars or expert consultants. Conclusions Public health organizations need greater supports for adopting evidence-based interventions, working with organizational-level change, partnership development and data management. Future capacity building efforts for the adoption of EBIs should focus on systems or provider level interventions and key processes for health promotion and should be delivered in a variety of ways to assist local organizations in cancer prevention and control

Data review for 3LN redfish in preparation for an updated management strategy evaluation

Data review for 3LN redfish in preparation for an updated management strategy evaluationVersión del editor

High levels of childhood obesity observed among 3- to 7-year-old New Zealand Pacific children is a public health concern.

This cross-sectional, community-based survey was designed to assess attained growth and body composition of 3- to 7-y-old Pacific children (n = 21 boys and 20 girls) living in Dunedin, New Zealand, and to examine nondietary factors associated with the percentage of body fat. Fat mass, lean tissue mass and the percentage of body fat were measured using dual energy X-ray absorptiometry. One trained anthropometrist also measured height, weight, skinfolds (triceps, subscapular) and circumferences (mid-upper arm, chest, waist, calf). Compared with the National Center for Health Statistics and National Health and Examination Surveys I and II reference data, these Pacific children were tall and heavy for their age with high arm-muscle-area-for-height. Median (quartiles) Z-scores for height and BMI-for-age and arm-muscle-area-for-height were 1.33 (0.60, 2.15), 1.20 (0.74, 4.43) and 1.09 (0.63, 1.85), respectively. Their median (quartile) percentage of body fat was 21.8% (15.0, 35.5) of which 38.5% was located in the trunk. The estimated percentage of children classified as obese ranged from 34 to 49% depending on the criterion used. Over 60% of the children had levels of trunk fat above 1 SD of reported age- and sex-specific Z-scores for New Zealand children. The nondietary factors examined (hours of television viewing and hours playing organized sports, as reported by parents) were not associated with variations in the percentage of body fat, after adjusting for age, sex and birth weight. These extremely high levels of obesity and truncal fat among very young New Zealand children will have major public health implications as these children age

Searching for maintenance in exercise interventions for cancer survivors

Translating evidence-based exercise interventions into practice is important for expanding the capacity to support cancer survivors. Using the reach, efficacy/effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and scoping study methodology, we addressed the research question, “What is known about the maintenance of exercise interventions for cancer survivors that would inform translation from research to practice and community settings?” Maintenance was investigated at the individual and setting level

A 1.8 million year history of Amazon vegetation

During the Pleistocene, long-term trends in global climate were controlled by orbital cycles leading to high amplitude glacial-interglacial variability. The history of Amazonian vegetation during this period is largely unknown since no continuous record from the lowland basin extends significantly beyond the last glacial stage. Here we present a paleoenvironmental record spanning the last 1800 kyr based on palynological data, biome reconstructions, and biodiversity metrics from a marine sediment core that preserves a continuous archive of sediments from the Amazon River. Tropical rainforests dominated the Amazonian lowlands during the last 1800 ka interchanging with surrounding warm-temperate rainforests and tropical seasonal forests. Between 1800 and 1000 ka, rainforest biomes were present in the Amazon drainage basin, along with extensive riparian wetland vegetation. Tropical rainforest expansion occurred during the relatively warm Marine Isotope Stages 33 and 31 (ca. 1110 to 1060 ka), followed by a contraction of both forests and wetlands until ca. 800 ka. Between 800 and 400 ka, low pollen concentration and low diversity of palynological assemblages renders difficult the interpretation of Amazonian vegetation. A strong synchronicity between vegetation changes and glacial-interglacial global climate cycles was established around 400 ka. After 400 ka, interglacial vegetation was dominated by lowland tropical rainforest in association with warmer temperatures and higher CO2. During cooler temperatures and lower CO2 of glacial stages, tropical seasonal forests expanded, presumably towards eastern Amazonia. While this study provides no evidence supporting a significant expansion of savanna or steppe vegetation within the Amazonian lowlands during glacial periods, there were changes in the rainforest composition in some parts of the basin towards a higher proportion of deciduous elements, pointing to less humid conditions and/or greater seasonality of precipitation. Nevertheless, rainforest persisted during both glacial and interglacial periods. These findings confirm the sensitivity of tropical lowland vegetation to changes in CO2, temperature, and moisture availability and the most suitable conditions for tropical rainforests occurred during the warmest stages of the Mid Pleistocene Transition and during the interglacial stages of the past 400 kyr

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives

The increased utilization of metrology resources and expanded application of its’ approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects

Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by infertility and the absence of puberty. Defects in GnRH neuron migration or altered GnRH secretion and/or action lead to a severe gonadotropin-releasing hormone (GnRH) deficiency. Given the close developmental association of GnRH neurons with the olfactory primary axons, CHH is often associated with anosmia or hyposmia, in which case it is defined as Kallmann syndrome (KS). The genetics of CHH are heterogeneous, and >40 genes are involved either alone or in combination. Several CHH-related genes controlling GnRH ontogeny encode proteins containing fibronectin-3 (FN3) domains, which are important for brain and neural development. Therefore, we hypothesized that defects in other FN3-superfamily genes would underlie CHH. Next-generation sequencing was performed for 240 CHH unrelated probands and filtered for rare, protein-truncating variants (PTVs) in FN3-superfamily genes. Compared to gnomAD controls the CHH cohort was statistically enriched for PTVs in neuron-derived neurotrophic factor (NDNF) (p = 1.40 x 10(-6)). Three heterozygous PTVs (p.Lys62*, p.Tyr128Thrfs*55, and p.Trp469*, all absent from the gnomAD database) and an additional heterozygous missense mutation (p.Thr201Ser) were found in four KS probands. Notably, NDNF is expressed along the GnRH neuron migratory route in both mouse embryos and human fetuses and enhances GnRH neuron migration. Further, knock down of the zebrafish ortholog of NDNF resulted in altered GnRH migration. Finally, mice lacking Ndnf showed delayed GnRH neuron migration and altered olfactory axonal projections to the olfactory bulb; both results are consistent with a role of NDNF in GnRH neuron development. Altogether, our results highlight NDNF as a gene involved in the GnRH neuron migration implicated in KS.Peer reviewe