Addressing Childhood Adversity and Social Determinants inPediatric Primary Care:Recommendations for New Hampshire

Research has clearly demonstrated the significant short- and long-term impacts of adverse childhood experiences (ACEs) and the social determinants of health (SDOH) on child health and well-being.1 Identifying and addressing ACEs and SDOH will require a coordinated and systems-based approach. Pediatric primary care* plays a critical role in this system, and there is a growing emphasis on these issues that may be impacting a family. As awareness of ACEs and SDOH grows, so too does the response effort within the State of New Hampshire. Efforts to address ACEs and the SDOH have been initiated by a variety of stakeholders, including non-profit organizations, community-based providers, and school districts. In late 2017, the Endowment for Health and SPARK NH funded the NH Pediatric Improvement Partnership (NHPIP) to develop a set of recommendations to address identifying and responding to ACEs and SDOH in NH primary care settings caring for children. Methods included conducting a review of literature and Key Informant Interviews (KII). Themes from these were identified and the findings are summarized in this report

Microultraound and small bowel inflammation:Tissue phantom studies

Capsule endoscopy represents a highly convenient but limited means of imaging inflammatory conditions of the small bowel. The inclusion of high frequency microultrasound into a capsule endoscope has the potential to enhance diagnostic capabilities with subsurface imaging of the bowel wall. Experimental studies on abattoir-obtained porcine small bowel have been carried out as an ethical means to characterize healthy and altered tissue in a preclinical setting as well as to explore other means of imaging pathology. Samples of small bowel were cannulated and perfused with phosphate buffered saline followed by variable dilutions of polystyrene microspheres. All samples were scanned with a purpose built step scanner employing a 47 MHz single element transducer. Results indicated that tissue high frequency ultrasound demonstrated sufficient sensitivity to detect the disruption normal histology with microsphere infusion. The combination of microultrasound and capsule endoscopy has the potential to enhance the diagnostic capabilities with improved qualitative and quantitative dimensions

The Effects of Phonotactic Probability and Neighborhood Density on Adults' Word Learning In Noisy Conditions

Purpose: Noisy conditions make auditory processing difficult. This study explores whether noisy conditions impact the effects of phonotactic probability (the likelihood of occurrence of a sound sequence) and neighborhood density (phonological similarity among words) on adults’ word learning. Method: Fifty-eight adults learned nonwords varying in phonotactic probability and neighborhood density in either an unfavorable (0dB Signal-to-Noise Ratio, SNR) or a favorable (+8dB SNR) listening condition. Word learning was assessed in a picture naming task by scoring the proportion of phonemes named correctly. Results: The unfavorable 0dB SNR condition showed a significant interaction between phonotactic probability and neighborhood density in the absence of main effects. Specifically, adults learned more words when phonotactic probability and neighborhood density were both low or both high. The +8dB SNR condition did not show this interaction. These results were inconsistent with those from a prior adult word learning study under quiet listening conditions that showed main effects of word characteristics. Conclusion: As the listening condition worsens, adult word learning benefits from a convergence of phonotactic probability and neighborhood density Clinical implications are discussed for potential populations who experience difficulty with auditory perception or processing making them more vulnerable to noise

Transcriptome analysis of chemically-induced sensory neuron ablation in zebrafish

Peripheral glia are known to have a critical role in the initial response to axon damage and degeneration. However, little is known about the cellular responses of non-myelinating glia to nerve injury. In this study, we analyzed the transcriptomes of wild-type and mutant (lacking peripheral glia) zebrafish larvae that were treated with metronidazole. This treatment allowed us to conditionally and selectively ablate cranial sensory neurons whose axons are ensheathed only by non-myelinating glia. While transcripts representing over 27,000 genes were detected by RNAseq, only a small fraction (~1% of genes) were found to be differentially expressed in response to neuronal degeneration in either line at either 2 hrs or 5 hrs of metronidazole treatment. Analysis revealed that most expression changes (332 out of the total of 458 differentially expressed genes) occurred over a continuous period (from 2 to 5 hrs of metronidazole exposure), with a small number of genes showing changes limited to only the 2 hr (55 genes) or 5 hr (71 genes) time points. For genes with continuous alterations in expression, some of the most meaningful sets of enriched categories in the wild-type line were those involving the inflammatory TNF-alpha and IL6 signaling pathways, oxidoreductase activities and response to stress. Intriguingly, these changes were not observed in the mutant line. Indeed, cluster analysis indicated that the effects of metronidazole treatment on gene expression was heavily influenced by the presence or absence of glia, indicating that the peripheral non-myelinating glia play a significant role in the transcriptional response to sensory neuron degeneration. This is the first transcriptome study of metronidazole-induced neuronal death in zebrafish and the response of non-myelinating glia to sensory neuron degeneration. We believe this study provides important insight into the mechanisms by which non-myelinating glia react to neuronal death and degeneration in sensory circuits

Production of the Neurotoxin BMAA by a Marine Cyanobacterium

Diverse species of cyanobacteria have recently been discovered to produce the neurotoxic non-protein amino acid β-methylamino-L-alanine (BMAA). In Guam, BMAA has been studied as a possible environmental toxin in the diets of indigenous Chamorro people known to have high levels of Amyotrophic Lateral Sclerosis/ Parkinsonism Dementia Complex (ALS/PDC). BMAA has been found to accumulate in brain tissues of patients with progressive neurodegenerative illness in North America. In Guam, BMAA was found to be produced by endosymbiotic cyanobacteria of the genus Nostoc which live in specialized cycad roots. We here report detection of BMAA in laboratory cultures of a free-living marine species of Nostoc. We successfully detected BMAA in this marine species of Nostoc with five different methods: HPLC-FD, UPLC-UV, Amino Acid Analyzer, LC/MS, and Triple Quadrupole LC/MS/MS. This consensus of five different analytical methods unequivocally demonstrates the presence of BMAA in this marine cyanobacterium. Since protein-associated BMAA can accumulate in increasing levels within food chains, it is possible that biomagnification of BMAA could occur in marine ecosystems similar to the biomagnification of BMAA in terrestrial ecosystems. Production of BMAA by marine cyanobacteria may represent another route of human exposure to BMAA. Since BMAA at low concentrations causes the death of motor neurons, low levels of BMAA exposure may trigger motor neuron disease in genetically vulnerable individuals

Academic drug discovery:Challenges and opportunities

There are many different approaches to drug discovery in academia, some of which are based broadly on the industrial model of discovering novel targets and then conducting screening within academic drug discovery centres to identify hit molecules. Here we describe our approach to drug discovery, which makes more efficient use of the capabilities and resources of the different stakeholders. Specifically, we have created a large portfolio of drug projects and conducted small amounts of derisking work to ensure projects are investment ready. In this feature we will describe this model, including its limitations and advantages, since we believe the ideas and concepts will be of interest to other academic institutions and consortia.</p

Design and Simulation of a Ring-Shaped Linear Array for Microultrasound Capsule Endoscopy

Video capsule endoscopy (VCE) has significantly advanced visualization of the gastrointestinal tract (GI tract) since its introduction in the last 20 years. Work is now under way to combine VCE with microultrasound imaging. However, small maximum capsule dimensions, coupled with the electronics required to integrate ultrasound imaging capabilities, pose significant design challenges. This paper describes a simulation process for testing transducer geometries and imaging methodologies to achieve satisfactory imaging performance within the physical limitations of the capsule size and outlines many of the trade-offs needed in the design of this new class of ultrasound capsule endoscopy (USCE) device. A hybrid MATLAB model is described, incorporating KLM circuit elements and digitizing and beamforming elements to render a grey-scale B-mode. This model is combined with a model of acoustic propagation to generate images of point scatterers. The models are used to demonstrate the performance of a USCE transducer configuration comprising a single, unfocused transmit ring of radius 5 mm separated into eight segments for electrical impedance control and a 512-element receive linear array, also formed into a ring. The MATLAB model includes an ultrasonic pulser circuit connected to a piezocrystal composite transmit transducer with a center frequency of 25 MHz. B-scan images are simulated for wire target phantoms, multilayered phantoms, and a gut wall model. To demonstrate the USCE system’s ability to image tissue, a digital phantom was created from single-element ultrasonic transducer scans of porcine small bowel ex vivo obtained at a frequency of 45 MHz