Implementing a Validated Developmental Screening Tool in a Rural Pediatric Primary Care Clinic to Enhance Early Diagnosis of Developmental Delays from Birth to 36 Months

Abstract Evaluation of childhood development with a validated screening tool has been the gold standard for best practice recommended by the American Academy of Pediatrics (AAP) since 2006. A rural pediatric clinic was the setting for this quality improvement project. The goals of the project were to 1) increase the number of children identified with developmental delays, 2) identify children with delays earlier, and 3) maximize the number of children receiving early intervention (EI) services between the ages of birth to 36 months. The Ages and Stages Questionnaire (ASQ-3) was the selected screening tool adopted by the clinic in June 2020. Data was collected on 1) the number of children screened, 2) the ages at the time of screening, 3) the number of EI referrals, and 4) the number of qualified EI referrals. Pre- and post-implementation data was analyzed and showed a statistically significant decrease in the number of referrals made for EI services, as well as those that qualified for EI services. The concluding results show that using a validated screening tool decreased the number of futile referrals made for EI services after screening for developmental delays in children birth to 36 months for this clinic. The ages of children referred for EI services did show that children were identified at a younger age comparative to the previous methods used by clinicians in the pediatric clinic, but the data was skewed due to COVID-19. Keywords: Developmental delays, pediatric growth and development, developmental screening, early intervention, EI, birth to 36 months, quality improvement, pediatric screening, primary care screenin

Mapping Water-Soluble Carbohydrate Content in Perennial Ryegrass

Perennial ryegrass (Lolium perenne L.) is the main species used in UK agriculture and shows considerable genetic variation for water-soluble carbohydrate (WSC) content (Humphreys, 1989, Turner et al., 2001, 2002). High-sugar grasses have already proved useful in UK livestock production (Miller et al., 2001), but can be unpredictable in the field. Increased understanding of carbon partitioning in ryegrass would benefit future breeding programmes

Mentoring, Training, and Scholarly Productivity Experiences of Cancer-Related Health Disparities Research Trainees: Do Outcomes Differ for Underrepresented Scientists?

The study aims to explore variation in scholarly productivity outcomes by underrepresented status among a diverse sample of researchers in a community-engaged training program. We identified 141 trainees from a web-based survey of researchers in the National Cancer Institute-funded, Community Networks Program Centers (CNPCs) (2011-2016). We conducted a series of multiple logistic regression models to estimate the effect of National Institutes of Health (NIH)-defined underrepresented status on four, self-reported, scholarly productivity outcomes in the previous 5 years: number of publications (first-authored and total) and funded grants (NIH and any agency). Sixty-five percent (n = 92) indicated NIH underrepresented status. In final adjusted models, non-NIH underrepresented (vs. underrepresented) trainees reported an increased odds of having more than the median number of total publications (> 9) (OR = 3.14, 95% CI 1.21-8.65) and any grant funding (OR = 5.10, 95% CI 1.77-14.65). Reporting ≥ 1 mentors (vs. none) was also positively associated (p < 0.05) with these outcomes. The CNPC underrepresented trainees had similar success in first-authored publications and NIH funding as non-underrepresented trainees, but not total publications and grants. Examining trainees' mentoring experiences over time in relation to scholarly productivity outcomes is needed

Interdisciplinary, Translational, and Community-Based Participatory Research: Finding a Common Language to Improve Cancer Research

Preventing cancer, downstaging disease at diagnosis, and reducing mortality require that relevant research findings be translated across scientific disciplines and into clinical and public health practice. Interdisciplinary research focuses on using the languages of different scientific disciplines to share techniques and philosophical perspectives to enhance discovery and development of innovations; (i.e., from the “left end” of the research continuum). Community-based participatory research (CBPR), whose relevance often is relegated to the “right end” (i.e., delivery and dissemination) of the research continuum, represents an important means for understanding how many cancers are caused as well as for ensuring that basic science research findings affect cancer outcomes in materially important ways. Effective interdisciplinary research and CBPR both require an ability to communicate effectively across groups that often start out neither understanding each other’s worldviews nor even speaking the same language. Both demand an ability and willingness to treat individuals from other communities with respect and understanding. We describe the similarities between CBPR and both translational and interdisciplinary research, and then illustrate our points using squamous cell carcinoma of the esophagus as an example of how to deepen understanding and increase relevance by applying techniques of CBPR and interdisciplinary engagement

Approaches for Associating Molecular Polymorphisms with Phenotypic Traits Based on Linkage Disequilibrium in Natural Populations of \u3cem\u3eLolium Perenne\u3c/em\u3e

Association mapping relies on linkage disequilibrium (LD) between haplotypes and quantitative trait loci (QTL). The level of LD in a genome determines the resolution of this approach. In out-breeding species, LD is expected to decay rapidly, thus allowing for high-resolution mapping. It has been most extensively used in human genetics, but recent work with maize populations has demonstrated its potential in plants (Thornsberry et al., 2001; Wilson et al., 2004), and used in L. perenne to identify AFLP markers associated with a major QTL for heading date on linkage group 7 (Skøt et al., 2004). The objective of the present work is to associate allelic variation in candidate genes for heading date and water soluble carbohydrates (WSC) in natural populations of L. perenne with phenotypic variation. Both these traits are important breeding targets in ryegrass

Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

BACKGROUND: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K(+), were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI. CONCLUSION/SIGNIFICANCE: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric G(i/o)-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors

Antimicrobial effects of liquid anesthetic isoflurane on Candida albicans

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections is associated with its morphological shift such that the hyphal morphology of the fungus is most invasive. Of importance, aberrant multiplication of Candida yeast is also associated with the pathogenesis of certain mucosal diseases. In this study, we assessed the anti-candidal activity of the volatile anesthetic isoflurane in liquid form in comparison with the anti-fungal agent amphotericin B in an in vitro culture system. Exposure of C. albicans to isoflurane (0.3% volume/volume and above) inhibited multiplication of yeast as well as formation of hyphae. These data suggest development of potential topical application of isoflurane for controlling a series of cutaneous and genital infections associated with this fungus. Elucidiation of the mechanism by which isoflurane effects fungal growth could offer therapeutic potential for certain systemic fungal infections

Biogenesis of JC Polyomavirus Associated Extracellular Vesicles

JC polyomavirus (JCPyV) is a small, non-enveloped virus that persists in the kidney in about half the adult population. In severely immune-compromised individuals JCPyV causes the neurodegenerative disease progressive multifocal leukoencephalopathy (PML) in the brain. JCPyV has been shown to infect cells by both direct and indirect mechanisms, the latter involving extracellular vesicle (EV) mediated infection. While direct mechanisms of infection are well studied indirect EV mediated mechanisms are poorly understood. Using a combination of chemical and genetic approaches we show that several overlapping intracellular pathways are responsible for the biogenesis of virus containing EV. Here we show that targeting neutral sphingomyelinase 2 (nSMase2) with the drug cambinol decreased the spread of JCPyV over several viral life cycles. Genetic depletion of nSMase2 by either shRNA or CRISPR/Cas9 reduced EV-mediated infection. Individual knockdown of seven ESCRT-related proteins including HGS, ALIX, TSG101, VPS25, VPS20, CHMP4A, and VPS4A did not significantly reduce JCPyV associated EV (JCPyV(+) EV) infectivity, whereas knockdown of the tetraspanins CD9 and CD81 or trafficking and/or secretory autophagy-related proteins RAB8A, RAB27A, and GRASP65 all significantly reduced the spread of JCPyV and decreased EV-mediated infection. These findings point to a role for exosomes and secretory autophagosomes in the biogenesis of JCPyV associated EVs with specific roles for nSMase2, CD9, CD81, RAB8A, RAB27A, and GRASP65 proteins

Introgression Mapping in The Grasses

Key points Lolium perenne/Festuca pratensis hybrids and their derivatives provide an ideal system for intergeneric introgression. The Lolium perenne/Festuca pratensis system is being exploited to elucidate genome organisation in the grasses, determination of the genetic control of target traits and the isolation of markers for MAS in breeding programmes. The potential of the system as an aid to contig the Lolium and Festuca genomes and for gene isolation is discussed

Genetic analysis of adaptation differences between highland and lowland tropical maize using molecular markers

Molecular-marker loci were used to investigate the adaptation differences between highland and lowland tropical maize. An F2 population from the cross of two inbred lines independently derived from highland and lowland maize germplasm was developed, and extracted F3:4 lines were phenotype in replicated field trials at four thermally diverse tropical testing sites, ranging from lowland to extreme highland (mean growing season temperature range 13.2–24.6°C). Traits closely related with adaptation, such as biomass and grain yield, yield components, days from sowing to male and female flowering, total leaf number, plant height and number of primary tassel branches (TBN), were analyzed. A large line ´ environment interaction was observed for most traits. The genetic basis of this interaction was reflected by significant, but systematic, changes from lowland to highland sites in the correlation between the trait value and genomic composition (designated by the proportion of marker alleles with the same origin). Joint analysis of quantitative trait loci (QTLs) over sites detected 5–8 QTLs for each trait (except disease scores, with data only from one site). With the exception of one QTL for TBN, none of these accounted for more than 15% of the total phenotypic variation. In total, detected QTLs accounted for 24–61% of the variation at each site on average. For yield, yield components and disease scores, alleles generally favored the site of origin. Highland-derived alleles had little effect at lowland sites, while lowland- derived alleles showed relatively broader adaptation. Gradual changes in the estimated QTL effects with increasing mean site temperature were observed, and paralleled the observed patterns of adaptation in high land and lowland germplasm. Several clusters of QTLs for different traits reflected the relative importance in the adaptation differences between the two germplasm types, and pleiotropy is suggested as the main cause for the clustering. Breeding for broad thermal adaptation should be possible by pooling genes showing adaptation to specific thermal regimes, though perhaps at the expense of reduced progress for adaptation to a specific site. Molecular marker-assisted selection would be an ideal tool for this task, since it could greatly reduce the linkage drag caused by the unintentional transfer of undesirable trait