Five-Phase Replication of Behavioral Health Integration in Pediatric Primary Care.

BACKGROUND AND OBJECTIVES: Because of severe and protracted shortages of pediatric behavioral health (BH) specialists, collaboration between pediatric primary care practitioners (PCPs) and BH specialists has the potential to increase access to BH services by expanding the BH workforce. In a previous study, we demonstrated that phase 1 of a behavioral health integration program (BHIP) enrolling 13 independently owned, community-based pediatric practices was associated with increased access to BH services while averting substantial cost increases and achieving high provider self-efficacy and professional satisfaction. The current study was undertaken to assess whether the initial access findings were replicated over 4 subsequent implementation phases and to explore the practicality of broad dissemination of the BHIP model. METHODS: After phase 1, BHIP was extended over 4 subsequent phases in a stepped-wedge design to 46 additional pediatric practices, for a total cohort of 59 practices (354 PCPs serving >300 000 patients). Program components comprised BH education and consultation and support for integrated practice transformation; these components facilitated on-site BH services by an interprofessional BH team. Outcomes were assessed quarterly, preprogram and postprogram launch. RESULTS: Across combined phases 1 to 5, BHIP was associated with increased primary care access to BH services (screening, psychotherapy, PCP BH visits, psychotropic prescribing) and performed well across 7 standard implementation outcome domains (acceptability, appropriateness, feasibility, fidelity, adoption, penetration, and sustainability). Emergency BH visits and attention-deficit/hyperactivity disorder prescribing were unchanged. CONCLUSIONS: These findings provide further support for the potential of integrated care to increase access to BH services in pediatric primary care.

Five-Year Outcomes of Behavioral Health Integration in Pediatric Primary Care.

BACKGROUND AND OBJECTIVES: In the context of protracted shortages of pediatric behavioral health (BH) specialists, BH integration in pediatric primary care can increase access to BH services. The objectives of this study were to assess the structure and process of pediatric BH integration and outcomes in patient experience (access and quality), cost, and provider satisfaction. METHODS: In 2013, we launched a multicomponent, transdiagnostic integrated BH model (Behavioral Health Integration Program [BHIP]) in a large pediatric primary care network in Massachusetts. Study participants comprised the first 13 practices to enroll in BHIP (Phase-1). Phase-1 practices are distributed across Greater Boston, with ∼105 primary care practitioners serving ∼114 000 patients. Intervention components comprised in-depth BH education, on-demand psychiatric consultation, operational support for integrated practice transformation, and on-site clinical BH service. RESULTS: Over 5 years, BHIP was associated with increased practice-level BH integration (P < .001), psychotherapy (P < .001), and medical (P = .04) BH visits and guideline-congruent medication prescriptions for anxiety and depression (P = .05) and attention-deficit/hyperactivity disorder (P = .05). Total ambulatory BH spending increased by 8% in constant dollars over 5 years, mainly attributable to task-shifting from specialty to primary care. Although an initial decline in emergency BH visits from BHIP practices was not sustained, total emergency BH spending decreased by 19%. BHIP providers reported high BH self-efficacy and professional satisfaction from BHIP participation. CONCLUSIONS: Findings from this study suggest that integrating BH in the pediatric setting can increase access to quality BH services while engendering provider confidence and satisfaction and averting substantial increases in cost.

Ginkgo and Welwitschia Mitogenomes Reveal Extreme Contrasts in Gymnosperm Mitochondrial Evolution.

Mitochondrial genomes (mitogenomes) of flowering plants are well known for their extreme diversity in size, structure, gene content, and rates of sequence evolution and recombination. In contrast, little is known about mitogenomic diversity and evolution within gymnosperms. Only a single complete genome sequence is available, from the cycad Cycas taitungensis, while limited information is available for the one draft sequence, from Norway spruce (Picea abies). To examine mitogenomic evolution in gymnosperms, we generated complete genome sequences for the ginkgo tree (Ginkgo biloba) and a gnetophyte (Welwitschia mirabilis). There is great disparity in size, sequence conservation, levels of shared DNA, and functional content among gymnosperm mitogenomes. The Cycas and Ginkgo mitogenomes are relatively small, have low substitution rates, and possess numerous genes, introns, and edit sites; we infer that these properties were present in the ancestral seed plant. By contrast, the Welwitschia mitogenome has an expanded size coupled with accelerated substitution rates and extensive loss of these functional features. The Picea genome has expanded further, to more than 4 Mb. With regard to structural evolution, the Cycas and Ginkgo mitogenomes share a remarkable amount of intergenic DNA, which may be related to the limited recombinational activity detected at repeats in Ginkgo Conversely, the Welwitschia mitogenome shares almost no intergenic DNA with any other seed plant. By conducting the first measurements of rates of DNA turnover in seed plant mitogenomes, we discovered that turnover rates vary by orders of magnitude among species.

Horizontal transfer of entire genomes via mitochondrial fusion in the angiosperm Amborella.

We report the complete mitochondrial genome sequence of the flowering plant Amborella trichopoda. This enormous, 3.9-megabase genome contains six genome equivalents of foreign mitochondrial DNA, acquired from green algae, mosses, and other angiosperms. Many of these horizontal transfers were large, including acquisition of entire mitochondrial genomes from three green algae and one moss. We propose a fusion-compatibility model to explain these findings, with Amborella capturing whole mitochondria from diverse eukaryotes, followed by mitochondrial fusion (limited mechanistically to green plant mitochondria) and then genome recombination. Amborella's epiphyte load, propensity to produce suckers from wounds, and low rate of mitochondrial DNA loss probably all contribute to the high level of foreign DNA in its mitochondrial genome.

The "fossilized" mitochondrial genome of Liriodendron tulipifera: ancestral gene content and order, ancestral editing sites, and extraordinarily low mutation rate.

BACKGROUND: The mitochondrial genomes of flowering plants vary greatly in size, gene content, gene order, mutation rate and level of RNA editing. However, the narrow phylogenetic breadth of available genomic data has limited our ability to reconstruct these traits in the ancestral flowering plant and, therefore, to infer subsequent patterns of evolution across angiosperms. RESULTS: We sequenced the mitochondrial genome of Liriodendron tulipifera, the first from outside the monocots or eudicots. This 553,721 bp mitochondrial genome has evolved remarkably slowly in virtually all respects, with an extraordinarily low genome-wide silent substitution rate, retention of genes frequently lost in other angiosperm lineages, and conservation of ancestral gene clusters. The mitochondrial protein genes in Liriodendron are the most heavily edited of any angiosperm characterized to date. Most of these sites are also edited in various other lineages, which allowed us to polarize losses of editing sites in other parts of the angiosperm phylogeny. Finally, we added comprehensive gene sequence data for two other magnoliids, Magnolia stellata and the more distantly related Calycanthus floridus, to measure rates of sequence evolution in Liriodendron with greater accuracy. The Magnolia genome has evolved at an even lower rate, revealing a roughly 5,000-fold range of synonymous-site divergence among angiosperms whose mitochondrial gene space has been comprehensively sequenced. CONCLUSIONS: Using Liriodendron as a guide, we estimate that the ancestral flowering plant mitochondrial genome contained 41 protein genes, 14 tRNA genes of mitochondrial origin, as many as 7 tRNA genes of chloroplast origin, >700 sites of RNA editing, and some 14 colinear gene clusters. Many of these gene clusters, genes and RNA editing sites have been variously lost in different lineages over the course of the ensuing ∽200 million years of angiosperm evolution.

Assessment of possible allergenicity of hypothetical ORFs in common food crops using current bioinformatic guidelines and its implications for the safety assessment of GM crops.

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins. Some regulatory authorities have broadened the scope of the assessment to include all DNA reading frames between stop codons across the insert and spanning the insert/genomic DNA junctions. To investigate the utility of this bioinformatic assessment, all naturally occurring stop-to-stop frames in the non-transgenic genomes of maize, rice, and soybean, as well as the human genome, were compared against the AllergenOnline (www.allergenonline.org) database using the Codex criteria. We discovered thousands of frames that exceeded the Codex defined threshold for potential cross-reactivity suggesting that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value for making decisions on the safety of GM crops.

Massive horizontal transfer of mitochondrial genes from diverse land plant donors to the basal angiosperm Amborella.

Several plants are known to have acquired a single mitochondrial gene by horizontal gene transfer (HGT), but whether these or any other plants have acquired many foreign genes is entirely unclear. To address this question, we focused on Amborella trichopoda, because it was already known to possess one horizontally acquired gene and because it was found in preliminary analyses to contain several more. We comprehensively sequenced the mitochondrial protein gene set of Amborella, sequenced a variable number of mitochondrial genes from 28 other diverse land plants, and conducted phylogenetic analyses of these sequences plus those already available, including the five sequenced mitochondrial genomes of angiosperms. Results indicate that Amborella has acquired one or more copies of 20 of its 31 known mitochondrial protein genes from other land plants, for a total of 26 foreign genes, whereas no evidence for HGT was found in the five sequenced genomes. Most of the Amborella transfers are from other angiosperms (especially eudicots), whereas others are from nonangiosperms, including six striking cases of transfer from (at least three different) moss donors. Most of the transferred genes are intact, consistent with functionality and/or recency of transfer. Amborella mtDNA has sustained proportionately more HGT than any other eukaryotic, or perhaps even prokaryotic, genome yet examined.

Plant genetics: gene transfer from parasitic to host plants.

Plant mitochondrial genes are transmitted horizontally across mating barriers with surprising frequency, but the mechanism of transfer is unclear. Here we describe two new cases of horizontal gene transfer, from parasitic flowering plants to their host flowering plants, and present phylogenetic and biogeographic evidence that this occurred as a result of direct physical contact between the two. Our findings complement the discovery that genes can be transferred in the opposite direction, from host to parasite plant.

Primary ciliary dyskinesia as a cause of neonatal respiratory distress: implications for the neonatologist.

We report two cases of term infants who presented with prolonged respiratory distress, rhinitis, and situs inversus. A high index of suspicion led to the diagnosis of Kartagener Syndrome, which is a subgroup of primary ciliary dyskinesia, in the immediate neonatal period.