Need for strategic communications and stakeholder engagement to advance acceptability of an overdose preventing vaccine targeting fentanyl.

BACKGROUND: Fentanyl is a synthetic opioid, exposure to which has led to hundreds of thousands of overdose deaths. Novel vaccines are being developed that might protect against fentanyl overdose. Proactive attention to strategic communications and stakeholder engagement may smooth uptake of a novel vaccine given known challenges around vaccine hesitancy and concern for stigma related to substance use. METHODS: Qualitative interviews (N = 74) with a purposive sample of adolescents/young adults with opioid use disorder (OUD), family members of persons with OUD, experts in substance use treatment and harm reduction, and community members were conducted and thematically analyzed to discern attitudes toward a fentanyl vaccine, and directions for communications and engagement. RESULTS: Major themes reflected personal concerns for biomedical risk and system-level concerns for alignment and integration of an overdose preventing vaccine with prevailing beliefs about addiction and associated frameworks and philosophies for treatment and response. CONCLUSION: Acceptability and implementation of a novel fentanyl vaccine targeting overdose will need precision communications that address biomedical, moral/spiritual, and structural perspectives about the nature of addiction. Education about the purpose and limits of a fentanyl vaccine, partnerships with diverse stakeholders from throughout the opioid response ecosystem and interweaving of a vaccine strategy into comprehensive prevention and treatment are recommended.

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.

Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

Affinities of the fern genus Ptisana (Marattiaceae) in the Solomon Islands, with descriptions of two new species.

In the process of undertaking a comprehensive review of the pteridophytes of the Solomon Islands, multiple unidentified specimens of the fern genus Ptisana Murdock (Marattiaceae) were collected. Morphological and molecular phylogenetic analyses as well as field observations were required to identify the Solomon Islands taxa. Four species and one variety are recognized from the Solomon Islands: Ptisana ambulans Murdock & C.W. Chen, sp. nov., Ptisana decipiens Murdock & C.W. Chen, sp. nov., Ptisana decipiens var. delicata Murdock & C.W. Chen, var. nov., Ptisana papuana (Alderw.) Murdock & C.W. Chen, comb. nov., and Ptisana smithii (Mett. ex Kuhn) Murdock. The complexities in the identification of Solomon Islands collections show the limits of morphology in the genus and illuminate a path forward for untangling the Ptisana taxonomy on a broader scale.

Consensus standards of healthcare for adults and children with inflammatory bowel disease in the UK.

OBJECTIVE: Symptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models. DESIGN: Led by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi. RESULTS: Consensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework. CONCLUSIONS: The Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD.

Human activities on the deep seafloor in the North East Atlantic: an assessment of spatial extent.

BACKGROUND: Environmental impacts of human activities on the deep seafloor are of increasing concern. While activities within waters shallower than 200 m have been the focus of previous assessments of anthropogenic impacts, no study has quantified the extent of individual activities or determined the relative severity of each type of impact in the deep sea. METHODOLOGY: The OSPAR maritime area of the North East Atlantic was chosen for the study because it is considered to be one of the most heavily impacted by human activities. In addition, it was assumed data would be accessible and comprehensive. Using the available data we map and estimate the spatial extent of five major human activities in the North East Atlantic that impact the deep seafloor: submarine communication cables, marine scientific research, oil and gas industry, bottom trawling and the historical dumping of radioactive waste, munitions and chemical weapons. It was not possible to map military activities. The extent of each activity has been quantified for a single year, 2005. PRINCIPAL FINDINGS: Human activities on the deep seafloor of the OSPAR area of the North Atlantic are significant but their footprints vary. Some activities have an immediate impact after which seafloor communities could re-establish, while others can continue to make an impact for many years and the impact could extend far beyond the physical disturbance. The spatial extent of waste disposal, telecommunication cables, the hydrocarbon industry and marine research activities is relatively small. The extent of bottom trawling is very significant and, even on the lowest possible estimates, is an order of magnitude greater than the total extent of all the other activities. CONCLUSIONS/SIGNIFICANCE: To meet future ecosystem-based management and governance objectives for the deep sea significant improvements are required in data collection and availability as well as a greater awareness of the relative impact of each human activity.

Chloroplast genome sequence of the moss Tortula ruralis: gene content, polymorphism, and structural arrangement relative to other green plant chloroplast genomes.

BACKGROUND: Tortula ruralis, a widely distributed species in the moss family Pottiaceae, is increasingly used as a model organism for the study of desiccation tolerance and mechanisms of cellular repair. In this paper, we present the chloroplast genome sequence of T. ruralis, only the second published chloroplast genome for a moss, and the first for a vegetatively desiccation-tolerant plant. RESULTS: The Tortula chloroplast genome is approximately 123,500 bp, and differs in a number of ways from that of Physcomitrella patens, the first published moss chloroplast genome. For example, Tortula lacks the approximately 71 kb inversion found in the large single copy region of the Physcomitrella genome and other members of the Funariales. Also, the Tortula chloroplast genome lacks petN, a gene found in all known land plant plastid genomes. In addition, an unusual case of nucleotide polymorphism was discovered. CONCLUSIONS: Although the chloroplast genome of Tortula ruralis differs from that of the only other sequenced moss, Physcomitrella patens, we have yet to determine the biological significance of the differences. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for mosses) of the generation of DNA markers for fine-level phylogenetic studies, or to investigate individual variation within populations.

Phylogeny of marattioid ferns (Marattiaceae): inferring a root in the absence of a closely related outgroup.

Closely related outgroups are optimal for rooting phylogenetic trees; however, such ideal outgroups are not always available. A phylogeny of the marattioid ferns (Marattiaceae), an ancient lineage with no close relatives, was reconstructed using nucleotide sequences of multiple chloroplast regions (rps4 + rps4-trnS spacer, trnS-trnG spacer + trnG intron, rbcL, atpB), from 88 collections, selected to cover the broadest possible range of morphologies and geographic distributions within the extant taxa. Because marattioid ferns are phylogenetically isolated from other lineages, and internal branches are relatively short, rooting was problematic. Root placement was strongly affected by long-branch attraction under maximum parsimony and by model choice under maximum likelihood. A multifaceted approach to rooting was employed to isolate the sources of bias and produce a consensus root position. In a statistical comparison of all possible root positions with three different outgroups, most root positions were not significantly less optimal than the maximum likelihood root position, including the consensus root position. This phylogeny has several important taxonomic implications for marattioid ferns: Marattia in the broad sense is paraphyletic; the Hawaiian endemic Marattia douglasii is most closely related to tropical American taxa; and Angiopteris is monophyletic only if Archangiopteris and Macroglossum are included.

Diagnostic criteria for coeliac disease: time for change?

A spectrum of histological changes may be seen in coeliac disease. Interpretation of duodenal biopsies can be problematic due to inadequate specimens or difficulties in detecting the minimal histological lesion. If serology is negative but clinical suspicion is high, a duodenal biopsy should always be performed. A combination of histology, serology, morphometry and HLA typing may be helpful in equivocal cases. Small intestinal histology is the current gold-standard diagnostic test for coeliac disease. Serological tests, immunohistochemistry and HLA typing may also have a role in the diagnostic algorithm. IgA antigliadin antibodies have mainly been replaced by IgA antiendomysial antibodies and IgA antitissue transglutaminase antibodies. The high sensitivity and specificity of these new markers have been used to challenge the necessity of obtaining a duodenal biopsy to confirm the diagnosis. It is widely recognized that relying on duodenal biopsies may be problematic. In equivocal cases where the biopsy material cannot be relied on accurately, further diagnostic tests are necessary. Quantitative morphometry and immunohistochemistry may be of value in identifying intraepithelial lymphocytes and a specific subset bearing the gamma/delta receptor. HLA-DQ2 may have a role in excluding the diagnosis in equivocal cases, its main limitation being its high frequency in the normal population. Each diagnostic test, namely histology, serology or genetic typing has limitations. A combination of these diagnostic tests should be used to clarify the full breadth of the gluten sensitivity spectrum, in particular, in those cases where duodenal histology may be equivocal.