Standardizing gross descriptions of skin lesions in common bottlenose dolphins (Tursiops truncatus) stranded in Southwest Florida, 2015–2019

As the first line of defense, the integumentary system is critical in comprehensively evaluating dolphin morbidity during stranding response. Most published studies on skin lesions in bottlenose dolphins (Tursiops truncatus) lack standardized gross descriptions and methodologies for evaluating lesions. The primary objective of this study was to evaluate the effectiveness of an assessment matrix designed to consistently describe skin lesions based on a set of standardized gross description characteristics. The matrix was implemented by reviewing necropsy reports, histopathology reports, and photographs collected from bottlenose dolphins stranded in Southwest Florida from 2015 through 2019. Of the 32 dolphins that met the inclusion criteria, 19 presented with skin lesions and five reviewers described each of the 46 lesions according to a novel, standardized assessment matrix. The most common descriptor selected, in each of the respective matrix categories, were, by anatomic location, head; distribution, multifocal to coalescing; quantity, moderate (10–30); size, <2 cm; shape, punctate; margin, rounded; color modifier, hyperpigmentation; texture, smooth; and texture modifier, flat. These prevalent descriptors coincided with the frequent occurrence of histologically described hydropic degeneration (n=7, 15.2%) and were confirmed poxviral lesions in 6.52% (n=3). Identifying lesion patterns using standardized descriptors capitalizes on the unique pathogen tissue tropism and the implementation of certain disease mechanisms in the integumentary system. Therefore, it can facilitate differential disease diagnoses and guide ancillary diagnostics testing. The use of standardized descriptors will aid in etiologic identification and monitoring of skin lesions and associated diseases, advancing our understanding of dolphin morbidity and mortality

Assessment of C, N, and Si Isotopes as Tracers of Past Ocean Nutrient and Carbon Cycling

28 pages, 6 figures, 1 box, 1 appendix.-- Data Availability Statement: Data sets presented in this research are available via the following repositories and study (listed by Figure): Figures 3 and 4: (1)δ13CDIC:(a) CLIVAR P16S (Feely et al., 2008) from GLODAPv2.2020 database (Olsen et al., 2020): https://www.glodap.info/index.php/merged-and-adjusted-data-product/. (b) GEOTRACES GA03 (Quay & Wu, 2015) and GP16 (P. Quay, unpublished data) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (2) δ15Nnitrate:(a) CLIVAR P16S (Rafter et al., 2013) from BCO-DMO: https://www.bco-dmo.org/dataset/651722. (b) GEOTRACES GA03 (Marconi et al., 2015) and GP16 (Peters et al., 2018) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (3) δ30Si: GEOTRACES GA03 (Brzezinski & Jones, 2015) and GIPY04 (Fripiat et al., 2012) from GEOTRACES IDP2017 (Schlitzer et al., 2018): https://www.bodc.ac.uk/geotraces/data/idp2017/. (4) Figure 4a POC Flux (DeVries & Weber, 2017): SIMPLE-TRIM Output from https://tdevries.eri.ucsb.edu/models-and-data-products/. Figure 5: (a) Antarctic CO2 composite: https://www.ncdc.noaa.gov/paleo-search/study/17975. (b) ∆δ13Cthermocline-deep from Ziegler et al. (2013) supporting information: https://www.nature.com/articles/ngeo1782; ∆δ13Cepifaunal-infaunal (Hoogakker et al., 2018): https://doi.pangaea.de/10.1594/PANGAEA.891185. (c) SAZ FB-δ15N (Martínez-García et al., 2014): https://www.ncdc.noaa.gov/paleo/study/18318; AZ DB-δ15N (Studer et al., 2015): https://doi.pangaea.de/10.1594/PANGAEA.848271. (d) SAZ Fe flux (Martínez-García et al., 2014): https://www.ncdc.noaa.gov/paleo/study/18318. (e) AZ diatom δ30Si (Robinson et al., 2014): https:// www.ncdc.noaa.gov/paleo/study/17917. Figure 6: (a) and (b) Benthic foraminifera δ18O and δ13C (Zachos et al., 2001): https:// www.ncdc.noaa.gov/paleo/study/8674. (c) FB-δ15N from Kast et al. (2019) supporting information data: https://science.sciencemag.org/content/suppl/2019/04/24/364.6438.386.DC1. (d) and (e) Diatom, sponge, and radiolarian δ30Si in Egan et al. (2013) supporting information: https://www.sciencedirect.com/science/article/pii/S0012821X13002185, Fontorbe et al. (2016) supporting information: https://www.sciencedirect.com/science/article/pii/S0012821X16304265, and Fontorbe et al. (2017) supporting information: https://agupubs.onlinelibrary.wiley.com/doi/full/10.1002/2017PA003090Biological productivity in the ocean directly influences the partitioning of carbon between the atmosphere and ocean interior. Through this carbon cycle feedback, changing ocean productivity has long been hypothesized as a key pathway for modulating past atmospheric carbon dioxide levels and hence global climate. Because phytoplankton preferentially assimilate the light isotopes of carbon and the major nutrients nitrate and silicic acid, stable isotopes of carbon (C), nitrogen (N), and silicon (Si) in seawater and marine sediments can inform on ocean carbon and nutrient cycling, and by extension the relationship with biological productivity and global climate. Here, we compile water column C, N, and Si stable isotopes from GEOTRACES-era data in four key ocean regions to review geochemical proxies of oceanic carbon and nutrient cycling based on the C, N, and Si isotopic composition of marine sediments. External sources and sinks as well as internal cycling (including assimilation, particulate matter export, and regeneration) are discussed as likely drivers of observed C, N, and Si isotope distributions in the ocean. The potential for C, N, and Si isotope measurements in sedimentary archives to record aspects of past ocean C and nutrient cycling is evaluated, along with key uncertainties and limitations associated with each proxy. Constraints on ocean C and nutrient cycling during late Quaternary glacial-interglacial cycles and over the Cenozoic are examined. This review highlights opportunities for future research using multielement stable isotope proxy applications and emphasizes the importance of such applications to reconstructing past changes in the oceans and climate systemThis workshop was funded by the United States National Science Foundation (NSF) through the GEOTRACES program, the international Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and NSF, and the French national program LEFE (Les Enveloppes Fluides et l'Environnement). [...] This study was supported by PAGES, LEFE, and GEOTRACES through NSF. J. R. Farmer acknowledges support from the Max Planck Society, the Tuttle Fund of the Department of Geosciences of Princeton University, the Grand Challenges Program of the Princeton Environmental Institute, and through Exxon Mobil via the Andlinger Center for Energy and the Environment of Princeton University. Open access funding enabled and organized by Projekt DEAL. [...] With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S

Enhancing interprofessional collaboration and interprofessional education in women\u27s health

This article is from the \u27To The Point\u27 series from the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee. The purpose of this review is to provide an understanding of the differing yet complementary nature of interprofessional collaboration and interprofessional education as well as their importance to the specialty of Obstetrics and Gynecology. We provide a historical perspective of how interprofessional collaboration and interprofessional education have become key aspects of clinical and educational programs, enhancing both patient care and learner development. Opportunities to incorporate interprofessional education within women\u27s health educational programs across organizations are suggested. This is a resource for medical educators, learners, and practicing clinicians from any field of medicine or any health-care profession

A Native Function for RAN Translation and CGG Repeats in Regulating Fragile X Protein Synthesis

Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5′-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human neurons. In human and rodent neurons, CGG RAN-blocking ASOs suppressed repeat toxicity and prolonged survival. These findings delineate a native function for CGG repeats and RAN translation in regulating basal and activity-dependent FMRP synthesis, and they demonstrate the therapeutic potential of modulating CGG RAN translation in fragile X-associated disorders

A review of the stable isotope bio-geochemistry of the global silicon cycle and its associated trace elements

Silicon (Si) is the second most abundant element in the Earth's crust and is an important nutrient in the ocean. The global Si cycle plays a critical role in regulating primary productivity and carbon cycling on the continents and in the oceans. Development of the analytical tools used to study the sources, sinks, and fluxes of the global Si cycle (e.g., elemental and stable isotope ratio data for Ge, Si, Zn, etc.) have recently led to major advances in our understanding of the mechanisms and processes that constrain the cycling of Si in the modern environment and in the past. Here, we provide background on the geochemical tools that are available for studying the Si cycle and highlight our current understanding of the marine, freshwater and terrestrial systems. We place emphasis on the geochemistry (e.g., Al/Si, Ge/Si, Zn/Si, δ13C, δ15N, δ18O, δ30Si) of dissolved and biogenic Si, present case studies, such as the Silicic Acid Leakage Hypothesis, and discuss challenges associated with the development of these environmental proxies for the global Si cycle. We also discuss how each system within the global Si cycle might change over time (i.e., sources, sinks, and processes) and the potential technical and conceptual limitations that need to be considered for future studies.The work by JS was supported by the “Laboratoire d’Excellence” LabexMER (ANR-10-LABX-19) and co-funded by a grant from the French government under the program “Investissements d’Avenir,” and by a grant from the Regional Council of Brittany (SAD programme). DJC was partially supported by the Knut and Alice Wallenberg Foundation (KAW Wallenberg Scholar) and the Swedish Research Council. This review article has benefited from funding by the European Union Seventh Framework Programme under grant agreement n◦294146 (project MuSiCC, Marie Curie CIG to DC). GdS is supported by a Marie Skłodowska-Curie Research Fellowship under EU Horizon2020 (GA #708407). JuD was supported by the American Chemical Society Petroleum Research Fund (Grant # 53798-DNI2). CE acknowledges financial support by the Institute for Chemistry and Biology of the Marine Environment (Oldenburg, Germany) and the Max Planck Institute for Marine Microbiology (Bremen, Germany). KH is funded by The Royal Society (UF120084) and the European Research Council (ERC-2015-StG - 678371_ICY-LAB). PG acknowledges funding by the Collaborative Research Centre 754 “ClimateBiogeochemistry interactions in the Tropical Ocean” (www. sfb754.de), supported by the Deutsche Forschungsgemeinschaft (DFG)

Expectations of and for Clerkship Directors 2.0: A Collaborative Statement from the Alliance for Clinical Education

This article presents an update of the collaborative statement on clerkship directors (CDs), first published in 2003, from the national undergraduate medical education organizations that comprise the Alliance for Clinical Education (ACE). The clerkship director remains an essential leader in the education of medical students on core clinical rotations, and the role of the CD has and continues to evolve. The selection of a CD should be an explicit contract between the CD, their department, and the medical school, with each party fulfilling their obligations to ensure the success of the students, the clerkship and of the CD. Educational innovations and accreditation requirements have evolved in the last two decades and therefore this article updates the 2003 standards for what is expected of a CD and provides guidelines for the resources and support to be provided. In their roles as CDs, medical student educators engage in several critical activities: administration, education/teaching, coaching, advising, and mentoring, faculty development, compliance with accreditation standards, and scholarly activity. This article describes (a) the work products that are the primary responsibility of the CD; (b) the qualifications for the CD; (c) the support structure, resources, and personnel that are necessary for the CD to accomplish their responsibilities; (d) incentives and career development for the CD; and (e) the dedicated time that should be provided for the clerkship and the CD to succeed. Given all that should rightfully be expected of a CD, a minimum of 50% of a full-time equivalent is recognized as appropriate. The complexity and needs of the clerkship now require that at least one full-time clerkship administrator (CA) be a part of the CD’s team. To better reflect the current circumstances, ACE has updated its recommendations for institutions and departments to have clear standards for what is expected of the director of a clinical clerkship and have correspondingly clear guidelines as to what should be expected for CDs in the support they are provided. This work has been endorsed by each of the eight ACE member organizations

Lessons learned from additional research analyses of unsolved clinical exome cases

BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. RESULTS: Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). CONCLUSION: An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Public health in community pharmacy: a systematic review of pharmacist and consumer views

BACKGROUND The increasing involvement of pharmacists in public health will require changes in the behaviour of both pharmacists and the general public. A great deal of research has shown that attitudes and beliefs are important determinants of behaviour. This review aims to examine the beliefs and attitudes of pharmacists and consumers towards pharmaceutical public health in order to inform how best to support and improve this service. METHODS Five electronic databases were searched for articles published in English between 2001 and 2010. Titles and abstracts were screened by one researcher according to the inclusion criteria. Papers were included if they assessed pharmacy staff or consumer attitudes towards pharmaceutical public health. Full papers identified for inclusion were assessed by a second researcher and data were extracted by one researcher. RESULTS From the 5628 papers identified, 63 studies in 67 papers were included. Pharmacy staff: Most pharmacists viewed public health services as important and part of their role but secondary to medicine related roles. Pharmacists' confidence in providing public health services was on the whole average to low. Time was consistently identified as a barrier to providing public health services. Lack of an adequate counselling space, lack of demand and expectation of a negative reaction from customers were also reported by some pharmacists as barriers. A need for further training was identified in relation to a number of public health services. Consumers: Most pharmacy users had never been offered public health services by their pharmacist and did not expect to be offered. Consumers viewed pharmacists as appropriate providers of public health advice but had mixed views on the pharmacists' ability to do this. Satisfaction was found to be high in those that had experienced pharmaceutical public health. CONCLUSIONS There has been little change in customer and pharmacist attitudes since reviews conducted nearly 10 years previously. In order to improve the public health services provided in community pharmacy, training must aim to increase pharmacists' confidence in providing these services. Confident, well trained pharmacists should be able to offer public health service more proactively which is likely to have a positive impact on customer attitudes and health

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07