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1.
Am J Primatol ; : e23622, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561573

RESUMO

The consumption of primates is integral to the traditional subsistence strategies of many Indigenous communities throughout Amazonia. Understanding the overall health of primates harvested for food in the region is critical to Indigenous food security and thus, these communities are highly invested in long-term primate population health. Here, we describe the establishment of a surveillance comanagement program among the Waiwai, an Indigenous community in the Konashen Amerindian Protected Area (KAPA). To assess primate health in the KAPA, hunters performed field necropsies on primates harvested for food and tissues collected from these individuals were analyzed using histopathology. From 2015 to 2019, hunters conducted 127 necropsies across seven species of primates. Of this sample, 82 primates (between 2015 and 2017) were submitted for histopathological screening. Our histopathology data revealed that KAPA primates had little evidence of underlying disease. Of the tissue abnormalities observed, the majority were either due to diet (e.g., hepatocellular pigment), degenerative changes resulting from aging (e.g., interstitial nephritis, myocyte lipofusion), or nonspecific responses to antigenic stimulation (renal and splenic lymphoid hyperplasia). In our sample, 7.32% of individuals had abnormalities that were consistent with a viral etiology, including myocarditis and hepatitis. Internal parasites were observed in 53.66% of individuals and is consistent with what would be expected from a free-ranging primate population. This study represents the importance of baseline data for long-term monitoring of primate populations hunted for food. More broadly, this research begins to close a critical gap in zoonotic disease risk related to primate harvesting in Amazonia, while also demonstrating the benefits of partnering with Indigenous hunters and leveraging hunting practices in disease surveillance and primate population health assessment.

2.
Am J Primatol ; : e23628, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605487

RESUMO

Nonhuman primate species currently face human-induced pressures and will continue to face them in the modern landscape. These pressures require conservation projects in primate habitat countries to aid in protection, preservation, and conservation. Though there are several examples of primate conservation projects, starting up an initiative can be a daunting task. The American Society of Primatology (ASP) Conservation Committee hosted a video webinar presenting on the first steps of developing, running and continuing a primate conservation program. Dr. Christopher Shaffer, Rahayu Oktaviani, and Dr. Jill Pruetz presented their early program experiences establishing wild primate conservation projects to educate primatologists around the world. The running themes of the presentations included establishing community, working locally, impacting locally and preparing for the future.

3.
Drug Metab Dispos ; 52(5): 323-336, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38360917

RESUMO

BIIB104 (formerly PF-04958242), N-((3S,4S)-4-(4-(5-cyanothiophen-2-yl)phenoxy)tetrahydrofuran-3-yl)propane-2-sulfonamide, is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiator investigated for the treatment of cognitive impairment associated with schizophrenia. Preliminary in vitro metabolism studies with non-radiolabeled BIIB104 in rat, dog, and human liver microsomes (RLM, DLM, and HLM) showed O-dealkylation in all three species, tetrahydrofuran hydroxylation dominating in DLM and HLM, and thiophene hydroxylation prevalent in RLM. However, a subsequent rat mass balance study with [nitrile-14C]BIIB104 showed incomplete recovery of administered radioactivity (∼80%) from urine and feces over 7 days following an oral dose, and an exceptionally long plasma total radioactivity half-life. Radiochromatographic metabolite profiling and identification, including chemical derivation, revealed that [14C]cyanide was a major metabolite of [nitrile-14C]BIIB104 in RLM, but a minor and trace metabolite in DLM and HLM, respectively. Correspondingly in bile duct-cannulated rats, [14C]thiocyanate accounted for ∼53% of total radioactivity excreted over 48 hours postdose and it, as an endogenous substance, explained the exceptionally long plasma radioactivity half-life. The release of [14C]cyanide from the 2-cyanothiophene moiety is postulated to follow an epoxidation-initiated thiophene-opening based on the detection of non-radiolabeled counterpart metabolites in RLM. This unusual biotransformation serves as a lesson regarding placement of the radioactive label on an aryl nitrile when material will be used for evaluating the metabolism of a new drug candidate. Additionally, the potential cyanide metabolite of nitrile-containing drug molecules may be detected in liver microsomes with liquid chromatography-mass spectrometry following a chemical derivatization. SIGNIFICANCE STATEMENT: Using [nitrile-14C]BIIB104, non-intuitive metabolites of BIIB104 were discovered involving a novel cyanide release from the 2-cyanothiophene motif via a postulated epoxidation-initiated thiophene-opening. This unusual biotransformation serves as a lesson regarding placement of the radioactive label on an aryl nitrile when material will be used for evaluating the metabolism of a new drug candidate.


Assuntos
Cianetos , Tiocianatos , Humanos , Ratos , Animais , Cães , Cianetos/análise , Tiocianatos/análise , Biotransformação , Fezes/química , Nitrilas , Tiofenos/análise , Furanos
4.
Molecules ; 29(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257338

RESUMO

The aim of this study was to measure the brain penetrance and kinetics of BIIB104, a first-in-class AMPA receptor potentiator developed for cognitive impairment associated with schizophrenia. It was recently halted in phase 2 clinical development, and there are a lack of tools to directly measure AMPA receptor engagement. To achieve this, the drug candidate was radiolabeled with carbon-11, and its brain penetrance and kinetics were measured in non-human primates via dynamic PET scans. Radiolabeling was achieved through a three-step nucleophilic [11C]cyanation reaction in one pot, resulting in the high radioactivity and radiochemical purity (>99%) of [11C]BIIB104. The study found that [11C]BIIB104 entered the non-human primate brains at 4-5% ID at peak, with a homogeneous distribution. However, a mild regional heterogeneity was observed in the thalamus. The lack of conclusive evidence for a change in regional values after BIIB104 dosing suggests that any specific binding component of BIIB104 is negligible compared to the free and non-specific components in the living brain. Overall, the study demonstrated high brain uptake with minor variability in [11C]BIIB104 distribution across various brain regions, its kinetics were consistent with those of passive diffusion, and the dominating components were the free concentration and non-specific binding. This information is valuable for understanding the potential effects and mechanisms of BIIB104 in the brain.


Assuntos
Tomografia por Emissão de Pósitrons , Receptores de AMPA , Animais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Encéfalo/diagnóstico por imagem , Primatas
5.
ISME J ; 17(12): 2381-2388, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37907733

RESUMO

Satellites are mobile genetic elements that are dependent upon the replication machinery of their helper viruses. Bacteriophages have provided many examples of satellite nucleic acids that utilize their helper morphogenic genes for propagation. Here we describe two novel satellite-helper phage systems, Mulch and Flayer, that infect Streptomyces species. The satellites in these systems encode for encapsidation machinery but have an absence of key replication genes, thus providing the first example of bacteriophage satellite viruses. We also show that codon usage of the satellites matches the tRNA gene content of the helpers. The satellite in one of these systems, Flayer, does not appear to integrate into the host genome, which represents the first example of a virulent satellite phage. The Flayer satellite has a unique tail adaptation that allows it to attach to its helper for simultaneous co-infection. These findings demonstrate an ever-increasing array of satellite strategies for genetic dependence on their helpers in the evolutionary arms race between satellite and helper phages.


Assuntos
Bacteriófagos , Streptomyces , Vírus Satélites/genética , Streptomyces/genética , Virulência , Vírus Auxiliares/genética , Bacteriófagos/genética
6.
Cancer Med ; 12(23): 21075-21096, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37997517

RESUMO

BACKGROUND: Pediatric brain tumors (PBT) stand as the leading cause of cancer-related deaths in children. Chemoradiation protocols have improved survival rates, even for non-resectable tumors. Nonetheless, radiation therapy carries the risk of numerous adverse effects that can have long-lasting, detrimental effects on the quality of life for survivors. The pursuit of chemotherapeutics that could obviate the need for radiotherapy remains ongoing. Several anti-tumor agents, including sunitinib, valproic acid, carboplatin, and panobinostat, have shown effectiveness in various malignancies but have not proven effective in treating PBT. The presence of the blood-brain barrier (BBB) plays a pivotal role in maintaining suboptimal concentrations of anti-cancer drugs in the central nervous system (CNS). Ongoing research aims to modulate the integrity of the BBB to attain clinically effective drug concentrations in the CNS. However, current findings on the interaction of exogenous chemical agents with the BBB remain limited and do not provide a comprehensive explanation for the ineffectiveness of established anti-cancer drugs in PBT. METHODS: We conducted our search for chemotherapeutic agents associated with the blood-brain barrier (BBB) using the following keywords: Chemotherapy in Cancer, Chemotherapy in Brain Cancer, Chemotherapy in PBT, BBB Inhibition of Drugs into CNS, Suboptimal Concentration of CNS Drugs, PBT Drugs and BBB, and Potential PBT Drugs. We reviewed each relevant article before compiling the information in our manuscript. For the generation of figures, we utilized BioRender software. FOCUS: We focused our article search on chemical agents for PBT and subsequently investigated the role of the BBB in this context. Our search criteria included clinical trials, both randomized and non-randomized studies, preclinical research, review articles, and research papers. FINDING: Our research suggests that, despite the availability of potent chemotherapeutic agents for several types of cancer, the effectiveness of these chemical agents in treating PBT has not been comprehensively explored. Additionally, there is a scarcity of studies examining the role of the BBB in the suboptimal outcomes of PBT treatment, despite the effectiveness of these drugs for other types of tumors.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Criança , Humanos , Barreira Hematoencefálica , Qualidade de Vida , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-37990750

RESUMO

Endogenous neuropeptide Oxytocin (OXT) plays a crucial role in modulating pro-social behavior and the neural response to social/emotional stimuli. Intranasal administration is the most common method of delivering OXT. Intranasal OXT has been implemented in clinical studies of various psychiatric disorders with mixed results, mainly related to lack of solid pharmacodynamics and pharmacokinetics model. Due to intranasal OXT's mechanism of reducing the activation of neural areas implicated in emotional responding and emotion regulation, a psychopathology with this target mechanism could be potentially excellent candidate for future clinical trial. In this regard, irritability in youth may be a very promising target for clinical studies of intranasal OXT. Here we provide a mini-review of fifteen randomized controlled trials in pediatric patients with diagnoses of autism spectrum disorder (ASD), Prader-Willi syndrome (PWS), or Phelan-McDermid syndrome (PMS). Most studies had small sample sizes and varying dosages, with changes in irritability, mainly as adverse events (AEs). Neuroimaging results showed modulation of the reward processing system and the neural areas implicated in social-emotional information processing by intranasal OXT administration. Further research is needed to determine the most effective dose and duration of OXT treatment, carefully select target psychopathologies, verify target engagement, and measure adverse event profiles.

8.
J Biomol Struct Dyn ; 41(21): 11671-11680, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36591705

RESUMO

We have performed molecular dynamics (MD) and replica-exchange (REMD) simulations of folding of the GB1 hairpin peptide in aqueous solution. REMD results were consistent with a cooperative zipper folding model. 120 µs MD trajectories at 320 K yielded relaxation times of 1.8 µs and 100 ns, with the slower assigned to global folding. The MD folding/unfolding transitions also followed the cooperative zipper model, specifying nucleation at the central turn followed by consecutive hydrogen bond formation. Formation of hydrogen bonds and hydrophobic contacts were highly correlated. Coarse-grained kinetic models constructed with the Optimal Dimensionality Reduction (ODR) approach found a folding time of 3.3 µs and unfolding time of 4.0 µs. Additionally, relaxation times in the 130-170 ns range could be assigned to formation of the transition state and off-path intermediates. The unfolded state was the most highly populated and, significantly, most heterogenous, assembling the largest number of microstates, primarily composed of extended and turn structures. The folded state was also heterogenous, but a to a lesser degree, involving the fully folded and partially folded in-register hairpins at early stages of the zipper pathway. The transition state corresponded to the nucleated hairpin, with central turn and first beta-sheet hydrogen bond, while the off-path intermediates were off-register partial hairpins. Our simulation results were in excellent agreement with experimental data on folded fraction, relaxation time and folding mechanism. The new findings from this work suggest a highly cooperative zipper folding mechanism, nascent hairpin transition state and ∼100 ns relaxation related to intermediate formation.Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Dobramento de Proteína , Estrutura Secundária de Proteína , Peptídeos/química , Água , Cinética , Termodinâmica , Ligação de Hidrogênio
9.
Sci Adv ; 8(32): eabn2927, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35947670

RESUMO

Primates, represented by 521 species, are distributed across 91 countries primarily in the Neotropic, Afrotropic, and Indo-Malayan realms. Primates inhabit a wide range of habitats and play critical roles in sustaining healthy ecosystems that benefit human and nonhuman communities. Approximately 68% of primate species are threatened with extinction because of global pressures to convert their habitats for agricultural production and the extraction of natural resources. Here, we review the scientific literature and conduct a spatial analysis to assess the significance of Indigenous Peoples' lands in safeguarding primate biodiversity. We found that Indigenous Peoples' lands account for 30% of the primate range, and 71% of primate species inhabit these lands. As their range on these lands increases, primate species are less likely to be classified as threatened or have declining populations. Safeguarding Indigenous Peoples' lands, languages, and cultures represents our greatest chance to prevent the extinction of the world's primates.

10.
J Pediatr Pharmacol Ther ; 27(6): 506-516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36042964

RESUMO

Acute kidney injury (AKI) is a common and serious condition that occurs in approximately 30% to 50% of pediatric patients that undergo cardiac surgery. Currently used parameters to measure kidney function (serum creatinine and urine output) are often unreliable and delay the prediction of AKI, despite their adoption into clinical guidelines. Emerging evidence suggests that biomarkers such as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, kidney injury molecule 1, and liver-type fatty acid- binding protein may be useful in the identification and location of pediatric renal injury. Ontogeny-related changes in tubular function and nephrogenesis result in reference values that differ based on age and sex. In addition, changes in endogenous concentrations may result from factors such as cardiopulmonary bypass. The use of urine samples to measure renal biomarkers offers a significant advantage compared with routine blood sampling, especially in the neonatal patient population. Future research is warranted to determine age-dependent changes in AKI biomarkers and the relationship with pharmacokinetic clearance of commonly used medications in the postoperative cardiac patient.

11.
PLoS Negl Trop Dis ; 16(6): e0010469, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35687596

RESUMO

Domestic dogs (Canis lupus familiaris) can transmit a variety of pathogens due to their ubiquitousness in urban, rural and natural environments, and their close interactions with wildlife and humans. In this study, we used a mixed-methods approach to assess the role of domestic dogs as potential intermediaries of disease transmission from wildlife to humans among indigenous Waiwai in the Konashen Community Owned Conservation Area, Guyana. To address these objectives we 1) performed physical examinations and collected biological samples to assess Waiwai domestic dog health, and 2) administered questionnaires to characterize the role of dogs in the community and identify potential transmission pathways between wildlife, dogs, and humans. We observed ectoparasites on all dogs (n = 20), including: fleas (100%), ticks (15%), botflies (30%), and jigger flea lesions (Tunga penetrans) (80%). Ten percent of dogs were seropositive for Ehrlichia canis/ewingii, 10% were positive for Dirofilaria immitis, and one dog was seropositive for Leishmania infantum. All dogs (n = 20) were seronegative for: canine distemper virus, Brucella canis, Leptospira serovars, Trypanosoma cruzi, Anaplasma phagocytophilum/platys and Borrelia burgdorferi. Our questionnaire data revealed that the Waiwai remove ectoparasites from their dogs, clean up dog feces, and administer traditional and/or Western medicine to their dogs. White blood cell, strongyle-type ova, and eosinophil counts were lower in dogs that were not frequently used for hunting, dogs that did receive traditional and/or western medicine, and dogs that were frequently kept in elevated dog houses, although differences were not statistically significant. While our results suggest that the Waiwai have developed cultural practices that may promote dog health and/or prevent zoonotic disease transmission, more research is necessary to determine the efficacy of these practices. Our study provides important data on the health of dogs and the potential for disease transmission to humans in a zoonotic hotspot.


Assuntos
Borrelia burgdorferi , Dirofilaria immitis , Doenças do Cão , Ehrlichiose , Doença de Lyme , Anaplasma , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Ehrlichia , Ehrlichiose/veterinária , Guiana , Estudos Soroepidemiológicos
12.
Science ; 376(6597): 1057-1059, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35653460

RESUMO

Outdated teaching methods amount to discrimination.

13.
Pharm Res ; 39(7): 1321-1341, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35411506

RESUMO

PURPOSE: More than 15 years have passed since the first description of the unbound brain-to-plasma partition coefficient (Kp,uu,brain) by Prof. Margareta Hammarlund-Udenaes, which was enabled by advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support the notion that the unbound (free) concentration of a drug at the site of action, such as the brain, is the driving force for pharmacological responses. Towards this end, Kp,uu,brain is the key parameter to obtain unbound brain concentrations from unbound plasma concentrations. METHODS: To understand the importance and impact of the Kp,uu,brain concept in contemporary drug discovery and development, a survey has been conducted amongst major pharmaceutical companies based in Europe and the USA. Here, we present the results from this survey which consisted of 47 questions addressing: 1) Background information of the companies, 2) Implementation, 3) Application areas, 4) Methodology, 5) Impact and 6) Future perspectives. RESULTS AND CONCLUSIONS: From the responses, it is clear that the majority of the companies (93%) has established a common understanding across disciplines of the concept and utility of Kp,uu,brain as compared to other parameters related to brain exposure. Adoption of the Kp,uu,brain concept has been mainly driven by individual scientists advocating its application in the various companies rather than by a top-down approach. Remarkably, 79% of all responders describe the portfolio impact of Kp,uu,brain implementation in their companies as 'game-changing'. Although most companies (74%) consider the current toolbox for Kp,uu,brain assessment and its validation satisfactory for drug discovery and early development, areas of improvement and future research to better understand human brain pharmacokinetics/pharmacodynamics translation have been identified.


Assuntos
Barreira Hematoencefálica , Fármacos do Sistema Nervoso Central , Descoberta de Drogas , Encéfalo , Descoberta de Drogas/métodos , Humanos
14.
Ecohealth ; 18(2): 169-181, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34508275

RESUMO

Echinococcus spp. are zoonotic cestode parasites with a worldwide distribution and a complex, two-host life cycle involving carnivore definitive hosts and small mammal or ungulate intermediate hosts. Surveillance for Echinococcus spp. in the Midwestern United States (USA) is rare. Using a mixed-methods approach, we examined Echinococcus infection risks in wildlife and domestic dogs in four Minnesota Tribal Nations. We hypothesized that the spillover of Echinococcus spp. into domestic dogs would vary with the presence or absence of suspected wildlife host species and certain behaviors associated with domestic dog ownership, like feeding wildlife host carcasses or frequency of veterinary care. Among 83 dogs tested, three (3.6%) were positive for Echinococcus spp. Despite low prevalence, pet owner survey and focus group findings indicated that dogs encounter peri-domestic wildlife most often when they roam freely or consume wildlife carcasses. This study demonstrates a need for further research into spillover potential of endemic zoonotic Echinococcus spp. in the Midwest USA.


Assuntos
Equinococose , Echinococcus , Animais , Animais Selvagens/parasitologia , Cães , Equinococose/epidemiologia , Equinococose/veterinária , Mamíferos , Minnesota/epidemiologia , Prevalência
15.
Primates ; 62(3): 477-489, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33751334

RESUMO

A growing body of research focuses on how anthropogenic factors affect the behavior and ecology of primates and their ecosystems. Infrastructural development, such as roads, is an increasingly pervasive anthropogenic impact that destroys primate habitat, affects the distribution and dispersal of primates, and facilitates human-primate interactions. At our field site in Bantimurung-Bulusaraung National Park, Sulawesi, Indonesia, a major road bisects the habitat of the endangered moor macaque (Macaca maura). Beginning in 2015, we observed a behavioral shift by our main study group: they began spending more time along the road foraging in trash pits and waiting for provisions from vehicles. Our objective in this study was to examine how access to anthropogenic foods has affected the group's ranging behavior by comparing ranging data collected before (2010-2011) and after the shift (2016-2017). In contrast to what we expected, home ranges were significantly larger and daily travel distance was significantly longer after the shift compared to before. As predicted, mean distance to the road decreased after the shift. These results likely reflect the irregular and spatially dispersed nature of provisioning at this site. The macaques appear to be attracted to the road because it presents opportunities to obtain palatable and energy-dense foods. Our results indicate that moor macaques are able to flexibly adjust their ranging behavior in response to anthropogenic impacts. However, given the risks of being in proximity to roads and humans, management of this emerging human-macaque interface is needed.


Assuntos
Comportamento Animal , Ecossistema , Animais , Haplorrinos , Indonésia , Macaca , Parques Recreativos
16.
Expert Rev Anti Infect Ther ; 19(9): 1107-1116, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33554692

RESUMO

Introduction: Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), remains a significant pathogen in children. Despite evidence of decreasing prevalence, MRSA bacteremia has been closely associated with complications, including certain infections (i.e. musculoskeletal and endovascular) linked to increased treatment failures.Areas covered: This expert review summarized recent published literature on the role of treatment, dosing and administration of antibiotics used to combat serious S. aureus infections in children. The pertinent antibiotics presented were vancomycin, oxazolidinones, semi-synthetic glycopeptides, daptomycin, tigecycline, novel cephalosporins, fosfomycin and lefamulin. Vancomycin has been the most commonly used antibiotic in empiric therapy for serious MRSA infection, with new key recommendations emphasizing a different approach to dosing and therapeutic monitoring. For other antibiotics, data remain limited or clinical trials are underway.Expert opinion: MRSA remains a significant pathogen in the pediatric population. As numerous therapeutic agents are available, many agents have limited data on usage in pediatric patients. Future studies require pharmacokinetic, safety and efficacy studies in pediatric patients to ensure appropriate therapeutic treatment and outcomes. Phage therapy has been used to treat deep-seated MRSA infections and is an emerging investigational treatment option.


Assuntos
Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Criança , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Terapia por Fagos/métodos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
17.
Learn Health Syst ; 5(1): e10255, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33490385

RESUMO

The volume of biomedical knowledge is growing exponentially and much of this knowledge is represented in computer executable formats, such as models, algorithms, and programmatic code. There is a growing need to apply this knowledge to improve health in Learning Health Systems, health delivery organizations, and other settings. However, most organizations do not yet have the infrastructure required to consume and apply computable knowledge, and national policies and standards adoption are not sufficient to ensure that it is discoverable and used safely and fairly, nor is there widespread experience in the process of knowledge implementation as clinical decision support. The Mobilizing Computable Biomedical Knowledge (MCBK) community was formed in 2016 to address these needs. This report summarizes the main outputs of the third annual MCBK public meeting, which was held virtually from June 30 to July 1, 2020 and brought together over 200 participants from various domains to frame and address important dimensions for mobilizing CBK.

18.
PLoS One ; 15(6): e0234636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555720

RESUMO

The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, and their G+C% content ranges from 51.4% to 71.4%, compared to ~67% for their Microbacterium hosts. The phages were isolated on five different Microbacterium species, but typically do not efficiently infect strains beyond the one on which they were isolated. These Microbacterium phages contain many novel features, including very large viral genes (13.5 kbp) and unusual fusions of structural proteins, including a fusion of VIP2 toxin and a MuF-like protein into a single gene. These phages and their genetic components such as integration systems, recombineering tools, and phage-mediated delivery systems, will be useful resources for advancing Microbacterium genetics.


Assuntos
Actinobacteria/virologia , Bacteriófagos/genética , Variação Genética , Genoma Viral , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Composição de Bases , DNA Viral/genética , Genes Virais , Genômica , Filogenia , Proteínas Virais de Fusão/genética
19.
Learn Health Syst ; 4(2): e10222, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32313839

RESUMO

The volume of biomedical knowledge is growing exponentially and much of this knowledge is represented in computer executable formats, such as models, algorithms and programmatic code. There is a growing need to apply this knowledge to improve health in Learning Health Systems, health delivery organizations, and other settings. However, most organizations do not yet have the infrastructure required to consume and apply computable knowledge, and national policies and standards adoption are not sufficient to ensure that it is discoverable and used safely and fairly, nor is there widespread experience in the process of knowledge implementation as clinical decision support. The Mobilizing Computable Biomedical Knowledge (MCBK) community formed in 2016 to address these needs. This report summarizes the main outputs of the Second Annual MCBK public meeting, which was held at the National Institutes of Health on July 18-19, 2019 and brought together over 150 participants from various domains to frame and address important dimensions for mobilizing CBK.

20.
Ecohealth ; 17(4): 424-436, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33792854

RESUMO

The hunting, butchery, and consumption of wild meat is an important interface for zoonotic disease transmission. Despite this, few researchers have used ethnography to understand the sociocultural factors that may increase zoonotic disease transmission from hunting, particularly in Amazonia. Here, we use ethnographic methods consisting of structured, semi-structured and unstructured interviews, and participant observation to address questions pertaining to wild meat consumption, pathways of zoonotic disease transmission, food security, and the cultural identity of indigenous Waiwai in the Konashen Community Owned Conservation Area, Guyana. Our data revealed that the majority of Waiwai eat wild meat two to three times/week and 60% of respondents reported butchery-related injuries. However, semi-structured and unstructured interviews, and participant observation data indicate that the Waiwai do not perceive most cuts from butchery as injuries, despite being a potential route of pathogen exposure. Additionally, participant observation revealed that hunting is integral to Waiwai identity and the Waiwai exhibit a cultural aversion to domestic meats. These findings provide valuable insights into the interplay of hunting and wild meat consumption and disease in Amazonia and demonstrate how an ethnographic approach provides the contextual data necessary for identifying potential pathways of zoonotic transmission from wild meat.


Assuntos
Animais Selvagens , Zoonoses , Animais , Antropologia Cultural , Guiana , Humanos , Carne
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