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[This corrects the article DOI: 10.1371/journal.pone.0190829.].
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The time of origin of the geodynamo has important implications for the thermal evolution of the planetary interior and the habitability of early Earth. It has been proposed that detrital zircon grains from Jack Hills, Western Australia, provide evidence for an active geodynamo as early as 4.2 billion years (Ga) ago. However, our combined paleomagnetic, geochemical, and mineralogical studies on Jack Hills zircons indicate that most have poor magnetic recording properties and secondary magnetization carriers that postdate the formation of the zircons. Therefore, the existence of the geodynamo before 3.5 Ga ago remains unknown.
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Immune checkpoint inhibitors are increasingly used to treat a variety of solid-organ and hematologic cancers. However, overactivation of the immune system can lead to immune-related adverse events, which are increasingly recognized in the kidney. There have been only rare reported cases of checkpoint inhibitor-associated glomerulonephritis and renal vasculitis, although vasculitis in other organs has been well described. We report 4 cases of renal vasculitis or pauci-immune glomerulonephritis after checkpoint inhibitor therapy. Three patients had renal small- to medium-vessel vasculitis and 1 had focally crescentic pauci-immune glomerulonephritis. Three patients presented with acute kidney injury, and 1 presented with nephrotic syndrome and hematuria. Three patients were tested for antineutrophil cytoplasmic antibodies, which were negative. The time from checkpoint inhibitor initiation to immune-related adverse event presentation ranged from 2 weeks to 24 months. Three patients were treated with glucocorticoids, resulting in clinical resolution. Our series demonstrates that renal vasculitis and pauci-immune glomerulonephritis are important considerations in the differential diagnosis of checkpoint inhibitor-related reductions in kidney function.
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Lesión Renal Aguda/inducido químicamente , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Glomerulonefritis Membranosa/inducido químicamente , Nivolumab/efectos adversos , Lesión Renal Aguda/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranosa/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Persona de Mediana Edad , Nivolumab/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Medición de Riesgo , Muestreo , Tasa de SupervivenciaRESUMEN
Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. Despite extensive research, infection remains one of the leading sources of complications in chronic wounds, resulting in improper healing, biofilm formation, and lower extremity amputation. To address the limitations of standard treatments, we have developed a hydrogel wound dressing with self-tuning moisture control that incorporates a novel antimicrobial agent to eliminate and prevent infection. 3D-printing of a hydrogel dressing with dual porosity resulted in a new dressing with greater flexibility, increased water uptake, and more rapid swelling than bulk hydrogel dressings. Additionally, gallium maltolate (GaM) was incorporated into the dressing to investigate the efficacy of this antimicrobial agent. Loading profiles, release kinetics, and the bactericidal activity against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) of GaM were investigated in vitro to identify target profiles that supported infection control. Finally, GaM-loaded hydrogel dressings were evaluated in vivo, utilizing a murine splinted-wound model that was inoculated with S. aureus. In comparison to an untreated control, GaM dressings markedly reduced the wound bacterial load without compromising wound closure rates. Overall, this work demonstrates the utility of a 3D-printed hydrogel dressing as an antimicrobial dressing to control infection in chronic wounds.
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Zircon crystals from the Jack Hills, Western Australia, are one of the few surviving mineralogical records of Earth's first 500 million years and have been proposed to contain a paleomagnetic record of the Hadean geodynamo. A prerequisite for the preservation of Hadean magnetization is the presence of primary magnetic inclusions within pristine igneous zircon. To date no images of the magnetic recorders within ancient zircon have been presented. Here we use high-resolution transmission electron microscopy to demonstrate that all observed inclusions are secondary features formed via two distinct mechanisms. Magnetite is produced via a pipe-diffusion mechanism whereby iron diffuses into radiation-damaged zircon along the cores of dislocations and is precipitated inside nanopores and also during low-temperature recrystallization of radiation-damaged zircon in the presence of an aqueous fluid. Although these magnetites can be recognized as secondary using transmission electron microscopy, they otherwise occur in regions that are indistinguishable from pristine igneous zircon and carry remanent magnetization that postdates the crystallization age by at least several hundred million years. Without microscopic evidence ruling out secondary magnetite, the paleomagnetic case for a Hadean-Eoarchean geodynamo cannot yet been made.
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Rhodococcus equi is an opportunistic, intracellular pathogen that causes pyogranulomatous pneumonia in foals and immunocompromised people. Currently, there is no experimental model of R. equi pneumonia other than intra-bronchial experimental infection of foals with R. equi, which is labor-intensive and costly. This study's objective was to develop a guinea pig (GP) model of R. equi pneumonia that would facilitate development of novel approaches for controlling and preventing this disease. Guinea pigs were infected with either 101, 102, 103, or 104 colony forming units (CFUs) of a virulent strain of R. equi using a Madison aerosol chamber, or 106 or 107 CFUs of this strain intratracheally. Animals were monitored daily for clinical signs of pneumonia, and were euthanized and necropsied on days 1, 3, 7, or 35 post-infection (PI). Lung homogenates were plated onto selective agar to determine bacterial load. No clinical signs of disease were observed regardless of the inoculum dose or infection method. No bacteria were recovered from GPs euthanized at 35â¯days PI. Histology and immunostaining of T-cells, B-cells, and macrophages in lungs showed that inflammatory responses in infected GPs were similarly unremarkable irrespective of dose or route of infection. Guinea pigs appear to be resistant to pulmonary infection with virulent R. equi even at doses that reliably produce clinical pneumonia in foals.
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Resistencia a la Enfermedad , Cobayas , Rhodococcus equi , Infecciones por Actinomycetales/inmunología , Animales , Modelos Animales de EnfermedadRESUMEN
Rhodococcus equi can cause severe infections in people, particularly in immunocompromised individuals. The R. equi virulence plasmids (vap) encoding vapA and vapB are linked to development of infections in domestic animals. Recently, a novel virulence plasmid, vapN, was identified in isolates cultured from cattle, but its prevalence or significance in human R. equi infections has not been extensively studied. To determine the prevalence of vapN in a diverse collection of human-derived isolates from different countries, 65 R. equi isolates collected by various institutions from 1984 to 2002 were screened for the presence of vapN and other virulence plasmids through polymerase chain reaction (PCR) using redesigned primer sets. Of the isolates that carried plasmids, 43% (16/37) were vapN-positive and fewer were vapB or vapA-positive (30 and 16%, respectively). This is the first report of vapN carriage in R. equi isolated from human infections in the United States. One isolate (H-30) carried vapN but did not amplify the conjugal plasmid transfer gene traA associated with carriage of vap, which could be explained by sequence variation within the traA gene. Another isolate (H-55) amplified traA, but did not amplify vapA, B, or N (traA+ vapABN-) with previously described primer sets or those developed for this study. The H-55 traA sequence had 98% identity to traA sequences in vapA plasmids, which suggests that it may carry a variant of previously characterized virulence plasmids or a novel virulence plasmid. Carriage of vapN in R. equi isolates derived from people is not uncommon and more research is needed to determine its significance in the epidemiology and pathogenesis of human R. equi infections.
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Infecciones por Actinomycetales/microbiología , Plásmidos/genética , Rhodococcus equi/genética , Rhodococcus equi/patogenicidad , Virulencia/genética , Proteínas Bacterianas/genética , Secuencia de Bases , Cartilla de ADN/genética , ADN Bacteriano/genética , Proteínas de Unión al ADN/genética , Genes Bacterianos , Variación Genética , Humanos , Glicoproteínas de Membrana/genética , Infecciones Oportunistas/microbiología , Plásmidos/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Rhodococcus equi/aislamiento & purificaciónRESUMEN
A western Massachusetts county jail began initiating extended-release naltrexone (XR-NTX) prior to release from incarceration and linking participants to community treatment providers upon release. Program barriers prevented the start of XR-NTX prior to release for a subset. METHODS: This report consists of the initial 67 jail releasees with opioid dependence, 47 who received XR-NTX before release, and 20 after release. Utility of the program was assessed by determining medication addiction treatment (MAT) retention rates at 4, 8, and 24 weeks. RESULTS: Forty-seven commenced XR-NTX approximately 7 days prior to release, and 20 were referred to commence XR-NTX at outpatient treatment centers. Rate of retention at week 4 was higher in group with treatment initiation prior to release as compared to those started in community: week 4: 55% (24 XR-NTX+2 agonist MAT out of 47) versus 25% (4 XR-NTX+1 agonist MAT out of 20) (p=0.03); week 8: 36% (13 XR-NTX+4 agonist) versus 25% (3 XR-NTX+2 agonist) (p=0.41); week 24: 21% (6 XR-NTX+4 agonist) versus 15% (1 XR-NTX+2 agonist) (p=0.74). Three patients died, all in the pre-release group, all from overdose at 3-5months after release and 2.5 or more months after stopping XR-NTX, compared to none of 20 in community group (p=0.55). Limitations include that cohorts were non-random and observational; substance use could not be consistently determined; and overdose deaths in MA occurred partly in clusters, limiting historical comparisons. CONCLUSIONS: Receiving XR-NTX prior to jail release for opioid use disorder appears to increase the treatment retention rate as compared to commencing after release. The treatment attrition and striking rate of overdose deaths are concerning, and support expanded availability of opioid agonist treatments prior to release and other evidence-based supports and retention strategies in the community.
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Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prisiones , Adulto , Atención Ambulatoria/métodos , Preparaciones de Acción Retardada , Sobredosis de Droga/mortalidad , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Massachusetts , Estudios ProspectivosRESUMEN
OBJECTIVE: Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation. METHODS: A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined. RESULTS: K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups. CONCLUSION: In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.