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1.
Proc Natl Acad Sci U S A ; 117(16): 8743-8749, 2020 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-32229562

RESUMEN

Earth's core is likely the largest reservoir of carbon (C) in the planet, but its C abundance has been poorly constrained because measurements of carbon's preference for core versus mantle materials at the pressures and temperatures of core formation are lacking. Using metal-silicate partitioning experiments in a laser-heated diamond anvil cell, we show that carbon becomes significantly less siderophile as pressures and temperatures increase to those expected in a deep magma ocean during formation of Earth's core. Based on a multistage model of core formation, the core likely contains a maximum of 0.09(4) to 0.20(10) wt% C, making carbon a negligible contributor to the core's composition and density. However, this accounts for ∼80 to 90% of Earth's overall carbon inventory, which totals 370(150) to 740(370) ppm. The bulk Earth's carbon/sulfur ratio is best explained by the delivery of most of Earth's volatiles from carbonaceous chondrite-like precursors.

2.
Proc Natl Acad Sci U S A ; 117(49): 30993-31001, 2020 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-33229590

RESUMEN

Rare high-3He/4He signatures in ocean island basalts (OIB) erupted at volcanic hotspots derive from deep-seated domains preserved in Earth's interior. Only high-3He/4He OIB exhibit anomalous 182W-an isotopic signature inherited during the earliest history of Earth-supporting an ancient origin of high 3He/4He. However, it is not understood why some OIB host anomalous 182W while others do not. We provide geochemical data for the highest-3He/4He lavas from Iceland (up to 42.9 times atmospheric) with anomalous 182W and examine how Sr-Nd-Hf-Pb isotopic variations-useful for tracing subducted, recycled crust-relate to high 3He/4He and anomalous 182W. These data, together with data on global OIB, show that the highest-3He/4He and the largest-magnitude 182W anomalies are found only in geochemically depleted mantle domains-with high 143Nd/144Nd and low 206Pb/204Pb-lacking strong signatures of recycled materials. In contrast, OIB with the strongest signatures associated with recycled materials have low 3He/4He and lack anomalous 182W. These observations provide important clues regarding the survival of the ancient He and W signatures in Earth's mantle. We show that high-3He/4He mantle domains with anomalous 182W have low W and 4He concentrations compared to recycled materials and are therefore highly susceptible to being overprinted with low 3He/4He and normal (not anomalous) 182W characteristic of subducted crust. Thus, high 3He/4He and anomalous 182W are preserved exclusively in mantle domains least modified by recycled crust. This model places the long-term preservation of ancient high 3He/4He and anomalous 182W in the geodynamic context of crustal subduction and recycling and informs on survival of other early-formed heterogeneities in Earth's interior.

3.
Kidney Int ; 94(6): 1205-1216, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30466566

RESUMEN

An epidemic of chronic kidney disease (CKD) of unknown etiology, known as Mesoamerican Nephropathy (MeN), has been ongoing in Latin America for at least two decades. MeN primarily affects young adults without traditional CKD risk factors, and agricultural workers are disproportionately afflicted. We previously identified an acute phase of MeN that involves acute kidney injury (AKI) with tubulointerstitial nephritis and systemic inflammation. Because clinical disease progression in MeN is not yet understood, we sought to determine clinical predictors for progression from acute MeN to CKD. Through ongoing surveillance in Nicaragua, local physicians reported cases of acute MeN and CKD among agricultural workers. We analyzed clinical data collected during the acute MeN encounter to identify factors associated with progression to CKD. From February 2015 to May 2017, 586 agricultural workers (median age 27.8 years, 90% male) presented with acute MeN. The majority had a normal baseline creatinine, and leukocyturia (98.8%) and peripheral leukocytosis (80.7%) were common. Ultimately, 49 (8.4%) progressed to CKD, the majority of those within 6 months. CKD was attributed to MeN in all cases, and none had diabetes or hypertension. The strongest predictors of CKD progression were anemia and paresthesias at presentation, while leukocytosis was associated with renal recovery. Clinical markers of acute MeN may help clinicians identify patients at high risk for rapid progression to CKD, which in turn can inform early clinical management. Future studies should seek to determine the underlying etiology of disease and identify optimal interventions to interrupt the pathophysiologic process of MeN.


Asunto(s)
Lesión Renal Aguda/patología , Nefritis Intersticial/patología , Insuficiencia Renal Crónica/diagnóstico , Lesión Renal Aguda/sangre , Adulto , Biomarcadores/análisis , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Incidencia , Masculino , Nicaragua/epidemiología , Pronóstico , Estudios Prospectivos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/patología , Medición de Riesgo/métodos , Factores de Riesgo , Adulto Joven
4.
Kidney Int ; 93(3): 681-690, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29162294

RESUMEN

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli.


Asunto(s)
Enfermedades de los Trabajadores Agrícolas/diagnóstico , Riñón/patología , Nefritis Intersticial/diagnóstico , Adulto , Enfermedades de los Trabajadores Agrícolas/epidemiología , Enfermedades de los Trabajadores Agrícolas/patología , Atrofia , Biomarcadores/sangre , Biomarcadores/orina , Biopsia , Diagnóstico Precoz , Edema/diagnóstico , Edema/epidemiología , Edema/patología , Fibrosis , Técnica del Anticuerpo Fluorescente , Humanos , Riñón/ultraestructura , Masculino , Microscopía Electrónica , Nefritis Intersticial/epidemiología , Nefritis Intersticial/patología , Nicaragua/epidemiología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Adulto Joven
5.
AIDS Care ; 29(8): 961-965, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28127988

RESUMEN

We sought to determine the clinical and epidemiologic determinants of Staphylococcus aureus nasal colonization in HIV-infected individuals at two outpatient centers in southern Botswana. Standard microbiologic techniques were used to identify S. aureus and methicillin-resistant S. aureus (MRSA). In a sample of 404 HIV-infected adults, prevalence of S. aureus nasal carriage was 36.9% (n = 152) and was associated with domestic overcrowding and lower CD4 cell count. MRSA prevalence was low (n = 13, 3.2%), but more common among individuals with asthma and eczema. The implications of these findings for HIV management are discussed.


Asunto(s)
Portador Sano/epidemiología , Infecciones por VIH/complicaciones , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Cavidad Nasal/microbiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Adulto , Botswana/epidemiología , Recuento de Linfocito CD4 , Portador Sano/microbiología , Aglomeración , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Prevalencia , Factores de Riesgo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/transmisión
6.
J Clin Microbiol ; 54(7): 1711-1719, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27076664

RESUMEN

Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital.


Asunto(s)
Bacteriemia/microbiología , Portador Sano/microbiología , Variación Genética , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Filogenia , Polimorfismo de Nucleótido Simple , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/patogenicidad , Adulto Joven
7.
Travel Med Infect Dis ; 59: 102699, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38452991

RESUMEN

Dengue virus (DENV) is one of the most significant vector-borne pathogens worldwide. In this report, we describe clinical features and laboratory detection of dengue in a 45-year-old traveler to Nicaragua on return home to the United States in 2019. Clinical presentation was mild, with rash, headache, and fatigue, with only low-grade transient fever. Infection dynamics were documented by serology and PCR of serially collected body fluids. DENV serotype 2 was detected in whole blood 1 day after symptoms emerged, with viral RNA isolated to the red cell fraction, and remained detectable through day 89. DENV-2 RNA was detected in serum only on day 4, and IgM was undetectable on day 4 but evident by day 13. Viral RNA was also detected in urine. This report of DENV-2 RNA persistence in blood cells but only transient appearance in serum, supports the potential diagnostic value of whole blood over serum for PCR and opportunity of an expanded testing window. Informed testing approaches can improve diagnostic accuracy and inform strategies that preserve individual and public health.


Asunto(s)
Virus del Dengue , Dengue , ARN Viral , Viaje , Humanos , Persona de Mediana Edad , Dengue/virología , Dengue/diagnóstico , Dengue/sangre , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Inmunoglobulina M/sangre , Nicaragua , ARN Viral/sangre , Serogrupo
8.
Mol Metab ; 87: 101981, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971403

RESUMEN

OBJECTIVE: The metabolism of different cells within the same microenvironment can differ and dictate physiological or pathological adaptions. Current single-cell analysis methods of metabolism are not label-free. METHODS: The study introduces a label-free, live-cell analysis method assessing endogenous fluorescence of NAD(P)H and FAD in surface-stained cells by flow cytometry. RESULTS: OxPhos inhibition, mitochondrial uncoupling, glucose exposure, genetic inactivation of glucose uptake and mitochondrial respiration alter the optical redox ratios of FAD and NAD(P)H as measured by flow cytometry. Those alterations correlate strongly with measurements obtained by extracellular flux analysis. Consequently, metabolically distinct live B-cell populations can be resolved, showing that human memory B-cells from peripheral blood exhibit a higher glycolytic flexibility than naïve B cells. Moreover, the comparison of blood-derived B- and T-lymphocytes from healthy donors and rheumatoid arthritis patients unleashes rheumatoid arthritis-associated metabolic traits in human naïve and memory B-lymphocytes. CONCLUSIONS: Taken together, these data show that the optical redox ratio can depict metabolic differences in distinct cell populations by flow cytometry.

9.
J Cancer Res Clin Oncol ; 149(6): 2551-2558, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35771262

RESUMEN

PURPOSE: The goal of this study is to examine the chronological development of hospitalized oncology and COVID-19 patients, and compare effects on oncology sub-disciplines for pre-pandemic (2017-19) and pandemic (2020-21) years in the setting of a German university maximum care provider. METHODS: Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with oncological main (nOnco) and COVID-19 secondary diagnosis (nCOVID-19). Data analysis is based on descriptive statistical assessment. RESULTS: The oncology patient collective (nOnco = 27,919) shows a decrease of hospitalized patients for the whole pandemic (- 4% for 2020 and - 2,5% for 2021 to 2019). The number of hospitalized COVID-19 patients increases from first to second pandemic year by + 106.71% (nCOVID-19 = 868). Maximum decline in monthly hospitalized oncology patients amounts to - 19% (May 2020) during the first and - 21% (December 2020) during the second lockdown. Relative monthly hospitalization levels of oncology patients reverted to pre-pandemic levels from February 2021 onwards. CONCLUSION: The results confirm a decline in hospitalized oncology patients for the entire pandemic in the setting of a maximum care provider. Imposed lockdown and contact restrictions, rising COVID-19 case numbers, as well as discovery of new virus variants have a negative impact on hospitalized treated oncological patients.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Estudios Retrospectivos , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Neoplasias/epidemiología , Neoplasias/terapia , Hospitales
10.
J Am Vet Med Assoc ; 261(4): 480-489, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36595371

RESUMEN

OBJECTIVE: To characterize clinical and epidemiologic features of SARS-CoV-2 in companion animals detected through both passive and active surveillance in the US. ANIMALS: 204 companion animals (109 cats, 95 dogs) across 33 states with confirmed SARS-CoV-2 infections between March 2020 and December 2021. PROCEDURES: Public health officials, animal health officials, and academic researchers investigating zoonotic SARS-CoV-2 transmission events reported clinical, laboratory, and epidemiologic information through a standardized One Health surveillance process developed by the CDC and partners. RESULTS: Among dogs and cats identified through passive surveillance, 94% (n = 87) had reported exposure to a person with COVID-19 before infection. Clinical signs of illness were present in 74% of pets identified through passive surveillance and 27% of pets identified through active surveillance. Duration of illness in pets averaged 15 days in cats and 12 days in dogs. The average time between human and pet onset of illness was 10 days. Viral nucleic acid was first detected at 3 days after exposure in both cats and dogs. Antibodies were detected starting 5 days after exposure, and titers were highest at 9 days in cats and 14 days in dogs. CLINICAL RELEVANCE: Results of the present study supported that cats and dogs primarily become infected with SARS-CoV-2 following exposure to a person with COVID-19, most often their owners. Case investigation and surveillance that include both people and animals are necessary to understand transmission dynamics and viral evolution of zoonotic diseases like SARS-CoV-2.


Asunto(s)
COVID-19 , Enfermedades de los Gatos , Enfermedades de los Perros , Animales , Gatos , Humanos , Perros , Estados Unidos/epidemiología , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/veterinaria , Enfermedades de los Gatos/epidemiología , Enfermedades de los Perros/epidemiología , Zoonosis/epidemiología , Mascotas
11.
Open Forum Infect Dis ; 10(11): ofad511, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38023544

RESUMEN

Background: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. Methods: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. Results: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. Conclusions: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. Clinical Trials Registration: NCT04811664.

12.
Geochim Cosmochim Acta ; 316: 295-308, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34866645

RESUMEN

Determining how and when Mars formed has been a long-standing challenge for planetary scientists. The size and orbit of Mars are difficult to reproduce in classical simulations of planetary accretion, and this has inspired models of inner solar system evolution that are tuned to produce Mars-like planets. However, such models are not always coupled to geochemical constraints. Analyses of Martian meteorites using the extinct hafnium-tungsten (Hf-W) radioisotopic system, which is sensitive to the timing of core formation, have indicated that the Martian core formed within a few million years of the start of the solar system itself. This has been interpreted to suggest that, unlike Earth's protracted accretion, Mars grew to its modern size very rapidly. These arguments, however, generally rely on simplified growth histories for Mars. Here, we combine likely accretionary histories from a large number of N-body simulations with calculations of metal-silicate partitioning and Hf-W isotopic evolution during core formation to constrain the range of conditions that could have produced Mars. We find that there is no strong correlation between the final masses or orbits of simulated Martian analogs and their 182W anomalies, and that it is readily possible to produce Mars-like Hf-W isotopic compositions for a variety of accretionary conditions. The Hf-W signature of Mars is very sensitive to the oxygen fugacity (fO2) of accreted material because the metal-silicate partitioning behavior of W is strongly dependent on redox conditions. The average fO2 of Martian building blocks must fall in the range of 1.3-1.6 log units below the iron-wüstite buffer to produce a Martian mantle with the observed Hf/W ratio. Other geochemical properties (such as sulfur content) also influence Martian 182W signatures, but the timing of accretion is a more important control. We find that while Mars must have accreted most of its mass within ~5 million years of solar system formation to reproduce the Hf-W isotopic constraints, it may have continued growing afterwards for over 50 million years. There is a high probability of simultaneously matching the orbit, mass, and Hf-W signature of Mars even in cases of prolonged accretion if giant impactor cores were poorly equilibrated and merged directly with the proto-Martian core.

13.
J Med Entomol ; 59(4): 1479-1483, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35640635

RESUMEN

Flies and other arthropods mechanically transmit multiple pathogens and a recent experimental study demonstrated house flies, Musca domestica L. (Diptera: Muscidae), can mechanically transmit SARS-CoV-2. The purpose of this study was to explore the possibility of mechanical transmission of SARS-CoV-2 by domestic insects and their potential as a xenosurveillance tool for detection of the virus. Flies were trapped in homes where at least one confirmed human COVID-19 case(s) resided using sticky and liquid-baited fly traps placed inside and outside the home in the Texas counties of Brazos, Bell, and Montgomery, from June to September 2020. Flies from sticky traps were identified, pooled by taxa, homogenized, and tested for the presence of SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR). Liquid traps were drained, and the collected fluid similarly tested after RNA concentration. We processed the contents of 133 insect traps from 40 homes, which contained over 1,345 individual insects of 11 different Diptera families and Blattodea. These individuals were grouped into 243 pools, and all tested negative for SARS-CoV-2 RNA. Fourteen traps in seven homes were deployed on the day that cat or dog samples tested positive for SARS-CoV-2 RNA by nasal, oral, body, or rectal samples. This study presents evidence that biting and nonbiting flies and cockroaches (Blattodea) are not likely to contribute to mechanical transmission of SARS-CoV-2 or be useful in xenosurveillance for SARS-CoV-2.


Asunto(s)
COVID-19 , Cucarachas , Enfermedades de los Perros , Moscas Domésticas , Muscidae , Animales , Perros , Humanos , Control de Insectos , ARN Viral , SARS-CoV-2
14.
Transbound Emerg Dis ; 69(3): 1656-1658, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33955193

RESUMEN

As part of a longitudinal household transmission study of pets living with persons with COVID-19 in Texas, two pets were confirmed to be infected with the SARS-CoV-2 B.1.1.7 variant of concern (VOC). The pets were a dog and a cat from the same household, sampled two days after their owner tested positive for COVID-19. The oral, nasal and fur swabs for both pets tested positive for SARS-CoV-2 by qRT-PCR and consensus whole-genome sequences from the dog and cat were 100% identical and matched the B.1.1.7 VOC. Virus was isolated from the cat's nasal swab. One month after initial detection of infection, the pets were re-tested twice at which time only the fur swabs (both pets) and oral swab (dog only) remained positive, and neutralizing antibodies for SARS-CoV-2 were present in both animals. Sneezing by both pets was noted by the owner in the weeks between initial and follow-up testing. This study documents the first detection of B.1.1.7. in companion animals in the United States, and the first genome recovery and isolation of B.1.1.7 variant of concern globally in any animal.


Asunto(s)
COVID-19 , Enfermedades de los Gatos , Enfermedades de los Perros , Animales , COVID-19/diagnóstico , COVID-19/veterinaria , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/epidemiología , Gatos , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología , Perros , Humanos , SARS-CoV-2 , Texas
15.
Clin J Am Soc Nephrol ; 17(9): 1293-1304, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35944911

RESUMEN

BACKGROUND AND OBJECTIVES: The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Migrants with Mesoamerican nephropathy kidney failure (n=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (n=63) and age/sex/place of origin-matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy. RESULTS: Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; P=0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy. CONCLUSIONS: Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.


Asunto(s)
Nefritis Intersticial , Insuficiencia Renal Crónica , Insuficiencia Renal , Masculino , Femenino , Animales , Ratones , Paraquat/toxicidad , Estudios Transversales , Ratones Endogámicos C57BL , Insuficiencia Renal Crónica/epidemiología , Nefritis Intersticial/patología , Enfermedades Renales Crónicas de Etiología Incierta , Agroquímicos , Cationes
16.
Nat Commun ; 12(1): 35, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397911

RESUMEN

The Earth and Moon have identical or very similar isotopic compositions for many elements, including tungsten. However, canonical models of the Moon-forming impact predict that the Moon should be made mostly of material from the impactor, Theia. Here we evaluate the probability of the Moon inheriting its Earth-like tungsten isotopes from Theia in the canonical giant impact scenario, using 242 N-body models of planetary accretion and tracking tungsten isotopic evolution, and find that this probability is <1.6-4.7%. Mixing in up to 30% terrestrial materials increases this probability, but it remains <10%. Achieving similarity in stable isotopes is also a low-probability outcome, and is controlled by different mechanisms than tungsten. The Moon's stable isotopes and tungsten isotopic composition are anticorrelated due to redox effects, lowering the joint probability to significantly less than 0.08-0.4%. We therefore conclude that alternate explanations for the Moon's isotopic composition are likely more plausible.

17.
PLoS One ; 16(4): e0250110, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33852642

RESUMEN

BACKGROUND: Prediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions. METHODS: Our approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree. RESULTS: We apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time. CONCLUSION: We presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.


Asunto(s)
COVID-19/epidemiología , Número Básico de Reproducción , COVID-19/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Predicción , Humanos , Incidencia , Modelos Estadísticos , Pandemias , Salud Pública , SARS-CoV-2/aislamiento & purificación , Estados Unidos/epidemiología
18.
Viruses ; 13(5)2021 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069453

RESUMEN

Understanding the ecological and epidemiological roles of pets in the transmission of SARS-CoV-2 is critical for animal and human health, identifying household reservoirs, and predicting the potential enzootic maintenance of the virus. We conducted a longitudinal household transmission study of 76 dogs and cats living with at least one SARS-CoV-2-infected human in Texas and found that 17 pets from 25.6% of 39 households met the national case definition for SARS-CoV-2 infections in animals. This includes three out of seventeen (17.6%) cats and one out of fifty-nine (1.7%) dogs that were positive by RT-PCR and sequencing, with the virus successfully isolated from the respiratory swabs of one cat and one dog. Whole-genome sequences of SARS-CoV-2 obtained from all four PCR-positive animals were unique variants grouping with genomes circulating among people with COVID-19 in Texas. Re-sampling showed persistence of viral RNA for at least 25 d-post initial test. Additionally, seven out of sixteen (43.8%) cats and seven out of fifty-nine (11.9%) dogs harbored SARS-CoV-2 neutralizing antibodies upon initial sampling, with relatively stable or increasing titers over the 2-3 months of follow-up and no evidence of seroreversion. The majority (82.4%) of infected pets were asymptomatic. 'Reverse zoonotic' transmission of SARS-CoV-2 from infected people to animals may occur more frequently than recognized.


Asunto(s)
COVID-19/epidemiología , COVID-19/veterinaria , Mascotas/virología , Animales , Anticuerpos Neutralizantes/inmunología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/virología , Gatos/virología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/virología , Perros/virología , Humanos , Estudios Longitudinales , Mascotas/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Texas/epidemiología
19.
Am J Trop Med Hyg ; 105(5): 1227-1229, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34544043

RESUMEN

To better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant lineage distribution in a college campus population, we carried out viral genome surveillance over a 7-week period from January to March 2021. Among the sequences were three novel viral variants: BV-1 with a B.1.1.7/20I genetic background and an additional spike mutation Q493R, associated with a mild but longer-than-usual COVID-19 case in a college-age person, BV-2 with a T478K mutation on a 20B genetic background, and BV-3, an apparent recombinant lineage. This work highlights the potential of an undervaccinated younger population as a reservoir for the spread and generation of novel variants. This also demonstrates the value of whole genome sequencing as a routine disease surveillance tool.


Asunto(s)
COVID-19/virología , Reservorios de Enfermedades/virología , Mutación , SARS-CoV-2/genética , Estudiantes/estadística & datos numéricos , Universidades , Adulto , COVID-19/etiología , Genoma Viral , Humanos , Pruebas de Neutralización , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Adulto Joven
20.
Lupus Sci Med ; 8(1)2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34819388

RESUMEN

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.


Asunto(s)
Lupus Eritematoso Sistémico , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisolona/uso terapéutico , Inducción de Remisión , Índice de Severidad de la Enfermedad
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