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1.
Artículo en Inglés | MEDLINE | ID: mdl-33746555

RESUMEN

The use of air sensor technology is increasing worldwide for a variety of applications, however, with significant variability in data quality. The United States Environmental Protection Agency held a workshop in July 2019 to deliberate possible performance targets for air sensors measuring particles with aerodynamic diameters of 10 µm or less (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), and sulfur dioxide (SO2). These performance targets were discussed from the perspective of non-regulatory applications and with the sensors operating primarily in a stationary mode in outdoor environments. Attendees included representatives from multiple levels of government organizations, sensor developers, environmental nonprofits, international organizations, and academia. The workshop addressed the current lack of sensor technology requirements, discussed fit-for-purpose data quality needs, and debated transparency issues. This paper highlights the purpose and key outcomes of the workshop. While more information on performance and applications of sensors is available than in past years, the performance metrics, or parameters used to describe data quality, vary among the studies reports and there is a need for more clear and consistent approaches for evaluating sensor performance. Organizations worldwide are increasingly considering, or are in the process of developing, sensor performance targets and testing protocols. Workshop participants suggested that these new guidelines are highly desirable, would help improve data quality, and would give users more confidence in their data. Given the wide variety of uses for sensors and user backgrounds, as well as varied sensor design features (e.g., communication approaches, data tools, processing/adjustment algorithms and calibration procedures), the need for transparency was a key workshop theme. Suggestions for increasing transparency included documenting and sharing testing and performance data, detailing best practices, and sharing data processing and correction approaches.

2.
Rheumatol Int ; 41(7): 1357-1367, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33620515

RESUMEN

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are systemic necrotizing vasculitides associated with significant morbidity and mortality. Given the immunosuppression used to manage these conditions, it is important for clinicians to recognize complications, especially infectious ones, which may arise during treatment. Kaposi sarcoma (KS) is a lymphoangioproliferative neoplasm caused by human herpes virus 8 (HHV-8). Its cutaneous manifestations can mimic vasculitis. We describe a 77-year-old man with microscopic polyangiitis with pulmonary-renal syndrome treated with prednisone and intravenous cyclophosphamide who developed KS (HHV-8 positive) after 2 months of treatment. Cyclophosphamide was discontinued and prednisone gradually lowered with improvement and clinical stabilization of KS lesions. This comprehensive review includes all published cases of KS in patients with AAV, with a goal to summarize potential risk factors including the clinical characteristics of vasculitis, treatment and outcomes of patients with this rare complication of immunosuppressive therapy. We also expanded our literature review to KS in other forms of systemic vasculitis. Our case-based review emphasizes the importance of considering infectious complications of immunosuppressive therapy, especially glucocorticoids, and highlights the rare association of KS in systemic vasculitis.


Asunto(s)
Ciclofosfamida/uso terapéutico , Poliangitis Microscópica/complicaciones , Prednisona/uso terapéutico , Sarcoma de Kaposi/complicaciones , Anciano , Humanos , Inmunosupresores/uso terapéutico , Masculino , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/patología , Inducción de Remisión , Sarcoma de Kaposi/patología
3.
Br J Cancer ; 123(3): 369-377, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32457364

RESUMEN

BACKGROUND: Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer. METHODS: In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice (n = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed. RESULTS: The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 (n = 6, p = 0.0001), with no associated damage of hepatic or renal tissue observed. CONCLUSIONS: Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.


Asunto(s)
Hidrogeles/administración & dosificación , Neoplasias Pulmonares/terapia , Poloxámero/administración & dosificación , Células A549 , Técnicas de Ablación , Animales , Células 3T3 BALB , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidrogeles/efectos adversos , Hidrogeles/farmacocinética , Neoplasias Pulmonares/sangre , Ratones , Poloxámero/efectos adversos , Poloxámero/farmacocinética , Termodinámica , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Epidemiol Infect ; 147: e178, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-31063098

RESUMEN

Understanding endemic infectious disease risk factors through traditional epidemiological tools is challenging. Population-based case-control studies are costly and time-consuming. A case-case analyses using surveillance data addresses these limitations by using resources more efficiently. We conducted a case-case analyses using routine surveillance data reported by 16 U.S. states (2005-2015), wherein reported cases of salmonellosis were used as a comparison group to identify exposure associations with reported cases of cryptosporidiosis and giardiasis. Odds ratios adjusted for age and reporting state (aOR) and 95% confidence intervals (95% CI) were calculated. A total of 10 704 cryptosporidiosis cases, 17 544 giardiasis cases, and 106 351 salmonellosis cases were included in this analyses. When compared with cases of salmonellosis, exposure to treated recreational water (aOR 4.7, 95% CI 4.3-5.0) and livestock (aOR: 3.2; 95% CI: 2.9-3.5) were significantly associated with cryptosporidiosis and exposure to untreated drinking (aOR 4.1, 95% CI 3.6-4.7) and recreational water (aOR 4.1, 95% CI 3.7-4.5) were associated with giardiasis. Our analyses shows that routine surveillance data with standardised exposure information can be used to identify associations of interest for cryptosporidiosis and giardiasis.


Asunto(s)
Criptosporidiosis/epidemiología , Cryptosporidium/aislamiento & purificación , Giardia/aislamiento & purificación , Giardiasis/epidemiología , Vigilancia de la Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Estados Unidos/epidemiología , Adulto Joven
5.
Epidemiol Infect ; 144(6): 1313-29, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26541938

RESUMEN

A number of sophisticated modelling approaches are available to investigate potential associations between antimicrobial use (AMU) and resistance (AMR) in animal health settings. All have their advantages and disadvantages, making it unclear as to which model is most appropriate. We used advanced regression modelling to investigate AMU-AMR associations in faecal non-type-specific Escherichia coli (NTSEC) isolates recovered from 275 pens of feedlot cattle. Ten modelling strategies were employed to investigate AMU associations with resistance to chloramphenicol, ampicillin, sulfisoxazole, tetracycline and streptomycin. Goodness-of-fit statistics did not show a consistent advantage for any one model type. Three AMU-AMR associations were significant in all models. Recent parenteral tetracycline use increased the odds of finding tetracycline-resistant NTSEC [odds ratios (OR) 1·1-3·2]; recent parenteral sulfonamide use increased the odds of finding sulfisoxazole-resistant NTSEC (OR 1·4-2·5); and recent parenteral macrolide use decreased the odds of recovering ampicillin-resistant NTSEC (OR 0·03-0·2). Other results varied markedly depending on the modelling approach, emphasizing the importance of exploring and reporting multiple modelling methods based on a balanced consideration of important factors such as study design, mathematical appropriateness, research question and target audience.


Asunto(s)
Antibacterianos/farmacología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Farmacorresistencia Bacteriana , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Modelos Biológicos , Animales , Canadá/epidemiología , Bovinos , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Heces/microbiología
6.
Am J Transplant ; 14(6): 1328-33, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24726020

RESUMEN

Invasive mold infections (IMIs) are a major source of morbidity and mortality among lung transplant recipients (LTRs), yet information regarding the epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter prospective surveillance for IMIs among LTR was conducted by the Transplant-Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance at 15 US centers developed IMI infections. The 12-month cumulative incidence of IMIs was 5.5%; 3-month all-cause mortality was 21.7%. Aspergillus caused the majority (72.7%)of IMIs; non-Aspergillus infections (39, 27.3%) included Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and "unspecified" or "other" mold infections (31, 21.7%). Late-onset IMI was common: 52% occurred within 1 year posttransplant (median 11 months, range 0-162 months). IMIs are common late-onset complications with substantial mortality in LTRs. LTRs should be monitored for late-onset IMIs and prophylactic agents should be optimized based on likely pathogen.


Asunto(s)
Enfermedades Pulmonares/epidemiología , Trasplante de Pulmón , Micosis/epidemiología , Estudios de Cohortes , Humanos , Enfermedades Pulmonares/microbiología , Micosis/microbiología
7.
Epidemiol Infect ; 142(11): 2314-25, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24477189

RESUMEN

The study objective was to use Bayesian latent class analysis to evaluate the accuracy of susceptibility test results obtained from disk diffusion and broth microdilution using bacteria recovered from beef feedlot cattle. Isolates of Escherichia coli and Mannheimia haemolytica were tested for susceptibility to ampicillin, ceftiofur, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. Results showed that neither testing method was always or even generally superior to the other. Specificity (ability to correctly classify non-resistant isolates) was extremely high for both testing methods, but sensitivity (ability to correctly classify resistant isolates) was lower, variable in the drugs evaluated, and variable between the two bacterial species. Predictive values estimated using Bayesian Markov chain Monte Carlo models showed that the ability to predict true susceptibility status was equivalent for test results obtained with the two testing methods for some drugs, but for others there were marked differences between results obtained from disk diffusion and broth microdilution tests.


Asunto(s)
Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Mannheimia haemolytica/efectos de los fármacos , Animales , Teorema de Bayes , Bovinos , Recuento de Colonia Microbiana , Pruebas Antimicrobianas de Difusión por Disco/métodos , Pruebas Antimicrobianas de Difusión por Disco/veterinaria , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/tratamiento farmacológico , Mannheimia haemolytica/aislamiento & purificación , Cadenas de Markov , Pruebas de Sensibilidad Microbiana , Proyectos Piloto , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
8.
Transpl Infect Dis ; 16(2): 213-24, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24589027

RESUMEN

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.


Asunto(s)
Blastomicosis/epidemiología , Coccidioidomicosis/epidemiología , Enfermedades Endémicas , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Histoplasmosis/epidemiología , Trasplante de Órganos/efectos adversos , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Blastomicosis/tratamiento farmacológico , Niño , Coccidioidomicosis/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Comorbilidad , Femenino , Histoplasmosis/tratamiento farmacológico , Humanos , Incidencia , Itraconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Factores de Tiempo , Estados Unidos/epidemiología , Adulto Joven
9.
Am J Transplant ; 13(8): 2207-10, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23763601

RESUMEN

Islet transplantation after successful kidney transplantation is a recognized treatment for adults with diabetes and end-stage renal disease (ESRD), but has not been considered an option in the pediatric population. To our knowledge, we report the first combined islet and kidney transplant in a child. The patient was born with bilateral renal hypoplasia and was diagnosed with type 1 diabetes mellitus at age 13 months. He had erratic glycemic control and hypoglycemia unawareness. At 6 years of age, the child safely underwent simultaneous islet and live donor kidney transplantation. Although function of the islet graft was transient, the combined transplant provided significant benefits in terms of glucose control and overall growth and development. Such an approach represents a viable treatment option for pediatric patients with ESRD and unstable diabetes.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 1/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Trasplante de Páncreas , Adulto , Niño , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Pronóstico
11.
Ecol Appl ; 23(5): 1156-69, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23967583

RESUMEN

Nitrogen deposition is a concern in many protected ecosystems around the world, yet few studies have quantified a complete reactive nitrogen deposition budget including all dry and wet, inorganic and organic compounds. Critical loads that identify the level at which nitrogen deposition negatively affects an ecosystem are often defined using incomplete reactive nitrogen budgets. Frequently only wet deposition of ammonium and nitrate are considered, despite the importance of other nitrogen deposition pathways. Recently, dry deposition pathways including particulate ammonium and nitrate and gas phase nitric acid have been added to nitrogen deposition budgets. However, other nitrogen deposition pathways, including dry deposition of ammonia and wet deposition of organic nitrogen, still are rarely included. In this study, a more complete seasonal nitrogen deposition budget was constructed based on observations during a year-long study period from November 2008 to November 2009 at a location on the east side of Rocky Mountain National Park (RMNP), Colorado, USA. Measurements included wet deposition of ammonium, nitrate, and organic nitrogen, PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 microm, nitrate, and ammonium) concentrations of ammonium, nitrate, and organic nitrogen, and atmospheric gas phase concentrations of ammonia, nitric acid, and NO2. Dry deposition fluxes were determined from measured ambient concentrations and modeled deposition velocities. Total reactive nitrogen deposition by all included pathways was found to be 3.65 kg N x ha(-1) yr(-1). Monthly deposition fluxes ranged from 0.06 to 0.54 kg N x ha(-1)yr(-1), with peak deposition in the month of July and the least deposition in December. Wet deposition of ammonium and nitrate were the two largest deposition pathways, together contributing 1.97 kg N x ha(-1)yr(-1) or 54% of the total nitrogen deposition budget for this region. The next two largest deposition pathways were wet deposition of organic nitrogen and dry deposition of ammonia; combined they contributed 1.37 kg N x ha(-1)yr(-1) or 37% of the total nitrogen deposition budget. To better understand the nitrogen cycle and key interactions between the atmosphere and biosphere we need to include as many sources and types of nitrogen as possible and understand their variability throughout the year. Here we examine the components of the nitrogen deposition budget to better understand the factors that influence the different deposition pathways and their seasonal variations.


Asunto(s)
Ecosistema , Ciclo del Nitrógeno , Nitrógeno/química , Nitrógeno/metabolismo , Estaciones del Año , Colorado , Monitoreo del Ambiente , Factores de Tiempo
12.
J Air Waste Manag Assoc ; 73(12): 951-968, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37850745

RESUMEN

Carlsbad Caverns National Park (CAVE) is located in southeastern New Mexico and is adjacent to the Permian Basin, one of the most productive oil and natural gas (O&G) production regions in the United States. Since 2018, ozone (O3) at CAVE has frequently exceeded the 70 ppbv 8-hour National Ambient Air Quality Standard. We examine the influence of regional emissions on O3 formation using observations of O3, nitrogen oxides (NOx = NO + NO2), a suite of volatile organic compounds (VOCs), peroxyacetyl nitrate (PAN), and peroxypropionyl nitrate (PPN). Elevated O3 and its precursors are observed when the wind is from the southeast, the direction of the Permian Basin. We identify 13 days during the July 25 to September 5, 2019 study period when the maximum daily 8-hour average (MDA8) O3 exceeded 65 ppbv; MDA8 O3 exceeded 70 ppbv on 5 of these days. The results of a positive matrix factorization (PMF) analysis are used to identify and attribute source contributions of VOCs and NOx. On days when the winds are from the southeast, there are larger contributions from factors associated with primary O&G emissions; and, on high O3 days, there is more contribution from factors associated with secondary photochemical processing of O&G emissions. The observed ratio of VOCs to NOx is consistently high throughout the study period, consistent with NOx-limited O3 production. Finally, all high O3 days coincide with elevated acyl peroxy nitrate abundances with PPN to PAN ratios > 0.15 ppbv ppbv-1 indicating that anthropogenic VOC precursors, and often alkanes specifically, dominate the photochemistry.Implications: The results above strongly indicate NOx-sensitive photochemistry at Carlsbad Caverns National Park indicating that reductions in NOx emissions should drive reductions in O3. However, the NOx-sensitivity is largely driven by emissions of NOx into a VOC-rich environment, and a high PPN:PAN ratio and its relationship to O3 indicate substantial influence from alkanes in the regional photochemistry. Thus, simultaneous reductions in emissions of NOx and non-methane VOCs from the oil and gas sector should be considered for reducing O3 at Carlsbad Caverns National Park. Reductions in non-methane VOCs will have the added benefit of reducing formation of other secondary pollutants and air toxics.


Asunto(s)
Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Ozono/análisis , Contaminantes Atmosféricos/análisis , Nitratos/análisis , Compuestos Orgánicos Volátiles/análisis , New Mexico , Cuevas , Parques Recreativos , Alcanos/análisis , Monitoreo del Ambiente/métodos , China
13.
Microbiol Resour Announc ; 12(6): e0025323, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37255446

RESUMEN

Five subcluster C1 mycobacteriophages, Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata, were isolated from soil using the host Mycobacterium smegmatis mc2155. The genome sizes range from 154,512 to 156,223 bp. The largest genome encodes 237 predicted proteins, 34 tRNAs, and 1 transfer-messenger RNA (tmRNA).

14.
J Air Waste Manag Assoc ; 72(11): 1201-1218, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35605169

RESUMEN

Carlsbad Caverns National Park in southeastern New Mexico is adjacent to the Permian Basin, one of the most productive oil and gas regions in the country. The 2019 Carlsbad Caverns Air Quality Study (CarCavAQS) was designed to examine the influence of regional sources, including urban emissions, oil and gas development, wildfires, and soil dust on air quality in the park. Field measurements of aerosols, trace gases, and deposition were conducted from 25 July through 5 September 2019. Here, we focus on observations of fine particles and key trace gas precursors to understand the important contributing species and their sources and associated impacts on haze. Key gases measured included aerosol precursors, nitric acid and ammonia, and oil and gas tracer, methane. High-time resolution (6-min) PM2.5 mass ranged up to 31.8 µg m-3, with an average of 7.67 µg m-3. The main inorganic ion contributors were sulfate (avg 1.3 µg m-3), ammonium (0.30 µg m-3), calcium (Ca2+) (0.22 µg m-3), nitrate (0.16 µg m-3), and sodium (0.057 µg m-3). The WSOC concentration averaged 1.2 µg C m-3. Sharp spikes were observed in Ca2+, consistent with local dust generation and transport. Ion balance analysis and abundant nitric acid suggest PM2.5 nitrate often reflected reaction between nitric acid and sea salt, forming sodium nitrate, and between nitric acid and soil dust containing calcium carbonate, forming calcium nitrate. Sulfate and soil dust are the major contributors to modeled light extinction in the 24-hr average daily IMPROVE observations. Higher time resolution data revealed a maximum 1-hr extinction value of 90 Mm-1 (excluding coarse aerosol) and included periods of significant light extinction from BC as well as sulfate and soil dust. Residence time analysis indicated enrichment of sulfate, BC, and methane during periods of transport from the southeast, the direction of greatest abundance of oil and gas development.Implications: Rapid development of U.S. oil and gas resources raises concerns about potential impacts on air quality in National Parks. Measurements in Carlsbad Caverns National Park provide new insight into impacts of unconventional oil and gas development and other sources on visual air quality in the park. Major contributors to visibility impairment include sulfate, soil dust (often reacted with nitric acid), and black carbon. The worst periods of visibility and highest concentrations of many aerosol components were observed during transport from the southeast, a region of dense Permian Basin oil and gas development.


Asunto(s)
Contaminantes Atmosféricos , Nitratos , Nitratos/análisis , Contaminantes Atmosféricos/análisis , Parques Recreativos , Monitoreo del Ambiente , Cuevas , Ácido Nítrico/análisis , Aerosoles/análisis , Polvo/análisis , Gases/análisis , Óxidos de Nitrógeno/análisis , Sulfatos/análisis , Suelo , Metano/análisis , Material Particulado/análisis
15.
Microbiol Resour Announc ; 11(8): e0028622, 2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-35863046

RESUMEN

Four lytic mycobacteriophages, namely, SynergyX, Abinghost, Bananafish, and Delton, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc2155. Analysis of the genomes revealed that they belong to two subclusters of actinobacteriophage cluster B (subclusters B2 and B3) and subcluster D1 of cluster D.

16.
Antibiotics (Basel) ; 10(5)2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34068975

RESUMEN

The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% ± 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 ± 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia.

17.
Microbiol Resour Announc ; 10(27): e0030421, 2021 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-34236221

RESUMEN

Two temperate mycobacteriophages, Dallas and Jonghyun, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc2155. Analysis of the genomes revealed that Dallas and Jonghyun belong to clusters J and G, respectively. The structures of the genomes are typical of their respective clusters.

18.
Mayo Clin Proc ; 96(10): 2653-2659, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34489099

RESUMEN

The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.


Asunto(s)
Inflamación/diagnóstico , Síndromes Mielodisplásicos/diagnóstico , Enzimas Activadoras de Ubiquitina/genética , Anciano , Células Precursoras Eritroides/patología , Enfermedades Genéticas Congénitas , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Inflamación/genética , Masculino , Mutación , Síndromes Mielodisplásicos/genética , Células Mieloides/patología , Vacuolas , Vasculitis/genética
19.
Hippocampus ; 20(6): 758-67, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19623539

RESUMEN

The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LTP that required voltage-dependent Ca(2+) channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.


Asunto(s)
Desamparo Adquirido , Hipocampo/fisiopatología , Potenciación a Largo Plazo/fisiología , Estrés Psicológico/fisiopatología , Animales , Electrofisiología , Potenciales Postsinápticos Excitadores , Masculino , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo
20.
Heliyon ; 6(9): e04845, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32995594

RESUMEN

BACKGROUND: Depression is associated with insulin resistance (IR). However, the potential beneficial effect, on antidepressant treatment response, of adjunctive therapy with insulin sensitivity-enhancing lifestyle and dietary interventions (exercise; supplementation with: vitamin D, magnesium, zinc, probiotics or omega-3 fatty acids) has not been systematically explored. AIMS: To determine the effect of the above stated adjuncts on antidepressant treatment response in clinically depressed patients via a systematic review and meta-analysis. METHODS: RCTs which assessed the effect, on antidepressant treatment response of adjunctive therapy with any of the interventions in comparison with treatment as usual were included. RESULTS: The interventions had a significant antidepressant effect, with SMD for follow-up (end of study) scores and change (from baseline) scores being -0.88, [95% CI: -1.19 to -0.57; P < 0.001] and -1.98 [95% CI -2.86 to -1.10; P < 0.001], respectively. The odds ratio (OR) for remission was 2.28 (95% CI 1.42 to 3.66; P < 0.001). The number-needed-to-treat (NNT) for remission was 6. Subgroup analysis of the follow-up scores revealed age effect: SMD significant in those with mean age ≤50 (-1.02 SMD; 95% CI: -1.40 to -0.64; p < 0.001) and insignificant in those with mean age >50 (-0.38 SMD (95% CI: -0.82 to 0.05; P = 0.08)). Also, the interventions were more beneficial among outpatients- SMD: -0.97 (95% CI: -1.32 to -0.62; P < 0.001) compared to inpatients- SMD: -0.34 (95% CI: -0.88 to 0.20; P = 0.22). Sensitivity analysis did not change the results. CONCLUSION: The finding that antidepressant treatment response may be improved using insulin sensitivity-enhancing lifestyle and dietary adjuncts is worthy of further exploration.

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