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OBJECTIVES: In response to the COVID-19 pandemic, agencies and organizations required trainings to support the needs of the public health workforce. To better understand the training resources available, this study identified, organized, and classified infection prevention and control (IPC) training and educational opportunities. STUDY DESIGN: Environmental scan. METHODS: A total of 306 IPC training resources were compiled between January and April 2021. Key themes and topics were identified and compared to the Healthcare Infection Control Practices Advisory Committee's (HICPAC) core IPC practices. RESULTS: Three hundred and six training resources, including webinars, fact sheets, module-based learning activities, infographics, and professional practice guidance materials, were identified. Common themes included proper use of personal protective equipment (e.g., masks, gloves), community reopening guidance, and mass vaccination resources. A large proportion (74.9%) of trainings were under 60 min. Using the HICPAC framework, the most frequently addressed content included standard precautions (40%), leadership support (31.6%), and transmission-based precautions (25.8%). Few trainings addressed performance monitoring and feedback (17.1%). CONCLUSIONS: A wide range of organizations developed IPC-specific content during the pandemic. However, these resources did not address the breadth of knowledge required to implement IPC concepts effectively. The creation of universally applicable IPC core competencies and the development of high-quality IPC education and trainings for public health and the overall responder workforces should be prioritized. Accessible high-quality online and just-in-time trainings are critical for future pandemic and disaster preparedness.
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COVID-19 , Humanos , COVID-19/prevención & control , Salud Pública , Pandemias/prevención & control , Control de Infecciones , Equipo de Protección PersonalRESUMEN
The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.
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We present an optimal-estimation-based retrieval framework, the microphysical aerosol properties from polarimetry (MAPP) algorithm, designed for simultaneous retrieval of aerosol microphysical properties and ocean color bio-optical parameters using multi-angular total and polarized radiances. Polarimetric measurements from the airborne NASA Research Scanning Polarimeter (RSP) were inverted by MAPP to produce atmosphere and ocean products. The RSP MAPP results are compared with co-incident lidar measurements made by the NASA High-Spectral-Resolution Lidar HSRL-1 and HSRL-2 instruments. Comparisons are made of the aerosol optical depth (AOD) at 355 and 532 nm, lidar column-averaged measurements of the aerosol lidar ratio and Ångstrøm exponent, and lidar ocean measurements of the particulate hemispherical backscatter coefficient and the diffuse attenuation coefficient. The measurements were collected during the 2012 Two-Column Aerosol Project (TCAP) campaign and the 2014 Ship-Aircraft Bio-Optical Research (SABOR) campaign. For the SABOR campaign, 73% RSP MAPP retrievals fall within ±0.04 AOD at 532 nm as measured by HSRL-1, with an R value of 0.933 and root-mean-square deviation of 0.0372. For the TCAP campaign, 53% of RSP MAPP retrievals are within 0.04 AOD as measured by HSRL-2, with an R value of 0.927 and root-mean-square deviation of 0.0673. Comparisons with HSRL-2 AOD at 355 nm during TCAP result in an R value of 0.959 and a root-mean-square deviation of 0.0694. The RSP retrievals using the MAPP optimal estimation framework represent a key milestone on the path to a combined lidar+polarimeter retrieval using both HSRL and RSP measurements.
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A thorough family history evaluation remains a critical tool that helps identify those patients who are at risk for hereditary cancer. The American College of Obstetricians and Gynecologists (ACOG) recommends that all women receive a family history evaluation to screen for inherited risk, and that this information be regularly updated. Patients with an abnormal cancer family history need additional follow-up that may include hereditary cancer testing. Multigene panel testing provides comprehensive profiling for hereditary cancer patients by identifying more health risks than single genome testing. If hereditary cancer is established, patients should be counseled about management options, including increased surveillance, chemoprevention, and/or surgery. Establishing workflow protocols may help clinicians integrate hereditary cancer risk assessment into their practice.
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Neoplasias de los Genitales Femeninos/genética , Femenino , Pruebas Genéticas/métodos , HumanosRESUMEN
AIMS: To optimize peroxidase production by Streptomyces sp. strain BSII#1, up to 3 l culture volumes. METHODS AND RESULTS: Peroxidase production by Streptomyces sp. strain BSII#1 was optimized in terms of production temperature and pH and the use of lignin-based model chemical inducers. The highest peroxidase activity (1·30 ± 0·04 U ml(-1) ) in 10 ml culture volume was achieved in a complex production medium (pH 8·0) at 37°C in the presence of 0·1 mmol l(-1) veratryl alcohol, which was greater than those reported previously. Scale-up to 100 and 400 ml culture volumes resulted in decreased peroxidase production (0·53 ± 0·10 and 0·26 ± 0·08 U ml(-1) , respectively). However, increased aeration improved peroxidase production with the highest production achieved using an airlift bioreactor (4·76 ± 0·46 U ml(-1) in 3 l culture volume). CONCLUSIONS: Veratryl alcohol (0·1 mmol l(-1) ) is an effective inducer of peroxidase production by Streptomyces sp. strain BSII#1. However, improved aeration increased peroxidase production in larger volumes without the use of an inducer, surpassing induced yields in an optimized small-scale process. SIGNIFICANCE AND IMPACT OF THE STUDY: Only a limited number of reports in literature have focused on the up-scaling of bacterial peroxidase production. There remains opportunity for feasible large-scale production of bacterial peroxidases with potentially novel biocatalytic properties.
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Peroxidasa/biosíntesis , Streptomyces/enzimología , Alcoholes Bencílicos/metabolismo , Reactores Biológicos , Lignina/metabolismo , TemperaturaRESUMEN
AIMS: To assess the impact of winery wastewater (WW) on biological sand filter (BSF) bacterial community structures, and to evaluate whether BSFs can constitute alternative and valuable treatment- processes to remediate WW. METHODS AND RESULTS: During 112 days, WW was used to contaminate a BSF mesocosm (length 173 cm/width 106 cm/depth 30 cm). The effect of WW on bacterial communities of four BSF microenvironments (surface/deep, inlet/outlet) was investigated using terminal-restriction fragment length polymorphism (T-RFLP). BSF achieved high Na (95·1%), complete Cl and almost complete chemical oxygen demand (COD) (98·0%) and phenolic (99·2%) removals. T-RFLP analysis combined with anosim revealed that WW significantly modified the surface and deep BSF bacterial communities. CONCLUSIONS: BSF provided high COD, phenolic and salt removals throughout the experiment. WW-selected bacterial communities were thus able to tolerate and/or degrade WW, suggesting that community composition does not alter BSF performances. However, biomass increased significantly in the WW-impacted surface sediments, which could later lead to system clogging and should thus be monitored. SIGNIFICANCE AND IMPACT OF THE STUDY: BSFs constitute alternatives to constructed wetlands to treat agri effluents such as WW. To our knowledge, this study is the first unravelling the responses of BSF bacterial communities to contamination and suggests that WW-selected BSF communities maintained high removal performances.
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Bacterias/clasificación , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/microbiología , Vino , Bacterias/genética , Bacterias/metabolismo , Análisis de la Demanda Biológica de Oxígeno , Restauración y Remediación Ambiental , Filtración/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Dióxido de SilicioRESUMEN
Winery wastewater is characterized by its high chemical oxygen demand (COD), seasonal occurrence and variable composition, including periodic high ethanol concentrations. In addition, winery wastewater may contain insufficient inorganic nutrients for optimal biodegradation of organic constituents. Two pilot-scale biological sand filters (BSFs) were used to treat artificial wastewater: the first was amended with ethanol and the second with ethanol, inorganic nitrogen (N) and phosphorus (P). A number of biochemical parameters involved in the removal of pollutants through BSF systems were monitored, including effluent chemistry and bacterial community structures. The nutrient supplemented BSF showed efficient COD, N and P removal. Comparison of the COD removal efficiencies of the two BSFs showed that N and P addition enhanced COD removal efficiency by up to 16%. Molecular fingerprinting of BSF sediment samples using denaturing gradient gel electrophoresis (DGGE) showed that amendment with high concentrations of ethanol destabilized the microbial community structure, but that nutrient supplementation countered this effect.
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Análisis de la Demanda Biológica de Oxígeno/métodos , Reactores Biológicos/microbiología , Etanol/química , Filtración/métodos , Aguas Residuales/microbiología , Bacterias/metabolismoRESUMEN
Oronasal communications are serious sequelae of chronic cocaine abuse. If left untreated, these communications can severely limit a patient's quality of life. The defects can be rehabilitated successfully utilizing either maxillofacial prosthetics or various surgical techniques. Considerations in deciding between prosthetic and surgical approaches are discussed, as well as the basics of maxillofacial prosthetic rehabilitation and the different surgical techniques available. Photographic documentation of both maxillofacial prosthetic and surgical treatments performed by the authors is shown.
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Trastornos Relacionados con Cocaína/complicaciones , Enfermedades Nasales/terapia , Fístula Oral/terapia , Obturadores Palatinos , Procedimientos de Cirugía Plástica/métodos , Fístula del Sistema Respiratorio/terapia , Diseño de Prótesis Dental , Colgajos Tisulares Libres , Humanos , Cavidad Nasal/patología , Tabique Nasal/patología , Enfermedades Nasales/cirugía , Fístula Oral/cirugía , Paladar Blando/patología , Planificación de Atención al Paciente , Calidad de Vida , Fístula del Sistema Respiratorio/cirugía , Colgajos Quirúrgicos/clasificaciónRESUMEN
BACKGROUND: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly OBJECTIVES: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. METHODS: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. RESULTS: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). CONCLUSIONS: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care.
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COVID-19 , Enfermedades Cardiovasculares , Toma de Decisiones , Aceptación de la Atención de Salud , Enfermedad Aguda , COVID-19/epidemiología , Enfermedades Cardiovasculares/terapia , Hospitales , Humanos , Pandemias , Aceptación de la Atención de Salud/psicología , Investigación Cualitativa , Reino Unido/epidemiologíaRESUMEN
The current SARS-CoV-2 pandemic has brought a number of major global clinical, sociological and economic issues into sharp focus. We address some of these issues, focusing on short-term factors such as virus mutations and vaccine efficacy, and also considering the longer-term implications of the current pandemic. We discuss societal responses to the presence of a pathogen that will probably remain in circulation for decades or longer, and to future new emergent viruses.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2/genética , Vacunas , Virus , COVID-19/epidemiología , COVID-19/genética , COVID-19/prevención & control , Humanos , Mutación , Pandemias/prevención & control , SARS-CoV-2/aislamiento & purificación , Sudáfrica , Eficacia de las Vacunas , Virus/patogenicidadRESUMEN
The COVID-19 pandemic has had a major impact on research at universities. Universities around the world, including in South Africa, have been or are still closed as part of national lockdown strategies. Students have not been attending classes or doing hands-on experimental work, and students and academics have been working from home. Many thousands of students have had their university education interrupted, and for them, the resumption of learning programmes online, and where possible in research laboratories, is critically important. There is no question that as we emerge from lockdown we will not be entering a world that resembles a 'norm' as lived in the pre-COVID-19 era, and many changes will be required. Here we discuss the importance of research, the urgency to get things up and running again, and strategies that will need to be implemented to ensure that research activities continue. At the same time, it is necessary to ensure that students and staff are not exposed to risk in their research endeavours, which will require the development and implementation of risk management plans.
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Investigación Biomédica , Control de Enfermedades Transmisibles , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Investigadores/educación , Universidades , Betacoronavirus , COVID-19 , Educación a Distancia , Humanos , Laboratorios , Pandemias , Edición , Investigación , SARS-CoV-2 , Sudáfrica/epidemiología , EstudiantesRESUMEN
Sodium-glucose cotransporter type-2 inhibitors (SGLT2is) reduce glomerular hyperfiltration in diabetic people with early diabetic nephropathy. The objective of this report was to assess changes in glomerular filtration rate in healthy cats after treatment with a SGLT2i. Eight healthy research adult castrated male cats were used in a randomized, controlled, cross-over study design. We induced isolated renal tubular glucosuria by dosing cats with the SGLT2i dapagliflozin. The cats received by mouth 10 mg dapagliflozin or control every 24 h in each of the 4, 5-d trial periods that were separated by a 7-d washout period. We assessed glomerular filtration rate (iohexol clearance method), serum urea, creatinine, symmetric dimethylarginine, and 24-h sodium and chloride urinary excretion on the fifth day of each trial period. We analyzed the data with a mixed linear model that included the fixed effects of treatment (treated and control) and trial period, and the random effect of the cat. Compared with controls, cats treated with dapagliflozin had a significant increase in mean (±SE) glomerular filtration rate (3.1 ± 0.2 vs 2.5 ± 0.2 mL/kg/min; P = 0.01), whereas there were no significant differences in serum urea, creatinine and symmetric dimethylarginine, and 24-h urine sodium and chloride excretion. We propose that dapagliflozin-mediated delivery of sodium and glucose distal from the proximal convoluted tubule induced compensatory increased sodium absorption at the thick ascending loop of Henle that resulted in decreased sodium delivery to the distal tubule leading to tubuloglomerular feedback-mediated glomerular hyperfiltration. Future studies should determine if SGLT2is' renoprotective effect in people can be enhanced with the addition of a Na+-K+-Cl- diuretic and whether dapagliflozin will be useful in mitigating proteinuria and hypertension that follow glomerular hyperfiltration in diabetic companion animals in a similar mechanism as in people.
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Compuestos de Bencidrilo/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Animales , Glucemia , Gatos , Estudios Cruzados , Glucosa/metabolismo , Glucosuria , MasculinoRESUMEN
Signal detection theory (SDT) makes the frequently challenged assumption that decision criteria have no variance. An extended model, the Law of Categorical Judgment, relaxes this assumption. The long accepted equation for the law, however, is flawed: It can generate negative probabilities. The correct equation, the Law of Categorical Judgment (Corrected), is derived; the SDT rating model is a special case. An example shows how to invert the Law of Categorical Judgment (Corrected) numerically, thereby extracting estimates of signal and criterion density parameters and their confidence limits from rating data. The SDT rating model predicts linear Zeta-transformed operating characteristics (ZetaROCs), whereas the new equation can produce nonlinear ZetaROCs. For single-criterion experiments (e.g., yes/no, two-alternative forced choice), however, the corrected law yields identical d' values and linear ZetaROCs whether criterion variance is nonzero or zero. Performance differences observed in such experiments can always be attributed equally well to altered perceptual sensitivity or to modified criterion variance. The Law of Categorical Judgment (Corrected) offers to resolve this ambiguity through rating experiments.
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Teoría de las Decisiones , Juicio , Modelos Estadísticos , Psicofísica/estadística & datos numéricos , Conducta de Elección , Toma de Decisiones , Aprendizaje Discriminativo , Humanos , Funciones de Verosimilitud , Distribución Normal , Teoría Psicológica , Curva ROCRESUMEN
The hippocampal formation (HF) plays a key role in novelty detection, but the mechanisms remain unknown. Novelty detection aids the encoding of new information into memory-a process thought to depend on the HF and to be modulated by the theta rhythm of EEG. We examined EEG recorded in the HF of rats foraging for food within a novel environment, as it became familiar over the next five days, and in two more novel environments unexpectedly experienced in trials interspersed with familiar trials over three further days. We found that environmental novelty produces a sharp reduction in the theta frequency of foraging rats, that this reduction is greater for an unexpected environment than for a completely novel one, and that it slowly disappears with increasing familiarity. These results do not reflect changes in running speed and suggest that the septo-hippocampal system signals unexpected environmental change via a reduction in theta frequency. In addition, they provide evidence in support of a cholinergically mediated mechanism for novelty detection, have important implications for our understanding of oscillatory coding within memory and for the interpretation of event-related potentials, and provide indirect support for the oscillatory interference model of grid cell firing in medial entorhinal cortex.
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Relojes Biológicos/fisiología , Conducta Exploratoria/fisiología , Hipocampo/fisiología , Memoria/fisiología , Ritmo Teta , Acetilcolina/metabolismo , Potenciales de Acción/fisiología , Animales , Fibras Colinérgicas/fisiología , Electroencefalografía , Potenciales Evocados/fisiología , Masculino , Modelos Neurológicos , Actividad Motora/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiología , Ratas , Núcleos Septales/fisiología , Factores de TiempoRESUMEN
BACKGROUND: Symmetric dimethylarginine (SDMA) is a screening tool for early kidney dysfunction and monitoring treatment in cases of chronic kidney disease (CKD). There are no current studies describing the suitability of this test for use with published population-based reference intervals. HYPOTHESIS/OBJECTIVES: To determine the components of biological variability, the index of individuality (IOI), the critical difference between sequential measurements (CD ) and the number of measurements required to assess the homeostatic set point (HSP), for both SDMA and serum creatinine (sCr), in apparently healthy dogs. ANIMALS: Twenty apparently healthy adult dogs owned by clients or staff at a veterinary teaching hospital. METHODS: Prospective, observational study. Blood was collected from each dog on 9 occasions, and SDMA and sCr were measured in duplicate using commercially available assays. RESULTS: SDMA and sCr had intermediate and low IOI values of 0.87 and 0.28, respectively. The CD of SDMA and sCr, was 1.34 µg/dL and 0.89 µmol/L, respectively. The sample numbers required for estimation of an individual's HSP (with 90 and 95% CI) for SDMA and sCr were 8 and 45, and 2 and 12 sequential measurements, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on our findings, in comparison to sCr, SDMA is better suited for use with population-based reference intervals. False-negative test results could occur when comparing a single test result from an individual to such intervals. Ideally CD should be used with sequential measurements.
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Arginina/análogos & derivados , Perros/sangre , Animales , Arginina/sangre , Biomarcadores/sangre , Creatinina/sangre , Femenino , Masculino , Estudios Prospectivos , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Lower urinary tract infections are common in dogs, and Escherichia coli is the most common bacterial pathogen isolated. The literature has conflicting evidence regarding the inhibitory effects of urine concentration and pH on E. coli growth. HYPOTHESIS/OBJECTIVES: To determine the effect of different pH and urine concentrations on E. coli growth in vitro. ANIMALS: Voided urine samples from 10 apparently healthy spayed female dogs were used. METHODS: A matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5, 7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided urine samples. Three E. coli isolates were obtained from urine of female dogs with signs of lower urinary tract infection and cultured at different urine pH and USG combinations in wells of a microtiter plate. The number of E. coli colony-forming units (CFU) per mL of urine was calculated after aerobic incubation of the urine at 37°C for 18 hours, and statistically compared. RESULTS: Significant differences were identified in the mean log CFU/mL among different combinations of pH and USG. The lowest log CFU/mL were observed in alkaline concentrated urine (pH 8.5 and USG 1.030). CONCLUSIONS AND CLINICAL IMPORTANCE: Escherichia coli in vitro growth was higher in neutral to acidic and diluted urine compared to alkaline and concentrated urine. The impact of non-alkalizing diluting diets on the incidence of E. coli lower urinary tract infections should be further explored.
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Perros/orina , Escherichia coli/crecimiento & desarrollo , Orina/química , Orina/microbiología , Animales , Perros/microbiología , Femenino , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Cell-free DNA (cfDNA) comprises short, double-stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. OBJECTIVES/HYPOTHESIS: Cell-free DNA will have a short biological half-life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half-life of cfDNA and to contrast them with those of creatine kinase (CK). ANIMALS: Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy. METHODS: Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery. RESULTS: The biological half-life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36-7.98 hours) and 28.7 hours (CI95, 25.3-33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6-12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma CK activity has a longer biological half-life than previously thought. In contrast to plasma CK activity, cfDNA has a short half-life and could be a useful marker for peracute severe tissue injury.
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Ácidos Nucleicos Libres de Células/sangre , Creatina Quinasa/sangre , Perros/lesiones , Animales , Ligamento Cruzado Anterior/cirugía , Biomarcadores/sangre , Modelos Animales de Enfermedad , Perros/cirugía , Femenino , Histerectomía/veterinaria , Cinética , Laminectomía/veterinaria , Masculino , Ovariectomía/veterinariaRESUMEN
To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.
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Trasplante de Células , Técnicas de Transferencia de Gen , Mesangio Glomerular/citología , Glomérulos Renales/metabolismo , Animales , Células Cultivadas , Galactósidos/análisis , Amplificación de Genes , Expresión Génica , Indoles/análisis , Glomérulos Renales/patología , Operón Lac , Masculino , Proteinuria/etiología , Ratas , Ratas Sprague-DawleyRESUMEN
Low-molecular-weight synthetic molecules that mimic the activity of native biological macromolecules have therapeutic potential, utility in large-scale production of biopharmaceuticals, and the capacity to act as probes to study molecular recognition events. We have developed a nonpeptidyl mimic for Staphylococcus aureus Protein A (SpA). The specific recognition and complexation elements between the B domain (Fb) of SpA and the Fc fragment of IgG were identified from the x-ray crystallographic structure. Computer-aided molecular modeling was used to design a series of biomimetic molecules around the Phe132-Tyr133 dipeptide involved in its binding to IgG. One of the ligands binds IgG competitively with SpA in solution and when immobilized on agarose beads, with an affinity constant of 10(5)-10(6) M-1. The immobilized artificial Protein A was used to purify IgG from human plasma and murine IgG from ascites fluid, and to remove bovine IgG from fetal calf serum.
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Diseño de Fármacos , Imitación Molecular , Proteína Estafilocócica A/química , Animales , Anticuerpos/aislamiento & purificación , Bovinos , Cromatografía de Afinidad , Diseño Asistido por Computadora , Cristalografía por Rayos X , Humanos , Concentración de Iones de Hidrógeno , Inmunoglobulina G/metabolismo , Ligandos , Ratones , Modelos Moleculares , Concentración Osmolar , Conformación Proteica , Proteína Estafilocócica A/metabolismoRESUMEN
BACKGROUND: Ovarian cancer is the eighth most common cancer among women, but ranks fifth in cancer-related causes of death, the majority of which are detected in late stages, after the cancer has metastasized. The CA125 test is the standard of care for assessing suspicious pelvic masses. However, the primary use of CA125 is to monitor treatment progress rather than to screen for disease, and its sensitivity is exceedingly low, unlike the multivariate assay OVA1. A cost-effective treatment of ovarian cancer requires early and accurate diagnosis of pelvic masses and reduced referrals of patients with benign tumors to a gynecologic oncologist. OBJECTIVE: To analyze the economic impact of increased utilization of a multivariate assay, such as OVA1, to guide the treatment of ovarian cancer. METHODS: The study population was drawn from Medicare and commercial health plan claims data. A budget impact model was constructed to estimate the economic consequences of substituting the multivariate assay OVA1 to replace the single biomarker assay CA125 to assess the likelihood of pelvic mass malignancy in premenopausal and/or postmenopausal women. All patients selected for the analysis had CA125 testing before surgical intervention. RESULTS: A total of 92,843 health plan members were included for analysis, comprising 48,113 commercially insured members and 44,730 Medicare beneficiaries. Estimates of future health plan expenditures, which were calculated from base-case assumptions, projected overall savings of $0.05 per-member per-month (PMPM) for commercially insured members and $0.01 PMPM for Medicare beneficiaries as a result of increased utilization of OVA1. Sensitivity analysis revealed potential savings of up to $0.17 PMPM for commercially insured patients and up to $0.05 for Medicare beneficiaries. CONCLUSION: The results of the budget impact model support the use of OVA1 instead of CA125 by indicating that modest cost-savings can be achieved, while reaping the clinical benefits of improved diagnostic accuracy, early disease detection, and reductions in multiple, and possibly unnecessary, referrals to gynecologic oncologists.