RESUMEN
The world is currently in a pandemic of COVID-19 (Coronavirus disease-2019) caused by a novel positive-sense, single-stranded RNA ß-coronavirus referred to as SARS-CoV-2. Here we investigated rates of SARS-CoV-2 infection in the greater Cincinnati, Ohio, USA metropolitan area from August 13 to December 8, 2020, just prior to initiation of the national vaccination program. Examination of 9,550 adult blood donor volunteers for serum IgG antibody positivity against the SARS-CoV-2 Spike protein showed an overall prevalence of 8.40%, measured as 7.56% in the first 58 days and 9.24% in the last 58 days, and 12.86% in December 2020, which we extrapolated to ~20% as of March, 2021. Males and females showed similar rates of past infection, and rates among Hispanic or Latinos, African Americans and Whites were also investigated. Donors under 30 years of age had the highest rates of past infection, while those over 60 had the lowest. Geographic analysis showed higher rates of infectivity on the West side of Cincinnati compared with the East side (split by I-75) and the lowest rates in the adjoining region of Kentucky (across the Ohio river). These results in regional seroprevalence will help inform efforts to best achieve herd immunity in conjunction with the national vaccination campaign.
Asunto(s)
Anticuerpos Antivirales/sangre , Donantes de Sangre/estadística & datos numéricos , COVID-19/epidemiología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Ohio/etnología , Pandemias , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: Patients diagnosed with metastatic cancer have almost uniformly poor prognoses. The treatments available for patients with disseminated disease are usually not curative and have side effects that limit the therapy that can be given. A treatment that is selectively toxic to tumors would maximize the beneficial effects of therapy and minimize side effects, potentially enabling effective treatment to be administered. METHODS AND FINDINGS: We postulated that the tumor-tropic property of stem cells or progenitor cells could be exploited to selectively deliver a therapeutic gene to metastatic solid tumors, and that expression of an appropriate transgene at tumor loci might mediate cures of metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells transduced to express an enzyme that efficiently activates the anti-cancer prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors. The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or anatomical location of the tumors. Mice were then treated systemically with CPT-11, and the efficacy of treatment was monitored. Mice treated with the combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001 compared to control groups). CONCLUSIONS: The novel and significant finding of this study is that it may be possible to exploit the tumor-tropic property of stem or progenitor cells to mediate effective, tumor-selective therapy for metastatic tumors, for which no tolerated curative treatments are currently available.
Asunto(s)
Camptotecina/análogos & derivados , Metástasis de la Neoplasia/terapia , Animales , Secuencia de Bases , Camptotecina/farmacocinética , Camptotecina/uso terapéutico , Hidrolasas de Éster Carboxílico/genética , Hidrolasas de Éster Carboxílico/metabolismo , Línea Celular , Línea Celular Tumoral , Cartilla de ADN/genética , Células Madre Embrionarias/enzimología , Células Madre Embrionarias/trasplante , Humanos , Irinotecán , Ratones , Ratones SCID , Células Madre Multipotentes/enzimología , Células Madre Multipotentes/trasplante , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Trasplante de Neoplasias , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/patología , Neuroblastoma/secundario , Neuroblastoma/terapia , Profármacos/farmacocinética , Profármacos/uso terapéutico , Conejos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción Genética , Trasplante HeterólogoRESUMEN
There is currently a debate about the role played by temporal patterns in neural activity in olfactory coding. An accurate analysis of this question, however, is only possible if the temporal properties of a stimulus itself are well defined. So far, no technique with sufficient temporal resolution has been available to accomplish this. Using a photoionization detector (PID), we show that the configuration of the odor delivery apparatus and the airflow settings greatly influence the integrity of a stimulus profile within an odor delivery apparatus. In a situation where pulsatile odor stimuli are applied to a stationary preparation, we tested the effect of 1) axial and off-center location within the airstream, 2) airflow of the odor delivery, 3) exit tube length, 4) exit tube diameter, 5) orientation of the odor delivery device in relation to the exhaust flow, and 6) exhaust tube air speed. This has important implications for the study of time in olfaction; significant planning must be incorporated into the design of the experiment to provide a well-defined odor delivery system.
Asunto(s)
Cromatografía de Gases/instrumentación , Cetonas/química , Odorantes , Movimientos del Aire , Diseño de Equipo , Sensibilidad y Especificidad , Estimulación Química , Factores de TiempoRESUMEN
OBJECTIVE: To prepare oncology, genetics and molecular medicine professionals for basic, translational and epidemiological cancer genetics research through advanced training in a novel specialized cancer genetics career development program (CGCDP). METHODS: Established in 2001, the City of Hope CGCDP is the only program in the NCI R25T portfolio focused on interdisciplinary training of oncologists and geneticists as cancer genetics and cancer prevention research program leaders. Program infrastructure, curriculum, recruitment strategies, implementation, evaluation and outcome are described. RESULTS: During the initial four-year period, twelve highly qualified health care professionals were recruited for cancer genetics academic, experiential, and research training. All trainees presented abstracts, published peer-reviewed journal articles, and/or were awarded cancer genetics research grants. Most are now in academic/research venues, following a cancer genetics research career trajectory. CONCLUSION: The CGCDP is an NIH-funded program that has successfully trained doctoral and mid-level professionals in cancer genetics research. Program graduates are addressing the burden of cancer by translating cancer genetics investigations into individual risk assessment tools and effective cancer screening and prevention interventions.
Asunto(s)
Investigación Biomédica/organización & administración , Investigación Genética , Capacitación en Servicio/organización & administración , Oncología Médica/educación , Neoplasias/prevención & control , Humanos , Neoplasias/genética , Estados Unidos , Orientación VocacionalRESUMEN
Trains of 20-ms-duration pulses of pheromone were delivered at rates of 1-33 Hz to antennal preparations of males of Bombyx mori and Lymantria dispar, two moth species with bipectinate antennae. Resolution of rapidly pulsed plumes of pheromone was not compromised by a complex antennal morphology or by moderate changes in wind speed (25-50 cm/s). Fourier analysis of the electroantennograms resolved the temporal structure of the signal at frequencies up to 25 Hz for B. mori and up to 5 Hz for L. dispar. The ability of these sensory structures to identify the original (unchanged) frequency of the pulse train is particularly noteworthy because air is slowed by about an order of magnitude as it passes through bipectinate antennae. Although an unchanging frequency in slowed airflow may be counterintuitive, this flow pattern, and its effects on odorant patch shape and spacing, is explained from fluid mechanical principles (i.e., the principle of continuity). An unchanging frequency suggests that as decelerating air passes through a bipectinate antenna, the slowed patches of odorant are stretched, thinned, and brought closer together by the same factor with which they are slowed.
Asunto(s)
Células Quimiorreceptoras/anatomía & histología , Mecanorreceptores/anatomía & histología , Feromonas/química , Alquenos/química , Animales , Bombyx , Células Quimiorreceptoras/fisiología , Electrofisiología , Femenino , Análisis de Fourier , Proteínas de Insectos , Insectos , Masculino , Mecanorreceptores/fisiología , Mariposas Nocturnas , Odorantes , Vías Olfatorias , Pulso Arterial , Receptores Odorantes , Órganos de los Sentidos , Olfato , Factores de Tiempo , VientoRESUMEN
Dynamic properties of pheromone plumes are behaviorally important in some moths for inducing upwind flight, but little is known about the time-dependent properties of odor transduction or the mechanisms that limit receptor dynamic sensitivity. We stimulated male antennae of two moth species, Cadra cautella and Spodoptera exigua, with pheromone plumes in a wind tunnel while recording electroantennograms (EAG) and concentration of a surrogate plume (propylene, which mimics a pheromone plume) using a photoionization detector (PID). Turbulent plumes were produced by mechanical baffles, creating broad frequency range dynamic concentration changes at the antennae. Frequency response functions and coherence functions between PID and EAG signals were used to measure the dynamic responses of the two species to pheromone blends and individual components. A single time constant filter fitted the responses of both species, but S. exigua was about three times faster than C. cautella. Responses to individual pheromone components were significantly different in S. exigua but not in C. cautella. We also fitted the data with a simple block-structured nonlinear cascade. This supported the simple filter model but also suggested that the response saturates at an early stage of chemotransduction.
Asunto(s)
Mariposas Nocturnas/fisiología , Feromonas/fisiología , Olfato/fisiología , Potenciales de Acción/fisiología , Animales , Masculino , Especificidad de la EspecieRESUMEN
Male antennae of Cadra cautella, Pectinophora gossypiella, and Spodoptera exigua were presented with 20-ms-duration pulses of their two-component pheromone at rates of 1 to 33 Hz. Fourier analyses of electroantennograms resolved the temporal structure of trains of pheromone filaments delivered at up to 33 Hz for C. cautella and S. exigua and 25 Hz for P. gossypiella. Pheromone components tested separately for each species were generally equivalent in filament resolution to complete blends. Ambient temperatures of 18, 23 and 28 degrees C affected filament resolution only slightly, with poorer ability to discriminate rapidly pulsed signals at 18 degrees C. The question of how, or indeed if, such frequencies are conserved beyond the peripheral nervous system, remains.