RESUMEN
The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.S.) from March 13th 2020 to July 3rd 2023. Our sequencing protocol ('Virseq') utilizes wet and dry lab procedures to generate mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control and Prevention national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale.
Asunto(s)
COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/epidemiología , COVID-19/virología , Estados Unidos/epidemiología , MutaciónRESUMEN
BACKGROUND AND PURPOSE: Falls are common and often take place in the home. Risk of fall increases if the environment is dimly lit. Longer sitting pause times, before standing, might improve postural stability after standing from a supine position. The purpose of this investigation was to measure the effects of sitting pause times on postural sway velocity immediately following a supine-to-standing transfer in a dimly lit room in older and younger adult women. METHODS: Five women aged 65 to 70 years and 5 aged 23 to 30 years participated in the study. On each of 2 consecutive days, study participants lay on a mat table with their eyes closed for 45 minutes before performing a supine-to-standing transfer in a dimly lit room. Sitting pause times of 2 seconds and 30 seconds preceded the transfers. RESULTS: Mean postural sway velocity for the whole sample and for younger and older groups was less after a 30-second pause time than that after a 2-second pause time (sample, P = .001; young, P = .019; old, P = .021). No significant difference in mean postural sway velocity was observed between the 2 groups (P > .05). CONCLUSIONS: Total mean postural sway velocity was less when study participants performed a sitting pause of 30 seconds before standing in a dimly lit room. These results suggest that longer sitting pause times may provide improved adaptability to dimly lit environments contributing to improved postural stability.
Asunto(s)
Accidentes por Caídas/prevención & control , Adaptación Fisiológica/fisiología , Ambiente , Equilibrio Postural/fisiología , Postura/fisiología , Adulto , Factores de Edad , Anciano , Envejecimiento/fisiología , Femenino , Humanos , Valores de Referencia , Muestreo , Posición Supina , Factores de Tiempo , Adulto JovenRESUMEN
The mechanisms mediating the effects of stress on immune function have yet to be fully described. In vitro studies have demonstrated a role for both the sympathetic nervous system (SNS) and the hypothalamic pituitary adrenal axis (HPAA) in regulating immune responses following exposure to various stressors. The purpose of the present set of experiments was to determine the in vivo contribution of the HPAA and SNS in regulating the effects of stress on lipopolysaccharide (LPS) induced splenic cytokine production. For this, rats with combinations of sham surgeries, splenic nerve cuts (SNC), and adrenalectomies (ADX) were exposed to 15 min of 1.6 mA intermittent footshock immediately following the intravenous (i.v.) injection of 0.1 microg of LPS. Although footshock was immunosuppressive to most indices of cytokine production, neither SNC nor ADX alone blocked the effects of stress on splenic immune function. However the combination of these two manipulations significantly abrogated the immunosuppressive effects of stress on cytokine production. Adrenal demedullation of animals with a SNC demonstrated that the SNS, not the HPAA, was primarily responsible for the immunosuppressive effects of stress.
Asunto(s)
Interleucina-1/biosíntesis , Lipopolisacáridos/farmacología , Neuroinmunomodulación/efectos de los fármacos , Bazo/inmunología , Estrés Psicológico/inmunología , Sistema Nervioso Simpático/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Adrenalectomía , Análisis de Varianza , Animales , Citocinas/efectos de los fármacos , Citocinas/inmunología , Citocinas/metabolismo , Desnervación , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/inmunología , Interleucina-1/inmunología , Interleucina-6/biosíntesis , Interleucina-6/inmunología , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/inmunología , Ratas , Ratas Sprague-Dawley , Bazo/efectos de los fármacos , Bazo/inervación , Bazo/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/cirugía , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Both the hypothalamic pituitary adrenal axis (HPAA) and the sympathetic nervous system (SNS) can inhibit immune function and are regarded as the primary efferent pathways for neural-immune interactions. To determine if this relationship is maintained in vivo in response to an inflammatory stimulus, rats were injected intravenously (iv) with various doses of lipopolysaccharide (LPS) and splenic cytokine mRNA and protein levels were measured at several dose and time intervals post-injection. The spleen was chosen as the target organ because both the neural and hormonal inputs to the spleen can be selectively removed by splenic nerve cut (SNC) and adrenalectomy (ADX), respectively. Data from our dose response studies established that maximum levels of splenic cytokines were induced in response to relatively low doses of LPS. Minimal changes in LPS-induced splenic cytokine levels were observed in response to ADX, SNC, or a combination of the two procedures across several doses of LPS. These results suggest that there are aspects of immune regulation that are functionally removed from these central modulatory systems and that the counter-regulatory responses induced by LPS have minimal impact on the concurrent induction of cytokines by this inflammatory stimulus. The conceptual model of neural-immune regulation as an inhibitory feedback system, at least with regards to the early activational effects induced by an inflammatory stimulus, was not supported by these studies.