RESUMEN
The use of traditional nicotine delivery products such as tobacco has long been linked to detrimental health effects. However, little work to date has focused on the emerging market of aerosolized nicotine delivery known as electronic nicotine delivery systems (ENDS) or electronic cigarettes, and their potential for new effects on human health. Challenges studying these devices include heterogeneity in the formulation of the common components of most available ENDS, including nicotine and a carrier (commonly composed of propylene glycol and vegetable glycerin, or PG/VG). In the present study, we report on experiments interrogating the effects of major identified components in e-cigarettes. Specifically, the potential concomitant effects of nicotine and common carrier ingredients in commercial "vape" products are explored in vitro to inform the potential health effects on the craniofacial skeleton through novel vectors as compared to traditional tobacco products. MC3T3-E1 murine pre-osteoblast cells were cultured in vitro with clinically relevant liquid concentrations of nicotine, propylene glycol (PG), vegetable glycerin (VG), Nicotine+PG/VG, and the vape liquid of a commercial product (Juul). Cells were treated acutely for 24 h and RNA-Seq was utilized to determine segregating alteration in mRNA signaling. Influential gene targets identified with sparse partial least squares discriminant analysis (sPLS-DA) implemented in mixOmics were assessed using the PANTHER Classification system for molecular functions, biological processes, cellular components, and pathways of effect. Additional endpoint functional analyses were used to confirm cell cycle changes. The initial excitatory concentration (EC50) studied defined a target concentration of carrier PG/VG liquid that altered the cell cycle of the calvarial cells. Initial sPLS-DA analysis demonstrated the segregation of nicotine and non-nicotine exposures utilized in our in vitro modeling. Pathway analysis suggests a strong influence of nicotine exposures on cellular processes including metabolic processes and response to stimuli including autophagic flux. Further interrogation of the individual treatment conditions demonstrated segregation by treatment modality (Control, Nicotine, Carrier (PG+VG), Nicotine+PG/VG) along three dimensions best characterized by: latent variable 1 (PLSDA-1) showing strong segregation based on nicotine influence on cellular processes associated with cellular adhesion to collagen, osteoblast differentiation, and calcium binding and metabolism; latent variable 2 (PLSDA-2) showing strong segregation of influence based on PG+VG and Control influence on cell migration, survival, and cycle regulation; and latent variable 3 (PLSDA-3) showing strong segregation based on Nicotine and Control exposure influence on cell activity and growth and developmental processes. Further, gene co-expression network analysis implicates targets of the major pathway genes associated with bone growth and development, particularly craniofacial (FGF, Notch, TGFß, WNT) and analysis of active subnetwork pathways found these additionally overrepresented in the Juul exposure relative to Nicotine+PG/VG. Finally, experimentation confirmed alterations in cell count, and increased evidence of cell stress (markers of autophagy), but no alteration in apoptosis. These data suggest concomitant treatment with Nicotine+PG/VG drives alterations in pre-osteoblast cell cycle signaling, specifically transcriptomic targets related to cell cycle and potentially cell stress. Although we suspected cell stress and well as cytotoxic effects of Nicotine+PG/VG, no great influence on apoptotic factors was observed. Further RNA-Seq analysis allowed for the direct interrogation of molecular targets of major pathways involved in bone and craniofacial development, each demonstrating segregation (altered signaling) due to e-cigarette-type exposure. These data have implications directed toward ENDS formulation as synergistic effects of Nicotine+PG/VG are evidenced here. Thus, future research will continue to interrogate how varied formulation of Nicotine+PG/VG affects overall cell functions in multiple vital systems.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Nicotina , Osteoblastos , Animales , Ratones , Nicotina/farmacología , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Propilenglicol , Línea CelularRESUMEN
Background: The impact of socioeconomic status on outcomes after sepsis has been challenging to define, and no polysocial metric has been shown to predict mortality in sepsis. The primary objective of this study was to evaluate the association between the Area Deprivation Index (ADI) and mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis. Patients and Methods: All patients admitted to the SICU with sepsis (Sequential Organ Failure Assessment [SOFA] score ≥2) were retrospectively reviewed. The ADI scores were obtained and classified as "high ADI" (≥85th percentile, n = 400, representative of high socioeconomic deprivation) and "control ADI" (ADI <85th percentile, n = 976). Baseline demographic and clinical characteristics were compared between groups. The primary outcome was 90-day mortality. Results: High ADI patients were younger (mean age 58.5 vs. 60.8; p = 0.01) and more likely to be non-white (23.7% vs. 10.0%; p < 0.0005) and to present with chronic obstructive pulmonary disease (26.5% vs. 19.0%; p = 0.002). High ADI patients had increased in-hospital (27.3% vs. 21.6%; p = 0.025) and 90-day mortality (35.0% vs. 28.9%; p = 0.03). High ADI patients also had increased rates of renal failure (20.3% vs. 15.3%; p = 0.02). Both cohorts had similar intensive care unit (ICU) lengths of stay and median hospital stay, Charlson comorbidity index, and rate of discharge to home. High ADI is an independent risk factor for 90-day mortality after admission for surgical sepsis (odds ratio [OR], 1.39 ± 0.24; p = 0.014). Conclusions: High ADI is an independent predictor of 90-day mortality in patients with surgical sepsis. Targeted community interventions are needed to reduce sepsis mortality for these at-risk patients.
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Enfermedad Crítica , Sepsis , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Puntuaciones en la Disfunción de Órganos , Mortalidad Hospitalaria , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: The United States Food & Drug Administration's emergency authorized use, in December 2020, of over-the-counter (OTC) rapid antigen COVID-19 tests was a pandemic control milestone. OBJECTIVE: To assess health literacy-related characteristics of OTC rapid antigen COVID-19 test materials. METHODS: Between September-December 2021, we identified eleven (n = 11) OTC rapid antigen COVID-19 tests available for purchase in the US. We assessed readability (Flesch Reading Ease and Fernández-Huerta), formatting and layout features of English- and Spanish-language step-by-step OTC rapid antigen COVID-19 test package insert instructions. Video-based step-by-step OTC rapid antigen COVID-19 test instructions were evaluated for understandability and actionability (Patient Education Materials Assessment Tool for Audiovisual Materials [PEMAT-A/V]), overall quality (Global Quality Scale [GQS]) and cultural diversity and inclusiveness. Descriptive analyses were performed using IBM® Statistical Package for the Social Sciences. RESULTS: Nine (81.8%) OTC rapid antigen COVID-19 tests included English-language (≈8th-9th reading grade level) step-by-step instructions, while 4 included Spanish-language (≈10th-12th reading grade level) instructions. On average, instructions were printed on a tabloid sized piece of paper, with text size ranging from 4 to 12 point and including nearly 20 illustrations. English-language step-by-step OTC rapid antigen COVID-19 test video-based instructions (n = 6) ranged from 1:04 to 5:41 min with PEMAT-A/V scores ranging from 80% to 100%. As indicated by GQS scores, English-language videos were of high quality (5 videos scored 5/5; 1 video scored 4/5). One COVID-19 test product manufacturing website included Spanish-language video-based instructions (time = 4:59 min; PEMAT-A/V = 100%; GQS = 5). CONCLUSIONS: OTC COVID-19 test step-by-step instructions-both package inserts and video-based-included features shown to foster patient understanding and facilitate proper use. Moving forward, greater attention needs to be placed on expanding both Spanish-language and video-based OTC COVID-19 test material availability to improve accessibility across diverse populations.
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COVID-19 , Alfabetización en Salud , Humanos , Estados Unidos , COVID-19/epidemiología , Comprensión , Lectura , LenguajeRESUMEN
Recent investigations have shown excess postexercise oxygen consumption (EPOC) to be elevated for up to 48 hours in both untrained and trained subjects after resistance training (RT). The purpose of this study was to investigate the effect of load-volume on EPOC. Eight trained men (aged 22 ± 3 years) participated in 2 randomized RT bouts separated by at least 1 week with total load-volumes of 10,000 and 20,000 kg, respectively. Intensity of RT (85% 1 repetition maximum) did not differ between trials. Exercise energy expenditure and resting metabolic rate (RMR) were measured by indirect calorimetry at 8.5 hours before, 1.5 hours before, and during RT bouts and 12, 24, 36, and 48 hours after exercise. Creatine kinase (CK) was measured before and after RT, and 12, 24, 36, and 48 hours postexercise; ratings of perceived muscle soreness were measured on a similar time course save the immediate postexercise time point. Analysis of variance with repeated measures was used to analyze dependent variables. During the 20,000 kg trial, subjects expended significantly (p < 0.01) more energy (484 ± 29 kcal) than the 10,000 kg lift (247 ± 18 kcal). After the 20,000 kg lift, 12 hours postexercise, CK (1,159 ± 729 U·L) was significantly elevated (p < 0.05) as compared with baseline (272 ± 280 U·L) and immediately postexercise (490 ± 402 U·L). No significant time or trial differences were found in RMR between the 10,000 and 20,000 kg trials. In conclusion, high-intensity RT with load-volumes of up to 20,000 kg using resistance-trained men does not significantly increase EPOC above baseline RMR.
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Consumo de Oxígeno/fisiología , Entrenamiento de Fuerza/métodos , Adaptación Fisiológica/fisiología , Adulto , Creatina Quinasa/sangre , Metabolismo Energético , Florida , Humanos , MasculinoRESUMEN
BACKGROUND AND PURPOSE: The purpose of this study was to compare functionality and strength among women with fibromyalgia (FM), women without FM, and older women. SUBJECTS: Twenty-nine women with FM (age [X+/-SD]=46+/-7 years), 12 age- and weight-matched women without FM (age=44+/-8 years), and 38 older women who were healthy (age=71+/-7 years) participated. METHODS: The Continuous Scale-Physical Functional Performance Test (CS-PFP) was used to assess functionality. Isokinetic leg strength was measured at 60 degrees/s, and handgrip strength was measured using a handgrip dynamometer. RESULTS: The women without FM had significantly higher functionality scores compared with women with FM and older women. There were no differences in functionality between women with FM and older women. Strength measures for the leg were higher in women without FM compared with women with FM and older women, and both women with and without FM had higher grip strengths compared with older women. DISCUSSION AND CONCLUSION: This study demonstrated that women with FM and older women who are healthy have similar lower-body strength and functionality, potentially enhancing the risk for premature age-associated disability.