RESUMO
Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 µm nylon 6,6 (nylon) and 15 × 52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate, and, 7 days later, organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects was recapitulated in human air-liquid interface cultures. Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.
Assuntos
Caprolactama/análogos & derivados , Microplásticos , Plásticos , Polímeros , Camundongos , Humanos , Animais , Nylons , Têxteis , PoliésteresRESUMO
BACKGROUND: In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying polymerase chain reaction (PCR)-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in 7 sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. METHODS: We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. RESULTS: Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. CONCLUSIONS: Despite a substantial decrease in reported pertussis cases in the setting of coronavirus disease 2019 (COVID-19), our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts.
Assuntos
Bordetella pertussis , Coqueluche , Coqueluche/epidemiologia , Coqueluche/diagnóstico , Coqueluche/prevenção & controle , Humanos , Estados Unidos/epidemiologia , Criança , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Pré-Escolar , Lactente , Adolescente , Adulto , Adulto Jovem , Masculino , Vigilância da População , Feminino , Notificação de Doenças/estatística & dados numéricos , Reação em Cadeia da PolimeraseRESUMO
The COVID-19 pandemic was one of the deadliest global public health events. In the United States, over 1.1 million individuals have died, and now COVID-19 is the third leading cause of death (CDC, 2023). Vaccine uptake has stalled among different demographics. Vaccine hesitancy, a delay in accepting or refusing vaccines, poses a significant challenge regardless of the availability of safe and effective COVID-19 vaccines. This study aimed to identify disparate COVID-19 vaccine uptake among individuals in Western New York. The primary objective was to identify the factors contributing to lower rates of COVID-19 vaccination within this population.Data were collected from 585 adults recruited from 20 Niagara and Erie Counties sites using a self-administered survey on vaccine hesitancy, vaccination status, and COVID-19-related characteristics. The survey included the adult Vaccine Hesitancy Scale (aVHS) and acquired information on demographic characteristics and COVID-19 impact, knowledge, and information sources. Data were analyzed using descriptive statistics, a chi-squared test, a Wilcoxon rank-sum test, and a logistic regression model.Findings suggest that unvaccinated participants (n = 35) were concerned about vaccine side effects (48.6%). For vaccinated/unboosted participants (n = 52), they (40.0%) reported clinical concerns. After adjusting for gender and age, healthcare provider guidance and family guidance remained significant predictors of vaccination status, while clinical research studies were significant predictors of booster status. Findings from this study suggest public health interventions that target vaccine education and facilitate well-informed decisions about COVID-19 vaccines lead to less vaccine hesitancy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Hesitação Vacinal , Humanos , Vacinas contra COVID-19/administração & dosagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , COVID-19/prevenção & controle , Hesitação Vacinal/estatística & dados numéricos , New York , Adulto Jovem , Idoso , Confiança , Conhecimentos, Atitudes e Prática em Saúde , SARS-CoV-2 , Adolescente , Inquéritos e Questionários , Área Carente de Assistência Médica , Populações Vulneráveis/estatística & dados numéricos , Fonte de InformaçãoRESUMO
BACKGROUND: Studies have demonstrated increased complication risk after total hip arthroplasty (THA) in patients who smoke cigarettes. It is unclear if smokeless tobacco use confers a similar impact. The purpose of this study was to (1) evaluate rates of postoperative complications after THA in smokeless tobacco users and people who smoke compared to matched controls, and (2) compare rates of postoperative complications in smokeless tobacco users versus patients who smoke. METHODS: A retrospective cohort study was conducted using a large national database. For patients who underwent primary THA, smokeless tobacco users (n = 950) and people who smoke (n = 21,585) were matched 1:4 with controls (n = 3,800 and 86,340, respectively), and smokeless tobacco users (n = 922) were matched 1:4 with people who smoke (n = 3,688). Joint complication rates within 2 years and medical complications within 90 days postoperatively were compared using multivariable logistic regressions. RESULTS: Within 90 days of primary THA, smokeless tobacco users demonstrated significantly higher rates of wound disruption, pneumonia, deep vein thrombosis, acute kidney injury (AKI), cardiac arrest, transfusion, readmission and longer length of stay compared to tobacco naïve controls. Within 2 years, smokeless tobacco users demonstrated significantly higher rates of prosthetic joint dislocations and overall joint-related complications compared to tobacco naïve controls. CONCLUSION: Smokeless tobacco use is associated with higher rates of medical- and joint-related complications following primary THA. Smokeless tobacco use may be under-diagnosed in patients undergoing elective THA. Surgeons may consider delineating between smoking and smokeless tobacco use during preoperative counseling.
Assuntos
Artroplastia de Quadril , Tabaco sem Fumaça , Humanos , Artroplastia de Quadril/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Heating is a major source of air pollution. To improve air quality, a range of clean heating policies were implemented in China over the past decade. Here, we evaluated the impacts of winter heating and clean heating policies on air quality in China using a novel, observation-based causal inference approach. During 2015-2021, winter heating causally increased annual PM2.5, daily maximum 8-h average O3, and SO2 by 4.6, 2.5, and 2.3 µg m-3, respectively. From 2015 to 2021, the impacts of winter heating on PM2.5 in Beijing and surrounding cities (i.e., "2 + 26" cities) decreased by 5.9 µg m-3 (41.3%), whereas that in other northern cities only decreased by 1.2 µg m-3 (12.9%). This demonstrates the effectiveness of stricter clean heating policies on PM2.5 in "2 + 26" cities. Overall, clean heating policies caused the annual PM2.5 in mainland China to reduce by 1.9 µg m-3 from 2015 to 2021, potentially avoiding 23,556 premature deaths in 2021.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/análise , Calefação , Monitoramento Ambiental , Poluição do Ar/prevenção & controle , Poluição do Ar/análise , China , Cidades , Estações do Ano , Políticas , Aprendizado de MáquinaRESUMO
BACKGROUND: Many regularly prescribed classes of drugs are known to negatively impact bone health. However, it is unclear if perioperative use of these drugs impacts total shoulder arthroplasty (TSA) outcomes. The purpose of this study was to analyze the impact of perioperative use of 10 drug classes with known negative effects on bone health on prosthesis-related outcomes of TSA. METHODS: Patients who underwent primary TSA were retrospectively identified in the PearlDiver database. Within this population, patients prescribed proton pump inhibitors (PPIs), thiazolidinediones (TZDs), loop diuretics, glucocorticoids, aromatase inhibitors, calcineurin inhibitors, selective serotonin reuptake inhibitors (SSRIs), antiepileptic drugs (AEDs), first-generation antipsychotics (FGAs), and second-generation antipsychotics (SGAs) within 6 months before or 6 months after primary TSA were identified (n = 23,748). These patients were propensity score matched 1:1 with controls (n = 23,748) on age, sex, and several comorbidities. After matching, patients with perioperative drug exposure were divided into 10 subgroups (ie, 1 for each drug class). Rates of prosthesis-related complications among patients taking each medication class vs. controls were compared with multivariable logistic regression. RESULTS: Relative to controls, SGA exposure was associated with significantly higher rates of all-cause revision (odds ratio [OR] 1.68) and aseptic revision (OR 1.57). Loop diuretic exposure was associated with significantly higher rates of all-cause revision (OR 1.44) and aseptic revision (OR 1.43). Glucocorticoid exposure was associated with significantly higher rates of all-cause revision (OR 1.32) and aseptic revision (OR 1.30). SSRI exposure was associated with significantly higher rates of all-cause revision (OR 1.27) and aseptic revision (OR 1.24). Periprosthetic fracture, aseptic loosening, and septic revision was comparable for all drug cohorts compared to matched controls (all P > .05). Patients with perioperative exposure to PPIs, TZDs, FGAs, AEDs, aromatase inhibitors, and calcineurin inhibitors displayed comparable rates of all queried complications compared with controls (all P > .05). CONCLUSION: Compared with matched controls, patients with perioperative exposure to SGAs, loop diuretics, glucocorticoids and SSRIs exhibited significantly higher rates of all-cause and aseptic revisions following primary TSA. Several other medications that are risk factors for osteoporosis and fragility fractures did not demonstrate significant associations with any complications, including periprosthetic fracture. These results highlight the need for a thorough review of patients' medical history and current medication usage prior to preoperative risk counseling for patients seeking TSA.
Assuntos
Artroplastia do Ombro , Fraturas Periprotéticas , Humanos , Fraturas Periprotéticas/etiologia , Artroplastia do Ombro/efeitos adversos , Estudos Retrospectivos , Densidade Óssea , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Inibidores Seletivos de Recaptação de Serotonina , Inibidores da Aromatase , Inibidores de Calcineurina , ReoperaçãoRESUMO
BACKGROUND: Studies have demonstrated increased complication risk after total knee arthroplasty (TKA) in patients who smoke cigarettes, but it is unclear if smokeless tobacco use confers a similar impact. The purpose of this study was to (1) evaluate rates of postoperative complications after TKA in smokeless tobacco users and smokers as compared to matched controls, and (2) compare rates of postoperative complications in smokeless tobacco users versus smokers to determine if one is associated with significantly higher rates of postoperative complications. METHODS: A retrospective cohort study was conducted using a national database. For patients who underwent primary TKA, smokeless tobacco users (n = 1,535) and smokers (n = 28,953) were matched at a 1:4 with controls (n = 6,140 and 115,812, respectively), and smokeless tobacco users (n = 1,481) were matched at a 1:4 with smokers (n = 5,924). Rates of joint complications within 2 years and medical complications within 90 days postoperatively were compared using multivariable logistic regressions. RESULTS: After primary TKA, compared to controls, smokeless tobacco users demonstrated significantly higher rates of aseptic loosening/mechanical failure within 2 years, longer lengths of stay, and higher rates of urinary tract infection, pneumonia, deep vein thrombosis, and acute kidney injury within 90 days. Compared to smokers, smokeless tobacco users demonstrated significantly lower rates of aseptic revision and lower rates of wound disruption. CONCLUSION: Smokeless tobacco use is associated with higher rates of both medical and joint complications following primary TKA. However, smoking is associated with higher risk for complications than smokeless tobacco use. LEVEL OF EVIDENCE: Level III.
Assuntos
Artroplastia do Joelho , Tabaco sem Fumaça , Humanos , Tabaco sem Fumaça/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Uso de Tabaco/efeitos adversos , Uso de Tabaco/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: The prevalence of gout is increasing along with the number of total knee arthroplasties (TKA) performed annually. The purpose of this study was to evaluate the incidence of gout following TKA in patients who had a previous history of gout and to determine if it is associated with an increased rate of postoperative joint complications. METHODS: Patients who did and did not have a preoperative diagnosis of gout and underwent a primary TKA were identified from a national database. The gout patients were matched 1:1 to patients who did not have gout and rates of postoperative gout diagnoses within 2 years of surgery were compared. Complication rates at mean 1 and 2 years were then compared for both patient cohorts using multivariable logistic regressions. A total of 17,463 patients with a prior diagnosis of gout were matched with 17,463 controls. RESULTS: There were 53.8% of patients who had previous gout and had a recurrence of gout within 2 years versus 3.6% of controls (Odds Ratios [OR]: 30.86). At mean 1-year, patients who had gout were significantly more likely to experience prosthetic joint infections (PJIs) and revision procedures. At mean 2 years, gout patients were at increased risk of prosthetic loosening, PJI, revision, and incision and debridement procedures. CONCLUSION: This study suggests that patients who had a prior diagnosis of gout are significantly more likely to experience recurrent episodes of gout after TKA. Gout attacks after TKA are associated with an increase in the rate of joint complications. LEVEL OF EVIDENCE: Level III.
Assuntos
Artrite Infecciosa , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/diagnóstico , Incidência , Artrite Infecciosa/etiologia , Reoperação/efeitos adversosRESUMO
BACKGROUND: It is unclear if hepatitis C virus (HCV) negatively impacts outcomes of revision total hip arthroplasty (rTHA). The purpose of this study is to trend recent rTHA utilization in patients who have HCV and compare postoperative complication rates versus a matched cohort. METHODS: All patients who underwent rTHA were retrospectively identified in a national database. Patients who had HCV (n = 1,746) were matched 1:3 with a matching group (n = 5,238) for age, gender, and several comorbidities. Cochran-Armitage tests were used to analyze trends in the annual proportion of rTHA performed in patients who had HCV from 2010 to 2019. Rates of 90-day medical and prosthesis-related complications within 2 years postoperatively were compared with multivariable logistic regressions. RESULTS: The annual proportion of rTHA performed in patients who had HCV significantly increased from 2010 to 2019 (P < .001). Patients who had HCV exhibited significantly higher rates of acute kidney injuries (7.6% versus 4.4%; odds ratio [OR] 1.50), transfusions (20.6% versus 14.6%; OR 1.38), and re-revisions for prosthetic joint infection (10.9% versus 6.5%; OR 1.73). In subgroup analyses, rates of re-revision for prosthetic joint infection after initial aseptic rTHA (7.1% versus 3.8%; OR 1.82) and periprosthetic fracture after initial septic rTHA (4.5% versus 1.6%; OR 2.77) were significantly higher in the HCV cohort. CONCLUSION: Similar to primary THA, patients who have HCV exhibit significantly increased complication rates after rTHA. With growing utilization in recent years, these data suggest that this population will comprise an increasingly larger proportion of rTHA procedures performed in the coming years.
Assuntos
Artroplastia de Quadril , Hepatite C , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Estudos de Coortes , Estudos Retrospectivos , Hepacivirus , Hepatite C/complicações , Hepatite C/epidemiologia , ReoperaçãoRESUMO
BACKGROUND: It is unclear how epilepsy may affect total joint arthroplasty outcomes. The purpose of this study is to analyze the impact of epilepsy on prosthesis-related complications following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A retrospective cohort study was conducted using a national database. Patients who have epilepsy underwent a primary THA (n = 6,981) and TKA (n = 4,987) and were matched 1:4 (THA, n = 27,924; TKA, n = 19,948). Rates of low-energy falls and prosthesis-related complications within 2 years postoperatively were compared for patients who did and did not have epilepsy with multivariable logistic regression. RESULTS: After primary TKA, patients who have epilepsy exhibited significantly higher rates of aseptic revision (4.3% versus 3.5%, odds ratio [OR] 1.21, P = .017) and revision for prosthetic joint infection (1.8% versus 1.3%, OR 1.29, P = .041). THA patients who have epilepsy exhibited significantly higher rates of prosthetic dislocation (3.2% versus 1.9%, OR 1.54, P < .001), periprosthetic fracture (2.2% versus 0.8%, OR 2.39, P < .001), and aseptic loosening (1.7% versus 1.1%, OR 1.40, P = .002). Rates of low-energy falls within 2 years after TKA (14.1% versus 6.4%, OR 2.19, P < .001) and THA (33.6% versus 7.5%, OR 5.95, P < .001) were also significantly higher for patients who have epilepsy. CONCLUSION: Epilepsy was associated with significantly higher rates of falls (P < .001) and prosthesis-related complications after primary THA (P < .05) and TKA (P < .05). Precautions should be implemented in this population during intraoperative and perioperative decision-making to reduce complication risk. LEVEL OF EVIDENCE: Level III.
Assuntos
Artroplastia de Quadril , Epilepsia , Humanos , Estudos de Coortes , Estudos Retrospectivos , Pontuação de Propensão , Fatores de Risco , Artroplastia de Quadril/efeitos adversos , Epilepsia/cirurgiaRESUMO
Resting metabolic rate (RMR) is an important component of total daily energy expenditure; however, it is currently not understood how it varies across a typical competitive match week in professional soccer players. For the first time, we aimed to assess RMR throughout an in-season competitive week in professional soccer players. Additionally, we aimed to assess energy and carbohydrate intake across the same week. Twenty-four professional soccer players from an English Premier League club (age: 18 ± 1.6 years) completed the study. RMR was assessed each morning of a typical competitive match week (match day [MD] -3, -2, -1, +1, +2, and + 3), and dietary intake (including MD) was assessed daily via the remote food photography method and 24-hr recall. Daily training load was quantified using Global Positioning System, daily muscle soreness ratings were recorded, and body composition was assessed via dual-energy X-ray absorptiometry. There was a significant (p = .0004) increase in mean RMR of â¼261 kcal/day on MD + 1, compared with MD - 1. Additionally, volume of oxygen consumed significantly increased at MD + 1 (p = .0002) versus MD - 1. There were no significant differences in daily energy or carbohydrate intake across the competitive week (p > .05), with inadequate carbohydrate intakes on MD - 1 (â¼3.9 g/kg body mass), MD (â¼4.2 g/kg body mass), and MD + 1 (â¼3.6 g/kg body mass) in relation to current recommendations. We report, for the first time, that RMR is significantly increased following a competitive match in professional soccer players. In addition, we confirm previous findings to reinforce that players exhibit inadequate nutrition periodization practices, which may impair physical performance and recovery.
Assuntos
Ingestão de Energia , Futebol , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Metabolismo Basal , Futebol/fisiologia , Estações do Ano , CarboidratosRESUMO
As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.§ To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men¶ aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection (5).
Assuntos
Mpox , Minorias Sexuais e de Gênero , Humanos , Masculino , Homossexualidade Masculina , Estados Unidos/epidemiologia , United States Food and Drug Administration , Mpox/prevenção & controle , Vacina Antivariólica/administração & dosagemRESUMO
BACKGROUND: Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-associated mortality in women. In particular, triple-negative BC (TNBC) has the highest rate of mortality due in large part to the lack of targeted treatment options for this subtype. Thus, there is an urgent need to identify new molecular targets for TNBC treatment. RALA and RALB are small GTPases implicated in growth and metastasis of a variety of cancers, although little is known of their roles in BC. METHODS: The necessity of RALA and RALB for TNBC tumor growth and metastasis were evaluated in vivo using orthotopic and tail-vein models. In vitro, 2D and 3D cell culture methods were used to evaluate the contributions of RALA and RALB during TNBC cell migration, invasion, and viability. The association between TNBC patient outcome and RALA and RALB expression was examined using publicly available gene expression data and patient tissue microarrays. Finally, small molecule inhibition of RALA and RALB was evaluated as a potential treatment strategy for TNBC in cell line and patient-derived xenograft (PDX) models. RESULTS: Knockout or depletion of RALA inhibited orthotopic primary tumor growth, spontaneous metastasis, and experimental metastasis of TNBC cells in vivo. Conversely, knockout of RALB increased TNBC growth and metastasis. In vitro, RALA and RALB had antagonistic effects on TNBC migration, invasion, and viability with RALA generally supporting and RALB opposing these processes. In BC patient populations, elevated RALA but not RALB expression is significantly associated with poor outcome across all BC subtypes and specifically within TNBC patient cohorts. Immunohistochemical staining for RALA in patient cohorts confirmed the prognostic significance of RALA within the general BC population and the TNBC population specifically. BQU57, a small molecule inhibitor of RALA and RALB, decreased TNBC cell line viability, sensitized cells to paclitaxel in vitro and decreased tumor growth and metastasis in TNBC cell line and PDX models in vivo. CONCLUSIONS: Together, these data demonstrate important but paradoxical roles for RALA and RALB in the pathogenesis of TNBC and advocate further investigation of RALA as a target for the precise treatment of metastatic TNBC.
Assuntos
Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Proteínas ral de Ligação ao GTP/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Camundongos , Metástase Neoplásica , Paclitaxel/uso terapêutico , Prognóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ral de Ligação ao GTP/antagonistas & inibidores , Proteínas ral de Ligação ao GTP/genéticaRESUMO
In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) received Emergency Use Authorization from the Food and Drug Administration.*, Both vaccines require 2 doses for a completed series. The recommended interval between doses is 21 days for Pfizer-BioNTech and 28 days for Moderna; however, up to 42 days between doses is permissible when a delay is unavoidable.§ Two analyses of COVID-19 vaccine administration data were conducted among persons who initiated the vaccination series during December 14, 2020-February 14, 2021, and whose doses were reported to CDC through February 20, 2021. The first analysis was conducted to determine whether persons who received a first dose and had sufficient time to receive the second dose (i.e., as of February 14, 2021, >25 days from receipt of Pfizer-BioNTech vaccine or >32 days from receipt of Moderna vaccine had elapsed) had received the second dose. A second analysis was conducted among persons who received a second COVID-19 dose by February 14, 2021, to determine whether the dose was received during the recommended dosing interval, which in this study was defined as 17-25 days (Pfizer-BioNTech) and 24-32 days (Moderna) after the first dose. Analyses were stratified by jurisdiction and by demographic characteristics. In the first analysis, among 12,496,258 persons who received the first vaccine dose and for whom sufficient time had elapsed to receive the second dose, 88.0% had completed the series, 8.6% had not received the second dose but remained within the allowable interval (≤42 days since the first dose), and 3.4% had missed the second dose (outside the allowable interval, >42 days since the first dose). The percentage of persons who missed the second dose varied by jurisdiction (range = 0.0%-9.1%) and among demographic groups was highest among non-Hispanic American Indian/Alaska Native (AI/AN) persons (5.1%) and persons aged 16-44 years (4.0%). In the second analysis, among 14,205,768 persons who received a second dose, 95.6% received the dose within the recommended interval, although percentages varied by jurisdiction (range = 79.0%-99.9%). Public health officials should identify and address possible barriers to completing the COVID-19 vaccination series to ensure equitable coverage across communities and maximum health benefits for recipients. Strategies to ensure series completion could include scheduling second-dose appointments at the first-dose administration and sending reminders for second-dose visits.
Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Esquemas de Imunização , Cobertura Vacinal/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The underlying mechanisms that influence microplastic ingestion in marine zooplankton remain poorly understood. Here, we investigate how microplastics of a variety of shapes (bead, fiber, and fragment), in combination with the algal-derived infochemicals dimethyl sulfide (DMS) and dimethylsulfoniopropionate (DMSP), affect the ingestion rate of microplastics in three species of zooplankton, the copepods Calanus helgolandicus and Acartia tonsa and larvae of the European lobster Homarus gammarus. We show that shape affects microplastic bioavailability to different species of zooplankton, with each species ingesting significantly more of a certain shape: C. helgolandicus-fragments (P < 0.05); A. tonsa-fibers (P < 0.01); H. gammarus larvae-beads (P < 0.05). Thus, different feeding strategies between species may affect shape selectivity. Our results also showed significantly increased ingestion rates by C. helgolandicus on all microplastics that were infused with DMS (P < 0.01) and by H. gammarus larvae and A. tonsa on DMS-infused fibers and fragments (P < 0.05). By using a range of more environmentally relevant microplastics, our findings highlight how the feeding strategies of different zooplankton species may influence their susceptibility to microplastic ingestion. Furthermore, our novel study suggests that species reliant on chemosensory cues to locate their prey may be at an increased risk of ingesting aged microplastics in the marine environment.
Assuntos
Poluentes Químicos da Água , Zooplâncton , Animais , Disponibilidade Biológica , Monitoramento Ambiental , Microplásticos , Plásticos , Poluentes Químicos da Água/análiseRESUMO
Microplastic debris is a prevalent global pollutant that poses a risk to marine organisms and ecological processes. It is also suspected to pose a risk to marine food security; however, these risks are currently poorly understood. In this review, we seek to understand the current knowledge pertaining to the contamination of commercially important fished and farmed marine organisms with microplastics, with the aim of answering the question "Does microplastic pollution pose a risk to marine food security?". A semi-systematic review of studies investigating the number of microplastics found in commercially important organisms of different trophic levels suggests that microplastics do not biomagnify, and that organisms at lower trophic levels are more likely to contaminated by microplastic pollution than apex predators. We address the factors that influence microplastic consumption and retention by organisms. This research has implications for food safety and highlights the risks of microplastics to fisheries and aquaculture, and identifies current knowledge gaps within this research field.
Assuntos
Microplásticos/toxicidade , Alimentos Marinhos/análise , Poluentes Químicos da Água/toxicidade , Animais , Aquicultura , Organismos Aquáticos , Monitoramento Ambiental , Cadeia Alimentar , Inocuidade dos Alimentos , Microplásticos/análise , Poluentes Químicos da Água/análiseRESUMO
In light of the existing preliminary evidence of a link between Covid-19 and poor air quality, which is largely based upon correlations, we estimate the relationship between long term air pollution exposure and Covid-19 in 355 municipalities in the Netherlands. Using detailed data we find compelling evidence of a positive relationship between air pollution, and particularly P M 2.5 concentrations, and Covid-19 cases, hospital admissions and deaths. This relationship persists even after controlling for a wide range of explanatory variables. Our results indicate that, other things being equal, a municipality with 1 µg/m3 more P M 2.5 concentrations will have 9.4 more Covid-19 cases, 3.0 more hospital admissions, and 2.3 more deaths. This relationship between Covid-19 and air pollution withstands a number of sensitivity and robustness exercises including instrumenting pollution to mitigate potential endogeneity in the measurement of pollution and modelling spatial spillovers using spatial econometric techniques.
RESUMO
We quantify the impact of the Wuhan Covid-19 lockdown on concentrations of four air pollutants using a two-step approach. First, we use machine learning to remove the confounding effects of weather conditions on pollution concentrations. Second, we use a new augmented synthetic control method (Ben-Michael et al. in The augmented synthetic control method. University of California Berkeley, Mimeo, 2019. https://arxiv.org/pdf/1811.04170.pdf) to estimate the impact of the lockdown on weather normalised pollution relative to a control group of cities that were not in lockdown. We find NO 2 concentrations fell by as much as 24 µ g/m 3 during the lockdown (a reduction of 63% from the pre-lockdown level), while PM10 concentrations fell by a similar amount but for a shorter period. The lockdown had no discernible impact on concentrations of SO 2 or CO. We calculate that the reduction of NO 2 concentrations could have prevented as many as 496 deaths in Wuhan city, 3368 deaths in Hubei province and 10,822 deaths in China as a whole.
RESUMO
Microplastic debris is a pervasive environmental contaminant that has the potential to impact the health of biota, although its modes of action remain somewhat unclear. The current study tested the hypothesis that exposure to fibrous and particulate microplastics would alter feeding, impacting on lipid accumulation, and normal development (e.g., growth, moulting) in an ecologically important coldwater copepod Calanus finmarchicus. Preadult copepods were incubated in seawater containing a mixed assemblage of cultured microalgae (control), with the addition of â¼50 microplastics mL-1 of nylon microplastic granules (10-30 µm) or fibers (10 × 30 µm), which are similar in shape and size to the microalgal prey. The additive chemical profiles showed the presence of stabilizers, lubricants, monomer residues, and byproducts. Prey selectivity was significantly altered in copepods exposed to nylon fibers (ANOVA, P < 0.01) resulting in a nonsignificant 40% decrease in algal ingestion rates (ANOVA, P = 0.07), and copepods exposed to nylon granules showed nonsignificant lipid accumulation (ANOVA, P = 0.62). Both microplastics triggered premature moulting in juvenile copepods (Bernoulli GLM, P < 0.01). Our results emphasize that the shape and chemical profile of a microplastic can influence its bioavailability and toxicity, drawing attention to the importance of using environmentally relevant microplastics and chemically profiling plastics used in toxicity testing.