RESUMO
Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Nav) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in infancy with intractable focal seizures and severe developmental delay. Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function.
Assuntos
Encefalopatias/genética , Epilepsia/genética , Fatores de Crescimento de Fibroblastos/genética , Mutação de Sentido Incorreto/genética , Isoformas de Proteínas/genética , Adolescente , Sequência de Aminoácidos , Criança , Éxons/genética , Feminino , Mutação com Ganho de Função/genética , Genes Ligados ao Cromossomo X/genética , Heterozigoto , Humanos , Masculino , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Neurônios/fisiologia , Convulsões/genéticaRESUMO
Uptake of HIV testing is a critical step in the HIV prevention and treatment care cascade. Barriers to HIV testing, however, remain and innovative research in this area is warranted to improve uptake of testing. As such, we investigated the role of HIV information avoidance - a novel construct potentially related to HIV testing. We analyzed this construct in relation to other factors known to impact HIV testing, namely HIV stigma and medical mistrust. Multiple linear regression analyses indicated that HIV information avoidance was negatively associated with HIV testing, while medical mistrust was positively associated with HIV testing. HIV testing stigma was not associated with HIV testing. This work contributes to the developing literature on HIV information avoidance and its relationships with HIV stigma and HIV testing uptake. Further, these findings can inform HIV testing interventions which often do not focus on HIV information avoidance. Future research on the mechanisms of information avoidance that are amenable to intervention, and the temporal ordering of the relationship between information avoidance and HIV testing is warranted.
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Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Estados Unidos/epidemiologia , Confiança , Evitação da Informação , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Estigma Social , Teste de HIV , Homossexualidade MasculinaRESUMO
Family-based microaggressions and discrimination experienced by youth with LGBTQ+ parents are important to understand from their perspectives. Using mixed methods, we examined such experiences among 12- to 25-year-old youth (N = 51) with at least one LGBTQ+ parent in the United States. Youth were diverse in race/ethnicity, family structure, gender and sexual identities, socioeconomic status, and geographic region. Using interviews, we explored LGBTQ+ family-based microaggressions (reported through scale items with feedback) and discrimination (assessed via thematic analysis). Microaggressions and discrimination based on having LGBTQ+ parents were common, yet there were distinctions in direct and indirect stigma across the quantitative items and qualitative themes. These results underscore the value of mixed methods research with youth and implications for future research, practice, and policy.
Assuntos
Minorias Sexuais e de Gênero , Humanos , Adolescente , Feminino , Masculino , Minorias Sexuais e de Gênero/psicologia , Estados Unidos , Adulto , Adulto Jovem , Estigma Social , Agressão/psicologia , Pais/psicologia , CriançaRESUMO
The LGBT People of Color Microaggressions Scale (LGBT-PCMS) is a widely used measure of intersectional microaggression experiences among sexual and gender minority people of color. Although it is widely used-and increasingly used in adolescent and young adult samples-it is unknown whether the LGBT-PCMS demonstrates similar measurement properties across subgroups of sexual and gender minority youth of color (SGMYOC). Among 4142 SGMYOC (ages 13-17) we found evidence for either partial or full scalar invariance (item loadings and intercepts were generally equal) across sexual orientation, race-ethnicity, and gender identity groups for all three subscales. Specific patterns of invariance and noninvariance across groups, as well as implications for the use of the LGBT-PCMS and its subscales among SGMYOC are discussed.
Assuntos
Agressão , Minorias Sexuais e de Gênero , Humanos , Adolescente , Minorias Sexuais e de Gênero/psicologia , Feminino , Masculino , Agressão/psicologia , Inquéritos e Questionários , PsicometriaRESUMO
Sexual and gender minority youth (SGMY) report greater alcohol use in comparison to their heterosexual counterparts. Prior research has found that elevated alcohol use among SGMY can be explained by minority stress experiences. Sexual identity outness may be another factor that drives alcohol use among SGMY, given that outness is associated with alcohol use among older sexual and gender minority samples. We examined how patterns of sexual identity outness were associated with lifetime alcohol use, past-30-day alcohol use, and past-30-day heavy episodic drinking. Data were drawn from the LGBTQ National Teen Survey (N = 8884). Participants were SGMY aged 13 to 17 (mean age = 15.59) years living in the US. Latent class analysis was used to identify sexual identity outness patterns. Multinomial regressions were used to examine the probability of class membership by alcohol use. Six outness classes were identified: out to all but teachers (n = 1033), out to siblings and peers (n = 1808), out to siblings and LGBTQ+ peers (n = 1707), out to LGBTQ+ peers (n = 1376), mostly not out (n = 1653), and very much not out (n = 1307). SGMY in classes characterized by greater outness to peers, friends, and family had greater odds of lifetime alcohol use compared with SGMY in classes characterized by lower outness. These findings suggest that SGMY with greater sexual identity outness may be a target for alcohol use prevention programming. Differences in sexual identity outness may be explained by minority stress factors.
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Revelação , Minorias Sexuais e de Gênero , Adolescente , Humanos , Identidade de Gênero , Comportamento Sexual , Consumo de Bebidas AlcoólicasRESUMO
OBJECTIVES: Using longitudinal data, this study investigated the association between parent racial colorblindness and discrimination toward children (reported by both parents and adolescents) in transracial, transnational adoptive families. METHOD: Eighty White adoptive parents with adopted Korean children (ages 5-12 years old) were surveyed in 2007 (Time 1 [T1]), and both parents and adolescents (ages 13-19 years old) were surveyed in 2014 (Time 2 [T2]). Parents completed a self-report measure of parent racial colorblindness toward their child at T1 and T2, and parents and adolescents completed a measure of discrimination experienced by adoptees at T2. RESULTS: Parent reports of racial colorblindness toward their child were not significantly different between T1 and T2. However, parent reports of discrimination increased between time points. Further, parent and adolescent reports of discrimination were not significantly different from one another. Using hierarchical regression models, racial colorblindness among parents at T1 (when children were in middle childhood) was significantly associated with parent reports of discrimination experienced by adolescent children at T2, even when controlling for T2 racial colorblindness. This association did not hold for adolescent reports of discrimination. CONCLUSION: Adoptive parents' acknowledgment of their children's race and ethnicity appears relatively stable from childhood into adolescence, and parent racial colorblindness toward their own child can affect their ability to recognize discrimination during adolescent development, a vital period when discrimination becomes more common and salient. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
RESUMO
Appropriate and effective antibiotic use is a critical component of veterinary medicine, but there are variations across species regarding dosage and administration of these drugs. Oral or rectal routes of administration are typically used in elephants, but not all medications can achieve adequate concentrations rectally. The fluoroquinolone antimicrobials are used in elephants because of their favorable antimicrobial spectrum and pharmacokinetics compared with other oral agents. They are commonly used as part of multiple antibiotic regimens for the treatment of tuberculosis (Mycobacterium tuberculosis). The objective of this study was to determine the pharmacokinetic profile of levofloxacin after oral and rectal administration in Asian elephants (Elephas maximus). Dosages of 5 mg/kg orally and 15 mg/kg rectally were evaluated in 13 Asian elephants. Blood was collected at various time points from 0 to 72 h for pharmacokinetic analysis. Pharmacokinetic parameters were determined and reached concentrations above minimum inhibitory concentrations of various bacterial organisms via both routes. A pharmacokinetic-pharmacodynamic assessment was used to estimate appropriate minimal inhibitory concentrations for bacteria that could be potentially treated with this antimicrobial. Based on these findings, levofloxacin may be a consideration for administration orally (5 mg/kg) and rectally (15 mg/kg) in Asian elephants. Antimicrobial stewardship principles, culture and susceptibility of suspected pathogens, and blood level monitoring should be used to tailor administration of levofloxacin in this species.
Assuntos
Anti-Infecciosos , Elefantes , Animais , Levofloxacino , Área Sob a Curva , AntibacterianosRESUMO
The rise of antimicrobial-resistant (AMR) bacteria is a global health emergency. One critical facet of tackling this epidemic is more rapid AMR diagnosis in serious multidrug-resistant pathogens like Pseudomonas aeruginosa. Here, we designed and then validated two multiplex quantitative real-time PCR (qPCR) assays to simultaneously detect differential expression of the resistance-nodulation-division efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM, the AmpC ß-lactamase, and the porin OprD, which are commonly associated with chromosomally encoded AMR. Next, qPCRs were tested on 15 sputa from 11 participants with P. aeruginosa respiratory infections to determine AMR profiles in vivo. We confirmed multiplex qPCR testing feasibility directly on sputa, representing a key advancement in in vivo AMR diagnosis. Notably, comparison of sputa with their derived isolates grown in Luria-Bertani broth (±2.5% NaCl) or a 5-antibiotic cocktail showed marked expression differences, illustrating the difficulty in replicating in vivo expression profiles in vitro. Cystic fibrosis sputa showed significantly reduced mexE and mexY expression compared with chronic obstructive pulmonary disease sputa, despite harboring fluoroquinolone- and aminoglycoside-resistant strains, indicating that these loci do not contribute to AMR in vivo. oprD was also significantly downregulated in cystic fibrosis sputa, even in the absence of contemporaneous carbapenem use, suggesting a common adaptive trait in chronic infections that may affect carbapenem efficacy. Sputum ampC expression was highest in participants receiving carbapenems (6.7 to 15×), some of whom were simultaneously receiving cephalosporins, the latter of which would be rendered ineffective by the upregulated ampC. Our qPCR assays provide valuable insights into the P. aeruginosa resistome, and their use on clinical specimens will permit timely treatment alterations that will improve patient outcomes and antimicrobial stewardship measures.
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Fibrose Cística , Infecções por Pseudomonas , Antibacterianos/uso terapêutico , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/uso terapêutico , Fibrose Cística/complicações , Farmacorresistência Bacteriana , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Reação em Cadeia da Polimerase em Tempo RealRESUMO
PURPOSE: Haploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS. METHODS: We report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status. RESULTS: The expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes. CONCLUSION: We refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature.
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Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Anormalidades Musculoesqueléticas , Haploinsuficiência , Humanos , Deficiência Intelectual/diagnóstico , Transtornos do Desenvolvimento da Linguagem/genética , Anormalidades Musculoesqueléticas/genética , FenótipoRESUMO
BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all cis triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.
Assuntos
Catálise , Aminação , Pirazóis , Estereoisomerismo , TriazinasRESUMO
While research that investigates the importance of school-level promotive factors (e.g., teacher support) for sexual and gender minority youth (SGMY) well-being has proliferated, less research has focused on state-level climate and policy implications for gender minority youth-specific experiences. This study investigated the impact of two youth-specific SGM state-level laws (i.e., "anti-LGBT laws" and conversion therapy bans) on social transition experiences (i.e., name/pronoun use and using desired bathroom/locker rooms) of GMY (n = 4000) aged 13-17. Through a series of multivariable regression models, it was determined that the absence of laws that restricted rights for sexual and gender minority people was associated with greater use of the correct name and correct pronouns for transgender youth. These differences were further explained by binary gender identity (transgender binary or nonbinary) status, region, and age in multivariable models. Findings highlight the importance of enacting more uniform protections for SGMY, especially to protect transgender youth that live in the southern region of the U.S.
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Minorias Sexuais e de Gênero , Pessoas Transgênero , Adolescente , Feminino , Identidade de Gênero , Humanos , Masculino , Políticas , Comportamento Sexual , BanheirosRESUMO
Prior scholarship has documented health-relevant consequences of sexual minority youth (SMY) sexual identity disclosure (i.e., "outness"), yet most of the extant work focuses on one social context at a time and/or measures outness as dichotomous: out or not out. However, SMY are out in some contexts (e.g., family, friends) and not in others, and to varying degrees (e.g., to some friends, but not to all). Using a national sample of 8884 SMY ages 13-17 (45% cisgender female, 67% White, 38% gay/lesbian and 34% bisexual, and 36% from the U.S. South), this study used latent class analysis to identify complex patterns of outness among SMY, as well differences in class membership by demographics, depression, family rejection, and bullying. The results indicated six distinct classes: out to all but teachers (n = 1033), out to siblings and peers (n = 1808), out to siblings and LGBTQ peers (n = 1707), out to LGBTQ peers (n = 1376), mostly not out (n = 1653), and very much not out (n = 1307). The findings reveal significant differences in class membership by age, sexual identity, gender identity, race and ethnicity, geography, and well-being outcomes. Moreover, these findings underscore the complex role of outness across social contexts in shaping health and well-being.
Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Adolescente , Bissexualidade , Feminino , Identidade de Gênero , Humanos , Análise de Classes Latentes , MasculinoRESUMO
Despite increasing efforts to better understand sexual and gender minority youth (SGMY), asexual youth remain understudied. This study examines differences in health, family support, and school safety among asexual youth (n = 938) from a national study of SGMY (N = 17,112) ages 13-17. Compared to non-asexual youth, asexual youth were more likely to identify as transgender and report a disability, and less likely to identify as Black or Hispanic/Latino. Transgender (versus cisgender) asexual youth fared worse on most study outcomes. Cisgender asexual (versus cisgender non-asexual) youth fared worse on all study outcomes. Transgender asexual (versus transgender non-asexual) youth reported lower sexuality-related family support. These findings underscore the role of gender identity in understanding the experiences of asexual youth.
Assuntos
Minorias Sexuais e de Gênero , Pessoas Transgênero , Adolescente , Feminino , Identidade de Gênero , Humanos , Masculino , Instituições Acadêmicas , Comportamento SexualRESUMO
During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.
Assuntos
Insuficiência Adrenal/genética , DNA Polimerase II/genética , Retardo do Crescimento Fetal/genética , Mutação/genética , Osteocondrodisplasias/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Anormalidades Urogenitais/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p57/genética , Replicação do DNA/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
Previous research on persuasion has used researcher-generated exemplars to manipulate source characteristics such as likeability, trustworthiness, expertise, or power. This approach has been fruitful, but it relies to some degree on an overlap between researcher understanding of these variables and lay understanding of these variables. Additionally, these exemplar manipulations may have unintentionally affected multiple characteristics and may be limited to certain topics or time periods. In the current work, we sought to provide persuasion researchers with a methodological tool to increase construct and potentially external validity by conducting a prototype analysis of the four traditional source characteristics: likeability, trustworthiness, expertise, and power. This bottom-up approach provided insight into the ways in which recipients perceive sources and allowed us to examine relations between the characteristics. Moving forward, a bottom-up understanding of source characteristics will allow researchers to more effectively develop manipulations that might transcend time and topic as well as isolate their effects to the intended source characteristic.
Assuntos
Comunicação Persuasiva , HumanosRESUMO
Understanding the risks of a developing unconventional hydrocarbons industry, including shale gas, to the chemical quality of surface water and groundwater involves firstly establishing baseline compositions against which any future changes can be assessed. Contaminants of geogenic origin are of particular interest and radon has been identified as one potential contaminant from shale sources. Robust measurement and monitoring of radon in water at environmental concentrations is essential for ensuring protection of water sources and maintaining public confidence. Traditional techniques for Rn-222 determination in water, such as inference by gamma spectrometry and direct alpha counting, are impractical for direct field measurement, and the relatively short half-life of Rn-222 (~ 3.82 days) means that longer analytical protocols from field to the laboratory may result in greater uncertainty for Rn-222 activity. Therefore, a rapid and low-cost method would be beneficial. We have developed and refined a laboratory procedure for Rn-222 monitoring using liquid scintillation counting (LSC). The accuracy of Rn-222 activities obtained via this procedure was evaluated by the analysis of almost 200 water samples collected from streams and boreholes as part of a detailed baseline investigation in the Vale of Pickering, Yorkshire, one potential location for future shale gas exploration. LSC was preferred for measurement of Rn-222 and had comparable accuracy to gamma spectrometry and direct alpha counting. The methodology provided a rapid, portable and low-maintenance option relative to the two established techniques and is shown to be a favourable choice for the measurement of radon in surface water and groundwater at environmental concentrations.
Assuntos
Água Doce/análise , Radônio/análise , Contagem de Cintilação/métodos , Poluentes Radioativos da Água/análise , Água Subterrânea/análise , Monitoramento de Radiação , Rios , Espectrometria gama/métodos , Reino UnidoRESUMO
The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non-Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.
Assuntos
Fibrose Cística/microbiologia , Infecções por Bactérias Gram-Negativas/transmissão , Infecções Estafilocócicas/transmissão , Staphylococcus aureus/crescimento & desenvolvimento , Achromobacter/isolamento & purificação , Adulto , Aerossóis , Burkholderia/isolamento & purificação , Contagem de Colônia Microbiana , Tosse/microbiologia , Estudos Transversais , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/crescimento & desenvolvimento , Escarro/microbiologia , Staphylococcus aureus/isolamento & purificação , Stenotrophomonas maltophilia/isolamento & purificação , Fatores de Tempo , Adulto JovemRESUMO
Current assumption for assessing carcinogenic risk of polycyclic aromatic hydrocarbons (PAHs) is that they function through a common mechanism of action; however, recent studies demonstrate that PAHs can act through unique mechanisms potentially contributing to cancer outcomes in a non-additive manner. Using a primary human 3D bronchial epithelial culture (HBEC) model, we assessed potential differences in mechanism of toxicity for two PAHs, benzo[a]pyrene (BAP) and dibenzo[def,p]chrysene (DBC), compared to a complex PAH mixture based on short-term biosignatures identified from transcriptional profiling. Differentiated bronchial epithelial cells were treated with BAP (100-500⯵g/ml), DBC (10⯵g/ml), and coal tar extract (CTE 500-1500⯵g/ml, SRM1597a) for 48â¯h and gene expression was measured by RNA sequencing or quantitative PCR. Comparison of BAP and DBC gene signatures showed that the majority of genes (~60%) were uniquely regulated by treatment, including signaling pathways for inflammation and DNA damage by DBC and processes for cell cycle, hypoxia and oxidative stress by BAP. Specifically, BAP upregulated targets of AhR, NRF2, and KLF4, while DBC downregulated these same targets, suggesting a chemical-specific pattern in transcriptional regulation involved in antioxidant response, potentially contributing to differences in PAH potency. Other processes were regulated in common by all PAH treatments, BAP, DBC and CTE, including downregulation of genes involved in cell adhesion and reduced functional measurements of barrier integrity. This work supports prior in vivo studies and demonstrates the utility of profiling short-term biosignatures in an organotypic 3D model to identify mechanisms linked to carcinogenic risk of PAHs in humans.
Assuntos
Benzopirenos/toxicidade , Brônquios/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Mucosa Respiratória/efeitos dos fármacos , Benzo(a)pireno , Brônquios/citologia , Brônquios/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Fator 4 Semelhante a Kruppel , L-Lactato Desidrogenase/metabolismo , Mucosa Respiratória/metabolismo , Análise de Sequência de RNA , Testes de Toxicidade/métodos , TranscriptomaRESUMO
BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts. METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness. RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified. CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.
Assuntos
Aerossóis , Bronquiectasia/complicações , Tosse/microbiologia , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Contagem de Colônia Microbiana , Tosse/etiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Escarro/microbiologiaRESUMO
RATIONALE: People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimize pathogen transmission between patients with CF. OBJECTIVES: To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolized during coughing. METHODS: Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Cascade Impactor was used to sample the aerosol at 2 meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed, and participants rated the mask comfort levels during the cough maneuvers. MEASUREMENTS AND MAIN RESULTS: During uncovered coughing (reference maneuver), 19 of 25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (measured as cfu/ml) and aerosol P. aeruginosa colony-forming units. There was a reduction in aerosol P. aeruginosa load during coughing with a surgical mask, coughing with an N95 mask, and cough etiquette compared with uncovered coughing (P < 0.001). A similar reduction in total colony-forming units was observed for both masks during coughing; yet, participants rated the surgical masks as more comfortable (P = 0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary coughing. Talking was a low viable aerosol-producing activity. CONCLUSIONS: Face masks reduce cough-generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.