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1.
PNAS Nexus ; 1(5): pgac145, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36712351

RESUMO

Nontuberculous mycobacteria (NTM) are frequently present in municipal drinking water and building plumbing, and some are believed to cause respiratory tract infections through inhalation of NTM-containing aerosols generated during showering. However, the present understanding of NTM transfer from water to air is insufficient to develop NTM risk mitigation strategies. This study aimed to characterize the contribution of shower water to the abundance of viable NTM in indoor air. Shower water and indoor air samples were collected, and 16S rRNA and rpoB genes were sequenced. The sequencing results showed that running the shower impacted the bacterial community structure and NTM species composition in indoor air by transferring certain bacteria from water to air. A mass balance model combined with NTM quantification results revealed that on average 1/132 and 1/254 of NTM cells in water were transferred to air during 1 hour of showering using a rain and massage showerhead, respectively. A large fraction of the bacteria transferred from water to air were membrane-damaged, i.e. they had compromised membranes based on analysis by live/dead staining and flow cytometry. However, the damaged NTM in air were recoverable as shown by growth in a culture medium mimicking the respiratory secretions of people with cystic fibrosis, implying a potential infection risk by NTM introduced to indoor air during shower running. Among the recovered NTM, Mycobacterium mucogenicum was the dominant species as determined by rpoB gene sequencing. Overall, this study lays the groundwork for future pathogen risk management and public health protection in the built environment.

2.
Otolaryngol Head Neck Surg ; 164(6): 1186-1192, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33079009

RESUMO

OBJECTIVE: To analyze patients' return to normal activity, pain scores, narcotic use, and adverse events after undergoing tonsillectomy or adenotonsillectomy with monopolar electrocautery or radiofrequency ablation. STUDY DESIGN: Randomized double-blinded clinical trial based on prospective parallel design. SETTING: Academic medical center and tertiary children's hospital between March 2018 and July 2019. METHODS: Inclusion criteria included patients aged ≥3 years with surgical indication of recurrent tonsillitis or airway obstruction/sleep-disordered breathing. Patients were randomly assigned to monopolar electrocautery or radiofrequency ablation. Patients were blinded to treatment assignment. Survey questions answered via text or email were collected daily until postoperative day 15. The primary outcome was the patient's return to normal activity. Secondary outcomes included daily pain score, total amount of postoperative narcotic use, and adverse events. RESULTS: Of the 236 patients who met inclusion criteria and were randomly assigned to radiofrequency ablation or monopolar electrocautery, 230 completed the study (radiofrequency ablation, n = 112; monopolar electrocautery, n = 118). There was no statistically significant difference between the groups in the number of days for return to normal activity (P = .89), daily pain scores over 15 postoperative days (P = .46), postoperative narcotic use (P = .61), or return to hospital for any reason (P = .60), including bleeding as an adverse event (P = .13). CONCLUSIONS: As one of the largest randomized controlled trials examining instrumentation in tonsillectomy, our data do not show a difference between monopolar electrocautery and radiofrequency ablation with regard to return to normal activity, daily pain scores, total postoperative narcotic use, or adverse events.


Assuntos
Adenoidectomia/métodos , Eletrocoagulação , Ablação por Radiofrequência , Tonsilectomia/métodos , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
3.
J Infect Dis ; 218(5): 739-747, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29878137

RESUMO

Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was observed in both fine aerosols and stationary droplets. Our data suggest, for the first time, that influenza viruses remain highly stable and infectious in aerosols across a wide range of relative humidities. These results have significant implications for understanding the mechanisms of transmission of influenza and its seasonality.


Assuntos
Aerossóis , Umidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Viabilidade Microbiana , Células Cultivadas , Exposição Ambiental , Células Epiteliais/virologia , Humanos , Fatores de Tempo
4.
PLoS One ; 11(3): e0151004, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26942410

RESUMO

Children's daycare centers appear to be hubs of respiratory infectious disease transmission, yet there is only limited information about the airborne microbial communities that are present in daycare centers. We have investigated the microbial community of the air in a daycare center, including seasonal dynamics in the bacterial community and the presence of specific viral pathogens. We collected filters from the heating, ventilation, and air conditioning (HVAC) system of a daycare center every two weeks over the course of a year. Amplifying and sequencing the 16S rRNA gene revealed that the air was dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes that are commonly associated with the human skin flora. Clear seasonal differences in the microbial community were not evident; however, the community structure differed when the daycare center was closed and unoccupied for a 13-day period. These results suggest that human occupancy, rather than the environment, is the major driver in shaping the microbial community structure in the air of the daycare center. Using PCR for targeted viruses, we detected a seasonal pattern in the presence of respiratory syncytial virus that included the period of typical occurrence of the disease related to the virus; however, we did not detect the presence of adenovirus or rotavirus at any time.


Assuntos
Microbiologia do Ar , Bactérias/metabolismo , Creches , Estações do Ano , Vírus/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Reação em Cadeia da Polimerase , Análise de Componente Principal
5.
Nucleic Acids Res ; 41(2): 754-63, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23180800

RESUMO

The DNA-binding specificity and affinity of the dimeric human transcription factor (TF) STAT1, were assessed by total internal reflectance fluorescence protein-binding microarrays (TIRF-PBM) to evaluate the effects of protein phosphorylation, higher-order polymerization and small-molecule inhibition. Active, phosphorylated STAT1 showed binding preferences consistent with prior characterization, whereas unphosphorylated STAT1 showed a weak-binding preference for one-half of the GAS consensus site, consistent with recent models of STAT1 structure and function in response to phosphorylation. This altered-binding preference was further tested by use of the inhibitor LLL3, which we show to disrupt STAT1 binding in a sequence-dependent fashion. To determine if this sequence-dependence is specific to STAT1 and not a general feature of human TF biology, the TF Myc/Max was analysed and tested with the inhibitor Mycro3. Myc/Max inhibition by Mycro3 is sequence independent, suggesting that the sequence-dependent inhibition of STAT1 may be specific to this system and a useful target for future inhibitor design.


Assuntos
DNA/metabolismo , Fator de Transcrição STAT1/metabolismo , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , DNA/química , Fosforilação , Multimerização Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/antagonistas & inibidores , Fator de Transcrição STAT1/química
6.
J Inorg Biochem ; 103(3): 427-31, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19187968

RESUMO

Reported herein are studies of the concentration and temperature dependent interactions with DNA of the stereochemically defined mixed-metal supramolecular complexes, [(tpy)Ru(tppz)PtCl](PF(6))(3) and [ClPt(tppz)Ru(tppz)PtCl](PF(6))(4) (tpy=2,2':6',2''-terpyridine and tppz=2,3,5,6-tetrakis(2-pyridyl)pyrazine). These metal complexes couple a ruthenium based light absorber (LA) to the bioactive platinum sites (BAS) using a tridentate bridging ligand (BL). The complexes exhibit intense Ru-->tppz(pi*) metal to ligand charge transfer (MLCT) transitions in the visible region and adopt a square planar geometry around the Pt(II) center. The effect of incubating these metal complexes with DNA on the subsequent migration of DNA through an agarose gel was found to be more dramatic than that observed for the well known anticancer drug, cis-[Pt(NH(3))(2)Cl(2)] (cisplatin). This effect was enhanced with increased incubation temperature. Unwinding of supercoiled plasmid DNA was found to be more pronounced for the trimetallic complex, [ClPt(tppz)Ru(tppz)PtCl](PF(6))(4), than for the bimetallic complex, [(tpy)Ru(tppz)PtCl](PF(6))(3).


Assuntos
Antineoplásicos/química , DNA/química , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Antineoplásicos/metabolismo , DNA/metabolismo
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