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1.
Sci Rep ; 11(1): 22725, 2021 11 22.
Article in English | MEDLINE | ID: mdl-34811449

ABSTRACT

We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.


Subject(s)
Flagellin/metabolism , Lung/metabolism , Mucin-1/metabolism , Pneumonia, Bacterial/metabolism , Pneumonia, Ventilator-Associated/metabolism , Pseudomonas Infections/metabolism , Pseudomonas aeruginosa/metabolism , A549 Cells , Aged , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/microbiology , Female , Flagellin/genetics , Host-Pathogen Interactions , Humans , Lung/microbiology , Male , Middle Aged , Mutation , Neuraminidase/metabolism , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/microbiology , Pneumonia, Ventilator-Associated/diagnosis , Pneumonia, Ventilator-Associated/microbiology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/pathogenicity
2.
Curr Psychiatry Rep ; 22(2): 7, 2020 01 18.
Article in English | MEDLINE | ID: mdl-31955278

ABSTRACT

PURPOSE OF REVIEW: Approximately 25% of employed individuals engage in shift work, which can substantially alter opportunities for restorative sleep. Being tired on the job can lead to safety risks in professions such as healthcare, first responders, manufacturing, and numerous others. In addition to the physical stress and health consequences of shift work, recent evidence links shift work to poor mental health outcomes. The current review examines the literature from 2016 onward, emphasizing the impact of shift work on mental health. RECENT FINDINGS: Shift work is associated with considerable impacts on sleep, depressed mood and anxiety, substance use, impairments in cognition, lower quality of life, and even suicidal ideation. Pronounced sleep disturbances frequently underlie the mental health consequences of shift work. Shift work can have physical, mental health, and safety consequences. Future research should aim to better understand the interplay of shift work, sleep, and mental health and seek to mitigate the adverse consequences of shift work.


Subject(s)
Mental Health/statistics & numerical data , Shift Work Schedule/psychology , Shift Work Schedule/statistics & numerical data , Fatigue/epidemiology , Fatigue/etiology , Humans , Quality of Life , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/psychology
3.
Patient Prefer Adherence ; 7: 741-9, 2013.
Article in English | MEDLINE | ID: mdl-23966772

ABSTRACT

INTRODUCTION: We aimed to inform the design of behavioral interventions by identifying patients' and their family members' perceived facilitators and barriers to hypertension self-management. MATERIALS AND METHODS: We conducted focus groups of African American patients with hypertension and their family members to elicit their views about factors influencing patients' hypertension self-management. We recruited African American patients with hypertension (n = 18) and their family members (n = 12) from an urban, community-based clinical practice in Baltimore, Maryland. We conducted four separate 90-minute focus groups among patients with controlled (one group) and uncontrolled (one group) hypertension, as well as their family members (two groups). Trained moderators used open-ended questions to assess participants' perceptions regarding patient, family, clinic, and community-level factors influencing patients' effective hypertension self-management. RESULTS: Patient participants identified several facilitators (including family members' support and positive relationships with doctors) and barriers (including competing health priorities, lack of knowledge about hypertension, and poor access to community resources) that influence their hypertension self-management. Family members also identified several facilitators (including their participation in patients' doctor's visits and discussions with patients' doctors outside of visits) and barriers (including their own limited health knowledge and patients' lack of motivation to sustain hypertension self-management behaviors) that affect their efforts to support patients' hypertension self-management. CONCLUSION: African American patients with hypertension and their family members reported numerous patient, family, clinic, and community-level facilitators and barriers to patients' hypertension self-management. Patients' and their family members' views may help guide efforts to tailor behavioral interventions designed to improve hypertension self-management behaviors and hypertension control in minority populations.

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