Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxic Acute Lung Injury.

Unlabelled: While delivery of supplemental oxygen is a life-saving therapy, exposure to high levels of oxygen, called hyperoxia, is associated with increased mortality in the intensive care unit (ICU). Hyperoxia leads to oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic acute lung injury (HALI). Elucidation of molecular mechanisms in HALI could identify therapeutic targets in ALI.

Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis.

Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent Pseudomonas aeruginosa pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22-46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant Pseudomonas that was refractory to prior courses of standard antibiotics.

A Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Infections.

(PsA) is an opportunistic bacterial pathogen that causes life-threatening infections in individuals with compromised immune systems and exacerbates health concerns for those with cystic fibrosis (CF). PsA rapidly develops antibiotic resistance; thus, novel therapeutics are urgently needed to effectively combat this pathogen. Previously, we have shown that a novel cationic Zinc (II) porphyrin (ZnPor) has potent bactericidal activity against planktonic and biofilm-associated PsA cells, and disassembles the biofilm matrix via interactions with eDNA In the present study, we report that ZnPor caused a significant decrease in PsA populations in mouse lungs within an in vivo model of PsA pulmonary infection.

Transitions of Care in Cystic Fibrosis.

The development of formal transition models emerged to reduce variability in care, including cystic fibrosis (CF) responsibility, independence, self-care, and education (RISE), which provides a standardized transition program, including knowledge assessments, self-management checklists, and milestones for people with CF. Despite these interventions, the current landscape of health care transition (HCT) remains suboptimal, and additional focused attention on HCT is necessary. Standardization of assessment tools to gauge the efficacy of transfer from pediatric to adult care is a high priority.

IFN- Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury.

The mechanisms by which excessive systemic activation of adaptive T lymphocytes, as in cytokine release syndrome (CRS), leads to innate immune cell-mediated acute lung injury (ALI) or acute respiratory distress syndrome, often in the absence of any infection, remains unknown. Here, we investigated the roles of IFN-γ and IL-17A, key T-cell cytokines significantly elevated in patients with CRS, in the immunopathogenesis of CRS-induced extrapulmonary ALI. CRS was induced in wild-type (WT), IL-17A- and IFN-γ knockout (KO) human leukocyte antigen-DR3 transgenic mice with 10 μg of the superantigen, staphylococcal enterotoxin B, given intraperitoneally.

An 84-Year-Old Physician With Progressive Dyspnea and Bilateral Upper Lobe Opacities.

An 84-year-old physician was seen in the pulmonary clinic with 10 days of progressive exertional dyspnea, night sweats, and dry cough. For the past 5 months, he had been taking ibuprofen for lumbar radiculopathy from spinal stenosis. Ten days earlier, ibuprofen was switched to naproxen 250 mg twice daily because of its longer half-life.

Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review.

Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures.

Cyclooxygenase-2 and the inflammogenesis of breast cancer.

Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2 (COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following: (1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis; (2) essential features of mammary carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin E2 (PGE-2) biosynthesis; (3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis; (4) extrahepatic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and (5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic.

Analyzing and predicting the thermodynamic effects of the metabolite trehalose on nucleic acids.

There is a lot of interest in exactly how nucleic acid duplexes are affected by the addition of certain stabilizing and destabilizing metabolites. Unfortunately, the differences in reaction conditions between published reports often precludes a comparison of the results, effectively preventing a cohesive strategy for predicting additive effects on nucleic acid stability. This information is critically important for obtaining a fundamental understanding of how additives, including metabolites, alter DNA and RNA stability and structure.