Cerebrospinal fluid proteomics reveals the innate immunity and blood-brain barrier dysregulation in a patient with multidrug-resistant ventriculitis treated with intrathecal and intravenous polymyxin B.

is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed to investigate host-pathogen-polymyxin interactions in a 69-year-old patient with multidrug-resistant ventriculitis treated with a combination of intrathecal (ITH; 50,000 IU q24h/q48h), intraventricular (IVT; 50,000 IU q48h), and intravenous (500,000 IU, q12h) polymyxin B.

Combined strategy of upfront CTCA and optimal treatment for stable chest pain: rationale and design of the CLEAR-CAD trial.

Background: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events.

Exploring Structure-Activity Relationships and Modes of Action of Laterocidine.

A significant increase in life-threatening infections caused by Gram-negative "superbugs" is a serious threat to global health. With a dearth of new antibiotics in the developmental pipeline, antibiotics with novel mechanisms of action are urgently required to prevent a return to the preantibiotic era. A key strategy to develop novel anti-infective treatments is to discover new natural scaffolds with distinct mechanisms of action.

PhageGE: an interactive web platform for exploratory analysis and visualization of bacteriophage genomes.

Background: Antimicrobial resistance is a serious threat to global health. Due to the stagnant antibiotic discovery pipeline, bacteriophages (phages) have been proposed as an alternative therapy for the treatment of infections caused by multidrug-resistant pathogens. Genomic features play an important role in phage pharmacology.

Which LGBTQ+ Inclusive School Strategies Support LGBTQ+ Student, Staff and Parent Perceptions of School Climate? A Latent Class Analysis.

Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) students, LGBTQ+ staff and LGBTQ+ parents report schools can be unsafe and unwelcoming environments. Yet few studies have explored LGBTQ+ student, LGBTQ+ staff and LGBTQ+ parent perceptions of the school climate simultaneously or adopted person-centered perspectives. The present study sought to identify LGBTQ+ related strategies adopted by schools, and whether these were differentially related to perceptions of school safety and community.

Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistant .

Carbapenem-resistant (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B, and colistin/sulbactam combination therapy.

Arginine catabolism is essential to polymyxin dependence in Acinetobacter baumannii.

Polymyxins are often the only effective antibiotics against the "Critical" pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures.

Discovery of Antimicrobial Lysins from the "Dark Matter" of Uncharacterized Phages Using Artificial Intelligence.

The rapid rise of antibiotic resistance and slow discovery of new antibiotics have threatened global health. While novel phage lysins have emerged as potential antibacterial agents, experimental screening methods for novel lysins pose significant challenges due to the enormous workload. Here, the first unified software package, namely DeepLysin, is developed to employ artificial intelligence for mining the vast genome reservoirs ("dark matter") for novel antibacterial phage lysins.

Phage resistance in Klebsiella pneumoniae and bidirectional effects impacting antibiotic susceptibility.

Objectives: Bacteriophage (phage) therapy is a promising anti-infective option to combat antimicrobial resistance. However, the clinical utilization of phage therapy has been severely compromised by the potential emergence of phage resistance. Although certain phage resistance mechanisms can restore bacterial susceptibility to certain antibiotics, a lack of knowledge of phage resistance mechanisms hinders optimal use of phages and their combination with antibiotics.

The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

Background: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS).

Methods: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients.

Distinguishing Inducible and Non-Inducible Resistance to Colistin in Pseudomonas aeruginosa by Quantitative and Systems Pharmacology Modeling at Low and Standard Inocula.

Colistin is a polymyxin and peptide antibiotic that can yield rapid bacterial killing, but also leads to resistance emergence. We aimed to develop a novel experimental and Quantitative and Systems Pharmacology approach to distinguish between inducible and non-inducible resistance. Viable count profiles for the total and less susceptible populations of Pseudomonas aeruginosa ATCC 27853 from static and dynamic in vitro infection models were simultaneously modeled.

Polysaccharide-Targeting Lipid Nanoparticles to Kill Gram-Negative Bacteria.

The rapid increase and spread of Gram-negative bacteria resistant to many or all existing treatments threaten a return to the preantibiotic era. The presence of bacterial polysaccharides that impede the penetration of many antimicrobials and protect them from the innate immune system contributes to resistance and pathogenicity. No currently approved antibiotics target the polysaccharide regions of microbes.

Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

Objective: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry.

Methods: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician.

Climate mitigation potentials of teleworking are sensitive to changes in lifestyle and workplace rather than ICT usage.

The growth in remote and hybrid work catalyzed by the COVID-19 pandemic could have significant environmental implications. We assess the greenhouse gas emissions of this transition, considering factors including information and communication technology, commuting, noncommute travel, and office and residential energy use. We find that, in the United States, switching from working onsite to working from home can reduce up to 58% of work's carbon footprint, and the impacts of IT usage are negligible, while office energy use and noncommute travel impacts are important.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort.

Quality of reporting of prospective in vivo and ex vivo studies published in the Journal of Veterinary Emergency and Critical Care over a 10-year period (2009-2019).

Objective: To evaluate the reporting of key items associated with risk of bias and weak study design over a 10-year period.

Design: Literature survey.

Setting: Not applicable.

Lipid A Modification and Metabolic Adaptation in Polymyxin-Resistant, New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae.

Polymyxins are last-line antibiotics employed against multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance is rapidly on the rise globally. Polymyxins initially target lipid A of lipopolysaccharides (LPSs) in the cell outer membrane (OM), causing disorganization and cell lysis.

Online support seeking, co-rumination, and mental health in adolescent girls.

Introduction: Adolescents frequently use informal support seeking to cope with stress and worries. Past research in face-to-face contexts has shown that the relationship between informal support seeking and mental health is influenced by the specific strategy used and the mode through which support is sought. To date, little research has considered the relationship between support seeking online and adolescent mental health.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B.

Synergistic Effects of Capric Acid and Colistin against Colistin-Susceptible and Colistin-Resistant .

Colistin is a last-line antibiotic against Gram-negative pathogens. However, the emergence of colistin resistance has substantially reduced the clinical effectiveness of colistin. In this study, synergy between colistin and capric acid was examined against twenty-one Gram-negative bacterial isolates (four colistin-susceptible and seventeen colistin-resistant).

Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae.

Carbapenemase-resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time-kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h.

Mnemicity: A Cognitive Gadget?

Episodic representations can be entertained either as "remembered" or "imagined"-as outcomes of experience or as simulations of such experience. Here, we argue that this feature is the product of a dedicated cognitive function: the metacognitive capacity to determine the of mental event simulations. We argue that mnemicity attribution should be distinguished from other metacognitive operations (such as reality monitoring) and propose that this attribution is a "cognitive gadget"-a distinctively human ability made possible by cultural learning.

Pharmacokinetics/pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant .

Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting. A prospective, multi-center clinical trial was undertaken with polymyxin B [2.

Transcriptomic Mapping of Neurotoxicity Pathways in the Rat Brain in Response to Intraventricular Polymyxin B.

Intraventricular or intrathecal administration of polymyxins are increasingly used to treat multidrug-resistant (MDR) Gram-negative bacteria caused infections in the central nervous system (CNS). However, our limited knowledge of the mechanisms underpinning polymyxin-induced neurotoxicity significantly hinders the development of safe and efficacious polymyxin dosing regimens. To this end, we conducted transcriptomic analyses of the rat brain and spinal cord 1 h following intracerebroventricular administration of polymyxin B into rat lateral ventricle at a clinically relevant dose (0.