Prediction of imipenem-resistant microorganisms among the nosocomial critically ill patients with Gram-negative bacilli septicemia: a simple risk score.

OBJECTIVES: The increasing number of reports on infections due to carbapenem-resistant Gram-negative bacilli (GNB) has raised concerns, because they have complicated empiric or guided antibiotic therapy for critically ill patients. We aimed to develop a scoring system to predict nosocomial imipenem-resistant GNB (IR-GNB) septicemia among the critically ill patients. MATERIALS AND METHODS: The study included critically ill adult patients with nosocomial GNB septicemia at Kaohsiung Chang Gung Memorial Hospital (CGMH) in 2013-2015, and the scoring system for predicting IR-GNB septicemia was developed, followed by prospective validation conducted among patients at Linkou CGMH and Kaohsiung CGMH between January and June, 2016. RESULTS: In the development of the scoring system, 748 patients were included. The independent factors associated with IR-GNB septicemia were prior exposure (days) to carbapenems (adjusted odds ratio [aOR] per 1-day increase, 1.1; 1-3 days: 2 points, 4-6 days: 5 points, 7-9 days: 8 points, and ≥10 days: 13 points), use of mechanical ventilation (aOR 3.7; 5 points), prior colonization with IR-GNB strains (aOR 3.5; 5 points) within 30 days before the onset of GNB septicemia, and comorbid condition with chronic kidney disease (aOR 2.1; 3 points). The internal validation showed an area under the receiver operating characteristic curve (ROC) of 0.75; and an external validation among 314 patients showed similarly good performance (ROC 0.77). Youden's index indicated the score of ≥6 as the best cutoff value with sensitivity of 75% and specificity of 79%. CONCLUSION: This scoring system might help clinicians stratify the risk for developing IR-GNB septicemia among critically ill patients and combined antibiotics may be used until antimicrobial de-escalation/adjustment is clearly indicated by the subsequently identified GNB and its susceptibility profile.

Infrared Video Pupillography Coupled with Smart Phone LED for Measurement of Pupillary Light Reflex.

Clinical assessment of pupil appearance and pupillary light reflex (PLR) may inform us the integrity of the autonomic nervous system (ANS). Current clinical pupil assessment is limited to qualitative examination, and relies on clinical judgment. Infrared (IR) video pupillography combined with image processing software offer the possibility of recording quantitative parameters. In this study we describe an IR video pupillography set-up intended for human and animal testing. As part of the validation, resting pupil diameter was measured in human subjects using the NeurOptics™ (Irvine, CA, USA) pupillometer, to compare against that measured by our IR video pupillography set-up, and PLR was assessed in guinea pigs. The set-up consisted of a smart phone with a light emitting diode (LED) strobe light (0.2 s light ON, 5 s light OFF cycles) as the stimulus and an IR camera to record pupil kinetics. The consensual response was recorded, and the video recording was processed using a custom MATLAB program. The parameters assessed were resting pupil diameter (D1), constriction velocity (CV), percentage constriction ratio, re-dilation velocity (DV) and percentage re-dilation ratio. We report that the IR video pupillography set-up provided comparable results as the NeurOptics™ pupillometer in human subjects, and was able to detect larger resting pupil size in juvenile male guinea pigs compared to juvenile female guinea pigs. At juvenile age, male guinea pigs also had stronger pupil kinetics for both pupil constriction and dilation. Furthermore, our IR video pupillography set-up was able to detect an age-specific increase in pupil diameter (female guinea pigs only) and reduction in CV (male and female guinea pigs) as animals developed from juvenile (3 months) to adult age (7 months). This technique demonstrated accurate and quantitative assessment of pupil parameters, and may provide the foundation for further development of an integrated system useful for clinical applications.

ADP-ribosylhydrolases: from DNA damage repair to COVID-19 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).