Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils.

Neutrophil extracellular trap (NET) formation is a unique self-defense mechanism of neutrophils; however, it is also involved in many diseases, including atherosclerosis. Resveratrol and catechin are antioxidants with anti-atherosclerotic properties. Here, we examined the effects of resveratrol, catechin, and other related compounds on NET formation. HL-60-derived neutrophils were pretreated with resveratrol and other compounds before stimulation with phorbol-myristate acetate (PMA). DNA and myeloperoxidase released from neutrophils were determined. Resveratrol suppressed the DNA release from neutrophils in a dose-dependent manner. NET formation was enhanced by 1-palmitoyl-2-oxovaleroyl phosphatidylcholine (POVPC), a truncated form of oxidized phospholipid, and resveratrol suppressed NET formation induced by POVPC and PMA. Furthermore, we designed several analogs of resveratrol or catechin whose conformation was restricted by the inhibition of the free rotation of aromatic rings. The conformationally constrained analogs were more effective at inhibiting NET formation; however, their inhibitory function decreased when compound was a large, hydrophobic analog. The most potent compounds, planar catechin and resveratrol, suppressed myeloperoxidase release from activated neutrophils. In addition, these compounds suppressed DNA release from neutrophils stimulated with calcium ionophore. These results suggest that resveratrol, catechin and their analogs exert anti-NET effects, and that constraining the geometry of these compounds enhanced their inhibitory effects.

Surgical productivity recovery after the COVID-19 pandemic in Japan.

Introduction: Previous studies demonstrated that the surgical productivity regressed in 2020. This study therefore explored whether the COVID-19 pandemic had any significant lasting effect of reducing the surgical productivity in Japan. This is a retrospective observational study which is an extension of the previous ones. Methods: The authors analyzed 18,805 surgical procedures performed during the study period from April 1 through September 30 in 2016-22. A non-radial and non-oriented Malmquist model under the variable returns-to-scale assumptions was employed. The decision-making unit (DMU) was defined as a surgical specialty department. Inputs were defined as (1) the number of assistants, and (2) the surgical duration. The output was defined as the surgical fee. The study period was divided into 42 one-month periods. The authors added all the inputs and outputs for each DMU during these study periods, and computed its Malmquist index, efficiency change and technical change. The outcome measures were its annual productivity, efficiency, and technical changes between the same months in each year. Results: There was no statistically significant difference in annual productivity, efficiency, and technical changes between pre-pandemic and post-pandemic periods. Discussion: No evidence was found to suggest that the COVID-19 pandemic has any significant lasting effect of reducing the surgical productivity.

Behavior of intracellular lipid droplets during cell division in HuH7 hepatoma cells.

Intracellular lipid droplets (LDs) are ubiquitous organelles found in many cell types. During mitosis, membranous organelles, including mitochondria, are divided into small pieces and transferred to daughter cells; however, the process of LD transfer to daughter cells is not fully elucidated. Herein, we investigated the behavior of LDs during mitosis in HuH7 human hepatoma cells. While fragments of the Golgi apparatus were scattered in the cytosol during mitosis, intracellular LDs retained their size and spherical morphology as they translocated to the two daughter cells. LDs were initially distributed throughout the cell during prophase but positioned outside the spindle in metaphase, aligning at the far sides of the centrioles. A similar distribution of LDs during mitosis was observed in another hepatocarcinoma HepG2 cells. When the spindle was disrupted by nocodazole treatment or never in mitosis gene A-related kinase 2A knockdown, LDs were localized in the area outside the chromosomes, suggesting that spindle formation is not necessary for LD localization at metaphase. The amount of major LD protein perilipin 2 reduced while LDs were enriched in perilipin 3 during mitosis, indicating the potential alteration of LD protein composition. Conclusively, the behavior of LDs during mitosis is distinct from that of other organelles in hepatocytes.

Fact-finding survey on the competencies and literacy of radiological technologists regarding radiation disasters.

BACKGROUND: Radiological technologists serve as risk communicators who aim to lessen patients' anxiety about radiation exposure, in addition to performing radiological examinations. OBJECTIVE: We conducted a fact-finding survey on knowledge and awareness of radiation disasters among the radiological technologists to reveal their literacy and competencies regarding radiation disasters. METHODS: A paper questionnaire was distributed to 1,835 radiological technologists at 166 National Hospital Organization facilities in Japan. The 28-item questionnaire covered knowledge and awareness of radiation protection and radiation disasters. Radiological technologists were divided into 2 groups by regionality: areas where a nuclear power station was present/nearby (NPS areas) and non-NPS areas. RESULTS: Completed questionnaires were returned from 148 facilities with a facility response rate of 89.2% and from 1,391 radiological technologists with a response rate of 75.8%. There were 1,290 valid responses with a valid response rate of 70.3%. The correct answer rate for knowledge of radiation protection and radiation disasters was high in the 24 NPS areas. There were no differences in awareness of radiation disasters between NPS and non-NPS areas. CONCLUSIONS: Establishing a nationwide, region-independent training system can be expected to improve literacy regarding radiation disasters among radiological technologists. Willingness to assist during disasters was high among radiological technologists irrespective of area, indicating that the competencies of radiological technologists represent a competency model for radiation disaster assistance.

Effect of surgeon experience on technical efficiency.

Surgeon experience certainly improves their technical efficiency although it also causes physiological changes with aging. The authors hypothesized that surgeons' technical efficiency improves with increasing experience up to a point where it then decreases, which is a concave relationship. The authors collected data from all the surgical procedures performed at University Hospital from April through September in 2013-19. The dependent variable was defined as surgeons' technical efficiency scores that were calculated using output-oriented Charnes-Cooper-Rhodes model of data envelopment analysis. Inputs were defined as (1) the number of assistants and (2) the duration of surgical operation. The output was defined as the surgical fee for each surgery. Surgeon experience was defined as the number of years since medical school graduation. Five control variables were selected: surgical volume, gender, academic rank, surgical specialty, and the year of surgery. Multiple regression analysis using pooled and random-effects Tobit models was performed for our panel data. Totally 20,375 surgical procedures performed by 264 surgeons in 42 months were analyzed. The coefficients of experience and the square of experience were not significantly different from zero. The other coefficients were also insignificant. Surgeons' technical efficiency does not have a concave relationship with experience.

Patients' acceptance of placebo antibiotics in Japan: a prescription for antimicrobial resistance.

BACKGROUND: The generalized use of antibiotics has led to the emergence of bacteria which are resistant to antimicrobial agents. This stems in part from the patient's tendencies to seek antibiotics for diseases when not necessary. Hence, this article investigated patient acceptance of prescribing placebos as a substitute for unnecessary antibiotics in Japan, where physicians are under severe time constraints and are unable to offer explanations and persuade patients who demand unnecessary antibiotics prescription. METHODS: A web-based questionnaire was administered to assess patients' acceptance of the placebo treatment under informed consent. One thousand participants representing all genders and age-class were randomly selected from the online panel of a web-survey company. RESULTS: The results showed that 67.9% of the participants were "satisfied" to receive such treatments, whereas 20.6% indicated acceptance of the prescription but without satisfaction. In total, 88.5% of the participants accepted the prescription of placebo, a result consistent with that of a preceding study on placebo treatments conducted in the United States. In the survey, tone of persuasion did not affect the patients' attitudes; however, patients who were loyal to their physicians exhibited lower refusal rates. CONCLUSION: The survey results showed that the prescription of "ethical placebos" could be an acceptable option for the patients in Japan. For ethical concerns, an additional literature survey was conducted and the result suggested that such a radical treatment option could be justified, provided that the prescription benefits patients and informed consent is properly obtained. Albeit it is impractical to use, because of ethical and operational concerns, it would be worth further investigation to ensure diversity in the countermeasures for antimicrobial resistance, a major public health threat nowadays.

High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids.

Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(-), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response.

Surgical productivity did not suffer despite the states of emergency against the COVID-19 pandemic in Japan: a retrospective observational study.

BACKGROUND: The purpose of this study is to compute surgical total factor productivity with Malmquist index, and to evaluate the effects of states of emergency against the novel coronavirus disease 2019 (COVID-19) pandemic on its productivity change. We hypothesized that the states of emergency significantly reduced surgical total factor productivity in Japan. METHODS: The authors collected data from all the surgical procedures performed in Teikyo University Hospital from April 1 through September 30 in 2019-21. Non-radial and non-oriented Malmquist model under the variable returns-to-scale assumptions was employed. The decision making unit (DMU) was defined as a surgical specialty department. Inputs were defined as (1) the number of medical doctors who assisted surgery, and (2) the duration of surgical operation from skin incision to closure. The output was defined as the surgical fee for each surgery. The study period was divided into fifty-one ten- (or eleven-) day periods. We added all the inputs and outputs of the surgical procedures for each DMU during these study periods, and computed its Malmquist index, efficiency change and technical change. RESULTS: Seven thousand nine hundred and thirty-one surgical procedures were analyzed. The overall productivity and efficiency progressed significantly both during states of emergency and during no states of emergency. Our subgroup analysis demonstrated that there were no surgical specialties that had significantly different productivity, efficiency or technical changes between states of emergency and no states of emergency. CONCLUSIONS: We demonstrated that the surgical productivity did not suffer despite the states of emergency against the COVID-19 pandemic in Japan.

Productivity Change of Surgeons During the Coronavirus Disease 2019 Pandemic in Japan.

The purpose of this study is to compute surgical total factor productivity before and during the pandemic with Malmquist index, and to evaluate the effect of coronavirus disease 2019 (COVID-19) on its productivity change. The COVID-19 pandemic has significantly shifted healthcare resources allocation; more healthcare resources have focused on measures against the COVID-19 pandemic. The authors collected data from all the surgical procedures performed in Teikyo University Hospital from April 1 through September 30 in 2019 and in 2020. Non-radial and non-oriented Malmquist model under the constant return-to-scale assumptions was employed. The decision-making unit was defined as a surgeon with the highest academic rank in surgery. Inputs were defined as (1) the number of medical doctors who assisted surgery and (2) the duration of surgical operation from skin incision to closure. The output was defined as the surgical fee for each surgery. The study period was divided into four 3-month periods. We added all the inputs and outputs of the surgical procedures for each decision-making unit during these study periods, and computed his/her Malmquist index, efficiency change, and technical change. Four thousand six hundred and two surgical procedures performed by 75 surgeons were analyzed. The productivity progressed significantly during 2019 (P = .008) while the productivity changes in 2020 were not significantly different from 0. On year-on-year comparisons, the productivity change was not significantly different from 0. The COVID-19 pandemic had a negative impact on the productivity progress of surgery that was unrelated to its countermeasures.

Sar1 Affects the Localization of Perilipin 2 to Lipid Droplets.

Lipid droplets (LDs) are intracellular organelles that are ubiquitous in many types of cells. The LD core consists of triacylglycerols (TGs) surrounded by a phospholipid monolayer and surface proteins such as perilipin 2 (PLIN2). Although TGs accumulate in the phospholipid bilayer of the endoplasmic reticulum (ER) and subsequently nascent LDs buds from ER, the mechanism by which LD proteins are transported to LD particles is not fully understood. Sar1 is a GTPase known as a regulator of coat protein complex Ⅱ (COPⅡ) vesicle budding, and its role in LD formation was investigated in this study. HuH7 human hepatoma cells were infected with adenoviral particles containing genes coding GFP fused with wild-type Sar1 (Sar1 WT) or a GTPase mutant form (Sar1 H79G). When HuH7 cells were treated with oleic acid, Sar1 WT formed a ring-like structure around the LDs. The transient expression of Sar1 did not significantly alter the levels of TG and PLIN2 in the cells. However, the localization of PLIN2 to the LDs decreased in the cells expressing Sar1 H79G. Furthermore, the effects of Sar1 on PLIN2 localization to the LDs were verified by the suppression of endogenous Sar1 using the short hairpin RNA technique. In conclusion, it was found that Sar1 has some roles in the intracellular distribution of PLIN2 to LDs in liver cells.