Photoreaction products of extract from the fruiting bodies of Polyozellus multiplex.

Photochemical reactions are powerful tools for synthesizing organic molecules. The input of energy provided by light offers a means to produce strained and unique molecules that cannot be assembled using thermal protocols, allowing for the production of immense molecular complexity in a single chemical step. Furthermore, unlike thermal reactions, photochemical reactions do not require active reagents such as acids, bases, metals, or enzymes. Photochemical reactions play a central role in green chemistry. This article reports the isolation and structure determination of four new compounds (1-4) from the photoreaction products of the Polyozellus multiplex MeOH ext. The structures of the new compounds were elucidated using MS, IR, comprehensive NMR measurements and microED. The four compounds were formed by deacetylation of polyozellin, the main secondary metabolite of P. multiplex, and addition of singlet oxygen generated by sunlight. To develop drugs for treating Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the compounds (1-4) obtained by photoreaction were evaluated for BACE1 inhibitory activity. The hydrolysates (5 and 6) of polyozellin, the main secondary metabolites of P. multiplex, were also evaluated. The photoreaction products (3 and 4) and hydrolysates (5 and 6) of polyozellin showed BACE1 inhibitory activity (IC50: 2.2, 16.4, 23.3, and 5.3 µM, respectively).

The open-first strategy is acceptable for ruptured abdominal aortic aneurysm even in the endovascular era.

PURPOSE: To examine the surgical findings of ruptured abdominal aortic aneurysm (RAAA) based on the open-first strategy in the last decade, and to analyze the predictors of in-hospital mortality for RAAA in the endovascular era. METHODS: The subjects of this retrospective study were 116 patients who underwent RAAA repair, for whom sufficient data were available [25% female, median age 76 (70-85) years]. Sixteen (13.8%) patients were managed with endovascular aneurysm repair (EVAR) and 100 patients (86.2%) were managed with open surgical repair (OSR). RESULTS: Univariate analysis identified base excess (BE) (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79-0.96; p = 0.006), and preoperative cardiopulmonary arrest (CPA) [OR] 15.4; 95% [CI] 1.30-181; p = 0.030), BE (OR 0.88; 95% CI 0.79-0.96; p = 0.006), shock index (OR 2.44; 95% CI 1.01-5.94; p = 0.050), lactic acid (Lac) (OR 1.18; 95% CI 1.02-1.36; p = 0.026), and blood sugar (BS) > 215 (OR 3.46; 95% CI 1.10-10.9; p = 0.034) as positive predictors of hospital mortality. CONCLUSIONS: The findings of this study suggest that a first-line strategy of OSR for ruptured AAAs is acceptable. Poor preoperative conditions, including a high shock index, CPA, low BE, high Lac, and a BS level > 215 mg/dl, were identified as predictors of hospital mortality, rather than the procedures themselves.

Citrobacter koseri inhibits the growth of Staphylococcus epidermidis by suppressing iron utilization.

The human skin microbiome consists of many species of bacteria, including Staphylococcus aureus and S. epidermidis. Individuals with atopic dermatitis (AD) have an increased relative abundance of S. aureus, which exacerbates the inflammation of AD. Although S. epidermidis, a main component of healthy skin microbiota, inhibits the growth of S. aureus, the balance between S. epidermidis and S. aureus is disrupted in the skin of individuals with AD. In this study, we found that Citrobacter koseri isolated from patients with AD produces substances that inhibit the growth of S. epidermidis. Heat-treated culture supernatant (CS) of C. koseri inhibited the growth of S. epidermidis but not S. aureus. The genome of C. koseri has gene clusters related to siderophores and the heat-treated CS of C. koseri contained a high concentration of siderophores compared with the control medium. The inhibitory activity of C. koseri CS against the growth of S. epidermidis was decreased by the addition of iron, but not copper or zinc. Deferoxamine, an iron-chelating agent, also inhibited the growth of S. epidermidis, but not that of S. aureus. These findings suggest that C. koseri inhibits the growth of S. epidermidis by interfering with its iron utilization.

In vitro anti-severe acute respiratory syndrome coronavirus 2 effect of Ephedra przewalskii Stapf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive. AIM OF THE STUDY: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains. MATERIALS AND METHODS: VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains-BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID50) method; in turn, the half-maximal inhibitory concentration (IC50) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID50 method. RESULTS: The antiviral efficacy (i.e., IC50) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7-10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation. CONCLUSIONS: The E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19.

A 5-year survivor of endarterectomy for sclerosing undifferentiated intimal sarcoma of the pulmonary artery: Importance of clinical suspicion and careful histologic evaluation.

We present a diagnostically challenging case of intimal sarcoma of the pulmonary artery (PA) due to the histologic finding of a sclerosing appearance with no appreciable spindle/pleomorphic cell proliferation. Initial endarterectomy specimens were composed of sclerosing extracellular matrix with a few bland cells, some recanalization, and fibrin thrombi, impeding the confirmation of intimal sarcoma as these findings were also consistent with chronic thromboembolic pulmonary hypertension. However, the patient experienced recurrence 5 years later, and the second endarterectomy specimens revealed more firm and solid mass and the proliferation of atypical spindle/pleomorphic cells within a myxomatous matrix in the distal PA, leading to the definitive diagnosis of undifferentiated intimal sarcoma of the PA. The archival specimens from the endarterectomy confirmed intense MDM2 expression by immunohistochemistry, suggesting its role as a potential diagnostic marker for intimal sarcoma. This case highlights that prominent sclerosing extracellular matrix with very few atypical cells should raise the possibility of intimal sarcoma of the PA and that high index of suspicion, generous sampling, and ancillary tests are critical for accurate diagnosis. In this case, the tumor was incidentally removed by endarterectomy, resulting in 5 years of survival.

Lower-profile stent graft reduces the risk of embolism during thoracic endovascular aortic repair in shaggy aorta.

OBJECTIVES: This study aimed to reveal the association between lower-profile stent graft (LPSG) and embolism during thoracic endovascular aortic repair for non-dissecting distal arch and descending thoracic aortic aneurysm. METHODS: This study reviewed data of 35 patients who underwent thoracic endovascular aortic repair with LPSG (27 males; age: 77 ± 9.2 years) and 312 who underwent thoracic endovascular aortic repair with conventional-sized stent graft (CSSG) (247 males; age: 77 ± 7.4 years) from 2009 to 2021. RESULTS: The rate of total embolic events was significantly lower in the LPSG group (0/35 [0%]) than the CSSG group (34/312 [11.2%]) (P = 0.035). Shaggy aorta (odds ratio: 5.220; P < 0.001) were identified as positive embolic event predictors. The rate of total embolic events in 68 patients with shaggy aorta (12 in LPSG/56 in CSSG) was significantly lower in the LPSG group (0/12 [0%]) than the CSSG group (19/56 [34%]) (P = 0.015). The rate of total embolic events in 279 patients with the non-shaggy aorta (23 in LPSG/256 in CSSG) reveals no difference between the 2 groups (0 [0%]/16 [6.3%]) (P = 0.377). CONCLUSIONS: LPSG usage could reduce embolism in thoracic endovascular aortic repair, and the difference was more pronounced in patients with the shaggy aorta. LPSG might be beneficial in preventing embolism in thoracic endovascular aortic repair for patients with a shaggy aorta.

Inhibition of Aß aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239.

Alzheimer's disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-ß (Aß) peptide plays a key role in AD pathogenesis in what is known as the Aß cascade hypothesis. This hypothesis suggests the importance of suppressing Aß aggregation and Aß production. The latter process is governed by ß-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aß aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aß aggregation inhibitory activity. Eleven known compounds (1-11) were isolated from CHCl3 and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2, 6, and 10 inhibited Aß aggregation with IC50 values of 2.8, 3.9, and 8.1 µM, respectively. The protective effect on SH-SY5Y cells against Aß toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aß toxicity. BACE1 inhibitory activity was also examined, and compounds 4, 5, 7, 10, and 11 inhibited BACE1 activity with IC50 values of 14.9, 70.0, 36.5, 28.0, and 72.8 µM, respectively. These data suggest that compound 10 could be useful in AD treatment.

Enniatins from a marine-derived fungus Fusarium sp. inhibit biofilm formation by the pathogenic fungus Candida albicans.

Candidemia is a life-threatening disease common in immunocompromised patients, and is generally caused by the pathogenic fungus Candida albicans. C. albicans can change morphology from yeast to hyphae, forming biofilms on medical devices. Biofilm formation contributes to the virulence and drug tolerance of C. albicans, and thus compounds that suppress this morphological change and biofilm formation are effective for treating and preventing candidemia. Marine organisms produce biologically active and structurally diverse secondary metabolites that are promising lead compounds for treating numerous diseases. In this study, we explored marine-derived fungus metabolites that can inhibit morphological change and biofilm formation by C. albicans. Enniatin B (1), B1 (2), A1 (3), D (4), and E (5), visoltricin (6), ergosterol peroxide (7), 9,11-dehydroergosterol peroxide (8), and 3ß,5α,9α-trihydroxyergosta-7,22-dien-6-one (9) were isolated from the marine-derived fungus Fusarium sp. Compounds 1-5 and 8 exhibited inhibitory activity against hyphal formation by C. albicans, and compounds 1-3 and 8 inhibited biofilm formation by C. albicans. Furthermore, compounds 1-3 decreased cell surface hydrophobicity and expression of the hypha-specific gene HWP1 in C. albicans. Compound 1 was obtained in the highest yield. An in vivo evaluation system using silkworms pierced with polyurethane fibers (a medical device substrate) showed that compound 1 inhibited biofilm formation by C. albicans in vivo. These results indicate that enniatins could be lead compounds for therapeutic agents for biofilm infections by C. albicans.

Role of initial medical treatment and effectiveness of thoracic endovascular aortic repair for acute type A aortic dissection with thrombosed false lumen.

OBJECTIVES: The optimal treatment for acute type A aortic dissection (AAAD) with thrombosed false lumen (T-FL) of the ascending aorta remains controversial. The goal of this study was to evaluate clinical outcomes of initial medical treatment (IMT) and the effectiveness of thoracic endovascular aortic repair (TEVAR) for AAAD with T-FL. METHODS: We retrospectively analysed 60 patients with AAAD with T-FL. Emergency aortic repair was performed in 33 patients, and IMT was selected in 27 uncomplicated patients with ascending aortic diameter < 50 mm and ascending T-FL thickness ≤ 10 mm. RESULTS: Among the 27 patients who received IMT, 14 had intramural haematomas at admission; however, new ulcer-like projections appeared in 7 (50%) during hospitalization. Before discharge, 12 (44%) were given medical treatment only, and 15 (56%) required delayed aortic repair including TEVAR in 8 and open repair in 7. The median interval from onset to delayed repair was 9 days, and significantly more patients received TEVAR compared to those receiving emergency repair (53% vs 21%; P = 0.043). Between the TEVAR (n = 15) and the open repair (n = 33) groups, 1 (7%) 30-day death occurred in the TEVAR group, whereas no in-hospital deaths occurred in the open repair group. During the median follow-up time of 24.8 months, no aorta-related death was observed, and there were no statistically significant differences in the rate of freedom from aortic events (TEVAR: 92.8%/3 years vs open repair: 88.4%/3 years; P = 0.871). CONCLUSIONS: Our management, using a combination of emergency aortic repair, IMT and delayed aortic repair for AAAD with T-FL, achieved favourable clinical outcomes. Among the selected Japanese patients, IMT with repeated multidetector computed tomography could detect a new intimal tear that could be closed by TEVAR in some cases. Using EVAR for this pathology resulted in acceptable early and midterm outcomes. Further investigations are required to validate the safety and efficacy of this management procedure.

Surgical outcomes of thoracic endovascular aortic repair for retrograde Stanford type a dissection.

OBJECTIVES: The optimal indications and contraindications for thoracic endovascular aortic repair of retrograde Stanford type A acute aortic dissection (R-AAAD) are not well known. The goal of this study was to determine the outcomes of thoracic endovascular aortic repair for R-AAAD at our institution and to discuss optimal indications. METHODS: The medical records of 359 patients admitted to our institution for R-AAAD between December 2016 and December 2022 were reviewed, and 83 patients were finally diagnosed with R-AAAD. We selected thoracic endovascular aortic repair as an alternative, considering the anatomy of aortic dissection and the risk to patients undergoing open surgery. RESULTS: Nineteen patients underwent thoracic endovascular aortic repair for R-AAAD. No in-hospital deaths or neurologic complications occurred. A type Ia endoleak was detected in 1 patient. All other primary entries were successfully closed. All dissection-related complications, such as cardiac tamponade, malperfusion distal to the primary entry and abdominal aortic rupture, were resolved. One patient required open conversion for intimal injury at the proximal edge of the stent graft; all other ascending false lumens were completely thrombosed and contracted at discharge. During the follow-up period, no aortic-related deaths or aortic events proximal to the stent graft occurred. CONCLUSIONS: The indications for thoracic endovascular aortic repair were expanded to low-risk and emergency cases at our institution. The early- and midterm outcomes of thoracic endovascular aortic repair for R-AAAD were acceptable. Further long-term follow-up is required.

Multimodal single-cell analyses of peripheral blood mononuclear cells of COVID-19 patients in Japan.

SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood. Peripheral blood mononuclear cells from COVID-19 patients were collected longitudinally, and single-cell transcriptome and T cell receptor repertoire analysis was performed. Comparison of molecular features and patients' clinical information revealed that the proportions of cells present, and gene expression profiles differed significantly between mild and severe cases; although even among severe cases, substantial differences were observed among the patients. In one severely-infected elderly patient, an effective antibody response seemed to have failed, which may have caused prolonged viral clearance. Naïve T cell depletion, low T cell receptor repertoire diversity, and aberrant hyperactivation of most immune cell subsets were observed during the acute phase in this patient. Through this study, we provided a better understanding of the diversity of immune landscapes and responses. The information obtained from this study can help medical professionals develop personalized optimal clinical treatment strategies for COVID-19.

Earliest histopathological changes in COVID-19 pneumonia with comprehensive gene expression analyses: A case series study.

AIMS: In COVID-19 pneumonia, early detection and appropriate treatment are essential to prevent severe exacerbation. Therefore, it is important to understand the initiating events of COVID-19 pneumonia. However, at present, the literature about early stage disease has been very limited. Here, we investigated the earliest histopathological changes and gene expression profiles associated with COVID-19 pneumonia. METHODS AND RESULTS: We carefully examined 25 autopsied cases with different clinical courses. Dilation of capillaries and edematous thickening of the alveolar septa were found even in areas that macroscopically looked almost normal. Pneumocytes, histocytes/macrophages, and vascular endothelial cells were immunohistochemically positive for tissue factor, which is an important early responder to tissue injuries. Comprehensive gene expression analyses revealed that those lesions presented differential profiles compared to those of control lungs and were associated with a significant upregulation of the lysosomal pathway. CONCLUSIONS: Alveolar capillary dilation and edematous thickening may be the earliest histopathological change detected in COVID-19 pneumonia. Intensive investigations of such lesions may lead to an understanding of the initiating event of not only COVID-19 pneumonia but also of general diffuse alveolar damage.

Long-term outcomes of combined pulmonary endarterectomy and additional balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: The early and long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been established by several high-volume centers, but the impact of postoperative residual pulmonary hypertension affecting postoperative clinical parameters remains unclear. This study aims to investigate the institutional surgical results of PEA and to evaluate the efficacy of additional balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension. PATIENTS AND METHODS: We retrospectively reviewed 222 patients (57.7 ± 12.9 years old, 141 female) who underwent PEA for CTEPH at the National Cerebral and Cardiovascular Center between 2000 and 2020. RESULTS: The preoperative mean pulmonary artery pressure (mPAP) was 45.6 ± 9.7 mmHg and pulmonary vascular resistance (PVR) was 1062 ± 451 dyne*sec/cm-5. Postoperative mPAP (23.4 ± 11 mmHg, 204 patients, P < 0.001) and PVR (419 ± 291 dyne*sec/cm-5, 199 patients, P < 0.001) significantly improved after PEA. Since 2011, 62 patients (28%) underwent BPA after PEA for "catecholamine dependent" residual PH 1 month after PEA in 14, "scheduled" BPA with residual PH 1 year after PEA in 32, and 16 "symptomatic" patients without residual PH. Their mPAP had significantly improved by PEA (48.1 ± 7.7 to 32.0 ± 10.2 mmHg, P < 0.001), and further improved (33.8 ± 11.1 to 26.5 ± 9.1 mmHg, P < 0.001) after BPA. CONCLUSIONS: PEA provided immediate and substantial improvements in pulmonary hemodynamics and favorable long-term survival. In addition, postoperative BPA improved postoperative clinical parameters for eligible patients regardless of the presence of residual PH.

Differences of mid-term outcomes in debranching thoracic endovascular aortic repair between zone 0 and zone 1-2 landing.

OBJECTIVE: Debranching thoracic endovascular aortic repair (d-TEVAR) for zone 0 landing (Z0-TEVAR) remained challenging in aortic arch aneurysms. This study aimed to compare the mid-term outcomes between Z0-TEVAR and Z1/2-TEVAR to assess the appropriateness of Z0-TEVAR as the first-line therapy for aortic arch aneurysms in high-risk patients. METHODS: Medical records of 200 patients who underwent d-TEVAR from 2007 to 2019 were retrospectively reviewed. Of these, 40 patients who underwent Z0-TEVAR (70% males; the median age of 82 years) and 160 Z1/2-TEVAR (78% males; the median age of 77 years) were compared. In each group, 39 patients were matched using propensity scores (PS) to adjust for differences in patient backgrounds. RESULTS: Freedom from all-cause mortality (p < 0.001), aorta-related mortality (p < 0.001), and stroke (p = 0.001) were significantly lower in Z0-TEVAR than in Z1/2-TEVAR. Freedom from reintervention was similar between the two groups (p = 0.326). Type A dissection post-TEVAR was observed in 3 (7.5%) of Z0-TEVAR, but none in Z1/2-TEVAR (p = 0.006). Pneumonia was also more frequent in Z0-TEVAR (n = 8, 30%) than Z1/2-TEVAR (n = 4, 2.5%) (p < 0.001). PS matching also yielded worse outcomes (all-cause mortality, p = 0.017; aorta-related mortality, p = 0.046; and stroke, p = 0.027) in Z0-TEVAR than Z1/2-TEVAR. CONCLUSIONS: Higher mid-term mortality and stroke rates after Z0-TEVAR were confirmed by PS matching. Z0-TEVAR would be an alternative for high-risk patients with arch aneurysms requiring zone 0 landing but not a reliable method.

Clinical features and antimicrobial treatment of skin infections caused by Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus.

Skin infections caused by Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL-positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL-positive MRSA that presented over a two-year period in our clinic. Genetic analyses revealed that 90% of the PVL-positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9-fold longer than those for non-AD patients (3.7 weeks). However, all cases were improved by a long-term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL-positive MRSA.

Heart Team Intervention for Calcified Left Main Coronary Disease and Jeopardized Left Internal Mammary Artery Graft.

It is sometimes difficult to identify the culprit lesion and treatment strategy in patients with acute coronary syndrome who have complex coronary lesions and jeopardized left internal mammary artery graft. This report describes a heart team approach for a non-ST-segment elevation myocardial infarction case with complex coronary vasculature. A 73-year-old man presented to the emergency department with crescendo angina. He had a history of total aortic arch replacement with concomitant coronary artery bypass graft using left internal mammary artery. Emergent coronary angiography demonstrated severe stenosis at left main trunk bifurcation caused by calcified nodule. While the bypass graft to left anterior descending coronary artery was patent, the proximal segment of left subclavian artery was occluded. Following the prompt discussion with our heart team, we performed percutaneous coronary intervention in the first step for treating the left main stenosis using rotational atherectomy into the unprotected left circumflex artery. After clinical recovery, stress myocardial scintigraphy identified the presence of anteroseptal ischemia, which indicated coronary subclavian steal syndrome due to left subclavian artery occlusion. Contrast-enhanced CT visualized that the occlusion originated from the anastomosis, suggesting the potential procedural risk of endovascular treatment by dilatation. Our heart team discussed again and decided to undergo axillo-axillary artery bypass surgery. He was discharged 8 days after the surgery without any sequelae. This is the rare case report of non-ST-segment elevation myocardial infarction who had similar condition to coronary subclavian steal syndrome after total aortic arch replacement. This case highlights the importance of a collaborative approach of the heart team to identify the best therapeutic strategy in a patient with complex coronary vasculature.

Prevalence, characteristics, and psychological outcomes of workplace cyberbullying during the COVID-19 pandemic in Japan: a cross-sectional online survey.

BACKGROUND: The rapid introduction of teleworking due to the coronavirus disease 2019 pandemic has led to concerns about increases in cyberbullying (CB) worldwide. However, little is known about workplace CB in non-Western countries. The first objective was to clarify the prevalence and characteristics regarding workplace CB victimization in Japan. The second objective was to demonstrate the psychological outcomes of CB victimization in combination with traditional bullying (TB). METHODS: We conducted an anonymous, cross-sectional, Internet-based survey targeting regular employees in Japan (N = 1200) in January 2021. We investigated CB victimization using the Inventory of Cyberbullying Acts at Work and TB victimization by using the Short Negative Act Questionnaire. Possible explanatory factors for TB/CB victimization were sociodemographic variables, personality trait, chronic occupational stress, organizational climate, and gratitude at work. We also measured psychological distress, insomnia, and loneliness to assess adverse effects of workplace bullying. Two-step cluster analysis was used in determining the patterns combined with TB and CB victimization. Hierarchical binomial logistic regression analysis was used. RESULTS: In total, 8.0% of employees reported experiencing CB on a weekly basis. CB victimization was associated with younger age, managerial position, higher qualitative workload, and active information dissemination via the Internet, and frequency of teleworking. Three clusters based on TB and CB victimization patterns were identified: those who belong to the first cluster suffered neither from TB and CB (81.0%), the second cluster suffered only from TB (14.3%), and the third cluster suffered from both TB and CB (4.8%). The third cluster exhibited higher odds ratios (ORs) and 95% confidence intervals (CIs) for psychological distress (OR = 12.63, 95% CI = 4.20-38.03), insomnia (OR = 6.26, 95% CI = 2.80-14.01), and loneliness (OR = 3.24, 95% CI = 1.74-6.04) compared to the first cluster. CONCLUSIONS: These findings firstly clarify the prevalence and correlated factors of CB victimization among employees in Japan. Further, we showed that psychological wellbeing can be impaired by the coexistence of TB and CB. Our research could be the first step to develop the effective countermeasures against workplace CB.

Comparison of the levels of neopterin, CRP, and IL-6 in patients infected with and without SARS-CoV-2.

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers especially in relatively early phase of patients to reveal the significance of NP measurements in pathological states. Methods: Plasma NP, biopterin, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 23 patients with non-COVID-19 disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently. Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while biopterin, CRP and IL-6 were not changed significantly. The NP levels were found to show a weak negative correlation against the days after onset in the COVID-19 patients (rs = -0.348, p = 0.0192), suggesting that the elevation of NP would be an early event of viral infection. Correlations between NP and CRP, or between NP and IL-6 in COVID-19 patients were weaker than that between CRP and IL-6. Conclusions: The elevation of NP levels was supposed to be distinct from those of CRP and IL-6 in relatively early and mild COVID-19 patients. Our data suggest that NP is produced at the early phase of infection by different signaling pathways and/or cells from those of CRP and IL-6. Further study on the signaling pathway to induce NP is expected.