To evaluate the current status of emotional exhaustion and peritraumatic distress of healthcare workers (HCWs) in the COVID-19 pandemic, and identify factors associated with their mental health ...status.
An online survey involving 1068 of consented HCWs that included nurses, physicians, and public health officers was conducted in May 2020. Descriptive statistics and multivariate regression analyses were performed on the collected data.
Although no significant difference in peritraumatic distress was observed among the surveyed HCWs, the workers' experience of emotional exhaustion varied according to work characteristics. Respondents who were female, older, living with a spouse, and/or full-time workers reported higher levels of emotional exhaustion. Public health officers and other medical personnel who did not have direct contact with confirmed patients and full-time workers had a higher level of peritraumatic distress. Forced involvement in work related to COVID-19, worry about stigma, worry about becoming infected, and perceived sufficiency of organizational support negatively predict emotional exhaustion and peritraumatic distress.
Job-related and emotional stress of HCWs should not be neglected. Evidence-based interventions and supports are required to protect HCWs from mental illness and to promote mental health of those involved in the response to the COVID-19 pandemic.
•IRB/AML fixed-dose regimens show superior antihypertensive efficacy over IRB monotherapy.•A potential benefit of IRB/AML regimens was noted in the elderly and T2DM patients.•IRB/AML combinations are ...well-tolerated and have comparable safety to IRB monotherapy.
This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy.
Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP MSSBP ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography.
In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were −14.78 (12.35) mmHg, −21.47 (12.78) mmHg, and −8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were −13.30 (12.47) mmHg and −7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study.
The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability.
ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).
Social distancing policies work in different ways and at different levels. In addition, various forms of monitoring systems have been implemented in different countries. However, there is an almost ...complete lack of specific monitoring system in Republic of Korea to effectively monitor social distancing measures compliance and outcome. This study aims to develop a monitoring system for social distancing measures compliance and outcome in Korea to evaluate and improve the implemented policy.
A draft monitoring system was developed after reviewing Korea's social distancing measures (central and local government briefings) and checking available data about social distancing behavior. The modified Delphi process was used to evaluate the draft of the social distancing monitoring system. In total, 27 experts participated in the evaluation. The round 1 evaluation includes (1) commenting on the composition of the monitoring fields (open response), (2) monitoring indicators for each monitoring field (10-point Likert scale), and (3) commenting on the source of data used to develop the monitoring system (open response). In the round 2 evaluation, 55 indicators, excepting open responses, were re-evaluated.
The response rate for the Delphi survey was 100% in both the first and second rounds. Of the 55 indicators, 1 indicator, which did not satisfy the quantitative criteria, was excluded. According to the experts' open response comments, 15 indicators were excluded, as these indicators overlapped with other indicators or had little relevance to social distancing. Instead, 23 new indicators were added. Finally, 62 indicators were included with 12 available data sources. The monitoring system domain was divided into 'social distancing measures state, social distancing measures compliance, social distancing outcome'.
This study is significant in that it is the first in Korea to develop a comprehensive monitoring system for checking if social distancing measures are being followed well, and is applicable to estimates utilizing data that are immediately available for each indicator. Furthermore, the developed monitoring system could be a reference for other countries that require the development of such systems to monitor social distancing.
Bone marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability.
The aim of the study was to ...investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy.
We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner. Flow cytometry analyses of these cultured cells at passage 4 showed expression of typical MSC markers such as CD44 and CD29, but not hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, we injected MSCs into the peri-infarct area after ligation of the left anterior descending coronary arteries of mice and, as separate experiments, injected the same batch of MSCs into hindlimb muscles of mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing tumors were observed in 30% of hearts in the MI model, and in 46% of hindlimbs in the diabetic neuropathy model. Histological examination of the tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and positive staining for α-smooth muscle actin, indicative of malignant sarcoma with myogenic differentiation. Chromosomal analysis of these MSCs showed multiple chromosomal aberrations including fusion, fragmentation, and ring formation.
Genetically unmodified MSCs can undergo chromosomal abnormalities even at early passages and form malignant tumors when transplanted in vivo. These results suggest that careful monitoring of chromosomal status is warranted when in vitro expanded MSCs are used for cell therapy such as for MI.
Dental caries is a biofilm-dependent oral disease and Streptococcus mutans is the known primary etiologic agent of dental caries that initiates biofilm formation on tooth surfaces. Although some ...Lactobacillus strains inhibit biofilm formation of oral pathogenic bacteria, the molecular mechanisms by which lactobacilli inhibit bacterial biofilm formation are not clearly understood. In this study, we demonstrated that Lactobacillus plantarum lipoteichoic acid (Lp.LTA) inhibited the biofilm formation of S. mutans on polystyrene plates, hydroxyapatite discs, and dentin slices without affecting the bacterial growth. Lp.LTA interferes with sucrose decomposition of S. mutans required for the production of exopolysaccharide, which is a main component of biofilm. Lp.LTA also attenuated the biding of fluorescein isothiocyanate-conjugated dextran to S. mutans, which is known to have a high affinity to exopolysaccharide on S. mutans. Dealanylated Lp.LTA did not inhibit biofilm formation of S. mutans implying that D-alanine moieties in the Lp.LTA structure were crucial for inhibition. Collectively, these results suggest that Lp.LTA attenuates S. mutans biofilm formation and could be used to develop effective anticaries agents.
Abstract
Bone resorption can be caused by excessive differentiation and/or activation of bone‐resorbing osteoclasts. While microbe‐associated molecular patterns can influence the differentiation and ...activation of bone cells, little is known about the role of lipoteichoic acid (LTA), a major cell wall component of Gram‐positive bacteria, in the regulation of bone metabolism. In this study, we investigated the effect of LTA on bone metabolism using wild‐type
Staphylococcus aureus
and the LTA‐deficient mutant strain. LTA‐deficient
S. aureus
induced higher bone loss and osteoclast differentiation than wild‐type
S. aureus
. LTA isolated from
S. aureus
(SaLTA) inhibited osteoclast differentiation from committed osteoclast precursors in the presence of various osteoclastogenic factors by downregulating the expression of NFATc1. Remarkably, SaLTA attenuated the osteoclast differentiation from committed osteoclast precursors of TLR2
−/−
or MyD88
−/−
mice and from the committed osteoclast precursors transfected with paired immunoglobulin‐like receptor B‐targeting siRNA. SaLTA directly interacted with gelsolin, interrupting the gelsolin‐actin dissociation which is a critical process for osteoclastogenesis. Moreover, SaLTA suppressed the mRNA expression of dendritic cell‐specific transmembrane protein, ATPase H
+
transporting V0 subunit D2, and
Integrin
, which encode proteins involved in cell‐cell fusion of osteoclasts. Notably, LTAs purified from probiotics, including
Bacillus subtilis
,
Enterococcus faecalis
, and
Lactobacillus
species, also suppressed Pam2CSK4‐ or RANKL‐induced osteoclast differentiation. Taken together, these results suggest that LTAs have anti‐resorptive activity through the inhibition of osteoclastogenesis by interfering with the gelsolin‐actin dissociation and may be used as effective therapeutic agents for the prevention or treatment of inflammatory bone diseases.
Bone‐resorbing osteoclasts are differentiated from macrophages (MΦ) by M‐CSF and RANKL. MΦ can be mainly classified into M1 and M2 MΦ, which are proinflammatory and anti‐inflammatory, respectively, ...but little is known about their osteoclastogenic potential. Here, we investigated the osteoclastogenic potential of MΦ subtypes. When the two MΦ subtypes were differentiated into osteoclasts using M‐CSF and RANKL, M2 MΦ more potently differentiated into osteoclasts than M1 MΦ. M2 MΦ generated with IL‐4 or IL‐10 also showed enhanced osteoclast differentiation compared with M1 MΦ induced by IFN‐γ and lipopolysaccharide. In addition, robust bone‐resorptive capacity and giant actin rings, which are features of mature osteoclasts, were observed in M2, but not M1 MΦ, under the osteoclast differentiation condition. Osteoclast differentiation was significantly increased in CD206+ M2 MΦ but not in CD86+ M1 MΦ. Compared with M1 MΦ, c‐Fms and RANK were highly expressed in M2 MΦ. Enhanced osteoclastogenesis of M2 MΦ was mediated through sustained ERK activation, followed by efficient c‐Fos and NFATc1 induction. Notably, the osteoclastogenic potential of M1 MΦ converted into M2 MΦ by exposure to M‐CSF was higher than that of M2 MΦ converted into M1 MΦ by exposure to GM‐CSF. Silencing IRF5, which is responsible for M1 MΦ polarization, increased osteoclast differentiation by enhancing c‐Fms expression and activation of ERK, c‐Fos, CREB, and NFATc1, which was inhibited by overexpression of IRF5. Collectively, M2 MΦ are suggested to be more efficient osteoclast precursors than M1 MΦ because of the attenuated expression of IRF5.
M2 MΦ were more potent osteoclast precursors than M1 MΦ. Unlike M1 MΦ, M2 MΦ exhibited a high level of c‐Fms and prolonged ERK activation upon stimulation with M‐CSF. Furthermore, M2 MΦ‐derived osteoclasts showed high bone‐resorptive capacity and giant actin ring formation. Interestingly, decreased IRF5 expression in M2 MΦ contributed to enhanced osteoclastogenic potential through induction of c‐Fms, c‐Fos, NFATc1, and CREB.
Objectives This study sought to investigate the predictors and outcomes of side branch (SB) occlusion after main vessel (MV) stenting in coronary bifurcation lesions. Background SB occlusion is a ...serious complication that occurs during percutaneous coronary intervention (PCI) for bifurcation lesions. Methods Consecutive patients undergoing PCI using drug-eluting stents for bifurcation lesions with SB ≥2.3 mm were enrolled. We selected patients treated with the 1-stent technique or MV stenting first strategy. SB occlusion after MV stenting was defined as Thrombolysis in Myocardial Infarction flow grade <3. Results SB occlusion occurred in 187 (8.4%) of 2,227 bifurcation lesions. In multivariate analysis, independent predictors of SB occlusion were pre-procedural percent diameter stenosis of the SB ≥50% (odds ratio OR: 2.34; 95% confidence interval CI: 1.59 to 3.43; p < 0.001) and the proximal MV ≥50% (OR: 2.34; 95% CI: 1.57 to 3.50; p < 0.001), SB lesion length (OR: 1.03; 95% CI: 1.003 to 1.06; p = 0.03), and acute coronary syndrome (OR: 1.53; 95% CI: 1.06 to 2.19; p = 0.02). Of 187 occluded SBs, flow was restored spontaneously in 26 (13.9%) and by SB intervention in 103 (55.1%) but not in 58 (31.0%). Jailed wire in the SB was associated with flow recovery (74.8% vs. 57.8%, p = 0.02). Cardiac death or myocardial infarction occurred more frequently in patients with SB occlusion than in those without SB occlusion (adjusted hazard ratio: 2.34; 95% CI: 1.15 to 4.77; p = 0.02). Conclusions Angiographic findings of SB, proximal MV stenosis, and clinical presentation are predictive of SB occlusion after MV stenting. Occlusion of sizable SB is associated with adverse clinical outcomes. (Korean Coronary Bifurcation Stenting Registry II COBIS; NCT01642992 )
Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing ...gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.
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