Alcoholism is a serious problem that is difficult to treat. This study investigated the effects of group counseling utilizing narrative therapy on self-esteem, stress response, and insight for ...alcoholism. We utilized a nonequivalent control group, non-synchronized design. Collected data were analyzed using descriptive statistics, Fisher's exact test, Chi-squared test, independent and paired t-tests, and repeated measures ANOVA. The experimental group showed significant improvements in self-esteem (F = 14.03, p < .001), stress response (F = 4.31, p <.05), and insight (F = 21.27, p < .001) after the intervention compared with the control group. Additionally, there were significant improvements in self-esteem (t = −6.32, p < .05), stress response (t = 4.93, p < .05), and insight (t = −5.02, p <. 05) within the experimental group after the intervention. Thus, narrative therapy is recommended as an autonomous regulation approach for developing strengths necessary to refrain from alcoholism.
To evaluate the association between anesthetic management before and after graft reperfusion and early graft regeneration in living donor liver transplantation (LDLT).
Sufficient graft regeneration ...is essential for the success of LDLT. Diverse signals start to trigger liver regeneration immediately after graft reperfusion.
Graft volume at 14 ± 2 days after LDLT was measured in 379 consecutive recipients using computed tomography images with 3-dimensional reconstruction. The association between anesthetic variables and the degree of graft regeneration for 2 weeks was analyzed using simple and multiple linear regressions. The anesthetic variables included hemodynamics, laboratory measurements, vasoactive drugs, and blood products transfusion.
The degree of graft regeneration for 2 weeks was 52% in median and ranged from 5% to 123%. Platelet transfusion was identified as the sole independent anesthetic factor contributing to graft regeneration. Platelet concentrate transfusion of 1 to 6 units vs none was correlated with a 6.5% increase in graft regeneration (P = 0.012). Platelet concentrate transfusion of more than 6 units vs none was further correlated with an 18.4% increase in regeneration (P < 0.001). In the subgroup of recipients without intraoperative platelet transfusion, mean platelet count measured during the intraoperative reperfusion phase was positively associated with graft regeneration (P = 0.033).
Graft regeneration after LDLT increased in relation to a graded increase in the amount of transfused platelets and higher postreperfusion platelet counts during surgery. These results offer additional evidence regarding the important role of platelets in initiating liver regeneration and, furthermore, the indications for and the benefits vs risks of platelet transfusion during LDLT.
Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of ...RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.
Because stress-induced cardiomyopathy (SIC) is increasingly being observed during routine daily practice, we sought to explore the clinical features and factors that determine the outcome of SIC in a ...tertiary referral hospital.
Patients with typical left ventricular (LV) takotsubo (apical ballooning) or inverted takotsubo on 2-dimensional echocardiography were prospectively enrolled, and their clinical data were analyzed.
Over a 63-month period, 56 consecutive patients (median age and interquartile range=64 years 52-74 years) were identified. Women comprised 79% (44/56) of all patients. The triggering events were acute medical illness, including sepsis and hypoxemia in 29 patients (52%, group A), in-hospital surgery/procedure in 17 patients (30%, group B), and emotional stress in 10 patients (18%, group C). Chest pain was more frequently observed in group C (50%) than in groups A (14%) and B (6%) (P=.021), whereas dyspnea was the presenting symptom in groups A and B. Typical takotsubo and inverted takotsubo were observed in 48 and 8 patients, with a median ejection fraction of 33%. Other abnormalities included dynamic LV outflow tract obstruction (n=2), LV thrombus (n=2), and right ventricular dysfunction (n=12). Nine deaths (16%) occurred during hospitalization. The groups did not differ in mortality. The Acute Physiology and Chronic Health Evaluation II score (odds ratio 1.405; 95% confidence interval, 1.091-1.810; P=.009) and absence of LV function recovery within 1 week (ejection fraction<50%) (odds ratio 14.080; 95% confidence interval, 1.184-167.475; P=.036) were independent factors associated with mortality. During clinical follow-up up to 6 months, 3 more patients died, 2 of whom had recurrences of SIC.
SIC in a tertiary referral hospital was mainly associated with physical stressors and characterized by diverse clinical presentations, high mortality, and occasional fatal recurrences.
Wild aquatic birds, a natural reservoir of avian influenza viruses (AIVs), transmit AIVs to poultry farms, causing huge economic losses. Therefore, the prevalence and genetic characteristics of AIVs ...isolated from wild birds in South Korea from October 2019 to March 2020 were investigated and analyzed. Fresh avian fecal samples (3256) were collected by active monitoring of 11 wild bird habitats. Twenty-eight AIVs were isolated. Seven HA and eight NA subtypes were identified. All AIV hosts were
species. The HA cleavage site of 20 representative AIVs was encoded by non-multi-basic amino acid sequences. Phylogenetic analysis of the eight segment genes of the AIVs showed that most genes clustered within the Eurasian lineage. However, the HA gene of H10 viruses and NS gene of four viruses clustered within the American lineage, indicating intercontinental reassortment of AIVs. Representative viruses likely to infect mammals were selected and evaluated for pathogenicity in mice. JB21-58 (H5N3), JB42-93 (H9N2), and JB32-81 (H11N2) were isolated from the lungs, but JB31-69 (H11N9) was not isolated from the lungs until the end of the experiment at 14 dpi. None of infected mice showed clinical sign and histopathological change in the lung. In addition, viral antigens were not detected in lungs of all mice at 14 dpi. These data suggest that LPAIVs derived from wild birds are unlikely to be transmitted to mammals. However, because LPAIVs can reportedly infect mammals, including humans, continuous surveillance and monitoring of AIVs are necessary, despite their low pathogenicity.
Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof‐of‐principle evidence is presented that a cell‐penetrable peptide (ACP52C) dissociates ...transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene‐addicted cancer cells through transcription activity‐independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2‐p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome‐wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C‐resistant cancers. This study enhances the understanding of ACP52C‐induced cancer‐specific apoptosis induction and supports the use of ACP52C in anticancer drug development.
Cancer‐specific synthetic lethality is demonstrated by targeting transcription factor CP2c with ACP52C, a cell‐penetrant peptide. ACP52C induces apoptosis, genomic instability, and G2/M arrest in most cancers, regardless of their driver mutations. Resistance in MDM2 p60‐expressing cells is overcome with CASP2 inhibition. Improved derivatives of ACP52C reduce cancer burden, supporting pan‐anticancer drug development.
Abstract
Background
Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent ...plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap.
Methods
We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge.
Results
Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss.
Conclusions
High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.
The detection of over 200 volatile organic compounds in exhaled breath has highlighted their potential in diagnosing diseases and monitoring health. Particularly, acetone has emerged as a key ...biomarker for monitoring ketosis in both healthy individuals and those diagnosed with diabetes. Although equipment-based gas sensor systems such as high-performance liquid chromatography are commonly used for acetone gas detection, they are expensive and require preprocessing. To address these challenges, we developed a cost-effective colorimetric sensor that uses silica-based hollow nanoparticles (SHNPs) and offers enhanced selectivity. We fabricated spherical and uniformly sized SHNPs and infused them with methyl red and brilliant green (M–B ion-pairing dye) to develop colorimetric sensors for acetone gas detection. The optimal color change response occurred at a particle size of 52 ( ± 3.4) nm and shell thickness of 7 ( ± 1.1) nm within the SHNPs, indicative of a significant increase in surface area. Furthermore, the use of hollow silica with a water barrier effect protected the dye, enabling acetone gas detection even in environments with 80% relative humidity. Notably, a substantial color change (Δ130) was noticeable in only 1 min. This robust sensor enables sensitive and rapid naked-eye detection of low concentrations of acetone gas (1 ppm). Consequently, the proposed methodology holds promise for real-time visualization of acetone gas and can be easily integrated into other colorimetric gas sensor systems to enhance both sensitivity and simplicity.
•Acetone is a biomarker for ketosis in healthy people and diabetic people.•Cost-effective colorimetric sensor based on silica hollow nanoparticles developed.•Methyl red–Brilliant green ion pair used as the colorimetric sensor for acetone.•The developed sensor allows rapid and sensitive acetone detection at trace level.
The purpose of this study was to describe and compare the duration of
bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent ...SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for
SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB;
= 995) than in patients with methicillin-susceptible SAB (MSSAB;
= 922) (median duration, 1 day interquartile range, 1 to 3 days for MSSAB and 1 day interquartile range, 0 to 5 days for MRSAB;
0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53;
0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.
Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced ...unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC.
We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan).
A total of 363 patients n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy) were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy.
No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.
This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).
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