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Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation. [ABSTRACT FROM AUTHOR]

Gram-positive bacteria are frequently resistant to empirical beta‐lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130–14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366–11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059–0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218–0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer. [ABSTRACT FROM AUTHOR]

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5–30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS +, and bauA – isolates showed higher virulence than non-ST191, bfmS –, and bauA + isolates, respectively. Conclusions ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management. [ABSTRACT FROM AUTHOR]

Background: The clinical outcomes and immunological features of coronavirus disease 2019 (COVID-19) patients receiving B-cell depletion therapy (BCDT), especially in Omicron variant era, have not been fully elucidated. We aimed to investigate the outcomes and immune responses of COVID-19 patients receiving BCDT during the Omicron period. Methods: We retrospectively compared clinical outcomes between COVID-19 patients treated with BCDT (the BCDT group) and those with the same underlying diseases not treated with BCDT (the non-BCDT group). For immunological analyses, we prospectively enrolled COVID-19 patients receiving BCDT and immunocompetent COVID-19 patients as controls. We measured humoral and cellular immune responses using the enzyme-linked immunosorbent assay and flow cytometry. Results: Severe to critical COVID-19 was more frequent in the BCDT group than in the non-BCDT group (41.9% vs. 28.3%, p =.030). BCDT was an independent risk factor for severe to critical COVID-19 (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21–4.04, p =.010) as well as for COVID-19-related mortality (aOR 4.03, 95% CI 1.17–13.86, p =.027). Immunological analyses revealed that patients receiving BCDT had lower anti-S1 IgG titres and a tendency to higher proportions of activated CD4+ T-cells than the controls. Conclusions: BCDT was associated with worse COVID-19 outcomes in the Omicron period. Humoral immune response impairment and T-cell hyperactivation were the main immunological features of COVID-19 patients treated with BCDT, which may have contributed to the worse outcomes of COVID-19 in this population. [ABSTRACT FROM AUTHOR]

Otitis media is a common disease but can cause severe inner ear inflammation and hearing loss if it persists for more than two weeks. This study elucidates the inflammation-inhibiting efficacy of conditioned medium (CM) and extracellular vesicles (EVs) derived from human trophoblast (TB) cells in lipopolysaccharide (LPS)-induced human middle ear epithelial cells (HMEECs). TB-conditioned medium (TB-CM) reduced the inflammatory response and regulated mucin and epithelial sodium channel genes in LPS-induced HMEECs. The underlying mechanism of cell migration during inflammatory healing in LPS-induced HMEECs treated with TB-CM was determined by RNA-sequencing analysis. Specifically, the NF-κB pathway related to the copper metabolism MURR1 domain protein was studied and verified through siRNA. This elucidation of the anti-inflammatory effect of TB-CM and TB-derived EVs demonstrates their clinical potential to treat chronic inflammation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of non-coding RNAs that act as regulators of disease. An evolutionary approach to the disease could reveal factors such as diagnosis, treatment, and prognosis prediction. The expression patterns of transposable element (TEs)-derived miRNAs could help elucidate diseases, and their evolutionary patterns are also valuable. The 34 miRNAs were compared in terms of stage survival and tumor status in 33 carcinomas from TCGA. Expression levels were compared using a t -test and presented as differentially expressed miRNAs (DEMs). For DEMs showing statistically specific expression patterns for 3 conditions (normal and cancer, early and advanced stage, and survival), interactions with related genes in 10 species, including humans, were compared. The enrichment term was discovered for the gene-miRNA interactions. In 18 out of the 33 carcinomas, at least one miRNA was retrieved with P <.05 and |fold change| >.05. A total of 128 DEMs for the 9 miRNAs were identified. Based on the TargetScan database, interactions between miRNAs and genes in 10 species, including humans, were confirmed. The evolutionarily conserved miR-130a was observed in all 10 species, whereas miR-151a was only observed in humans. GO terms of related genes were selected for the miRNAs commonly found in each species. Evolutionary analysis of TE-derived disease-associated miRNAs was performed, and the evolutionarily conserved miR-130a-related carcinomas included renal and thyroid cancers. Human and rhesus monkey-specific miR-625 is associated with various carcinomas. [ABSTRACT FROM AUTHOR]

Trophoblasts play an important role in the regulation of the development and function of the placenta. Our recent study demonstrated the skin regeneration capacity of trophoblast-derived extracellular vesicles (EV). Here, we aimed to determine the potential of trophoblast-derived conditioned medium (TB-CM) in enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). We found that TB-CM promoted the osteogenic differentiation of MSCs in a dose-dependent manner. Furthermore, it inhibited adipogenesis of MSCs. We also found that the primary trophoblast-derived conditioned medium (PTB-CM) significantly enhanced the proliferation and osteogenic differentiation of human MSCs. Our study demonstrated the regulatory mechanisms underlying the TB-CM-induced osteogenesis in MSCs. An upregulation of genes associated with cytokines/chemokines was observed. The treatment of MSCs with TB-CM stimulated osteogenesis by activating several biological processes, such as mitogen-activated protein kinase (MAPK) and bone morphogenetic protein 2 (BMP2) signaling. This study demonstrated the proliferative and osteogenic efficacies of the trophoblast-derived secretomes, suggesting their potential for use in clinical interventions for bone regeneration and treatment. [ABSTRACT FROM AUTHOR]

• The positivity rates of culture in tuberculous spondylitis were 69.0-85.3%. • The culture positivity rates were different according to biopsy methods and sites. • Targeting paraspinal tissues during needle biopsy might be the best method. We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13–11.99, P = 0.030). We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0–85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed. [ABSTRACT FROM AUTHOR]

Chemotherapy promotes phosphatidylserine (PS) externalization in tumors undergoing apoptosis, forms an immunosuppressive tumor microenvironment (TME), and inhibits dendritic cell (DC) maturation and antigen presentation by binding PS receptors expressed in DCs, thereby limiting naive T cell education and activation. In this study, we demonstrate a selective nanocarrier system composed of annexin A5-labeled poly (lactide- co -glycolide) nanoparticles (PLGA_NPs) encapsulating tumor specific antigen or neoantigen, to target apoptotic tumor cells expressing PS as an innate immune checkpoint inhibitor (ICI) that induces active cancer immunotherapy. Moreover, PLGA_NPs enhanced tumor-specific antigen-based cytotoxic T cell immunity via the original function of DCs by converting the tumor antigen-rich environment. Therefore, chemotherapy combined with an immunomodulatory nanocarrier system demonstrated an enhanced anticancer immune response by increasing survival rates, immune-activating cells, and pro-inflammatory cytokines in the spleen and TME. In contrast, the tumor mass, immune-suppressive cells, and anti-inflammatory cytokines were decreased. Furthermore, the combination of a nanocarrier system with other ICIs against large tumors showed therapeutic efficacy by immunosuppression in the TME and further amplified the anticancer immunity of interferon gamma+ (IFN-γ) CD8+ (cluster of differentiation 8) T cells. Taken together, our Annexin A5-labeled PLGA-NPs can be applied in various combination therapeutic techniques for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To report our institution’s experience with patients who underwent subtotal petrosectomy (STP) for refractory ear disease who are candidates for cochlear implant (CI) and to highlight simultaneous STP with CI its advantages, surgical outcomes, post-operative complications management, and considerations for staging a procedure.A retrospective study was performed in a single tertiary referral university hospital. The medical records of seventy patients (70 ears) who underwent STP for refractory ear disease who were candidates for CI were retrospectively evaluated.Seventy adults (age range 30–85) underwent STP with a median follow-up of 4.8 years (range 1.5–18.2). Twenty-seven (38.5%) had previous mastoid surgeries before STP. Most patients underwent simultaneous STP and CI (n = 36, 51.5%), followed by STP only (n = 28, 40%), with a smaller group having staged CI after STP (n = 6, 8.5%).Patients who underwent simultaneous STP and CI showed significant improvements in several measures, with mean pre-operative pure tone audiometry (PTA) of 98.7 dB HL (range 85–118; SD: ± 9.2) improving to 39.3 dB HL post-operatively (range 25–50; SD: ± 9.3, p < 0.001), mean pre-operative categories of auditory performance (CAP) score of 1.6 (range 0–4; SD: ± 1.3), increasing to 5.6 post-operatively (range 4–7; SD: ± 1.3, p < 0.001), and mean pre-operative open-set adult sentence score of 6.8% (range 0–40%), improving to 78.4% post-operatively (range 40–100%, p < 0.001). Three of the 36 patients (8.3%) who had simultaneous STP and CI developed post-operative complications (median follow-up: 4.2 years). No disease recurrence was reported.STP is an effective intervention for refractory middle ear and mastoid diseases. It allows for a thorough disease removal and prepares the ear for subsequent implantation procedures. Simultaneous STP and CI provide the advantage of hearing rehabilitation, disease control, and a comparable complication rate to that of conventional CI procedures.Methods: To report our institution’s experience with patients who underwent subtotal petrosectomy (STP) for refractory ear disease who are candidates for cochlear implant (CI) and to highlight simultaneous STP with CI its advantages, surgical outcomes, post-operative complications management, and considerations for staging a procedure.A retrospective study was performed in a single tertiary referral university hospital. The medical records of seventy patients (70 ears) who underwent STP for refractory ear disease who were candidates for CI were retrospectively evaluated.Seventy adults (age range 30–85) underwent STP with a median follow-up of 4.8 years (range 1.5–18.2). Twenty-seven (38.5%) had previous mastoid surgeries before STP. Most patients underwent simultaneous STP and CI (n = 36, 51.5%), followed by STP only (n = 28, 40%), with a smaller group having staged CI after STP (n = 6, 8.5%).Patients who underwent simultaneous STP and CI showed significant improvements in several measures, with mean pre-operative pure tone audiometry (PTA) of 98.7 dB HL (range 85–118; SD: ± 9.2) improving to 39.3 dB HL post-operatively (range 25–50; SD: ± 9.3, p < 0.001), mean pre-operative categories of auditory performance (CAP) score of 1.6 (range 0–4; SD: ± 1.3), increasing to 5.6 post-operatively (range 4–7; SD: ± 1.3, p < 0.001), and mean pre-operative open-set adult sentence score of 6.8% (range 0–40%), improving to 78.4% post-operatively (range 40–100%, p < 0.001). Three of the 36 patients (8.3%) who had simultaneous STP and CI developed post-operative complications (median follow-up: 4.2 years). No disease recurrence was reported.STP is an effective intervention for refractory middle ear and mastoid diseases. It allows for a thorough disease removal and prepares the ear for subsequent implantation procedures. Simultaneous STP and CI provide the advantage of hearing rehabilitation, disease control, and a comparable complication rate to that of conventional CI procedures.Result: To report our institution’s experience with patients who underwent subtotal petrosectomy (STP) for refractory ear disease who are candidates for cochlear implant (CI) and to highlight simultaneous STP with CI its advantages, surgical outcomes, post-operative complications management, and considerations for staging a procedure.A retrospective study was performed in a single tertiary referral university hospital. The medical records of seventy patients (70 ears) who underwent STP for refractory ear disease who were candidates for CI were retrospectively evaluated.Seventy adults (age range 30–85) underwent STP with a median follow-up of 4.8 years (range 1.5–18.2). Twenty-seven (38.5%) had previous mastoid surgeries before STP. Most patients underwent simultaneous STP and CI (n = 36, 51.5%), followed by STP only (n = 28, 40%), with a smaller group having staged CI after STP (n = 6, 8.5%).Patients who underwent simultaneous STP and CI showed significant improvements in several measures, with mean pre-operative pure tone audiometry (PTA) of 98.7 dB HL (range 85–118; SD: ± 9.2) improving to 39.3 dB HL post-operatively (range 25–50; SD: ± 9.3, p < 0.001), mean pre-operative categories of auditory performance (CAP) score of 1.6 (range 0–4; SD: ± 1.3), increasing to 5.6 post-operatively (range 4–7; SD: ± 1.3, p < 0.001), and mean pre-operative open-set adult sentence score of 6.8% (range 0–40%), improving to 78.4% post-operatively (range 40–100%, p < 0.001). Three of the 36 patients (8.3%) who had simultaneous STP and CI developed post-operative complications (median follow-up: 4.2 years). No disease recurrence was reported.STP is an effective intervention for refractory middle ear and mastoid diseases. It allows for a thorough disease removal and prepares the ear for subsequent implantation procedures. Simultaneous STP and CI provide the advantage of hearing rehabilitation, disease control, and a comparable complication rate to that of conventional CI procedures.Conclusion: To report our institution’s experience with patients who underwent subtotal petrosectomy (STP) for refractory ear disease who are candidates for cochlear implant (CI) and to highlight simultaneous STP with CI its advantages, surgical outcomes, post-operative complications management, and considerations for staging a procedure.A retrospective study was performed in a single tertiary referral university hospital. The medical records of seventy patients (70 ears) who underwent STP for refractory ear disease who were candidates for CI were retrospectively evaluated.Seventy adults (age range 30–85) underwent STP with a median follow-up of 4.8 years (range 1.5–18.2). Twenty-seven (38.5%) had previous mastoid surgeries before STP. Most patients underwent simultaneous STP and CI (n = 36, 51.5%), followed by STP only (n = 28, 40%), with a smaller group having staged CI after STP (n = 6, 8.5%).Patients who underwent simultaneous STP and CI showed significant improvements in several measures, with mean pre-operative pure tone audiometry (PTA) of 98.7 dB HL (range 85–118; SD: ± 9.2) improving to 39.3 dB HL post-operatively (range 25–50; SD: ± 9.3, p < 0.001), mean pre-operative categories of auditory performance (CAP) score of 1.6 (range 0–4; SD: ± 1.3), increasing to 5.6 post-operatively (range 4–7; SD: ± 1.3, p < 0.001), and mean pre-operative open-set adult sentence score of 6.8% (range 0–40%), improving to 78.4% post-operatively (range 40–100%, p < 0.001). Three of the 36 patients (8.3%) who had simultaneous STP and CI developed post-operative complications (median follow-up: 4.2 years). No disease recurrence was reported.STP is an effective intervention for refractory middle ear and mastoid diseases. It allows for a thorough disease removal and prepares the ear for subsequent implantation procedures. Simultaneous STP and CI provide the advantage of hearing rehabilitation, disease control, and a comparable complication rate to that of conventional CI procedures. [ABSTRACT FROM AUTHOR]

To date, placental trophoblasts have been of interest in the fields of obstetrics and gynecology, mainly due to their involvement in the formation of a connection between the mother and fetus that aids in placental development and fetal survival. However, the regenerative capacities of trophoblasts for application in regenerative medicine and tissue engineering are poorly understood. Here, we aim to determine the skin regeneration and anti-aging capacities of trophoblast-derived conditioned medium (TB-CM) and exosomes (TB-Exos) using human normal dermal fibroblasts (HNDFs). TB-CM and TB-Exos treatments significantly elevated the migration and proliferation potencies of HNDF cells in a dose- and time-dependent manner. When RNA sequencing (RNA-seq) was used to investigate the mechanism underlying TB-CM-induced cell migration on scratch-wounded HNDFs, the increased expression of genes associated with C-X-C motif ligand (CXCL) chemokines, toll-like receptors, and nuclear factor-kappa B (NF-κB) signaling was observed. Furthermore, treatment of intrinsically/extrinsically senescent HNDFs with TB-CM resulted in an enhanced rejuvenation of HNDFs via both protection and restoration processes. Gene expression of extracellular matrix components in the skin dermis significantly increased in TB-CM- and TB-Exos-treated HNDFs. These components are involved in the TB-CM and Exo-mediated regeneration and anti-aging of HNDFs. Thus, this study demonstrated the regenerative and anti-aging efficacies of trophoblast-derived secretomes, suggesting their potential for use in interventions for skin protection and treatment. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsBecause patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus.The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared.The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm3 vs. 7616/mm3, p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients.Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults. [ABSTRACT FROM AUTHOR]

Background When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. Objectives We aimed to identify independent risk factors for IE in patients with VGS BSI. Methods This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. Results Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14–32.58; P  < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03–12.94; P  = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96–1.00; P =  0.015), solid cancer (aOR, 0.26; 95% CI, 0.13–0.53; P <  0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01–0.41; P =  0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87–14.68; P  < 0.001). Conclusions Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors. [ABSTRACT FROM AUTHOR]

Background: There is an ongoing controversy regarding whether single-occupancy rooms are superior to multiple-occupancy rooms in terms of infection prevention. We investigated whether treatment in a multiple-occupancy room is associated with an increased incidence of nosocomial coronavirus disease 2019 (COVID-19) compared with treatment in a single-occupancy room. Methods: In this retrospective cohort study, every hospitalization period of adult patients aged ≥ 18 years at a tertiary hospital in Korea from January 1, 2022, to December 31, 2022, was analyzed. If COVID-19 was diagnosed more than 5 days after hospitalization, the case was classified as nosocomial. We estimated the association between the number of patients per room and the risk of nosocomial COVID-19 using a Cox proportional hazards regression model. Results: In total, 25,143 hospitalizations per room type were analyzed. The incidence rate of nosocomial COVID-19 increased according to the number of patients per room; it ranged from 3.05 to 38.64 cases per 10,000 patient-days between single- and 6-bed rooms, respectively. Additionally, the hazard ratios of nosocomial COVID-19 showed an increasing trend according to the number of patients per room, ranging from 0.14 (95% confidence interval 0.001–1.03) to 2.66 (95% confidence interval 1.60–4.85) between single- and 6-bed rooms, respectively. Conclusions: We demonstrated that the incidence of nosocomial COVID-19 increased according to the number of patients per room. To reduce nosocomial infections by respiratory viruses, the use of multiple-occupancy rooms should be minimized. [ABSTRACT FROM AUTHOR]

• The empirical use of broad-spectrum antifungal agents in prolonged febrile neutropenia during induction chemotherapy for acute myelogenous leukaemia should be re-evaluated in the era of antimould prophylaxis. • There were no significant differences in clinical outcomes between the empirical and pre-emptive groups, although the incidence of probable or proven invasive fungal infection (IFI) tended to be lower in the empirical group than in the pre-emptive group. • In the current era of antimould prophylaxis, broad-spectrum antifungal therapy in patients receiving antimold prophylaxis may be deferred until clinical or mycological evidence of IFI is obtained. This study compared clinical outcomes in patients with acute myelogenous leukaemia (AML) who developed prolonged (≥4 days) febrile neutropenia (FN) and received either empirical or pre-emptive antimould prophylaxis in order to evaluate the need for routine empirical antifungal therapy. This retrospective study reviewed adult patients (aged ≥18 years) with AML who developed prolonged FN and received antimould prophylaxis during induction or re-induction chemotherapy at a single centre between September 2016 and December 2020. Patients were categorized into pre-emptive or empirical groups based on whether or not there was clinical evidence of invasive fungal infection (IFI) at the start of antifungal treatment, respectively. Clinical outcomes were compared between the two groups after propensity score matching (PSM). In total, 229 chemotherapy episodes (36 and 193 in the empirical and pre-emptive groups, respectively) were analysed. In the pre-emptive group, broad-spectrum antifungal therapy was administered in 45 (23.3%) episodes. After 1:3 PSM, there were no significant differences between the empirical and pre-emptive groups in terms of the incidence of proven or probable IFI [0/36 (0%) vs 5/97 (5.2%); P =0.323], all-cause mortality [3/36 (8.3%) vs 4/97 (4.1%); P =0.388] and IFI-related mortality [0/36 (0.0%) vs 1/45 (2.2%); P =0.556]. The differences in clinical outcomes between empirical and pre-emptive antifungal therapy in patients with AML who received antimould prophylaxis were not significant. Therefore, broad-spectrum antifungal therapy in patients receiving antimould prophylaxis may be delayed until there is clear evidence of IFI. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the sensitivity and specificity of the Panbio™ COVID-19 Ag rapid test device using nasal swabs and those of the SSf-COVID19 kit, one of RT-PCR tests, using saliva specimens. These tests were compared with RT-PCR tests using nasopharyngeal swabs for the diagnosis of SARS-CoV-2 infection. The three diagnostic tests were simultaneously conducted for patients aged ≥ 18 years, who were about to be hospitalized or had been admitted for COVID-19 confirmed by RT-PCR in two research hospitals from August 20 to October 29, 2021. Nasal swabs were tested using the Panbio™ COVID-19 Ag rapid test device. More than 1 mL of saliva was self-collected and tested using the SSf-COVID19 kit. Results: In total, 157 patients were investigated; 124 patients who were about to be hospitalized and 33 patients already admitted for COVID-19. The overall sensitivity and specificity of the Panbio™ COVID-19 Ag rapid test device with nasal swabs were 64.7% (95% confidence interval [CI] 47.9–78.5%) and 100.0% (95% CI 97.0–100.0%), respectively. The median time to confirm a positive result was 180 s (interquartile range 60–255 s). The overall sensitivity and specificity of the SSf-COVID19 kit with saliva specimens were 94.1% (95% CI 80.9–98.4%) and 100.0% (95% CI 97.0–100.0%), respectively. [ABSTRACT FROM AUTHOR]

A hybrid device that combines the properties of organic and inorganic semiconductors was fabricated and studied. It incorporated poly[2-methoxy-5-(2-ethylhexyloxy)- 1,4-phenylenevinylene] (MEH-PPV) and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as organic polymers and GaN nanoneedles as an inorganic semiconductor. Layers of the two polymers were spin coated on to the GaN nanoneedles. The one peak in the electroluminescence spectrum originated from the MEH-PPV layer owing to the different potential barriers of electrons and holes at its interface with the GaN nanoneedles. However, the photoluminescence spectrum showed peaks due to both GaN nanoneedles and MEH-PPV. Such hybrid structures, suitably developed, might be able to improve the efficiency of optoelectronic devices. [ABSTRACT FROM AUTHOR]

Highlights: [•] Fucosterol exhibited mixed-type inhibition against RLAR and HRAR activities. [•] Fucosterol showed noncompetitive-type inhibition against PTP1B activity. [•] Due to the sterol structure, fucosterol can bind tightly to AR in the docking result. [•] Fucosterol showed weak or no activity against AGE formation and α-glucosidase. [Copyright &y& Elsevier]

Abstract: The leaves of Saussurea grandifolia (Compositae) are used as chwinamul, a well-known Korean mountainous vegetable, or to treat hepatitis and hematuria. Since the methanolic extract of S. grandifolia leaves exhibit a potent peroxynitrite-scavenging effect, phytochemical and high-performance liquid chromatographic (HPLC) analyses were employed to identify and simultaneously quantify the active components: chlorogenic acid and 3,5-di-O-caffeoylquinic acid (3,5-DQ) as caffeoylquinic acids, and quercetin, isoquercitrin (quercetin-3-glucoside), saxifragin (quercetin-5-glucoside), and rutin (quercetin-3-rutinoside). Validation of HPLC methods was performed to verify the linearity, LOD, LOQ, intra-day and inter-day variabilities, recovery, and repeatability to ensure that this method is selective, sensitive, precise, accurate and reproducible. In particular, leaves contained saxifragin with potent peroxynitrite-scavenging activity (IC50, 0.67μM) as 4.65mg/g dry weight, which is equivalent to 33.74mg/g extract. [Copyright &y& Elsevier]

Microelectromechanical systems remain an area of significant interest in fundamental and applied research due to their wide ranging applications. Most device designs, however, are largely 2D and constrained to only a few simple geometries. Achieving tunable resonant frequencies or broad operational bandwidths requires complex components and/or fabrication processes. The work presented here reports unusual classes of 3D micromechanical systems in the form of vibratory platforms assembled by controlled compressive buckling. Such 3D structures can be fabricated across a broad range of length scales and from various materials, including soft polymers, monocrystalline silicon, and their composites, resulting in a wide scope of achievable resonant frequencies and mechanical behaviors. Platforms designed with multistable mechanical responses and vibrationally decoupled constituent elements offer improved bandwidth and frequency tunability. Furthermore, the resonant frequencies can be controlled through deformations of an underlying elastomeric substrate. Systematic experimental and computational studies include structures with diverse geometries, ranging from tables, cages, rings, ring-crosses, ring-disks, two-floor ribbons, flowers, umbrellas, triple-cantilever platforms, and asymmetric circular helices, to multilayer constructions. These ideas form the foundations for engineering designs that complement those supported by conventional, micro-electromechanical systems, with capabilities that could be useful in systems for biosensing, energy harvesting, and others. [ABSTRACT FROM AUTHOR]

Since recurrence and metastasis of pancreatic cancer has a worse prognosis, chemotherapy has been typically performed to attack the remained malignant cells after resection. However, it is difficult to achieve the therapeutic concentration at the tumor site with systemic chemotherapy. Numerous local drug delivery systems have been studied to overcome the shortcomings of systemic delivery. However, because most systems involve dissolution of the drug within the carrier, the concentration of the drug is limited to the saturation solubility, and consequently cannot reach the sufficient drug dose. Therefore, we hypothesized that 3D printing of a biodegradable patch incorporated with a high drug concentration would provide a versatile shape to be administered at the exact tumor site as well as an appropriate therapeutic drug concentration with a controlled release. Here, we introduce the 3D-printed patches composed of a blend of poly(lactide- co -glycolide), polycaprolactone, and 5-fluorouracil for delivering the anti-cancer drug in a prolonged controlled manner and therapeutic dose. 3D printing technology can manipulate the geometry of the patch and the drug release kinetics. The patches were flexible, and released the drug over four weeks, and thereby suppressed growth of the subcutaneous pancreatic cancer xenografts in mice with minimized side effects. Our approach reveals that 3D printing of bioabsorbable implants containing anti-cancer drugs could be a powerful method for an effective local delivery of chemotherapeutic agents to treatment of cancers. [ABSTRACT FROM AUTHOR]

Sustained expression of the CFTR gene is a major challenge to gene therapy with either viral or nonviral vectors with immune response to vector and transgene products. One strategy to achieve sustained CFTR expression is to modulate the host immune system through transient immunosuppression. In this study, we examined cyclophosphamide (cytoxan), dexamethasone (Dex), and a combination of cyclosporin, methylprednisolone, and azathioprine (combination) for their effects on long-term expression of the human CFTR delivered with helper-dependent adenoviral vectors in mouse airways. We found that cyclophosphamide significantly enhanced long-term expression of the transgenic human CFTR and the reporter gene LacZ by reducing host immune responses. Dex administration greatly reduced neutralizing antibody production but had no effect on transgene expression. Treatment with a combination of cyclosporin A, azathioprine, and methylprednisolone affected neither CFTR gene expression nor inflammation. Our data suggest that transient immunosuppression might be a strategy to improve sustained expression in gene therapy. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) patients suffer from chronic airway inflammation with excessive neutrophil infiltration. Migration of neutrophils to the lung requires chemokine and cytokine signaling as well as cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), which plays an important role in mediating adhesive interactions between effector and target cells in the immune system. In this study, we investigated the relationship between ICAM-1 and epithelium-specific ETS-like transcription factor 1 (ESE-1) and found that ICAM-1 expression is upregulated in cell lines of CF (IB3-1) as well as non-CF (BEAS-2B and A549) epithelial origin in response to inflammatory cytokine stimulation. Since ESE-1 is highly expressed in A549 cells without stimulation, we examined the effect of ESE-1 knockdown on ICAM-1 expression in these cells. We found that ICAM-1 expression was downregulated when ESE-1 was knocked down in A549 cells. We also tested the effect of ESE-1 knockdown on cell-cell interactions and demonstrate that the knocking down ESE-1 in A549 cells reduce their interactions with HL-60 cells (human promyelocytic leukemia cell line). These results suggest that ESE-1 may play a role in regulating airway inflammation by regulating ICAM-1 expression. [ABSTRACT FROM AUTHOR]

Highlights: [•] E. bicyclis inhibit NF-κB-regulated inflammatory gene expression via ROS inhibition. [•] The CH2Cl2 fraction harboring fucosterol, exhibited strong anti-inflammatory activity. [•] Fucosterol suppressed protein levels of iNOS and COX-2 in LPS-stimulated macrophages. [•] Phlorotannins inhibited LPS-induced NO and ROS production in RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Abstract: Silicon photomultipliers (SiPMs) are outstanding photosensors for the development of compact imaging devices and hybrid imaging systems such as positron emission tomography (PET)/ magnetic resonance (MR) scanners because of their small size and MR compatibility. The wide use of this sensor for various types of scintillation detector modules is being accelerated by recent developments in tileable multichannel SiPM arrays. In this work, we present the development of a front-end readout module for multi-channel SiPMs. This readout module is easily extendable to yield a wider detection area by the use of a resistive charge division network (RCN). We applied this readout module to various PET detectors designed for use in small animal PET/MR, optical fiber PET/MR, and double layer depth of interaction (DOI) PET. The basic characteristics of these detector modules were also investigated. The results demonstrate that the PET block detectors developed using the readout module and tileable multi-channel SiPMs had reasonable performance. [Copyright &y& Elsevier]