Bukwang Pharmaceutical (South Korea)

This paper deals with numerical simulation analysis on non-conventional lightning protection system (SKAOR380) by charge transfer system (CTS). SK-AOR380 plays a role to reduce the probability of lightning strike by increasing electric field concentration between SK-AOR380 shade and ionizer, besides electric field at the lightning rod tip part is relieved. In other words, the corona dischrage is early initiated before lightning strike due to early generation of ionized free electrons between SK-AOR380 shade and ionizer by accumulating the induced charge from charged clouds with opposite polarity. To analyze charge behaviors, we considered fully coupled numerical model based on the charge continuity equations for positively charged ion, negatively charged ion and electrons. The results revealed that the SK-AOR380 creates a non-uniform electric field distribution with a large field enhancement causing ionization to initiate corona discharge under 300 kV lightning impulse voltage. This result is expected that the probability of direct lightning strike can be reduced by improved lightning protection rod.

Abstract BackgroundClevudine, an antiviral drug for chronic hepatitis B virus infection, is expected to inhibit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Therefore, we conducted a prospective, single-blind, proof of concept clinical study to examine the antiviral efficacy and safety of clevudine compared to placebo in Korean corona virus disease 19 (COVID-19) patients with moderate severity.MethodsAdults with confirmed SARS-CoV-2 infection and symptom onset within 7 days were randomized 2:1 to 120 mg clevudine or placebo to receive one of treatments orally once-daily for 14 days. Antiviral efficacy outcomes were the proportion of patients with real-time reverse transcription polymerase chain reaction (RT-PCR) negative result for SARS-CoV-2 infection and cycle threshold (Ct) value changes from baseline. Clinical efficacy outcomes included proportion of patients who showed improvement in lung involvement by imaging tests, proportion of patients with normal body temperature, proportion of patients with normal oxygen saturation, and the changes in C-reactive protein (CRP) from baseline. Safety outcomes included changes in clinical laboratory tests, vital signs measurement, and physical examination from baseline, and incidence of adverse events.ResultsThe proportion of patients with real-time RT-PCR negative test and Ct value changes showed no significant difference between clevudine group and placebo group. The changes in Ct value from baseline were significantly greater in clevudine group compared to placebo group in patients with hypertension, and patients who underwent randomization during the first 5 and 7 days after the onset of symptoms. All clinical efficacy outcomes had no significant difference between clevudine group and placebo group. Clevudine was well tolerated and there was no significant difference in safety profile between two treatment groups.ConclusionsThis is the first clinical study to compare the antiviral efficacy and safety of clevudine to placebo in Korean COVID-19 patients with moderate severity. The study has demonstrated a possible favorable outcome for the reduction of SARS-CoV-2 replication, with acceptable safety profile, when COVID-19 patients were treated with clevudine. Further large-scale clinical studies, preferably with various clinical endpoints and virus titer evaluation, are required to better understand the effectiveness of using clevudine in COVID-19 treatment. Considering recent trend in clinical development for antiviral drugs, we need to design a clinical study aiming for reducing clinical risk of COVID-19 in mild to moderate patients with at least one risk factor for serious illness.

Abstract Rationale We aimed to evaluate the impact of daily cat exposure in cat allergic asthmatics by both clinical symptom and immunological measures. Methods Twenty adults with history of cat-induced asthma and rhinitis, positive serum cat dander-specific IgE (sIgE>0.35kU/L) and Skin Prick Test (SPT) were enrolled at a 1:1 ratio according to cat ownership. For comparison, cat extract- and Fel d1- specific basophil sensitivity test (BST), serum sIgE, sIgG4 and SPT were measured on Day 1 and 28; ambulatory spirometry and symptom measures were obtained daily. Feld1 and 4-reactive CD4+ T cells were profiled using a CD154 upregulation assay. Results Cat owners had higher clinical symptom scores & medication use and a trend toward lower FEV1 vs. those not living with cats. Significantly higher levels of cat dander sIgG4 were observed among cat owners, but no significant difference was observed for cat-dander sIgE or SPT. All subjects tested positive on BST to Fel d1 and cat dander. Cat-ownership was associated with reduced basophil sensitivity to Fel d1, but had positive BST to Fel d4 and 7. T-cell response to Fel d1 and 4 were differentially polarized, with Fel d1 responses strongly polarized toward Th2 in both groups. No significant correlation was observed between basophil and T cell responses against cat allergen components. Conclusions Cat allergic subjects living with a cat demonstrated reduced pulmonary function and greater clinical symptom severity, despite higher medication use and sIgG4. An immunological difference between cat-owners vs. non cat-owners was detected by basophil assay but not by T-cell response.

Abstract Chimeric antigen receptor (CAR) T cell therapies have shown striking clinical efficacy in the treatment of hematological malignancies, but limited success so far against solid tumors, suggesting that solid tumors may harbor mechanisms of resistance. To investigate mechanisms of CAR T cell therapy resistance in solid tumors, we developed immunocompetent mouse models to explore immune cell interactions and the effect of an immunosuppressive tumor microenvironment on CAR T cell behavior. We generated murine CAR T cells against a model antigen that contained a CD3z intracellular signaling domain linked to either a CD28 or a 4-1BB signaling domain. We found that murine CAR T cells exhibited a predominantly central memory phenotype together with potent cytotoxic activity and antigen-dependent cytokine release in vitro. Further, we found that murine CAR T cells exhibited strong anti-tumor efficacy against both disseminated (EL4) and subcutaneous (MC38) murine tumors in vivo, whereas non-binding control CAR T cells had no anti-tumor effect. However, in both the disseminated and subcutaneous models, tumors were suppressed but not completely eradicated. Although murine CAR T cells possessing either CD28 or 41BB co-stimulatory domains demonstrated similar in vitro activities, they exhibited strikingly different efficacies and resistance mechanisms in vivo. Collectively, these results highlight the contributions of specific co-stimulatory signaling pathways to CAR T cell therapy in immunocompetent murine models and provide a platform to explore resistance mechanisms to CAR T therapy against solid tumors.

Mesenchymal stem cells (MSCs) may hold great promise for treating diabetic wounds. However, it is difficult for a clinician to use MSCs because they have not been commercialized. Meanwhile, a new commercial drug that contains adipose-derived stem cells (ASCs) has been developed. The purpose of this study was to examine the potential of allogeneic ASC sheets for treating diabetic foot ulcers. Fifty-nine patients with diabetic foot ulcers were randomized to either the ASC treatment group (n = 30) or a control group treated with polyurethane film (n = 29). Either an allogeneic ASC sheet or polyurethane film was applied on diabetic wounds weekly. These wounds were evaluated for a maximum of 12 weeks. Complete wound closure was achieved for 73% in the treatment group and 47% in the control group at week 8. Complete wound closure was achieved for 82% in the treatment group and 53% in the control group at week 12. The Kaplan-Meier median times to complete closure were 28.5 and 63.0 days for the treatment group and the control group, respectively. There were no serious adverse events related to allogeneic ASC treatment. Thus, allogeneic ASCs might be effective and safe to treat diabetic foot ulcers.

Radiography remains the imaging standard for fracture detection after trauma. The radiographic diagnosis of most fractures and dislocations poses little difficulty to radiologists: however, occasionally these injuries are quite subtle or even impossible to detect on radiographs. Missed diagnoses of fracture potentially have important consequences for patients, clinicians, and radiologists. Radiologists play a pivot role in the diagnostic assessment of the trauma patients: emergency radiologists who are more practiced at seeking out and discerning traumatic fractures can provide an invaluable service to their clinical colleagues by ensuring that patients do not endure delayed diagnoses. This is a narrative review article aims to highlight the spectrum of fractures in adults potentially missed on plain radiographs, the causes of error in diagnosis of fractures in the emergency setting and the key elements to reduce misdiagnosis of fractures. (www.actabiomedica.it)