SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

Usefulness of serial measurement of the mean platelet volume to predict multipleorgan dysfunction syndrome in patients with severe trauma

Objective@#The early prediction of multiple organ dysfunction syndrome (MODS) in trauma patients and provision ofprompt treatment may improve their outcomes. We investigated the efficacy of the mean platelet volume (MPV) for predictingMODS in cases of severe trauma. @*Methods@#This retrospective, observational cohort study was performed with patients prospectively integrated in a criticalpathway of TRAUMA. We analyzed the severe trauma patients admitted to the emergency department (ED), based onthe Advanced Trauma Life Support guideline, between January 1, 2011 and May 31, 2017. The outcomes were developedfrom MODS at least 48 hours after ED admission. @*Results@#A total of 348 patients were enrolled. An increase in the MPV at 12 hours (odds ratio [OR], 2.611; P8.6 fL (OR, 4.831; P<0.001). The area under the receiver operating characteristic curve(AUROC) value of the MPV at 12 hours (0.751; 95% confidence interval [CI], 0.687-0.818; P<0.01) was not inferior thanthat of Acute Physiology and Chronic Health Evaluation II score, injury severity score, lactate, and total CO2 for predictingMODS. @*Conclusion@#MPV was an independent predictor of MODS development in severe trauma patients. Emergency physicianscan use the MPV as an ancillary biomarker for predicting MODS.

The Progression of SARS Coronavirus 2 (SARS-CoV2): Mutation in the Receptor Binding Domain of Spike Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

The Progression of SARS Coronavirus 2 (SARS-CoV2): Mutation in the Receptor Binding Domain of Spike Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

Lactate/albumin ratio for the prediction of the development of sepsis-induced acute kidney injury in the emergency department

OBJECTIVE: The early prediction of acute kidney injury (AKI) in sepsis and the provision of prompt treatment may improve the outcomes. This study investigated the efficacy of the lactate/albumin ratio (LAR) in predicting severe AKI in cases of septic shock. METHODS: This retrospective, observational cohort study was performed on patients integrated prospectively in a critical pathway of early-goal-directed therapy (EGDT)/SEPSIS. Adult patients with septic shock, who were admitted to the emergency department with a normal kidney function or stage 1 disease based on the Acute Kidney Injury Network classification between January 1, 2014 and September 30, 2017, were analyzed. The outcomes were the development of sepsis-induced severe AKI within 7 days. RESULTS: A total of 343 patients were enrolled. An increase in the LAR value at admission (odds ratio [OR], 1.85; P=0.001) was a strong independent predictor of the development of severe AKI. The increasing predictability of AKI was closely associated with a L/A ratio≥0.794 at admission (OR, 14.66; P < 0.001). The area under the receiver operating characteristic curve value of the L/A ratio (0.821; 95% confidence interval [CI], 0.774–0.861; P < 0.01) was higher than that of lactate (0.795; 95% CI, 0.747–0.838; P < 0.01) for predicting severe AKI (P=0.032). CONCLUSION: L/A ratio was found to be an independent predictor of the development of severe AKI in septic shock. The prognostic performance of the L/A ratio for predicting AKI of critically ill sepsis patients was superior to that of lactate measurements.

The usefulness of lactate as an early predictor of the severity of emergency department patients with postpartum hemorrhage

OBJECTIVE: Only a few studies have examined the role of lactate reflecting on tissue hypoperfusion determining the severity of postpartum hemorrhage (PPH) patients in the emergency department (ED). This study evaluated the utility of the arterial lactate level as a prognostic marker of severity in PPH patients admitted to an ED. METHODS: This retrospective, observational cohort study was conducted on patients integrated prospectively in a critical pathway of SPEED (Severance Protocol to save postpartum bleeding through Expeditious care Delivery). Adult primary PPH patients admitted to the ED between July 1, 2010 and March 31, 2017 were analyzed. The outcomes were the development of severe PPH including death, hysterectomy, surgical treatment, and massive transfusion. RESULTS: A total of 112 patients were enrolled in this study. An increase in the arterial lactate value was a strong independent predictor of severe PPH. The increasing predictability of severe PPH was closely associated with an arterial lactate ≥3.15 mL/L at admission (odds ratio, 13.870; P < 0.001). CONCLUSION: Lactate is an independent predictor of severe PPH and is suitable for a rapid and simple estimation of the severity of PPH. Emergency physicians can use lactate to determine the initial treatment strategies more precisely.

Ultrasound Feature-Based Diagnostic Model Focusing on the “Submarine Sign” for Epidermal Cysts among Superficial Soft Tissue Lesions

OBJECTIVE: To develop a diagnostic model for superficial soft tissue lesions to differentiate epidermal cyst (EC) from other lesions based on ultrasound (US) features. MATERIALS AND METHODS: This retrospective study included 205 patients who had undergone US examinations for superficial soft tissue lesions and subsequent surgical excision. The study population was divided into the derivation set (n = 112) and validation set (n = 93) according to the imaging date. The following US features were analyzed to determine those that could discriminate EC from other lesions: more-than-half-depth involvement of the dermal layer, “submarine sign” (focal projection of the hypoechoic portion to the epidermis), posterior acoustic enhancement, posterior wall enhancement, morphology, shape, echogenicity, vascularity, and perilesional fat change. Using multivariable logistic regression, a diagnostic model was constructed and visualized as a nomogram. The performance of the diagnostic model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve and calibration plot in both the derivation and validation sets. RESULTS: More-than-half-depth involvement of the dermal layer (odds ratio [OR] = 3.35; p = 0.051), “submarine sign” (OR = 12.2; p < 0.001), and morphology (OR = 5.44; p = 0.002) were features that outweighed the others when diagnosing EC. The diagnostic model based on these features showed good discrimination ability in both the derivation set (AUC = 0.888, 95% confidence interval [95% CI] = 0.825–0.950) and validation set (AUC = 0.902, 95% CI = 0.832–0.972). CONCLUSION: More-than-half-depth of involvement of the dermal layer, “submarine sign,” and morphology are relatively better US features than the others for diagnosing EC.

Structural Characteristics of Seven IL-32 Variants

IL-32 exists as seven mRNA transcripts that can translate into distinct individual IL-32 variants with specific protein domains. These translated protein domains of IL-32 variants code for specific functions that allow for interaction with different molecules intracellularly or extracellularly. The longest variant is IL-32γ possessing 234 amino acid residues with all 11 protein domains, while the shortest variant is IL-32α possessing 131 amino acid residues with three of the protein domains. The first domain exists in 6 variants except IL-32δ variant, which has a distinct translation initiation codon due to mRNA splicing. The last eleventh domain is common domain for all seven IL-32 variants. Numerous studies in different fields, such as inflammation, autoimmunity, pathogen infection, and cancer biology, have claimed the specific biological activity of individual IL-32 variant despite the absence of sufficient data. There are 4 additional IL-32 variants without proper transcripts. In this review, the structural characteristics of seven IL-32 transcripts are described based on the specific protein domains.

L1 Recombinant Proteins of HPV Tested for Antibody Forming Using Sera of HPV Quadrivalent Vaccine

Virus-like particles (VLPs) derived from human papillomavirus (HPV) L1 capsid proteins were used for HPV quadrivalent recombinant vaccine. The HPV quadrivalent vaccine is administrated in a 3-dose regimen of initial injection followed by subsequent doses at 2 and 6 months to prevent cervical cancer, vulvar, and vaginal cancers. The type 6, 11, 16, or 18 of HPV infection is associated with precancerous lesions and genital warts in adolescents and young women. The HPV vaccine is composed of viral L1 capsid proteins are produced in eukaryotic expression systems and purified in the form of VLPs. Four different the L1 protein of 3 different subtypes of HPV: HPV11, HPV16, and HPV18 were expressed in Escherichia coli divided into 2 fragments as N- and C-terminal of each protein in order to examine the efficacy of HPV vaccine. Vaccinated sera failed to recognize N-terminal L1 HPV type 16 and type 18 by western blot while they detected N-terminal L1 protein of HPV type 11. Moreover, the recombinant C-terminal L1 proteins of type 16 was non-specifically recognized by the secondary antibody conjugated with horseradish peroxidase. This expression and purification system may provide simple method to obtain robust recombinant L1 protein of HPV subtypes to improve biochemical analysis of antigens with immunized sera.

Risk of complications and urinary incontinence following cytoreductive prostatectomy: a multi-institutional study / 亚洲男科学杂志(英文版)

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

Beneficial aspect of dexmedetomidine as a postoperative sedative for cardiac surgery

BACKGROUND: The aim of this study was to compare the clinical outcomes of the sedative, analgesic, and hemodynamic effects of dexmedetomidine and midazolam for sedation after coronary artery bypass grafting (CABG). METHODS: The adult patients undergoing elective CABG surgery under general anesthesia were randomly assigned to the dexmedetomidine (DEX) and midazolam (MDZ) groups. From the time of the sternal closure, dexmedetomidine (0.5–0.7 μg/kg/h) was continuously administered (DEX group), and midazolam (0.03–0.1 mg/kg) was administered by bolus (MDZ group). To maintain the target sedation level (Richmond Agitation-Sedation Scale [RASS] range, −2 to −1) until extubation in the intensive care unit (ICU), continuous doses of dexmedetomidine were regulated and midazolam was administered intermittently. Sedation (RASS) and pain scores (visual analogue scale) and hemodynamic changes were recorded every two hours, until the end of the mechanical ventilation assistance after entering the ICU. RESULTS: The mean of the fraction within the target sedation level in each patient's total sedation time was 41.0% in the DEX group and 20.7% in the MDZ group (P = 0.026). In the DEX group, the RASS (P < 0.001) and cardiac index were lower (P = 0.047) than those in the MDZ group, but the other hemodynamic parameters and pain scores were not different. CONCLUSIONS: This study showed that post-operative infusion of dexmedetomidine maintained a stable sedation without side effects in patients who underwent CABG surgery.

IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells

The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.

Usefulness of Serial Measurement of the Platelet Volume Indices to Predict 30-day Mortality in Patients with ST Segment Elevation Myocardial Infarction

PURPOSE: Among the survivors of a ST elevation myocardial infarction (STEMI), higher platelet volume indices (mean platelet volume, MPV; platelet distribution width, PDW) are associated with impaired reperfusion and ventricular dysfunction. This study examined the relationship between the platelet volume indices and 30-day mortality with STEMI patients who underwent primary percutaneous coronary intervention (PCI). METHODS: This retrospective cohort study included patients presenting to the emergency department with STEMI between January 2011 and May 2016. The platelet volume indices were measured serially, using an automatic hematology analyzer, from admission to 24 hours after admission. The prognostic value of MPV, PDW for the 30-day mortality was determined by Cox proportional hazards model analysis. RESULTS: A total of 608 STEMI patients, who underwent reperfusion, were enrolled in this study. According to the multivariable Cox proportional hazard model, higher MPV (hazard ratio [HR], 1.414; 95% confidence interval [CI], 1.024-1.953; p=0.035) and PDW (HR, 1.043; 95% CI, 1.006-1.083; p=0.024) values at time-24 (24 hours after admission) were significant risk factors for the 30-day mortality. A MPV value >8.6 fL (HR, 5.953; 95% CI, 2.973-11.918; p56.1% (HR, 5.117; 95% CI, 2.640-9.918; p<0.001) at time-24 were associated with an increased risk of 30-day mortality. CONCLUSION: The platelet volume indices without an additional burden of cost or time, can be measured rapidly and simply. Higher MPV and PDW levels predict independently the 30-day mortality in patients with STEMI after PCI.

Species Specific Antiviral Activity of Porcine Interferon-α8 (IFNα8)

Interferons (IFNs) have been known as antiviral genes and they are classified by type 1, type 2, and type 3 IFN. The type 1 IFN consists of IFNα, IFNβ, IFNτ, and IFNω whereas the type 2 IFN consists of only IFNγ, which is a key cytokine driving T helper cell type 1 immunity. IFNλ belongs to the type 3 IFN, which is also known as IL-28 and IL-29 possessing antiviral activities. Type 1 IFN is produced by viral infection whereas type 2 IFN is induced by mitogenic or antigenic T-cell stimuli. The IFNτ of bovine was first discovered in an ungulate ruminant recognition hormone. IFNτ belongs to the type 1 IFN with the common feature of type 1 IFN such as antiviral activity. IFNs have been mostly studied for basic research and clinical usages therefore there was no effort to investigate IFNs in industrial animals. Here we cloned porcine IFNα8 from peripheral blood mononuclear cells of Korean domestic pig (Sus scrofa domestica). The newly cloned IFNα8 amino acid sequence from Korean domestic pig shares 98.4% identity with the known porcine IFNα8 in databank. The recombinant porcine IFNα8 showed potent antiviral activity and protected bovine Madin-Darby bovine kidney epithelial (MDBK) cells from the cytopathic effect of vesicular stomatitis virus, but it failed to protect human Wistar Institute Susan Hayflick (WISH) cells and canine Madin-Darby canine kidney epithelial-like (MDCK) cells. The present study demonstrates species specific antiviral activity of porcine IFNα8.

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.

Cytokine-like Activity of Liver Type Fatty Acid Binding Protein (L-FABP) Inducing Inflammatory Cytokine Interleukin-6

It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.

Change of bronchial permeability in patients with bronchial asthma / 결핵

No abstract available.