Immunogenicity of COVID-19 Vaccination in Patients With End-Stage Renal Disease Undergoing Maintenance Hemodialysis: The Efficacy of a Mixand-Match Strategy

Background@#The objective of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with end-stage renal disease (ESRD) on hemodialysis. @*Methods@#ESRD patients at the hemodialysis center of a tertiary-care university-affiliated hospital and healthy employees at the clinical laboratory center were prospectively recruited between March and June 2021. For severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) antibody analysis, blood samples were collected serially on days 0, 14, 28, and 56 after the first vaccine dose, and on days 7 and 50 after the second dose. Antibodies against the SARS-CoV-2 spike protein were quantified, and SARS-CoV-2 neutralizing antibodies were measured in the serum and plasma. @*Results@#Thirty-one ESRD patients and 55 healthy employees were regularly monitored.Twenty-five (80.6%) ESRD patients on hemodialysis received a mix-and-match strategy with ChAdOx1-BNT162b2 (AZ–Pf group) and six (19.4%) received two doses of ChAdOx1 (AZ–AZ group). ESRD patients on hemodialysis showed lower binding antibody titers and neutralizing antibody activities compared to healthy participants following the first vaccination with ChAdOx1. After the second dose, AZ-Pf group had higher immunogenicity than healthy people on days 7 and 50. The binding antibody titer and neutralizing antibody activities on days 7 and 50 were significantly higher in the AZ–Pf group than in the AZ–AZ group. @*Conclusion@#ESRD patients on hemodialysis receiving the mix-and-match strategy (ChAdOx1–BNT162b2) have COVID-19 vaccine immunogenicity comparable to healthy individuals receiving two doses of ChAdOx1.

Missed nursing care and its influencing factors among neonatal intensive care unit nurses in South Korea: a descriptive study

Purpose@#Preventing missed care is important in neonatal intensive care units (NICUs) due to neonates’ vulnerabilities. This study examined missed care and its influencing factors among NICU nurses. @*Methods@#Missed care among 120 Korean NICU nurses was measured using a cross-culturally adapted online questionnaire. The frequency of missed care for 32 nursing activities and the significance of 23 reasons for missed care were collected. @*Results@#All participants had missed at least 1 activity, missing on average 19.35 activities during a typical work-day. The most common missed item was “provide developmental care for the baby”. The most common reason for missed care was “emergency within the unit or deterioration of one of the assigned patients”. The final regression model explained 9.6% of variance in missed care. The average daily number of assigned patients receiving inotropes or sedation over the last month influenced the total number of missed care items. @*Conclusion@#Missed care was affected by nurses’ workload related to the number of patients taking medication. Frequently missed activities, especially those related to developmental care, require patience and time, conflicting with safety prioritization and inadequate working conditions. NICU nurses’ working conditions should be improved to ensure adequate time for nursing activities.

Effects of Education Program for Combined Management of Lymphedema with regard to Breast Cancer Patients with Axillary Lymph Node Dissection: A Quasi-Experimental Study

Purpose@#This study aimed to evaluate the effectiveness of a combined management of lymphedema education (CMLE) program which was designed for the prevention of breast cancer related lymphedema. @*Methods@#We applied a quasi-experimental study, pretest, and posttest design with a non-equivalent control group. Breast cancer survivors with partial or total mastectomy and axillary lymph node dissection were recruited and assigned to either an intervention or control group at S hospital in Seoul. The outcomes were measured using the Breast Cancer Lymphedema Symptom Experience Index, Lymphedema Risk Reduction Behavior Checklist, Patients Activation Measure 13, Functional assessment of cancer therapy-General, and Disabilities of the Arm, Shoulder and Hand. The circumferences of both arms were measured by a nurse. These measurements were conducted and compared at baseline and two weeks after completing the (CMLE) program. @*Results@#There were statistically significant changes in quality of life, physical wellbeing, and lymphedema risk behaviors in both groups after the CMLE program. There were significant differences in the circumference of right forearm, elbow, and upper arm between the two groups. @*Conclusion@#It can be concluded that the CMLE program is viable tool to prevent and manage breast cancer related lymphedema and is effective in improving the quality of life in breast cancer survivors with axillary lymph node dissection.

Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

SARS-CoV-2 Delta (B.1.617.2) Variant:A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

Over two hundred twenty-eight million cases of coronavirus disease 2019 (COVID-19) in the world have been reported until the 21st of September 2021 after the first rise in December 2019. The virus caused the disease called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 4 million deaths blame COVID-19 during the last one year and 8 months in the world. Currently, four SARS-CoV-2 variants of concern are mainly focused by pandemic studies with limited experiments to translate the infectivity and pathogenicity of each variant. The SARS-CoV-2 α, β, γ, and δ variant of concern was originated from United Kingdom, South Africa, Brazil/Japan, and India, respectively. The classification of SARS-CoV-2 variant is based on the mutation in spike (S) gene on the envelop of SARS-CoV-2. This review describes four SARS-CoV-2 α, β, γ, and δ variants of concern including SARS-CoV-2 ε, ζ, η, ι, κ, and B.1.617.3 variants of interest and alert. Recently, SARS-CoV-2 δ variant prevails over different countries that have 3 unique mutation sites: E156del/R158G in the N-terminal domain and T478K in a crucial receptor binding domain. A particular mutation in the functional domain of the S gene is probably associated with the infectivity and pathogenesis of the SARS-CoV-2 variant.

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.

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.

The Moderating Effect of Sleep Disturbance on the Association of Stress with Impulsivity and Depressed Mood

Objective@#This study was performed to investigate the associations of life event stress with impulsivity, anxiety, and depressed mood as a function of the presence of a sleep disturbance. @*Methods@#In total, 214 participants (age 38.96±10.53 years; 111 females) completed self-report questionnaires, including the Life Experience Survey (LES), Pittsburgh Sleep Quality Index (PSQI), Barratt’s Impulsivity Scale (BIS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). The presence of a sleep disturbance was defined as a PSQI score >5. @*Results@#In total, 127 participants presented with a sleep disturbance (age 39.33±10.92 years; 64 females), whereas the remaining 87 did not (age 38.43±9.97 years; 47 females). Negative LES scores were significantly correlated with BIS (r=0.22, p=0.001), BAI (r=0.46, p< 0.001), and BDI (r=0.51, p<0.001) scores, and PSQI scores were significantly correlated with BAI (r=0.49, p<0.001) and BDI (r=0.60, p< 0.001) scores. Moderation analysis revealed statistically significant interactions between negative LES scores and the presence of a sleep disturbance on BIS (p=0.044) and BDI (p=0.014) but not on BAI (p=0.194) scores. @*Conclusion@#The findings of the present study suggest that life event stress has varying degrees of influence on mental health, especially impulsivity and depressed mood, depending on the presence or absence of a sleep disturbance.

Experiences of localization and removal of non-palpable subdermal contraceptive implants with ultrasound

OBJECTIVE: The aim of this study was to present experiences in localization and removal of non-palpable subdermal contraceptive implants with ultrasonography. METHODS: Medical records from January 1, 2016, to April 30, 2018, were retrospectively reviewed for 21 patients who were referred to a single institution and had an impalpable implant despite following the removal instruction. In all the cases, more than one attempt was made to remove the implant before referral. The rod was detected using radiography and ultrasonography. In all the cases, localization of the single implant was achieved with ultrasonography. The distal depth of the rod was measured, and skin marking was made following the echogenicity. The implants were subsequently removed under anesthesia. RESULTS: In 18 cases, the rods were localized using ultrasonography and successfully removed under local anesthesia. In the other three cases, removal with local anesthesia failed. Although the rod was detected successful with ultrasonography, the implants were removed under general anesthesia in the operating room. The depth from skin to rod, measured with ultrasonography, was >12.0 mm in all the cases and located deep in the muscular layer in the failure cases. The depth of the implants positively correlated with the time spent for removal (r=0.525; P=0.015). CONCLUSION: High frequency ultrasonography is a highly accurate tool for localization and measurement of the skin-to-rod depth. It is also useful for removing non-palpable implants. If the depth of the implant is >12.0 mm, removal of the implant in the operating room under general anesthesia is recommended.

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.

Role of IL-32 Gamma on Bone Metabolism in Autoimmune Arthritis

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.

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.

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.

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.

Next-generation sequencing enables the discovery of more diverse positive clones from a phage-displayed antibody library

Phage display technology provides a powerful tool to screen a library for a binding molecule via an enrichment process. It has been adopted as a critical technology in the development of therapeutic antibodies. However, a major drawback of phage display technology is that because the degree of the enrichment cannot be controlled during the bio-panning process, it frequently results in a limited number of clones. In this study, we applied next-generation sequencing (NGS) to screen clones from a library and determine whether a greater number of clones can be identified using NGS than using conventional methods. Three chicken immune single-chain variable fragment (scFv) libraries were subjected to bio-panning on prostate-specific antigen (PSA). Phagemid DNA prepared from the original libraries as well as from the Escherichia coli pool after each round of bio-panning was analyzed using NGS, and the heavy chain complementarity-determining region 3 (HCDR3) sequences of the scFv clones were determined. Subsequently, through two-step linker PCR and cloning, the entire scFv gene was retrieved and analyzed for its reactivity to PSA in a phage enzyme immunoassay. After four rounds of bio-panning, the conventional colony screening method was performed for comparison. The scFv clones retrieved from NGS analysis included all clones identified by the conventional colony screening method as well as many additional clones. The enrichment of the HCDR3 sequence throughout the bio-panning process was a positive predictive factor for the selection of PSA-reactive scFv clones.

Comparative Effects of Mattress Type on Subjective and Objective Sleep Quality: A Preliminary Study / 수면정신생리

OBJECTIVES: We aimed to evaluate the effects of mattress type on both objective and subjective sleep quality in healthy good sleepers. METHODS: Fifteen healthy good sleepers with a mean age of 30.8 years participated in this study. A randomized crossover trial was carried out using two different mattress types: a standard mattress and a contour coil mattress. After a night of adaptation, all participants were randomized to either a standard mattress or a contour coil mattress. Then, nocturnal polysomnography was conducted for two consecutive nights. Subjective evaluations were obtained using a self-report questionnaire before and after the polysomnographic recording sessions. RESULTS: The polysomnographic showed no differences in total sleep time, sleep stage, or wake time after sleep onset between the two mattress conditions. Of the polysomnographic variables, only sleep onset latency was significantly reduced for the contour coil mattress. Additionally, participants reported better subjective sleep quality when sleeping on the contour coil mattress, according to the questionnaires. CONCLUSION: The type of mattress might affect not only subjective, but also objective sleep quality, including sleep onset latency.

Effects of Psychiatric Symptoms on Attention in North Korean Refugees

OBJECTIVE: We investigated the performance of North Korean refugees on attention tasks, and the relationship between that performance and psychiatric symptoms. METHODS: Sustained and divided attention was assessed using the computerized Comprehensive Attention Test in North Korean refugees and in South Koreans. All participants also completed the Beck Depression Inventory, the Beck Anxiety Inventory, the Impact of Event Scale-Revised and the Dissociative Experiences Scale-II (DES-II). RESULTS: The North Korean refugees showed slower reaction times (RTs) on the visual sustained attention task compared to the South Koreans after controlling for age and sex. North Korean refugees had a greater number of omission errors (OEs) on the divided attention task and a higher standard deviation (SD) of RT. Total DES-II scores of the North Korean refugees were associated with the number of OEs and the SD of RT on the sustained attention task, and with the number of OEs on the divided attention task. CONCLUSION: North Korean refugees showed poorer performance on computerized attention tasks. In addition, attention deficit among North Korean refugees was associated with their dissociative experiences. Our results suggest that refugees may have attention deficits, which may be related to their psychiatric symptoms, particularly dissociation.

The Impact of Celebrity Suicide on Subsequent Suicide Rates in the General Population of Korea from 1990 to 2010

The association between celebrity suicide and subsequent increase in suicide rates among the general population has been suggested. Previous studies primarily focused on celebrity suicides in the 2000s. To better understand the association, this study examined the impacts of celebrity suicides on subsequent suicide rates using the data of Korean celebrity suicides between 1990 and 2010. Nine celebrity suicides were selected by an investigation of media reports of suicide deaths published in three major newspapers in Korea between 1990 and 2010. Suicide mortality data were obtained from the National Statistical Office of Korea. Seasonal autoregressive integrated moving average models with intervention analysis were used to test the impacts of celebrity suicides, controlling for seasonality. Six of the 9 celebrity suicides had significant impacts on suicide rates both in the total population and in the same gender- or the same age-subgroups. The incident that occurred in the 1990s had no significant impact on the overall suicide rates, whereas the majority of the incidents in the 2000s had significant influences for 30 or 60 days following each incident. The influence of celebrity suicide was shown to reach its peak following the suicide death of a renowned actress in 2008. The findings may suggest a link between media coverage and the impact of celebrity suicide. Future studies should focus more on the underlying processes and confounding factors that may contribute to the impact of celebrity suicide on subsequent suicide rates.