A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Effect of Regdanvimab on Mortality in Patients Infected with SARS-CoV-2 Delta Variants: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Regdanvimab, a monoclonal antibody pharmaceutical, is the first Korean drug approved for treating coronavirus disease 2019 (COVID-19). We analyzed the therapeutic efficacy of regdanvimab in patients with the COVID-19 delta variant infection. METHODS: We retrospectively reviewed the electronic medical records of patients hospitalized at two Korean tertiary COVID-19 hospitals with COVID-19 delta variant infection between May 26, 2021, and January 30, 2022. To analyze the therapeutic efficacy of regdanvimab, the patients were divided into regdanvimab and non-regdanvimab groups and were 1:1 propensity-score (PS)-matched on age, severity at admission, and COVID-19 vaccination history. RESULTS: Of 492 patients, 262 (53.3%) and 230 (46.7%) were in the regdanvimab and non-regdanvimab groups, respectively. After PS matching the groups on age, severity at admission, and COVID-19 vaccination history, each group comprised 189 patients. The 30-day hospital mortality rates (0.0% vs. 1.6%, p = 0.030), proportions of patients with exacerbated conditions to severe/critical/died (9.5% vs. 16.4%, p = 0.047), proportions who received oxygen therapy because of pneumonia exacerbation (7.4% vs. 16.4%, p = 0.007), and proportions with a daily National Early Warning Score ≥ 5 from hospital day 2 were significantly lower in the regdanvimab group. CONCLUSIONS: We showed that regdanvimab reduced the exacerbation rates of conditions and mortality in patients with the COVID-19 delta variant infection. Thus, it is recommended to streamline the drug approval system during epidemics of new variant viruses to improve the availability and usage of therapeutics for patients. To facilitate this, relevant institutional support is required.

Clonal Distribution and Its Association With the Carbapenem Resistance Mechanisms of Carbapenem-Non-Susceptible Pseudomonas aeruginosa Isolates From Korean Hospitals.

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC ß-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates. Two high-risk clones, ST235 (N=41) and ST111 (N=20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metallo-ß-lactamase (MBL) genes, blaIMP-6 (N=38), blaVIM-2 (N=3), and blaNDM-1 (N=2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene-negative isolates. Conclusions: Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.

Synchronous Diagnosis of Respiratory Viruses Variants via Receptonics Based on Modeling Receptor-Ligand Dynamics.

The transmission and pathogenesis of highly contagious fatal respiratory viruses are increasing, and the need for an on-site diagnostic platform has arisen as an issue worldwide. Furthermore, as the spread of respiratory viruses continues, different variants have become the dominant circulating strains. To prevent virus transmission, the development of highly sensitive and accurate on-site diagnostic assays is urgently needed. Herein, a facile diagnostic device is presented for multi-detection based on the results of detailed receptor-ligand dynamics simulations for the screening of various viral strains. The novel bioreceptor-treated electronics (receptonics) device consists of a multichannel graphene transistor and cell-entry receptors conjugated to N-heterocyclic carbene (NHC). An ultrasensitive multi-detection performance is achieved without the need for sample pretreatment, which will enable rapid diagnosis and prevent the spread of pathogens. This platform can be applied for the diagnosis of variants of concern in clinical respiratory virus samples and primate models. This multi-screening platform can be used to enhance surveillance and discriminate emerging virus variants before they become a severe threat to public health.

Recombinant protein embedded liposome on gold nanoparticle based on LSPR method to detect Corona virus.

Antibody sensor to detect viruses has been widely used but has problems such as the difficulty of right direction control of the receptor site on solid substrate, and long time and high cost for design and production of antibodies to new emerging viruses. The virus detection sensor with a recombinant protein embedded liposome (R/Li) was newly developed to solve the above problems, in which R/Li was assembled on AuNPs (Au@R/Li) to increase the sensitivity using localized surface plasmon resonance (LSPR) method. Recombinant angiotensin-converting enzyme-2 (ACE2) was used as host receptors of SARS-CoV and SARS-CoV-2, and the direction of enzyme active site for virus attachment could be controlled by the integration with liposome. The recombinant protein embedded liposomes were assembled on AuNPs, and LSPR method was used for detection. With the sensor platform S1 protein of both viruses was detected with detection limit of 10 pg/ml and SARS-CoV-2 in clinical samples was detected with 10 ~ 35 Ct values. In the selectivity test, MERS-CoV did not show a signal due to no binding with Au@R/Li. The proposed sensor platform can be used as promising detection method with high sensitivity and selectivity for the early and simple diagnosis of new emerging viruses.

Asymmetric TMO-Metal-TMO Structure for Enhanced Efficiency and Long-Term Stability of Si-Based Heterojunction Solar Cells.

In this study, we fabricated Si-based heterojunction solar cells (HSCs) with an asymmetric TMO-metal-TMO (TMT) structure using both MoO3 and V2O5 as the hole-selective contacts. Our HSCs offer enhanced long-term stability and effective passivation for crystal defects on the Si sur-face. We analyzed the oxygen vacancy state and surface morphology of the MoO3- and V2O5-TMO thin films using X-ray photoelectron spectroscopy and atomic force microscopy to investigate their passivation characteristics for Si surface defects. From the measured minority carrier lifetime, V2O5 revealed a highly improved lifetime (590 µs) compared to that of MoO3 (122.3 µs). In addition, we evaluated the long-term stability of each TMO thin film to improve the operation stability of the HSCs. We deposited different types of TMOs as the top- and bottom-TMO layers and assessed the effect of the thickness of each TMO layer. The fabricated asymmetric TMT/Si HSCs showed noticeable improvements in efficiency (7.57%) compared to 6.29% for the conventional symmetric structure which used the same TMO material for both the top and bottom layers. Furthermore, in terms of long-term stability, the asymmetric TMT/Si HSCs demonstrated an efficiency that was 250% higher than that of symmetric TMT/Si HSCs, as determined via power conversion efficiency degradation over 2000 h which is mainly attributed by the lower oxygen vacancy of the top-TMO, V2O5. These results suggest that the asymmetric TMT structure is a promising approach for the fabrication of low-cost and high-efficiency Si-based HSCs with enhanced long-term stability.

First Case of Pseudoclavibacter alba Bacteremia in a Patient with Cholangitis.

BACKGROUND: Pseudoclavibacter alba isolated from human urine in culture collection was introduced as a new species, but since then, no other reports on P. alba isolated from the environment or organisms have been published. We thus present the first case report of P. alba bacteremia. METHODS: An 85-year-old female patient was admitted with intermittent abdominal pain and chills that had persisted for one week. She was diagnosed cholangitis with common bile duct stones. RESULTS: Gram-positive bacteria were detected in her peripheral blood culture and identified Pseudoclavibacter species by matrix-assisted laser desorption-ionization-time of flight mass spectrometry. Pseudoclavibacter alba was identified by performing the 16S ribosomal RNA gene sequence. CONCLUSIONS: This is the first case report of P. alba bacteremia in a patient with cholangitis.

Insight into gut dysbiosis of patients with inflammatory bowel disease and ischemic colitis.

The collection of whole microbial communities (bacteria, archaea, fungi, and viruses) together constitutes the gut microbiome. Diet, age, stress, host genetics, and diseases cause increases or decreases in the relative abundance and diversity of bacterial species (dysbiosis). We aimed to investigate the gut microbial composition at different taxonomic levels of healthy controls (HCs) with active Crohn's disease (CD), ulcerative colitis (UC), and ischemic colitis (IC) using culture- and non-culture-based approaches and identify biomarkers to discriminate CD, UC, or IC. We determined the specific changes in the gut microbial profile using culture-independent (16S rRNA gene amplicon sequencing) as well as culture-based (culturomic) approaches. Biomarkers were validated using quantitative Real-Time PCR (qPCR). In both methods, bacterial diversity and species richness decreased in disease-associated conditions compared with that in HCs. Highly reduced abundance of Faecalibacterium prausnitzii and Prevotella sp. and an increased abundance of potentially pathogenic bacteria such as Enterococcus faecium, Enterococcus faecalis, and Escherichia coli in all CD, UC, or IC conditions were observed. We noted a high abundance of Latilactobacillus sakei in CD patients; Ligilactobacillus ruminis in UC patients; and Enterococcus faecium, Escherichia coli, and Enterococcus faecalis in IC patients. Highly reduced abundance of Faecalibacterium prausnitzii in all cases, and increased abundance of Latilactobacillus sakei and Enterococcus faecium in CD, Ligilactobacillus ruminis and Enterococcus faecium in UC, and Enterococcus faecium, Escherichia coli, and Enterococcus faecalis in IC could be biomarkers for CD, UC, and IC, respectively. These biomarkers may help in IBD (CD or UC) and IC diagnosis.

Novel, thalidomide-like, non-cereblon binding drug tetrafluorobornylphthalimide mitigates inflammation and brain injury.

BACKGROUND: Quelling microglial-induced excessive neuroinflammation is a potential treatment strategy across neurological disorders, including traumatic brain injury (TBI), and can be achieved by thalidomide-like drugs albeit this approved drug class is compromised by potential teratogenicity. Tetrafluorobornylphthalimide (TFBP) and tetrafluoronorbornylphthalimide (TFNBP) were generated to retain the core phthalimide structure of thalidomide immunomodulatory imide drug (IMiD) class. However, the classical glutarimide ring was replaced by a bridged ring structure. TFBP/TFNBP were hence designed to retain beneficial anti-inflammatory properties of IMiDs but, importantly, hinder cereblon binding that underlies the adverse action of thalidomide-like drugs. METHODS: TFBP/TFNBP were synthesized and evaluated for cereblon binding and anti-inflammatory actions in human and rodent cell cultures. Teratogenic potential was assessed in chicken embryos, and in vivo anti-inflammatory actions in rodents challenged with either lipopolysaccharide (LPS) or controlled cortical impact (CCI) moderate traumatic brain injury (TBI). Molecular modeling was performed to provide insight into drug/cereblon binding interactions. RESULTS: TFBP/TFNBP reduced markers of inflammation in mouse macrophage-like RAW264.7 cell cultures and in rodents challenged with LPS, lowering proinflammatory cytokines. Binding studies demonstrated minimal interaction with cereblon, with no resulting degradation of teratogenicity-associated transcription factor SALL4 or of teratogenicity in chicken embryo assays. To evaluate the biological relevance of its anti-inflammatory actions, two doses of TFBP were administered to mice at 1 and 24 h post-injury following CCI TBI. Compared to vehicle treatment, TFBP reduced TBI lesion size together with TBI-induction of an activated microglial phenotype, as evaluated by immunohistochemistry 2-weeks post-injury. Behavioral evaluations at 1- and 2-weeks post-injury demonstrated TFBP provided more rapid recovery of TBI-induced motor coordination and balance impairments, versus vehicle treated mice. CONCLUSION: TFBP and TFNBP represent a new class of thalidomide-like IMiDs that lower proinflammatory cytokine generation but lack binding to cereblon, the main teratogenicity-associated mechanism. This aspect makes TFBP and TFNBP potentially safer than classic IMiDs for clinical use. TFBP provides a strategy to mitigate excessive neuroinflammation associated with moderate severity TBI to, thereby, improve behavioral outcome measures and warrants further investigation in neurological disorders involving a neuroinflammatory component.

Seasonal Trends in the Prevalence and Incidence of Viral Encephalitis in Korea (2015-2019).

Viral infections are a common cause of encephalitis. This study investigated the relationship between the incidence of encephalitis and that of respiratory and enteric viral infections in all age groups from 2015 to 2019, using the Health Insurance Review and Assessment (HIRA) Open Access Big Data Platform. We identified monthly incidence patterns and seasonal trends using the autoregressive integrated moving average (ARIMA). The Granger causality test was used to analyze correlations between encephalitis incidence and the positive detection rate (PDR) at 1-month intervals. A total of 42,775 patients were diagnosed with encephalitis during the study period. The incidence of encephalitis was highest in the winter (26.8%). The PDRs for respiratory syncytial virus (HRSV) and coronavirus (HCoV) were associated with the trend in encephalitis diagnosis in all age groups, with a 1-month lag period. In addition, an association with norovirus was observed in patients aged over 20 years, and with influenza virus (IFV) in patients aged over 60 years. This study found that HRSV, HCoV, IFV, and norovirus tended to precede encephalitis by 1 month. Further research is required to confirm the association between these viruses and encephalitis.

Seasonal Trend of Viral Prevalence and Incidence of Febrile Convulsion: A Korea Public Health Data Analysis.

Febrile convulsion (FC) is the most common seizure disease in children, which occurs with a fever. We investigated the Korean Health Insurance Review and Assessment Service data of patients aged between 6 months and 5 years at the time of FC diagnosis. Diseases that can cause seizures with fever, such as neoplasms, metabolic disorders, nervous system disorders, cerebrovascular diseases, perinatal problems, and congenital abnormalities, were excluded. Weekly virus-positive detection rate (PDR) data were obtained from the Korea Disease Control and Prevention Agency for adenovirus, parainfluenza virus, respiratory syncytial virus (HRSV), influenza virus, coronavirus (HCoV), rhinovirus (HRV), bocavirus, metapneumovirus (HMPV), rotavirus, norovirus, and astrovirus. Using the Granger test, we then analyzed the monthly PDR and investigated the association between FC incidence and monthly PDR. We additionally identified monthly and seasonal FC incidence trends using the autoregressive integrated moving average. Between 2015 and 2019, 64,291 patients were diagnosed with FC. Annually, the incidence was the highest in May and the lowest in October. Most patients were diagnosed during the spring (26.7%). The PDRs for HRSV, HCoV, HRV, HMPV, and norovirus were associated with FC incidence after 1 month.

Clonal evolution and antimicrobial resistance of Acinetobacter baumannii isolates from Korean hospitals over the last decade.

The wide-spread of drug-resistant Acinetobacter baumannii is a global health problem. This study investigated the clonal distribution and antimicrobial resistance of 167 A. baumannii isolates from two Korean university hospitals from 2009 to 2019 by analyzing the sequence types (STs), antimicrobial resistance, and resistance determinants of carbapenems and aminoglycosides. Twenty STs, including 16 pre-existing STs and four unassigned STs, were identified in A. baumannii isolates using the Oxford multilocus sequence typing scheme. Two STs, ST191 (n = 77) and ST451 (n = 40), were prevalent, and majority (n = 153) of the isolates belonged to clonal complex 208. The ST191 isolates were detected during the study period, whereas ST451 isolates were detected after 2016. One hundred forty-seven (87%) of 167 A. baumannii isolates were non-susceptible to carbapenems. The ST191 and ST451 isolates exhibited higher resistance to antimicrobial agents than that of the sporadic ST isolates. Interestingly, ST451 isolates exhibited lower susceptibility to minocycline and tigecycline than the other ST isolates. All carbapenem-non-susceptible A. baumannii isolates, except four, carried the ISAbaI-blaOXA-23 structure. armA was detected in all amikacin-non-susceptible isolates (n = 128) except for one isolate. Five aminoglycoside-modifying enzyme (AME) genes were detected, but their carriage varied between STs; ant(3″)-Ia and aac(6')-Ib were more common in ST191 than in ST451, while aph(3')-Ia was more common in ST451 than in ST191. This study demonstrated the clonal evolution related to antimicrobial resistance in A. baumannii.

Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Causing Invasive Pneumococcal Disease in Korea Between 2017 and 2019 After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine.

Background: Streptococcus pneumoniae is a serious pathogen causing various infections in humans. We evaluated the serotype distribution and antimicrobial resistance of S. pneumoniae causing invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine (PCV)13 in Korea and investigated the epidemiological characteristics of multidrug-resistant (MDR) isolates. Methods: S. pneumoniae isolates causing IPD were collected from 16 hospitals in Korea between 2017 and 2019. Serotyping was performed using modified sequential multiplex PCR and the Quellung reaction. Antimicrobial susceptibility tests were performed using the broth microdilution method. Multilocus sequence typing was performed on MDR isolates for epidemiological investigations. Results: Among the 411 S. pneumoniae isolates analyzed, the most prevalent serotype was 3 (12.2%), followed by 10A (9.5%), 34 (7.3%), 19A (6.8%), 23A (6.3%), 22F (6.1%), 35B (5.8%), 11A (5.1%), and others (40.9%). The coverage rates of PCV7, PCV10, PCV13, and pneumococcal polysaccharide vaccine (PPSV)23 were 7.8%, 7.8%, 28.7%, and 59.4%, respectively. Resistance rates to penicillin, ceftriaxone, erythromycin, and levofloxacin were 13.1%, 9.2%, 80.3%, and 4.1%, respectively. MDR isolates accounted for 23.4% of all isolates. Serotypes 23A, 11A, 19A, and 15B accounted for the highest proportions of total isolates at 18.8%, 16.7%, 14.6%, and 8.3%, respectively. Sequence type (ST)166 (43.8%) and ST320 (12.5%) were common among MDR isolates. Conclusions: Non-PCV13 serotypes are increasing among invasive S. pneumoniae strains causing IPD. Differences in antimicrobial resistance were found according to the specific serotype. Continuous monitoring of serotypes and antimicrobial resistance is necessary for the appropriate management of S. pneumoniae infections.

Activity of a Novel Anti-Inflammatory Agent F-3,6'-dithiopomalidomide as a Treatment for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major risk factor for several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). Neuroinflammation is a cause of later secondary cell death following TBI, has the potential to aggravate the initial impact, and provides a therapeutic target, albeit that has failed to translate into clinical trial success. Thalidomide-like compounds have neuroinflammation reduction properties across cellular and animal models of TBI and neurodegenerative disorders. They lower the generation of proinflammatory cytokines, particularly TNF-α which is pivotal in microglial cell activation. Unfortunately, thalidomide-like drugs possess adverse effects in humans before achieving anti-inflammatory drug levels. We developed F-3,6'-dithiopomalidomide (F-3,6'-DP) as a novel thalidomide-like compound to ameliorate inflammation. F-3,6'-DP binds to cereblon but does not efficiently trigger the degradation of the transcription factors (SALL4, Ikaros, and Aiolos) associated with the teratogenic and anti-proliferative responses of thalidomide-like drugs. We utilized a phenotypic drug discovery approach that employed cellular and animal models in the selection and development of F-3,6'-DP. F-3,6'-DP significantly mitigated LPS-induced inflammatory markers in RAW 264.7 cells, and lowered proinflammatory cytokine/chemokine levels in the plasma and brain of rats challenged with systemic LPS. We subsequently examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) in mice, a model of moderate TBI known to induce inflammation. F-3,6'-DP decreased CCI-induced neuroinflammation, neuronal loss, and behavioral deficits when administered after TBI. F-3,6'-DP represents a novel class of thalidomide-like drugs that do not lower classical cereblon-associated transcription factors but retain anti-inflammatory actions and possess efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.

Red Blood Cell Deformability and Distribution Width in Patients with Hematologic Neoplasms.

BACKGROUND: Despite increasing evidence that red blood cell (RBC) deformability is impaired in pathologic conditions, little research has been done on RBC deformability in hematologic diseases. The authors measured RBC deformability in patients with various hematologic diseases, including hematologic malignancies. METHODS: A total of 568 patients who underwent bone marrow (BM) examination for initial diagnosis were enrolled. We collected the subjects' age, gender, diagnosis of BM examination, and complete blood count results. The RBC deformability, which was quantified by an elongation index, was measured by a microfluidic ektacytometer. RESULTS: RBC deformability was lower in primary myelofibrosis, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) from least to greatest. When the correlation between red blood cell distribution width (RDW) and RBC deformability was analyzed for 370 subjects in hematologic neoplasms, the correlation coefficient of RDW was -0.2974 (p < 0.01). When comparing MDS and aplastic anemia (AA), the deformability of MDS was significantly lower than that of AA. CONCLUSIONS: RBC deformability was decreased in leukemic diseases such as AML, MDS, CML, and ALL compared to control, and RDW showed a negative correlation with deformability. RBC deformability may be used as a complementary differential diagnostic test for MDS and AA.

Automated and manual microscopic analyses for leukocyte differential counts in exudative pleural effusions: Real-world disagreement and clinical application.

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and <30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.

Clinical evaluation of an innovative isothermal amplification detection system for COVID-19 diagnosis.

A pre-integrated system design intended for a point-of-care (POC) and sample-to-result diagnostic platform with nucleic acid amplification has been developed, which is equipment/electricity-free without any permanent instruments or manual sample processing. This semi-integrated system focuses on pandemic situations that are suitable for the Affordable, Sensitive, Specific, User-friendly, Robust and rapid, Equipment-free, and Deliverable to the end-user "ASSURED" concept recommended by the World Health Organization (WHO). Nucleic acid amplification is an essential rate-limiting factor in the performance of integrated systems that involve sample preparation and detection. The ORF1ab (RdRp) gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been targeted by RT-LAMP optimization and evaluation using a commercial hot-pack as a heat source that successfully achieves a femto-scale (<6.8 × 102 copies per rxn) limit of detection (LOD) within 40 min (except for the RNA extraction step). Therefore, the prototype system was assessed using COVID-19-suspected clinical samples (eighty eight) and compared with the results of a commercial real-time reverse transcription polymerase chain reaction (RT-qPCR) assay (Allplex SARS-CoV-2 Assay kit (Seegene, Seoul, Republic of Korea)). These innovative approaches achieved over 95% sensitivity and specificity. In conclusion, the developed system using a hot-pack as a heat source is a promising tool that enables the rapid identification of infectious diseases in the real world.

Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis.

OBJECTIVE: Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline. BACKGROUND: Amyloid-ß (Aß) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver. NEW HYPOTHESIS: AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aß generation will define the role of neuroinflammation in AD progression. MAJOR CHALLENGES: Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes. LINKAGE TO OTHER MAJOR THEORIES: Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aß. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.

Comparing SARS-CoV-2 Antibody Responses after Various COVID-19 Vaccinations in Healthcare Workers.

Coronavirus disease 2019 (COVID-19) vaccination began for healthcare workers in South Korea at the end of February 2021. This study investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses after various COVID-19 vaccinations in healthcare workers. Blood specimens of 497 vaccinated healthcare workers were collected. Inoculated vaccines were ChAdOx1 (AstraZeneca/Oxford), BNT162b2 (Pfizer/BioNTech), JNJ-78436735 (Janssen), and mRNA-1273 (Moderna). Each specimen was tested for antibodies against SARS-CoV-2 using Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics), SARS-CoV-2 IgG II Quant assay (Abbott), and R-FIND SARS-CoV-2 Neutralizing Antibody kit (SG medical Inc.). A questionnaire was used to investigate adverse events related to vaccination. We found that 99.5% of the subjects showed a 96-100% positive rate in all three antibody assays, regardless of the vaccine type. The antibody-positive rate of completed vaccination groups reached 96-100%, and antibody quantities significantly increased 2 weeks after vaccination. The antibody values measured approximately 3 months after BNT162b2 inoculation significantly correlated with adverse events.