Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

BACKGROUND: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC. METHODS: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis. RESULTS: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range. CONCLUSION: Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

Modulation of osteoblastogenesis by NRF2: NRF2 activation suppresses osteogenic differentiation and enhances mineralization in human bone marrow-derived mesenchymal stromal cells.

Mesenchymal stromal stem cells (MSCs) or skeletal stem cells (SSCs) play a major role in tissue repair due to their robust ability to differentiate into osteoblasts, chondrocytes, and adipocytes. Complex cell signaling cascades tightly regulate this differentiation. In osteogenic differentiation, Runt-related transcription factor 2 (RUNX2) and ALP activity are essential. Furthermore, during the latter stages of osteogenic differentiation, mineral formation mediated by the osteoblast occurs with the secretion of a collagenous extracellular matrix and calcium deposition. Activation of nuclear factor erythroid 2-related factor 2 (NRF2), an important transcription factor against oxidative stress, inhibits osteogenic differentiation and mineralization via modulation of RUNX2 function; however, the exact role of NRF2 in osteoblastogenesis remains unclear. Here, we demonstrate that NRF2 activation in human bone marrow-derived stromal cells (HBMSCs) suppressed osteogenic differentiation. NRF2 activation increased the expression of STRO-1 and KITLG (stem cell markers), indicating NRF2 protects HBMSCs stemness against osteogenic differentiation. In contrast, NRF2 activation enhanced mineralization, which is typically linked to osteogenic differentiation. We determined that these divergent results were due in part to the modulation of cellular calcium flux genes by NRF2 activation. The current findings demonstrate a dual role for NRF2 as a HBMSC maintenance factor as well as a central factor in mineralization, with implications therein for elucidation of bone formation and cellular Ca2+ kinetics, dystrophic calcification and, potentially, application in the modulation of bone formation.

Effect of dialysis on structural brain connectivity in patients with end-stage renal disease.

INTRODUCTION: Patients with end-stage renal disease (ESRD) are known to have reduced structural and functional brain connectivity in the brain regions associated with cognitive function. However, the effect of dialysis on brain connectivity remains unclear. This study aimed to evaluate the effects of dialysis on structural brain connectivity in patients with ESRD. METHODS: This prospective study included 20 patients with ESRD in the pre-dialysis stage and 35 healthy controls. The patients underwent T2-weighted and three-dimensional T1-weighted magnetic resonance imaging before and 3 months after dialysis initiation. Moreover, the cortical thickness was calculated. We applied graph theoretical analysis to calculate the structural covariance network based on cortical thickness. We compared the cortical thickness and structural covariance network of patients with ESRD in the pre-dialysis stage with those of healthy controls and with those of patients with ESRD in the post-dialysis stage. RESULTS: The mean cortical thickness in both hemispheres was lower in patients with ESRD in the pre-dialysis stage than in healthy controls (2.296 vs. 2.354, p=0.030; 2.282 vs. 2.362, p=0.004, respectively) and was higher in patients with ESRD in the post-dialysis stage than in those in the pre-dialysis stage (2.333 vs. 2.296, p=0.001; 2.322 vs. 2.282, p=0.002, respectively). Analysis of the structural covariance network revealed that the assortative coefficient was lower in patients with ESRD in the pre-dialysis stage than in healthy controls (-0.062 vs. -0.031, p=0.029) and was higher in patients with ESRD in the post-dialysis stage than in those in the pre-dialysis stage (-0.002 vs. -0.062, p=0.042). CONCLUSION: We observed differences in the cortical thickness and structural covariance networks before and after dialysis in patients with ESRD. This indicates that dialysis affects structural brain connectivity, contributing to the understanding of the pathophysiological mechanism of cognitive function alterations resulting from dialysis in patients with ESRD. .

Effects of charge distribution and degree of methylesterification of pectin emulsifier on bioaccessibility of curcumin incorporated in nanoemulsions.

The objectives of this study were to elucidate the effects of degree of methyl esterification (DM) and charge distribution of pectin on the stability of emulsions and to analyze bioaccessibility of curcumin incorporated in emulsions stabilized by pectins. Three commercial pectins, CP72 (DM72), CP50 (DM50), and CP7 (DM7), were used. MP50 (DM50) with consecutive demethylesterified galacturonic acid residues was prepared from CP72 via demethylesterification to induce different charge distributions. Emulsions containing curcumin were prepared and were stored for 30 days. The CP72 and CP50 emulsions remained relatively stable for 30 days. However, MP50 and CP7 were less effective at forming stable emulsions. When the pectin emulsions passed through each phase of the simulated gastrointestinal tract (GIT), the CP72 and CP50 emulsions retained their initial droplet structures after in vitro mouth and gastric digestion, whereas the MP50 and CP7 emulsions exhibited gel-like clusters, although the gel-like formation of MP50 was distinct from that observed in CP7. MP50 emulsion showed a high degree of final lipid digestion and high bioaccessibility of curcumin while CP72 emulsion displayed a low degree of final lipid digestion. CP50 exhibited low bioaccessibility of curcumin, which might have been contributed by its fast lipid digestion profiles.

Analysis of prefrontal cerebral blood volume and flow changes in ESKD patients undergoing hemodialysis using functional near-infrared spectroscopy.

BACKGROUND: End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. METHODS: ESKD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 - HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. RESULTS: Thirty hemodialysis patients were analyzed. The change in HbO2, HbT, and HbD levels showed significant differences according to the hemodialysis period. Between the pre-HD and post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p = .046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p = .029). Additionally, between pre-HD and post-HD periods, HbD tended to increase (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p = .094). CONCLUSIONS: We demonstrated that during one hemodialysis session, the relative change in prefrontal CBV increased post-HD compared with pre-HD. These results are expected to help understanding the mechanisms underlying the effects of hemodialysis on brain function.

The Destiny of the Subscapularis Tendon after Arthroscopic Supraspinatus Repair.

Background: The purpose of this study was to identify the changes in untreated subscapularis in patients who underwent supraspinatus repair and to evaluate the factors related to the changes in the subscapularis. Methods: A cohort of patients who underwent isolated supraspinatus repair with preservation of the subscapularis was reviewed. Changes in the subscapularis, including any newly formed lesion and aggravation of an existing lesion, were evaluated 12 months postoperatively on magnetic resonance imaging along with an examination to identify causative factors after supraspinatus repair. Clinical scores were compared between patients with and without subscapularis changes. Results: A total of 528 patients were reviewed. Changes in the subscapularis, including newly formed lesions and aggravation of an existing lesion, were shown in 90 patients (17.0%). Upon regression analysis, changes in the subscapularis were associated with the initial existence of a subscapularis lesion (grade I: p = 0.042, grade II: p = 0.025), an accompanying biceps lesion (p = 0.038), and a retear of the repaired supraspinatus (p = 0.024). No significant differences were shown in clinical scores between patients with and without subscapularis changes after supraspinatus repair. Conclusions: Untreated asymptomatic subscapularis may undergo morphological changes even after repair of the torn supraspinatus. Preoperative subscapularis lesions, biceps long head pathology, and retears of the repaired supraspinatus were associated with subscapularis pathology in patients who underwent supraspinatus repair.

Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P = .024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

The study aims to investigate the coinfection between mucormycosis and aspergillosis. Key findings reveal that approximately 31% of patients demonstrated evidence of coinfection, which emphasizes the importance of considering both pathogens in diagnosis and treatment decisions.

Clinical and microbiological characteristics of persistent Staphylococcus aureus bacteremia, risk factors for mortality, and the role of CD4+ T cells.

This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.

Complete genome sequencing of three methicillin-resistant Staphylococcus aureus isolated from the blood of patients with persistent bacteremia.

We report the complete genome sequences of three molecular types of methicillin-resistant Staphylococcus aureus (MRSA) clinical strains isolated from the blood of three patients diagnosed with persistent MRSA bacteremia: KNIH_5618 (ST5-t5076-SCCmecII), KNIH_5844 (ST72-t664-SCCmecIV), and KNIH_6268 (ST89-t375-SCCmecII). These genome sequences contribute to an enhanced understanding of the underlying causes of persistent MRSA infection.

MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes.

Abnormal adipose tissue formation is associated with metabolic disorders such as obesity, diabetes, and liver and cardiovascular diseases. Thus, identifying the novel factors that control adipogenesis is crucial for understanding these conditions and developing targeted treatments. In this study, we identified the melanosome-related factor MLPH as a novel adipogenic factor. MLPH was induced during the adipogenesis of 3T3-L1 cells and human mesenchymal stem cells. Although MLPH did not affect lipid metabolism, such as lipogenesis or lipolysis, adipogenesis was severely impaired by MLPH depletion. We observed that MLPH prevented excess reactive oxygen species (ROS) accumulation and lipid peroxidation during adipogenesis and in mature adipocytes. In addition, increased MLPH expression was observed under cirrhotic conditions in liver cancer cells and its overexpression also reduced ROS and lipid peroxidation. Our findings demonstrate that MLPH is a novel adipogenic factor that maintains redox homeostasis by preventing lipid peroxidation and ROS accumulation, which could lead to metabolic diseases.

Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

Bursal Acromial Resurfacing Improves Shoulder Biomechanics in a Cadaveric Model of Massive Rotator Cuff Tear.

PURPOSE: To investigate the effectiveness of bursal acromial resurfacing (acromiograft) on acromiohumeral distance, subacromial contact area, and pressure in a cadaveric model of massive rotator cuff tear. METHODS: Eight fresh-frozen cadaveric shoulders were tested using a customized shoulder testing system. Humeral head translation, subacromial contact pressure, and the subacromial contact area were evaluated across 4 conditions: (1) intact shoulder; (2) simulated massive rotator cuff tear, (3) 3-mm acromiograft condition, and (4) 6-mm acromiograft condition. The acromiografts were simulated using Teflon and a reported technique. The values were measured at 0°, 20°, and 40° abduction and 0°, 30°, 60°, and 90° external rotation for each abduction status. RESULTS: Compared with a massive cuff tear, the 6-mm acromiograft significantly reduced the superior translation of the humeral head at all abduction/external rotation angles (P < .05). The 3-mm acromiograft also decreased superior translation of the humeral head compared with massive cuff tear, but not all differences were significant. The 3- and 6-mm acromiografts significantly decreased the subacromial contact pressure and increased the subacromial contact area in almost all positions (P < .05). The 3-mm acromiograft maintained biomechanical properties similar to the intact condition, whereas the 6-mm acromiograft increased the contact area. CONCLUSIONS: This biomechanical study demonstrated that both 3- and 6-mm acromiografts using Teflon in a cadaveric model of a massive cuff tear resulted in recentering of the superiorly migrated humeral head, increased the subacromial contact area, and decreased the subacromial contact pressure. The 3-mm graft was sufficient for achieving the intended therapeutic effects. CLINICAL RELEVANCE: The acromiograft can normalize altered biomechanics and may aid in the treatment of massive cuff tears. Because grafting the acromion's undersurface is new with limited clinical outcomes, further observation is crucial. Using a Teflon instead of an acellular dermal matrix allograft for bursal acromial resurfacing could yield different results, requiring careful interpretation.

Structural stability for surface display of antigen 43 and application to bacterial outer membrane vesicles production.

Antigen 43 (Ag43) proteins, found on the outer membrane of Escherichia coli, are ß-sheets that fold into a unique cylindrical structure known as a ß-barrel. There are several known structural similarities between bacterial Ag43 autotransporters and physical components; however, the factors that stabilize the barrel and the mechanism for Ag43 passenger domainmediated translocation across the pore of the ß-barrel remain unclear. In this study, we analyzed Ag43ß-enhanced green fluorescent protein chimeric variants to provide new insights into the autotransporter Ag43ß-barrel assembly, focusing on the impact of the α-helical linker domain. Among the chimeric variants, Ag43ß700 showed the highest surface display, which was confirmed through extracellular protease digestion, flow cytometry, and an evaluation of outer membrane vesicles (OMVs). The Ag43ß700 module offered reliable information on stable barrel folding and chimera expression at the exterior of the OMVs. [BMB Reports 2024; 57(8): 369-374].

Effect of RANKL on Lower Depressive Symptoms In Hemodialysis Patients.

Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (ß - 4.527, 95% CI - 8.310 to - 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (ß - 5.603, 95% CI - 9.715 to -1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19-0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12-0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients.Trial registration WHO registry, No. KCT0003281, date: January 12, 2017.

Chloroplast Genomes of Vitis flexuosa and Vitis amurensis: Molecular Structure, Phylogenetic, and Comparative Analyses for Wild Plant Conservation.

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges.

Comparative analysis of the incidence and mortality of COVID-19 in Korean end-stage kidney disease patients: hemodialysis, peritoneal dialysis, and transplantation.

Background: Patients with end-stage kidney disease (ESKD) are more susceptible to viral epidemics and are known to have higher incidence and death rates of coronavirus disease 2019 (COVID-19) compared to the general population. We determined COVID-19 incidence and mortality among chronic hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT) patients in Korea. Methods: We conducted a retrospective cohort study and data regarding Korean ESKD adults (aged ≥18 years) were obtained from the National Health Insurance Service of Korea from October 2020 to December 2021. We examined and compared the incidence of COVID-19-related infections and deaths among the patients receiving HD, PD, and KT. Results: Of all ESKD patients, 85,018 (68.1%) were on HD, 8,399 (6.7%) on PD, and 31,343 (25.1%) on KT. The COVID-19 incidence was 1.3% for HD, 1.2% for PD, and 1.5% for KT. COVID-19 mortality was 16.3% for HD, 12.2% for PD, and 4.7% for KT. PD patients had a lower incidence of infection compared to HD patients (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.607-0.93), but KT patients had a significantly higher risk of infection (OR, 1.28; 95% CI, 1.13-1.44). Compared with HD, the risk of COVID-19-related death was not different for PD patients but was significantly lower for KT patients (hazard ratio, 0.55; 95% CI, 0.35-0.88). Conclusion: COVID-19 incidence was lower in PD patients than in HD patients, but mortality was not different between them. KT was associated with a higher risk of COVID-19 infection but lower mortality compared to HD.

Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study.

OBJECTIVE: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. METHODS: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. RESULTS: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DISCUSSION: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.

Photo- and Stress-Induced Bending of (E)-1,2-Bis(pyridinium-4-yl)ethene Dinitrate Crystals.

We report on the elastic and photodynamic properties of (E)-1,2-bis(pyridinium-4-yl)ethene dinitrate [H2Ebpe](NO3)2, whose needle-like crystals can be reversibly deformed by applying external mechanical stress. The macro-scale mechanical properties of [H2Ebpe](NO3)2 crystals were quantified by a three-point bending test, which gave a stress-strain curve with an elastic modulus of 1.18 GPa, and its values are lower than those of other flexible elastic organic crystals. It can also be reversibly bent through the [2+2] cycloaddition reaction of the olefin moiety, depending on the direction of UV irradiation.

miRNA profiling of B16F10 melanoma cell exosomes reveals melanin synthesis-related genes.

This study investigates the communication between skin cells, specifically melanocytes, keratinocytes, and fibroblasts, which is crucial for the process of melanin production known as melanogenesis. We aimed to understand the role of melanocyte exosomes in regulating melanogenesis and to uncover the microRNAs influencing this process. We isolated exosomes and characterized them using advanced microscopy and protein analysis to achieve this. We conducted experiments on melanoma cells to study melanin production regulation and examined how exosomes influenced gene expression related to melanogenesis. The results revealed that melanocyte exosomes increased certain types of tyrosinases, thereby enhancing melanin production. Furthermore, we acquired the miRNA profile of exosomes and hypothesized that specific siRNAs, such as miR-21a-5p, could potentially facilitate melanin synthesis. Our findings shed light on the importance of exosomes in skin health and provide valuable insights into intercellular communication mechanisms. Understanding these processes can pave the way for innovative therapies to treat melanin-related disorders and maintain healthy skin.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.