Risk of post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants: a cohort study using the common data model.

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Dibutyl phthalate disrupts glycogen synthase kinase 3α essential for sperm motility.

To unravel the toxic mechanism of phthalate ester plasticizer endocrine disruptor in spermatozoa, we examined the effect of dibutyl phthalate (DBP) on the stability and inhibitory phosphorylation of glycogen synthase kinase 3α (GSK3α), a protein kinase crucial for sperm motility in mice. In DBP-treated spermatozoa, reactive oxygen species (ROS) and lipid peroxide were significantly increased. In computer-assisted sperm analysis, DBP at concentrations of 10 - 100 µg/mL significantly decreased total motility and progressive motility of spermatozoa. On western blots, DBP decreased p-GSK3α(Ser21) and increased p-GSK3α(Tyr279) in spermatozoa. Similarly, hydrogen peroxide decreased p-GSK3α(Ser21) but not p-GSK3α(Tyr279) in spermatozoa. Immunofluorescent labeling demonstrated that DBP markedly decreased immunoreactivities of GSK3α and p-GSK3α(Ser21) but increased immunoreactivity of p-GSK3α(Tyr279) in spermatozoa. DBP at a concentration of 100 µg/mL significantly increased phosphatase activity in spermatozoa. Calyculin A, a protein phosphatase 1 and 2 A inhibitor, markedly increased p-GSK3α(Ser21) and sperm motility and attenuated a DBP-induced decrease of p-GSK3α(Ser21) and sperm motility. On western blot, 1-100 µg/mL DBP decreased GSK3α in spermatozoa. On immunoprecipitation western blot, DBP at 10 - 100 µg/mL increased polyubiquitinated sperm proteins including GSK3α. The MG115, proteasome inhibitor attenuated degradation of GSK3α in DBP-treated spermatozoa. Hydrogen peroxide at 10 µM increased polyubiquitinated sperm proteins, suggesting that DBP may increase ubiquitination of GSK3α via ROS induction. Together, DBP may decrease the cellular amount of GSK3α through the ubiquitin-proteasome pathway and p-GSK3α(Ser21) through ROS generation and activation of protein phosphatases, impairing sperm motility.

Inhibition of mitochondrial cyclophilin D, a downstream target of glycogen synthase kinase 3α, improves sperm motility.

BACKGROUND: Cyclophilin D (CypD) negatively regulates ATP production by opening of the mitochondrial permeability transition pore. This study aimed to understand the role of CypD in sperm motility regulation. METHODS: Changes in CypD during sperm capacitation and its interaction with glycogen synthase kinase 3α (GSK3α), a key kinase regulating sperm motility, were examined in mouse spermatozoa. The effects of CypD inhibitor cyclosporin A (CsA) and GSK3 inhibitor 6-bromo-indirubin-3'-oxime (BIO) on sperm motility, p-GSK3α(Ser21), mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (MMP), and ATP production were examined. The effect of proteasome inhibitor MG115 on the cellular levels of CypD was examined. RESULTS: In cauda epididymal spermatozoa, GSK3α was found in both cytosolic and mitochondrial fractions whereas CypD was primarily found in the mitochondrial fraction together with ATP synthase F1 subunit alpha (ATP5A), a mitochondrial marker. GSK3α and CypD were co-localized in the sperm midpiece. Interaction between GSK3α and CypD was identified in co-immunoprecipitation. CsA, a CypD inhibitor, significantly increased sperm motility, tyrosine phosphorylation, mPTP closing, MMP, and ATP levels in spermatozoa, suggesting that CypD acts as a negative regulator of sperm function. Under capacitation condition, both GSK3α and CypD were decreased in spermatozoa but ATP5A was not. The GSK3 inhibitor BIO markedly increased p-GSK3α(Ser21) and decreased CypD but significantly increased mPTP closing, MMP, ATP production, and motility of spermatozoa. This suggests that inhibitory phosphorylation of GSK3α is coupled with degradation of CypD, potentiating the mitochondrial function. Degradation of CypD was attenuated by MG115, indicative of involvement of the ubiquitin proteasome system. CONCLUSIONS: During sperm capacitation, CypD act as a downstream target of GSK3α can be degraded via the ubiquitin proteasome system, stimulating mitochondrial function and sperm motility.

Head dysgenesis and disruption of cranial neural crest stem cells behaviour by 4-octylphenol in fire-bellied toad Bombina orientalis embryos.

Alkylphenolic endocrine disruptors (Eds) have been known to affect development of the descendants of multipotent neural crest cells (NCCs) in amphibian embryos. To unravel the mechanism of head dysgenesis induced by alkylphenols in amphibians, the effect of 4-octylphenol (OP) on the differentiation of cranial NCCs in developing embryos and tadpoles, ex vivo NC explant, and isolated NCCs was examined in fire-bellied toad Bombina orientalis with 0, 1, 2, 5, 10, 25 and 50 µM concentrations. Following OP treatment, head cartilages were frequently absent together with the decreased col2a1 mRNA level in tadpoles. While the lipid hydroperoxide (LPO), endoplasmic reticulum stress (ERS), apoptosis, and DNA fragmentation were significantly increased in stage 22 neulurae and heads of stage 45 tadpoles. In stage 22 neulurae, OP decreased sox9 mRNA, the master transcription factor for chondrogenic differentiation and increased undifferentiated NCC markers. The ectopic NCCs were found in endoderm while mesodermal SOX10(+) cells were decreased. In cranial NCCs isolated from stage 22 embryos, OP treatment decreased cellular survival and increased apoptosis, epithelial-mesenchymal transition (EMT) and cell migration. In chondrogenic induced cranial NC explants, OP treatment decreased SOX9(+) chondrocytes and cartilage development. Together, OP potentiated oxidative damage, apoptosis, EMT, and ectopic migration of NCCs. Considering that tissue differentiation requires stem cells to activate the molecular mechanism of differentiation at the correct location during embryonic development, these changes caused by OP may inhibit sox9-dependent chondrogenic differentiation of cranial NCCs, leading to head dysgenesis in B. orientalis embryos. Therefore, developing multipotent NCCs could be an important target of OP, provides new direction for the estimation of the risk of EDs exposure in human and wildlife animals.

Methodological rigour in preclinical urology: a systematic review reporting research quality over a 14-year period.

OBJECTIVE: To investigate the prevalence and trends of essential study design elements in preclinical urological studies, as well as key factors that may improve methodological rigour, as the demand for methodological rigour in preclinical studies is increasing since research reproducibility and transparency in the medico-scientific field are being questioned. METHODS AND RESULTS: PubMed was searched to include preclinical urological studies published between July 2007 to June 2021. A total of 3768 articles met the inclusion criteria. Data on study design elements and animal models used were collected. Citation density was also examined as a surrogate marker of study influence. We performed an analysis of the prevalence of seven critical study design elements and temporal patterns over 14 years. Randomisation was reported in 50.0%, blinding in 15.0%, sample size estimation in 1.0%, inclusion of both sexes in 6.3%, statistical analysis in 97.1%, housing and husbandry in 47.7%, and inclusion/exclusion criteria in 5.0%. Temporal analysis showed that the implementation of these study design elements has increased, except for inclusion of both sexes and inclusion/exclusion criteria. Reporting study design elements were associated with increased citation density in randomisation and statistical analysis. CONCLUSIONS: The risk of bias is prevalent in 14-year publications describing preclinical urological research, and the quality of methodological rigour is barely related to the citation density of the article. Yet five study design elements (randomisation, blinding, sample size estimation, statistical analysis, and housing and husbandry) proposed by both the National Institutes of Health and Animal Research: Reporting of In Vivo Experiments guidelines have been either well reported or are being well reported over time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022233125.

Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human.

PURPOSE: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human. MATERIALS AND METHODS: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions. RESULTS: In human spermatozoa, GSK3α/ß was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca2+ containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3'-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa. CONCLUSIONS: Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca2+, PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility.

Association between shift work and serum homocysteine level in female electronic manufacturing services workers.

Background: Shift work has been shown to increase the risk of cardiovascular disease (CVD) based on several evidences. The classic risk factors of CVD include age, hypertension, smoking, obesity and diabetes. Recently, the serum homocysteine level has been reported to be a valuable indicator of CVD risk. This study aimed to determine the variation in serum homocysteine level as a cardiovascular risk indicator among female workers according to shift work. Methods: The data of regular health examination of workers at an electronic manufacturing services company in Yeongnam region, South Korea in 2019 were examined in this study. The investigation was based on a cross-sectional study conducted on 697 female workers (199 day workers and 498 shift workers). The sociodemographic and biochemical characteristics were compared between day workers and shift workers. Through a logistic regression analysis, the odds ratio (OR) of the increased serum homocysteine level in relation to shift work was determined. Results: Compared to female day workers, female shift workers showed significantly higher level of serum homocysteine (8.85 ± 2.16 vs. 9.42 ± 2.04 µmol/mL; p = 0.001). The OR of day workers against shift workers was 1.81 (95% confidence interval [CI]: 1.25-2.63). With the adjustment of variables that may influence the level of serum homocysteine, the adjusted OR was 1.68 (95% CI: 1.09-2.60). Conclusions: The serum homocysteine level was significantly higher in shift workers than in day workers. It is thus likely to be a useful predictor of CVD in shift workers.

Glycogen Synthase Kinase-3 Isoform Variants and Their Inhibitory Phosphorylation in Human Testes and Spermatozoa.

PURPOSE: To clarify (phospho-) glycogen synthase kinase-3 (GSK3) isoform variants in the germline and soma of human testes and spermatozoa. MATERIALS AND METHODS: GSK3 isoform variants in normospermatogenic and Sertoli cell-only (SCO) testicular biopsies and spermatozoa were examined. RESULTS: In normospermatogenic testes, GSK3α and GSK3ß variants 1 and 2 different in low complexity region (LCR) were expressed and their levels were decreased in SCO testes. GSK3ß variant 3 was only expressed in SCO testes. GSK3ß as well as GSK3α, the dominant isoforms in testes were decreased in SCO testes. In normospermatogenic testes, GSK3ß were found in spermatogonia and markedly decreased in meiotic germ cells in which GSK3α was dominant. p-GSK3α/ß were marginal in spermatogonia and early spermatocytes. In SCO testes, GSK3α/ß immunoreactivity in seminiferous epithelia was weaker than those of normospermatogenic testes whereas p-GSK3α/ß(Ser) immunoreactivity was visibly increased in Sertoli cells. GSK3α was dominant in ejaculated spermatozoa in which GSK3α and p-GSK3α(Ser) were found in the head, midpiece, and tail. In acrosome-reacted spermatozoa, GSK3α was found in the equatorial region of head, midpiece, and tail, and p-GSK3α(Ser) was only found in midpiece. During sperm capacitation, p-GSK3α(Ser) was significantly increased together with phosphotyrosine proteins and motility. CONCLUSIONS: In human male germ cells, GSK3 isoforms different in LCRs switch from GSK3ß to GSK3α during meiotic entry, suggesting the isoform-specific roles of GSK3α and GSK3ß in meiosis and stemness or proliferation of spermatogonia, respectively. In dormant Sertoli cells of SCO testes kinase activity of GSK3 might be downregulated via inhibitory phosphorylation. In spermatozoa, inhibitory phosphorylation of GSK3α might be coupled with activation of motility during capacitation.

Review of chemical pretreatment of lignocellulosic biomass using low-liquid and low-chemical catalysts for effective bioconversion.

Chemical pretreatment of lignocellulosic biomass (LCB) is essential for effective biological conversion in subsequent steps to produce biofuels or biochemicals. For effective pretreatment, high lignin content and its recalcitrant nature of LCB are major factors influencing bioconversion, especially lignin is known to be effectively solubilized by alkaline, organic, and deep eutectic solvents, ionic liquids, while hemicellulose is effectively dissolved by various acid catalysts and organic solvents. Depending on the pretreatment method/catalyst used, different pretreatment process scheme should be applied with different amounts of catalyst and water inputs to achieve a satisfactory effect. In addition, the amount of processing water required in the following processes such as washing, catalyst recovery, and conditioning after pretreatment is critical factor for scale-up (commercialization). In this review, the amount of catalyst and/or water used, and the effect of pretreatment, properties of the products, and recovery of liquid are also discussed.

Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.

Phthalate plasticizer decreases the prion-like protein doppel essential for structural integrity and function of spermatozoa.

Di-n-butyl phthalate (DBP), a well-known endocrine disruptor, causes male reproductive dysfunction. To understand the underlying mechanisms, we performed histological, endocrinological, and biochemical analyses and assessed the expression of genes involved in spermatogenesis and sperm function according to OECD test guideline 407. Following 28 days of administration of the lowest observed adverse effect level dose of DBP to mice, no significant changes in body weight, testis and epididymis weights and histology, serum testosterone level, or testicular daily sperm production were found. Nonetheless, the motility of the epididymal sperm of the DBP group was significantly decreased together with an increase in the incidence of bent tails and abnormal heads. In the testes of the DBP group, lipid peroxidation (LPO) level was significantly increased and testicular Bcl-2 mRNA level was significantly decreased together with an increase in the Bax/Bcl-2 mRNA ratio. In the testes of the DBP group, levels of Prnd mRNA and protein and Pou4f1 mRNA, an activator of the Prnd promotor, were significantly decreased. Of note, prion-like protein doppel (PRND) was significantly decreased together with decreased PRND immunoreactivity in the head, midpiece, and tail of sperm. In the testes of the DBP group, levels of Sox9, Sgp1, and Sgp2 mRNA, which are functional Sertoli cell markers, were significantly decreased. Level of Amh mRNA, a Sertoli cell immaturity marker, was significantly increased together with that of Inha mRNA, suggesting deregulation of the brain-gonadal axis. Together, our findings suggest that DBP at present dosage may potentiate LPO generation and Sertoli cell immaturity via downregulation of Sox9 and disruption of the Pou4f1-Prnd gene network in post-meiotic germ cells without visible changes in spermatogenesis or testosterone level. This may result in structural and functional abnormalities in spermatozoa. Additionally, our findings suggest that assessment of the male reproductive toxicity of phthalate ester plasticizers based on conventional OECD test guidelines should be reconsidered.

Association between coronavirus disease 2019-related workplace interventions and prevalence of depression and anxiety.

Background: Although coronavirus disease 2019 is causing a variety of psychological problems for workers, there are few longitudinal studies on changes in workers' mental health by workplace intervention. This study aimed to evaluate the change in the prevalence of depression and anxiety according to the active involvement of the workplace. Methods: This study was conducted on 1,978 workers at a workplace who underwent a health screening from January 2019 to August 2020, and classified depression and anxiety disorders using a self-report questionnaire. After the first pandemic, the company stopped health screening, took paid leave and telecommuting, and conducted interventions such as operating its own screening clinic. To see if this workplace intervention affects workers' mental health, we conducted generalized estimating equations to compare odds ratio (OR). Results: In the pre-intervention group, 384 people (16.86%) had depression, and 507 people (22.26%) had anxiety disorder. Based on the OR before intervention, the OR of depression decreased to 0.76 (0.66-0.87) and the OR of anxiety disorder decreased to 0.73 (0.65-0.82). Conclusions: As a result of this study, it was confirmed that workplace intervention was related to a decrease in depression and anxiety. This study provides basic data to improve workers' mental health according to workplace intervention, and further research is needed according to workplace intervention in the future.

Profile of vascular markers and CT enhancement of hyaline vascular type Castleman's disease.

Blood vessels in lymph nodes (LNs) are unique in comprising both capillaries and high endothelial venules (HEVs). Hyaline vascular type Castleman's disease accompanies robust angiogenesis, but it is unclear how the capillaries and HEVs respond. We retrospectively examined surgical specimens of hyaline vascular type unicentric Castleman's disease patients (n = 24) and control LNs (n = 9). We performed immunohistochemistry of CD 31 for capillaries and MECA-79 for HEVs and calculated their microvascular density. We measured CT enhancement as the ratio of Hounsfield Units (HUs) of the target lesion against muscle compared with microvascular density. The microvascular density of Castleman's disease specimen were (CD 31+) 169.7 ± 77.6, (MECA-79+) 203.5 ± 96.7, and the microvascular density of control LNs were (CD 31+) 80.7 ± 20.1, (MECA-79+) 67.4 ± 23.7, respectively. The microvascular density of both CD 31+ (P < 0.001) and MECA-79+ (P < 0.001) was higher in Castleman's disease. A positive correlation existed between CT HU ratio and microvascular density for both markers (CD 31: r = 0.517, P = 0.002; MECA-79: r = 0.521, P = 0.002). Intra-nodal angiogenesis of Castleman's disease involves robust proliferation of not only CD 31+ capillaries, but also MECA-79+ HVEs, which each correlated with degree of CT enhancement.

LI-RADS Version 2018 Targetoid Appearances on Gadoxetic Acid-Enhanced MRI: Interobserver Agreement and Diagnostic Performance for the Differentiation of HCC and Non-HCC Malignancy.

BACKGROUND. In LI-RADS version 2018, observations showing at least one of five targetoid appearances in different sequences or postcontrast phases are categorized LR-M, indicating likely non-hepatocellular carcinoma (HCC) malignancy. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement for LI-RADS targetoid appearances among a large number of radiologists of varying experience and the diagnostic performance of targetoid appearances for differentiating HCC from non-HCC malignancy. METHODS. This retrospective study included 100 patients (76 men, 24 women; mean age, 58 ± 9 [SD] years) at high risk of HCC who underwent gadoxetic acid-enhanced MRI within 30 days before hepatic tumor resection (25 randomly included patients with non-HCC malignancy [13, intrahepatic cholangiocarcinoma; 12, combined HCC-cholangiocarcinoma]; 75 matched patients with HCC). Eight radiologists (four more experienced [8-15 years]; four less experienced [1-5 years]) from seven institutions independently assessed observations for the five targetoid appearances and LI-RADS categorization. Interobserver agreement and diagnostic performance for non-HCC malignancy were evaluated. RESULTS. Interobserver agreement was poor for peripheral washout (κ = 0.20); moderate for targetoid transitional phase or hepatobiliary phase appearance (κ = 0.33), delayed central enhancement (κ = 0.37), and targetoid restriction (κ = 0.43); and substantial for rim arterial phase hyperenhancement (κ = 0.61). Agreement was fair for at least one targetoid appearance (κ = 0.36) and moderate for at least two, three, or four targetoid appearances (κ = 0.43-0.51). Agreement for individual targetoid appearances was not significantly different between more experienced and less experienced readers other than for targetoid restriction (κ = 0.63 vs 0.43; p = .001). Agreement for at least one targetoid appearance was fair among more experienced (κ = 0.29) and less experienced (κ = 0.37) reviewers. Agreement for at least two, three, or four targetoid appearances was moderate to substantial among more experienced reviewers (κ = 0.45-0.63) and moderate among less experienced reviewers (κ = 0.42-0.56). Existing LR-M criteria of at least one targetoid appearance had median accuracy for non-HCC malignancy of 62%, sensitivity of 84%, and specificity of 54%. For all reviewers, accuracy was highest when at least three (median accuracy, 79%; sensitivity, 68%; specificity, 82%) or four (median accuracy, 80%; sensitivity, 54%; specificity, 88%) targetoid appearances were required. CONCLUSION. Targetoid appearances and LR-M categorization exhibited considerable interobserver variation among both more and less experienced reviewers. CLINICAL IMPACT. Requiring multiple targetoid appearances for LR-M categorization improved interobserver agreement and diagnostic accuracy for non-HCC malignancy.

Clinical significance of hepatosplenic thrombosis in vaccine-induced immune thrombotic thrombocytopenia after ChAdOx1 nCoV-19 vaccination.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, serious complication after adenoviral COVID-19 vaccine administration that can involve various organ systems. We aimed to investigate the clinical significance of hepatosplenic thrombosis in patients with VITT. METHODS: We searched PubMed ePubs, Scopus, Embase, and Web of Science databases for studies published until April 28, 2021, involving patients with VITT after ChAdOx1 nCoV-19 vaccination. Demographic and clinical characteristics, including laboratory measurements, were collected and compared. RESULTS: Four case series and three case reports involving 48 cases of VITT were included. Hepatosplenic thrombosis was present in 8 cases (17%). Patients with hepatosplenic thrombosis had lower platelet counts (13,000 vs. 29,500/µL, p=0.016) and higher D-dimer levels (140.0 vs. 57.3 times upper limit of normal range, p=0.028). Multiple-site thrombosis was also associated with hepatosplenic thrombosis (88% vs. 15%, p<0.001). CONCLUSIONS: This is the first study comparing clinical profiles of patients with VITT according to the presence of hepatosplenic thrombosis. Patients with hepatosplenic thrombosis had more severe presentations with lower platelet counts, higher D-dimer levels, and a higher rate of multiple-site thrombosis. Further studies with larger sample sizes are required to establish definitive evidence regarding the significance of hepatosplenic thrombosis in VITT.

Distribution of Lung-RADS categories according to job type in a single shipyard workers.

BACKGROUND: Recently, lung cancer screenings based on age and smoking history using low-dose computed tomography (LDCT) have begun in Korea. This study aimed to evaluate the distribution of lung imaging reporting and data system (Lung-RADS) categories in shipyard workers exposed to lung carcinogens such as nickel, chromium, and welding fumes according to job type, to provide basic data regarding indications for LDCT in shipyard workers. METHODS: This study included 6,326 workers from a single shipyard, who underwent health examinations with LDCT between January 2010 and December 2018. Data on age, smoking status and history, medical history, and job type were investigated. The participants were categorized into high-exposure, low-exposure, and non-exposure job groups based on the estimated exposure level of nickel, chromium, and welding fumes according to job type. Cox proportional hazard regression analysis was used to determine the difference between exposure groups in Lung-RADS category ≥ 3 (3, 4A, and 4B). RESULTS: Out of all participants, 97 (1.5%) participants were classified into Lung-RADS category ≥ 3 and 7 (0.1%) participants were confirmed as lung cancer. The positive predictive value (ratio of diagnosed lung cancer cases to Lung-RADS category ≥ 3) was 7.2%. The hazard ratio (HR) of Lung-RADS category ≥ 3 was 1.451 (95% confidence interval [CI]: 0.911-2.309) in low-exposure and 1.692 (95% CI: 1.007-2.843) in high-exposure job group. Adjusting for age and pack-years, the HR was statistically significant only in the high-exposure job group (HR: 1.689; 95% CI: 1.004-2.841). CONCLUSIONS: Based on LDCT and Lung-RADS, among male shipyard workers, Lung-RADS category ≥ 3 were significantly higher in the high-exposure job group. Their HR tended to be > 1.0 and was statistically significant in the high-exposure job group. Additional studies should be conducted to establish more elaborate LDCT indications for occupational health examination.

Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: the FAPIC score.

AIMS: The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality. METHODS AND RESULTS: PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732-0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration. CONCLUSIONS: Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants.

Workers' Exposure to Indium Compounds at the Electronics Industry in Republic of Korea.

OBJECTIVES: The aim of this study was to provide baseline data for the assessment of exposure to indium and to prevent adverse health effects among workers engaged in the electronics and related industries in Republic of Korea. METHODS: Total (n = 369) and respirable (n = 384) indium concentrations were monitored using personal air sampling in workers at the following 19 workplaces: six sputtering target manufacturing companies, four manufacturing companies of panel displays, two companies engaged in cleaning of sputtering components, two companies dedicated to the cleaning of sputtering target, and five indium recycling companies. RESULTS: The level of exposure to total indium ranged from 0.9 to 609.3 µg/m3 for the sputtering target companies; from 0.2 to 2,782.0 µg/m3 for the panel display companies and from 0.5 to 2,089.9 µg/m3 for the indium recycling companies. The level of exposure to respirable indium was in the range of 0.02 to 448.6 µg/m3 for the sputtering target companies; 0.01 to 419.5 µg/m3 for the panel display companies; and 0.5 to 436.3 µg/m3 for the indium recycling companies. The indium recycling companies had the most samples exceeding the exposure standard for indium, followed by sputtering target companies and panel display companies. CONCLUSIONS: The main finding from this exposure assessment is that many workers who handle indium compounds in the electronics industry are exposed to indium levels that exceed the exposure standards for indium. Hence, it is necessary to continuously monitor the indium exposure of this workforce and take measures to reduce its exposure levels.

Adjunctive use of metronidazole-minocycline ointment in the nonsurgical treatment of peri-implantitis: A multicenter randomized controlled trial.

BACKGROUND: Clinical benefits of local antibiotics as an adjunct to nonsurgical treatment of peri-implantitis have been widely reported, but most studies evaluated incipient peri-implantitis lesions, and showed incomplete treatment success rates. PURPOSE: To assess the clinical and microbiological outcomes of administering metronidazole in combination with minocycline as a local adjunct to the nonsurgical treatment of peri-implantitis. MATERIALS AND METHODS: One hundred and eighteen subjects with peri-implantitis were recruited in a four-center, three-arm, and 12-week randomized controlled trial. Subjects were randomly assigned to receive one of the following treatments: (a) MM-mechanical debridement + metronidazole-minocycline ointment, (b) MC-mechanical debridement + minocycline ointment, (c) NST-mechanical debridement only. RESULTS: Except for four subjects who was excluded during the trial, a total of 114 patients with 114 implants (one implant per each patient) finally completed the trial and were included in the analyses. Multivariate logistic regression analysis revealed that the treatment success rates (absence of bleeding or suppuration on probing, and sites showing pocket probing depth [PPD] ≥5 mm) on at 12 weeks were higher in MM-group patients (31.6%) and MC-group patients (20.5%) compared to NST-group patients (2.7%; p = 0.011 and 0.040, respectively). Subjects with deepest PPD ≥8 mm showed a significant difference in the PPD reduction between MM and MC groups at week 4 (p = 0.025) and week 12 (p = 0.047). Detection ratio of Tannerella forsythia was significantly lower for MM group than MC group (p = 0.038). CONCLUSIONS: Additive use of either MM or MC results in significantly higher treatment success rates compared to sole mechanical debridement in nonsurgical treatment of peri-implantitis. Moreover, MM contributes to a significantly greater reduction in the PPD compared to MC in deep pockets (cris.nih.go.kr KCT0004557).

Diclofenac impairs autophagic flux via oxidative stress and lysosomal dysfunction: Implications for hepatotoxicity.

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest that mitochondrial damage and oxidative stress are important mediators of toxicity, yet the underlying mechanisms are poorly understood. In this study, we identified that some NSAIDs, including diclofenac, inhibit autophagic flux in hepatocytes. Further detailed studies demonstrated that diclofenac induced a reactive oxygen species (ROS)-dependent increase in lysosomal pH, attenuated cathepsin activity and blocked autophagosome-lysosome fusion. The reactivation of lysosomal function by treatment with clioquinol or transfection with the transcription factor EB restored lysosomal pH and thus autophagic flux. The production of mitochondrial ROS is critical for this process since scavenging ROS reversed lysosomal dysfunction and activated autophagic flux. The compromised lysosomal activity induced by diclofenac also inhibited the fusion with and degradation of mitochondria by mitophagy. Diclofenac-induced cell death and hepatotoxicity were effectively protected by rapamycin. Thus, we demonstrated that diclofenac induces the intracellular ROS production and lysosomal dysfunction that lead to the suppression of autophagy. Impaired autophagy fails to maintain mitochondrial integrity and aggravates the cellular ROS burden, which leads to diclofenac-induced hepatotoxicity.