Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells.

The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated. In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells. Z-Leu-D-Leu-Leu-al (MG132), a proteasome inhibitor, induced apoptosis in SH-SY5Y cells in a concentration- and time-dependent manner. Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase (NOX), an enzyme that produces superoxide anions, also attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells. These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5.

Assessing anti-SARS-CoV-2 cellular immunity in 571 vaccines by using an IFN-γ release assay.

Memory T cell responses have been analyzed only in small cohorts of COVID-19 vaccines. Herein, we aimed to assess anti-SARS-CoV-2 cellular immunity in a large cohort using QuantiFERON assays, which are IFN-γ release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals receiving the viral spike (S) protein-expressing BNT162b2 mRNA vaccine. QuantiFERON assays revealed antigen-specific IFN-γ production in most individuals 8 weeks after the second dose. Simultaneous flow cytometric assays to detect T cells expressing activation-induced markers (AIMs) performed for 28 randomly selected individuals provided data correlating with the QuantiFERON data. Simultaneous IFN-γ enzyme-linked immunospot and AIM assays for another subset of 31 individuals, based on short-term peripheral blood mononuclear cell culture, also indicated a correlation between IFN-γ production and AIM positivity. These observations indicated the acquisition of T cell memory responses and supported the usability of IGRAs to assess cellular immunity. The QuantiFERON results were weakly correlated with serum IgG titers against the receptor-binding domain of the S protein and were associated with pre-vaccination infection and adverse reactions after the second dose. The present study revealed cellular immunity after COVID-19 vaccination, providing insights into the effects and adverse reactions of vaccination.

An Increase in Peroxiredoxin 6 Expression Induces Neurotoxic A1 Astrocytes in the Lumbar Spinal Cord of Amyotrophic Lateral Sclerosis Mice Model.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with selective degeneration of motor neurons. It has been reported that an increase in the levels of inflammatory cytokines and glial cells such as reactive astrocytes is closely involved in the pathological progression of ALS. Recently, the levels of neuropathic cytotoxic (A1) astrocytes among reactive astrocytes have reportedly increased in the central nervous system of ALS mice, which induce motor neuron degeneration through the production of inflammatory cytokines and secretion of neuropathic factors. Hence, elucidating the induction mechanism of A1 astrocytes in ALS is important to understand the mechanism of disease progression in ALS. In this study, we observed that the expression of peroxiredoxin 6 (PRDX6), a member of the peroxiredoxin family, was markedly upregulated in astrocytes of the lumbar spinal cord of SOD1G93A mice model for ALS. Additionally, when PRDX6 was transiently transfected into the mouse astrocyte cell line C8-D1A and human astrocytoma cell line U-251 MG, the mRNA expression of complement C3 (a marker for A1 astrocyte phenotype) and inflammatory cytokines was increased. Furthermore, the mRNA expression of C3 and inflammatory cytokine was increased in C8-D1A and U-251 MG cells stably expressing PRDX6, and the increased mRNA expression was significantly suppressed by MJ33 (lithium[1-hexadecoxy-3-(2,2,2-trifluoroethoxy) propan-2-yl] methyl phosphate), an inhibitor of the phospholipase A2 activity of PRDX6. Our results suggest that the expression of PRDX6 in astrocytes plays an important role in the induction of A1 astrocytes and expression of inflammatory cytokines in the ALS mice model.

Schwann cell derived-peroxiredoxin protects motor neurons against hydrogen peroxide-induced cell death in mouse motor neuron cell line NSC-34.

Schwann cells and oligodendrocytes secrete proteins that promote neuron survival, but their role in amyotrophic lateral sclerosis (ALS) is unclear. To address this question, we evaluated the effect of molecules secreted by Schwann cells on reactive oxygen species (ROS)-induced motor neuronal cell death. We observed that in motor neuron cell line NSC-34 cultures, the conditioned medium (CM) from Schwann cell line YST-1 (YST-1 CM) cultures had a protective effect against hydrogen peroxide-induced cell death. However, this protective effect of YST-1 CM was abolished by removing peroxiredoxin 1-4 (PRDX1-4) from the CM. We found that the expression of PRDX1 mRNA was markedly downregulated in the lumbar spinal cord of the superoxide dismutase 1 (SOD1)G93A mouse model of ALS. We also found that transient transfection of YST-1 cells with G93A SOD1 resulted in reduced PRDX1 mRNA expression. Additionally, in the mutant transfected cells, YST-1 CM showed decreased neuroprotective effect against hydrogen peroxide-induced NSC-34 cell death compared to those transfected with WT SOD1. Our results suggest that Schwann cells protect motor neurons from oxidative stress by secreting PRDX1 and that the reduction of PRDX secreted from Schwann cells contributes to increased ROS and associated motor neuronal death in ALS.

Immunostick colorimetric assay for highly sensitive detection of food allergens by bio-nanocapsule-scaffolding technology.

The detection sensitivity of immunostick colorimetric assay has been increased by using a bio-nanocapsule as a scaffold for oriented immobilization of immunoglobulin Gs. This immunostick produced ∼82-folds stronger coloration in the detection of food allergens and reduced detection time by a factor of 5.

Comparison of Lung, Lobe, and Airway Volumes between Supine and Upright Computed Tomography and Their Correlation with Pulmonary Function Test in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Correlations between upright CT and pulmonary function test (PFT) measurements, and differences in lung/lobe/airway volumes between supine and standing positions in patients with chronic obstructive pulmonary disease (COPD) remain unknown. OBJECTIVES: The study aimed to evaluate correlations between lung/airway volumes on both supine and upright CT and PFT measurements in patients with COPD, and compare CT-based inspiratory/expiratory lung/lobe/airway volumes between the two positions. METHODS: Forty-eight patients with COPD underwent both conventional supine and upright CT in a randomized order during inspiration and expiration breath-holds, and PFTs within 2 h. We measured the lung/lobe/airway volumes on both CT. RESULTS: The correlation coefficients between total lung volumes on inspiratory CT in supine/standing position and PFT total lung capacity and vital capacity were 0.887/0.920 and 0.711/0.781, respectively; between total lung volumes on expiratory CT in supine/standing position and PFT functional residual capacity and residual volume, 0.676/0.744 and 0.713/0.739, respectively; and between airway volume on inspiratory CT in supine/standing position and PFT forced expiratory volume in 1 s, 0.471/0.524, respectively. Inspiratory/expiratory bilateral upper and right lower lobe, bilateral lung, and airway volumes were significantly higher in the standing than supine position (3.6-21.2% increases, all p < 0.05); however, inspiratory/expiratory right middle lobe volumes were significantly lower in the standing position (4.6%/15.9% decreases, respectively, both p < 0.001). CONCLUSIONS: Upright CT-based volumes were more correlated with PFT measurements than supine CT-based volumes in patients with COPD. Unlike other lobes and airway, inspiratory/expiratory right middle lobe volumes were significantly lower in the standing than supine position.

Differences in airway lumen area between supine and upright computed tomography in patients with chronic obstructive pulmonary disease.

BACKGROUND: No clinical studies to date have compared the inspiratory and expiratory airway lumen area between supine and standing positions. Thus, the aims of this study were twofold: (1) to compare inspiratory and expiratory airway lumen area (IAA and EAA, respectively) on computed tomography (CT) among supine and standing positions; and (2) to investigate if IAA and EAA are associated with lung function abnormality in patients with chronic obstructive pulmonary disease (COPD). METHODS: Forty-eight patients with COPD underwent both low-dose conventional (supine position) and upright CT (standing position) during inspiration and expiration breath-holds and a pulmonary function test (PFT) on the same day. We measured the IAA and EAA in each position. RESULTS: For the trachea to the third-generation bronchi, the IAA was significantly larger in the standing position than in the supine position (4.1-4.9% increase, all p < 0.05). The EAA of all bronchi was significantly larger in the standing position than in the supine position (9.7-62.5% increases, all p < 0.001). The correlation coefficients of IAA in the standing position and forced expiratory volume in 1 s were slightly higher than those in the supine position. The correlation coefficients of EAA or EAA/IAA in the standing position and residual volume, and the inspiratory capacity/total lung capacity ratio were higher than those in the supine position. CONCLUSIONS: Airway lumen areas were larger in the standing position than in the supine position. IAAs reflect airway obstruction, and EAAs reflect lung hyperinflation. Upright CT might reveal these abnormalities more precisely. Trial registration University Hospital Medical Information Network (UMIN 000026587), Registered 17 March 2017. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000030456 .

Difference in the airway luminal area between the standing and supine positions using upright and conventional computed tomography.

No clinical studies to date have compared the airway luminal area between supine and standing positions. Our aim was therefore to compare the airway luminal area between these two positions on computed tomography (CT) and to determine its correlation with forced expiratory volume in 1 s (FEV1). Thirty-two asymptomatic volunteers underwent both conventional (supine position) and upright (standing position) CT during deep inspiration breath-holding. Pulmonary function tests were conducted on the same day. We measured the airway luminal area on CT in each position. Paired t-tests and Pearson's correlation coefficients were used for statistical analysis. The average luminal areas of the trachea, right and left main bronchi, and average third-generation airway were greater in the standing than the supine position by 3.4%, 6.1%, 5.5%, and 5.2%, respectively. The correlation coefficients between airway luminal areas and FEV1 tended to be higher in the standing than the supine position; this correlation was highest for the average third-generation airway (r = 0.70, P < 0.0001). The airway luminal areas of the trachea, bilateral main bronchi, and average third-generation airway were greater in the standing than the supine position. The average third-generation airway area in the standing position had the highest correlation with FEV1.

Differences in Lung and Lobe Volumes between Supine and Standing Positions Scanned with Conventional and Newly Developed 320-Detector-Row Upright CT: Intra-Individual Comparison.

BACKGROUND: No clinical studies to date have compared unilateral lung or lobe volumes between the supine and standing positions. OBJECTIVES: To compare lung/lobe volumes on computed tomography (CT) between these two positions and evaluate the correlation between the total lung volume and total lung capacity (TLC) on pulmonary function tests (PFTs). METHODS: Thirty-two asymptomatic volunteers underwent both conventional CT (supine position) and upright CT (standing position), during deep inspiration breath-hold, and PFTs on the same day. We measured lung/lobe volumes on CT in each position. Paired t tests were used for statistical analysis. RESULTS: The volumes of the total lung (10.9% increase), right lung (10.3% increase), right upper lobe (8.6% increase), right lower lobe (14.6% increase), left lung (11.6% increase), left upper lobe (7.1% increase), and left lower lobe (16.0% increase) were significantly greater in the standing position than in the supine position (all p < 0.0001). The right middle lobe volume was similar between the two positions (p = 0.16). Intraclass correlation coefficients for agreement between total lung volumes on CT in the supine/standing positions and the TLC on PFT were 0.891/0.938, respectively. CONCLUSIONS: While the volumes of the bilateral upper and lower lobes and bilateral lungs were significantly greater in the standing than in the supine position, with lower lobes showing larger changes, the right middle lobe volume did not change significantly between positions. The total lung volume on upright CT in the standing position was more similar to TLC on PFT than that in the supine position.

Estradiol-mediated hepatocyte growth factor is involved in the implantation of endometriotic cells via the mesothelial-to-mesenchymal transition in the peritoneum.

The pathogenesis of endometriosis, a chronic painful gynecological disease characterized by the presence of endometrial tissue located outside of the uterus and often adhering to the peritoneum, is known to be estrogen dependent. However, the precise pathophysiology of endometriosis remains elusive. Recent studies indicate that the epithelial-to-mesenchymal transition (EMT) of human endometrial cells is important for the progression of endometriosis, and another previous study has implicated hepatocyte growth factor (HGF) in endometriosis progression. The aim of the present study was to examine the role of estradiol in the regulation of HGF production and progression of peritoneal endometriosis, focusing on the interactions between the peritoneum and endometriotic cells. Consequently, estradiol was found to promote the proliferation, invasion, and migration of immortalized human endometrial epithelial cells (hEECs) via HGF upregulation, and the estradiol-induced direct binding of estrogen receptor-α to the HGF promoter was confirmed on a chromatin immunoprecipitation (ChIP) assay. Estradiol also induced the EMT in hEECs by promoting HGF production. Furthermore, human mesothelial cells underwent the mesothelial-to-mesenchymal transition (MMT) during culture with estradiol-stimulated hEEC conditioned medium. Importantly, estradiol itself did not induce the MMT, and the estradiol-stimulated hEEC-conditioned medium in the presence of HGF antibodies reversed the MMT process. These results, which were obtained using immortalized hEECs, indicate that estradiol-induced HGF production may play a crucial role in the peritoneal implantation of human endometriotic cells by exerting proliferative and invasive effects via the EMT in hEECs and promoting the MMT in mesothelial cells.

Fibrates protect against vascular endothelial dysfunction induced by paclitaxel and carboplatin chemotherapy for cancer patients: a pilot study.

BACKGROUND: Although we previously demonstrated that paclitaxel and carboplatin chemotherapy (TCchem) is associated with vascular toxicities, the underlying mechanisms remain unclear. Cisplatin is known to inhibit PPARα following microvascular damage to the kidneys. The primary aim of this study was to evaluate whether TCchem induces vascular endothelial dysfunction via systemic PPARα deficiency. In addition, human umbilical vein endothelial cells (HUVECs) were used to elucidate the mechanisms responsible for TCchem-induced vascular toxicities. METHODS: This study enrolled 45 gynecological cancer patients with normal lipid profiles who underwent surgical treatment followed by TCchem. The elevated triglyceride (TG) group included patients (n = 19) who exhibited hypertriglyceridemia during TCchem, and the stable TG group (n = 15) included patients with a normal TG level. Eleven patients exhibiting hypertriglyceridemia during TCchem were administered bezafibrate (fibrate group). Endothelial dysfunction was evaluated based on flow-mediated dilation (FMD) values and serum pentraxin-3 levels measured before TCchem and immediately after the final TCchem. HUVECs were used to elucidate the biological mechanisms underlying the endothelial dysfunction induced by TCchem. RESULTS: The administration of TCchem induced hypertriglyceridemia in 66 percent of the participants, and bezafibrate reduced the serum TG levels. Meanwhile, the decrease in flow-mediated dilatation (%FMD) induced by TCchem improved following treatment with bezafibrate. The serum pentraxin-3 level increased rapidly after TCchem and decreased following bezafibrate treatment. An in vitro examination demonstrated TCchem attenuated nitric oxide production and PPARα activity in HUVECs, which was partially improved by treatment with bezafibrate. CONCLUSION: Bezafibrate prevents endothelial dysfunction induced by TCchem via TG-dependent and TG-independent mechanisms.

Postmenopausal patients with endometrial cancer of type 1 have elevated serum estradiol levels in the ovarian vein.

OBJECTIVE: Type 1 endometrial cancer (EC) is typically sex hormone sensitive; however, most women diagnosed with EC have already gone through menopause. Several studies have reported that the postmenopausal ovary is hormonally active, and estradiol (E2) production from the ovaries persists for as much as 10 years beyond menopause. The aim of this study was to evaluate whether sex steroid production from the ovaries contributes to the pathogenesis of type 1 EC. MATERIALS AND METHODS: This was a prospective study of 53 women treated for EC (28 cases of type 1 disease and 25 cases of type 2 disease). Serum specimens were collected from the peripheral and ovarian veins of participants undergoing bilateral oophorectomy. The sex steroid hormone levels and hormonal milieu on cervical cytology were evaluated as maturation value (MV). In addition, the degree of stromal hyperplasia of the ovary was evaluated histologically. RESULTS: Although the E2 levels of the peripheral veins did not show any significant differences [8.2 (5.1-12.4) vs 7.4 (5.1-11.7) pg/mL, respectively; P < 0.05], the patients with type 1 EC had a higher E2 level in the ovarian vein than those with type 2 EC [25 (13.8-42.5) vs 15 (10.0-23.0) pg/mL, respectively; P < 0.05]. There were also no significant differences in the rate of moderate to marked hyperplasia of the ovarian stroma between the groups; however, the thickness of the ovarian cortex demonstrated a correlation with the ovarian E2 level. In addition, the MV displayed a strong correlation with the ovarian E2 level, but not the peripheral E2 level. CONCLUSIONS: The postmenopausal ovary is hormonally active, especially in patients with type 1 EC. The degree of ovarian stromal hyperplasia may (at least in part) contribute to the progression of type 1 EC, and MV may predict the level of E2 production from the ovaries in postmenopausal women.

Local injection of vasopressin reduces the blood loss during cesarean section in placenta previa.

AIM: The aim of this study was to evaluate the effect of local injection of vasopressin on blood loss and secondary impact on complications during cesarean section in patients with placenta previa. MATERIAL AND METHODS: We retrospectively reviewed the medical records of all patients diagnosed with placenta previa admitted to our hospital. Two consecutive periods were compared. During period B, 59 patients underwent the local injection of a vasopressin solution (4 U in 20 mL of saline) into the placental implantation site after placental delivery. During period A, 50 patients underwent cesarean section without vasopressin injection, and were analyzed as a control group. The estimated blood loss was recorded, as were the complications during surgery. In addition, the expression of the vasopressin V1α receptor in uterine smooth muscle was evaluated by immunohistochemistry. RESULTS: The mean estimated blood loss was significantly lower in the vasopressin group than in the control group. There were no statistically significant differences with surgical complications. The vasopressin V1α receptor was highly expressed in smooth muscle cells in the lower segment of the uterine body, whereas the immunoreactivity for the oxytocin receptor was faint in the lower segment. CONCLUSION: The local injection of vasopressin into the placental implantation site significantly reduced the blood loss without increasing the morbidity.

The expression status of G protein-coupled receptor GPR30 is associated with the clinical characteristics of endometriosis.

INTRODUCTION: GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates endometrial cellular responses to estrogen. GPR30 is often highly expressed in cancer cells from aggressive tumors. The aim of this study was to evaluate the expression patterns of GPR30 in endometriosis during medical treatment. PATIENTS: A total of 38 females, 28 patients with endometriosis and 10 patients with leiomyoma who underwent laparoscopic surgery were included this study. INTERVENTION: Eutopic endometrial tissue sampling from women without endometriosis and ectopic endometrial tissue sampling from women with endometriosis. MAIN OUTCOME MEASURE: A quantitative real-time polymerase chain reaction analysis of the mRNA expression in eutopic and ectopic endometrial tissues with or without GnRH agonist treatment. The expression of GPR30 was confirmed by immunohistochemistry. RESULTS: There was an increased level of GPR30 mRNA in eutopic endometrium during the proliferative phase, whereas higher expression was observed in the ectopic endometrium during the secretory phase. Increased GPR30 mRNA was observed in ectopic endometrium in comparison to eutopic endometrium. GnRH agonist treatment before laparoscopic surgery decreased GPR30 mRNA in ectopic endometrium. The immunohistochemical analysis also revealed that GPR30 was strongly expressed in epithelial cells in ectopic endometrium, whereas GnRH agonist treatment decreased the GPR30 expression. CONCLUSION: High levels of GPR30 expression can play an important role in the progression of endometriosis.

[A case of advanced gastric cancer with regional lymph node metastasis showing pathological complete response after preoperative chemotherapy with docetaxel, cisplatin, and S-1].

A 64-year-old man was diagnosed with advanced gastric cancer type 3 and regional celiac trunk lymph node metastases. We performed preoperative chemotherapy with docetaxel, cisplatin, and S-1(DCS therapy). Total gastrectomy with lymph node dissection was performed after 2 courses of DCS. Pathologically, no viable cells were found in the primary lesion or in the dissected lymph nodes. The pathological response to preoperative DCS therapy was classified as grade 3. The postoperative course was uneventful; the patient is currently healthy and receives periodic medical examinations.

Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine.

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose. UMIN Clinical Trials Registry ID: UMIN000043340.

Comparison of inspiratory and expiratory airway volumes and luminal areas among standing, sitting, and supine positions using upright and conventional CT.

Upright computed tomography (CT) provides physiologically relevant images of daily life postures (sitting and standing). The volume of the human airway in sitting or standing positions remains unclear, and no clinical study to date has compared the inspiratory and expiratory airway volumes and luminal areas among standing, sitting, and supine positions. In this prospective study, 100 asymptomatic volunteers underwent both upright (sitting and standing positions) and conventional (supine position) CT during inspiration and expiration breath-holds and the pulmonary function test (PFT) within 2 h of CT. We compared the inspiratory/expiratory airway volumes and luminal areas on CT among the three positions and evaluated the correlation between airway volumes in each position on CT and PFT measurements. The inspiratory and expiratory airway volumes were significantly higher in the sitting and standing positions than in the supine position (inspiratory, 4.6% and 2.5% increase, respectively; expiratory, 14.9% and 13.4% increase, respectively; all P < 0.001). The inspiratory and expiratory luminal areas of the trachea, bilateral main bronchi, and average third-generation airway were significantly higher in the sitting and standing positions than in the supine position (inspiratory, 4.2‒10.3% increases, all P < 0.001; expiratory, 6.4‒12.8% increases, all P < 0.0001). These results could provide important clues regarding the pathogenesis of orthopnea. Spearman's correlation coefficients between the inspiratory airway volume on CT and forced vital capacity and forced expiratory volume in 1 s on PFT were numerically higher in the standing position than in the supine position (0.673 vs. 0.659 and 0.669 vs. 0.643, respectively); however, no statistically significant differences were found. Thus, the airway volumes on upright and conventional supine CT were moderately correlated with the PFT measurements.

Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine.

BACKGROUND: The antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection. METHODS: This prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination. RESULTS: A total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic. CONCLUSIONS: Both humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent. UMIN CLINICAL TRIALS REGISTRY ID: UMIN000043340.

The Effect of Maternal Coagulation Parameters on Fetal Acidemia in Placental Abruption.

This study aimed to identify factors predicting the probability of serious fetal acidemia at delivery in placental abruption. We identified 5769 women who delivered at >22 weeks' gestation at two institutions in a tertiary referral unit specializing in neonatal infant care between January 2007 and December 2011. Ninety-one abruption cases were identified based on clinical and histological diagnoses. Serious fetal acidemia was defined as a pH < 7.0 in the umbilical arterial blood at delivery. Using a linear discriminant function, we calculated the score to determine the probability of serious fetal acidemia. Serious fetal acidemia was observed in 34 patients (37.4%). A logistic regression model showed that abnormal fetal heart rate patterns (bradycardia and late decelerations), uterine spasm, and maternal plasma concentration of fibrinogen less than 288 ng/dL were significantly associated with the occurrence of serious fetal acidemia. We suggest that the implementation of maternal fibrinogen in patients with placental abruption is a prognostic factor for serious fetal acidemia at delivery.

Young age, female sex, and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: An observational study of 646 Japanese healthcare workers and university staff.

BACKGROUND: SARS-CoV-2 vaccination has started worldwide, including Japan. Although high rates of vaccine response and adverse reactions of BNT162b2 vaccine have been reported, knowledge about the relationship between sex differences and antibody response is limited. Furthermore, it is uncertain whether adverse reactions are associated with the vaccine response. METHODS: This prospective observational study included 673 Japanese participants working in a medical school and its affiliated hospital in Tokyo, Japan (UMIN000043340). Serum samples were collected before the first dose and three weeks after the second dose of BNT162b2 vaccine, and antibody titers against the receptor-binding domain of the spike protein of SARS-CoV-2 were measured. Answers to questionnaires about background characteristics and adverse reactions were obtained at the time of sample collection, and the relationship between antibody titers was analyzed. RESULTS: After excluding participants who did not complete receiving two doses of vaccination or two series of serum sample collection, 646 participants were analyzed. Although all participants became sero-positive after vaccination, antibody titers were highly variable among individuals (260.9-57,399.7A U/mL), with a median titer of 13478.0AU/mL. Mean titer was higher in females than in males and higher in young (≤45 years old) participants than in aged (>45 years old) participants. Participants who experienced adverse reactions demonstrated a higher antibody titer after vaccination than those without adverse reactions. Multivariable analysis demonstrated that young age, female sex, and adverse reactions after the second dose were independently related to higher antibody titers after the second dose. DISCUSSION: A favorable antibody response was observed after two doses of BNT162b2 vaccination among mostly healthy Japanese participants, especially among female and young participants. Although further investigation is essential, our results imply that the systemic adverse reactions (i.e., fever and general fatigue) are associated with a higher antibody response that indicates the acquisition of humoral immunity.