Adverse events after BNT162b2 mRNA COVID-19 vaccination in health care workers and medical students in Japan.

To control the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the promotion of vaccination is important. However, adverse reactions following vaccination remain a concern. To investigate adverse events in the vaccinated Japanese population, we conducted a survey-based study among health care workers, including medical doctors and nurses; other medical staff; and medical university faculty, staff, and students in a single medical school and affiliated hospital in Japan. In addition, we analyzed the association of different adverse events with individual factors (e.g., age, sex) by performing network analysis. While young age and female sex are often considered risk factors for more severe adverse events, the regression models showed neither age nor sex was associated with local injection-site reactions after the second dose in this study. In contrast to local reactions, systemic adverse events were associated with young age and female sex. However, myalgia was unique in that it was not associated with younger age even though the network analysis showed that myalgia was consistently related to arthralgia and belonged to the group of systemic events after both the first and second vaccine doses. Further study is needed to ensure safe and effective vaccination to aid in controlling the COVID-19 pandemic.

The association of three doses of the BNT162b2 mRNA vaccine with abnormal bleeding and an irregular menstrual cycle among premenopausal females: A single institute observation study.

BACKGROUND: The COVID-19 vaccine is effective in preventing severe cases of COVID-19. For women, gynecological adverse events, such as menstrual irregularities and irregular bleeding, could be a concern after COVID-19 vaccination. In this study, we investigated gynecological adverse events in the vaccinated Japanese female population. METHODS: We conducted a survey-based study with health-care workers, including medical doctors and nurses, medical coworkers, and medical university faculty, staff, and students, at a single medical school and affiliated hospital in Japan. We used McNemar's test and network analysis. RESULTS: Overall, we obtained 819 responses, and 424 were from females. After the exclusion of contradictory answers, 309 surveys were finally considered appropriate for the analysis. The frequencies of abnormal bleeding were 0.6%, 1.0%, and 3.0% for the first, second, and third doses, respectively. An irregular menstrual cycle was more common than abnormal bleeding: 1.9%, 4.9%, and 6.6% for the first, second, and third doses, respectively. Network analysis revealed that abnormal bleeding and an irregular menstrual cycle were not associated with other adverse reactions. CONCLUSION: The present study showed that the effects of COVID-19 vaccination on menstruation seem limited.

TAFRO Syndrome: Guidance for Managing Patients Presenting Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly.

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.

Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome.

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.

Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions.

Rubella virus (RuV) infections in pregnant women, especially first-trimester infections, can lead to congenital rubella syndrome (CRS). However, the mechanisms of fetal RuV infection are not completely understood, and it is not observed in every pregnant woman infected with RuV. As gestational diabetes mellitus is a risk factor for congenital viral infections, we investigated the possible roles of hypoglycemia-related endoplasmic reticulum (ER) stress as a key factor for vertical RuV infection using immortalized human first-trimester trophoblasts. Low-glucose stress was induced prior to RuV infection by culturing HTR-8/SVneo and Swan.71 cells in low-glucose (LG) medium for 24 h or high-glucose medium for 6 h and then LG medium for an additional 18 h. Clinically isolated RuV was inoculated at a multiplicity of infection of 5 to 10. The intracellular localization of the RuV capsid protein was investigated 24 to 48 h post-infection (pi) with flow cytometry (FCM) analysis and fluorescence microscopy. Viral progeny production was monitored by FCM analysis. Increases in RuV infection in LG-induced ER-stressed trophoblasts were observed. No significant increase in apoptosis of RuV-infected cells was noted at days 2 and 5 pi, and substantial viral progeny production was observed until day 5 pi. An approximate fivefold increase in viral binding was noted for the LG-stressed cells. Although the detailed mechanisms underlying viral entry into LG-stressed cells are not known and require further investigation, these findings suggest that a certain degree of LG stress in early pregnancy may facilitate infection and cause CRS.

Recombinant BCG-Prime and DNA-Boost Immunization Confers Mice with Enhanced Protection against Mycobacterium kansasii.

The incidence of infections with nontuberculous mycobacteria (NTM) has been increasing worldwide. The emergence of multidrug-resistant NTM is a serious clinical concern, and a vaccine for NTM has not yet been developed. We previously developed a new recombinant Bacillus Calmette-Guérin (rBCG) vaccine encoding the antigen 85B (Ag85B) protein of Mycobacterium kansasii-termed rBCG-Mkan85B-which was used together with a booster immunization with plasmid DNA expressing the same M. kansasii Ag85B gene (DNA-Mkan85B). We reported that rBCG-Mkan85B/DNA-Mkan85B prime-boost immunization elicited various NTM strain-specific CD4+ and CD8+ T cells and induced Mycobacterium tuberculosis-specific immunity. In this study, to investigate the protective effect against M. kansasii infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime-boost strategy with virulent M. kansasii. Although BCG and rBCG-Mkan85B immunization each suppressed the growth of M. kansasii in the mouse lungs, the rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination reduced the bacterial burden more significantly. Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination induced antigen-specific CD4+ and CD8+ T cells. Our data suggest that rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination effectively enhances antigen-specific T cells. Our novel rBCG could be a potential alternative to clinical BCG for preventing various NTM infections.

Possible importance of carcasses for ebolavirus persistence in the ecosystem.

Some outbreaks caused by ebolaviruses have been associated with wildlife mortalities in the past. Here, we discuss the possible roles played by animal carcasses during an ebolavirus outbreak. Corpses of wild animals that died due to ebolavirus infection or other reasons might be eaten by vertebrates and invertebrates, spreading live ebolaviruses to other animals, including humans. To prevent and contain an ebolavirus outbreak, not only potential reservoirs but also all organisms with a high likelihood of virus exposure need to be investigated.

Cow milk exosomes activate NK cells and γδT cells in human PBMCs in vitro.

Cow milk is a nourishing food containing numerous essential nutrients. In Japan, the consumption of cow milk is thought to enhance resistance to exhaustion-related diseases. Although several nutrients in cow milk, such as lactoferrin, are thought to modulate immune cells, the mechanisms remain unclear. Recently, the immunoregulatory functions of food-derived microRNAs or exosomes have been reported. Therefore, we studied the effects of exosomes derived from cow milk (CM-Exs) on immune cells in the present study. We obtained blood samples from healthy adult donors with the approval of the ethics committee. Peripheral blood mononuclear cells (PBMCs) were stimulated with CM-Exs in the absence or presence of interleukin-2 (IL-2) and IL-12. Cell surface markers and intracellular cytokine production were analysed by flow cytometry. CM-Ex stimulation enhanced the expression of CD69 on NK cells. Although CM-Ex stimulation alone did not induce interferon-γ (IFN-γ) production by NK cells or γδT cells, simultaneous stimulation with CM-Ex, IL-2 and IL-12 significantly enhanced IFN-γ production. In conclusion, cow milk consumption alone may not activate immune cells; however, CM-Exs could enhance immune cells under inflammatory conditions.

Relationship between water structure and properties of poly(methyl methacrylate-b-2-hydroxyethyl methacrylate) by solid-state NMR.

We previously reported that the platelet compatibility of methyl methacrylate (MMA)-2-hydroxyethyl methacrylate (HEMA) diblock copolymers is related to the characteristic water structure in the copolymer, as the copolymer has an excess amount of nonfreezing water when compared with that estimated from the amounts of water in HEMA and MMA homopolymers. Thus, in this study, the relationship between water structure and polymer structure, including the heterogeneity and mobility of the copolymer, was investigated using differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR) spectroscopy. The prepared copolymers were classified into two groups: copolymers with a short, constant polyMMA segment length (Mn = ~2900) and copolymers with a constant polyHEMA segment length (Mn = ~9500), whereas the lengths of the counter segments varied. DSC analysis showed that when the polyMMA and polyHEMA segment lengths are similar, the amount of nonfreezing water increases, regardless of the total molecular weight of the copolymer. NMR analysis showed that heterogeneity of the copolymer is enhanced and the mobility of the copolymer decreases when the segment lengths are similar. These findings suggested that the excess amount of nonfreezing water is formed when the properties of water near the HEMA unit change from freezing to nonfreezing owing to interactions with the MMA unit. In addition, it is suggested that the heterogeneity of the copolymer structure or the mobility of the polymer are involved in the generation of excess nonfreezing water.

Study of the water structure in poly(methyl methacrylate-block-2-hydroxyethyl methacrylate) and its relationship to platelet adhesion on the copolymer surface.

The water structure and platelet compatibility of poly(methyl methacrylate (MMA)-block-2-hydroxyethyl methacrylate (HEMA)) were investigated. The molecular weight (Mn) of the polyHEMA segment was kept constant (average: 9600), while the Mn of the polyMMA segment was varied from 1340 to 7390. The equilibrium water content of the copolymers was found to be mainly governed by the HEMA content. The water structure in the copolymers was characterized in terms of the amounts of non-freezing and freezing water (abbreviated as Wnf and Wfz, respectively) using differential scanning calorimetry. It was found that the Wnf for the copolymers were higher than those estimated from the Wnf for the HEMA and MMA homopolymers and that the amount of excess non-freezing water depended on the polyMMA segment length. In addition, X-ray diffraction analysis revealed that some of the copolymers had cold-crystallizable water. These facts suggested that the polyMMA segments were involved in determining the water structures in the copolymers. Furthermore, the platelet compatibility of the copolymers was improved as compared to that of the HEMA homopolymer. It was therefore concluded that the platelet compatibility of the copolymer was related to the amount of excess non-freezing water.

Collection, mapping, and annotation of over 28,000 cDNA clones from japonica rice.

We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.