Young Age, Female Sex, and No Comorbidities Are Risk Factors for Adverse Reactions after the Third Dose of BNT162b2 COVID-19 Vaccine against SARS-CoV-2: A Prospective Cohort Study in Japan

Background: This study compared the adverse events (AEs) of the second and third doses of BNT162b2, as well as investigated the impact of vaccine recipients’ background and vaccination interval on the AEs of the third dose. Methods: We conducted a questionnaire survey of AEs among health care workers at Osaka University Dental Hospital. Chi-square tests were performed to compare AEs to the administration of second and third vaccine doses. Logistic regression analyses were conducted to identify factors influencing the presence of AEs using age, sex, comorbidities, and the vaccination interval. Spearman’s rank correlation coefficient was calculated to investigate the correlation between age, vaccination interval, and severity of each AE. Results: The third dose of BNT162b2 was associated with significantly more frequent or milder AEs than the second dose. Logistic regression analyses detected significant differences in six items of AEs by age, three by sex, two by comorbidities, and zero by vaccination interval. Consistently, the risk of AEs was greater among younger persons, females, and those without comorbidities. Significant negative correlations were detected between age and vaccination interval, and between age and the severity of most AEs. Conclusions: Young, female, and having no comorbidities are risk factors for AEs after the third dose of BNT162b2, while vaccination interval is not.Urakawa R., Isomura E.T., Matsunaga K., et al. Young Age, Female Sex, and No Comorbidities Are Risk Factors for Adverse Reactions after the Third Dose of BNT162b2 COVID-19 Vaccine against SARS-CoV-2: A Prospective Cohort Study in Japan. Vaccines, 10, 8, 1357. https://doi.org/https://doi.org/10.3390/vaccines10081357

Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain

<p>Abstract</p> <p>Background</p> <p>Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel α2δ-1 subunit.</p> <p>Results</p> <p>Mice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the anti-allodynic effects varied according to its dosing time. The protein levels of α2δ-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of α2δ-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when α2δ-1 subunit protein was abundant.</p> <p>Conclusions</p> <p>These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain.</p

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

〈Originals〉Initial swallowing function in those undergoing subtotal mobile tongue component resection and reconstruction with a myocutaneous pectoralis major flap

[Abstract] Purpose : The swallowing function was evaluated 2 months postoperatively in eight tongue cancer patients who had undergone subtotalresection of the mobile tongue component and reconstruction with a pectoralis major myocutaneous flap. The association between the form of the flap and initial postoperative swallowing function was also evaluated. Materials and methods : Video fluorography was used to evaluate swallowing function. The test food consisted of 10 ml liquid. Results : The form of the flap was a bulge and flat in 6 and 2 patients, respectively. Contact between the flap and hard palate was favorable in 6 patients but poor in 2. The 6 patients with favorable flap and hard palate contact showed neither residue of the test food in the recessus piriformis nor aspiration. The 2 patients with poor flap and hard palate contact showed marked test food residue in the recessus piriformis and aspiration. Conclusion : It is suggested that decreased flap volume could reduce swallowing pressure, promoting aspiration, and so the mobile tongue component should be reconstructed with a bulge flap to facilitate flap and hard palate contact, considering initial postoperative swallowingfunction

Young Age, Female Sex, and No Comorbidities Are Risk Factors for Adverse Reactions after the Third Dose of BNT162b2 COVID-19 Vaccine against SARS-CoV-2: A Prospective Cohort Study in Japan

Background: This study compared the adverse events (AEs) of the second and third doses of BNT162b2, as well as investigated the impact of vaccine recipients’ background and vaccination interval on the AEs of the third dose. Methods: We conducted a questionnaire survey of AEs among health care workers at Osaka University Dental Hospital. Chi-square tests were performed to compare AEs to the administration of second and third vaccine doses. Logistic regression analyses were conducted to identify factors influencing the presence of AEs using age, sex, comorbidities, and the vaccination interval. Spearman’s rank correlation coefficient was calculated to investigate the correlation between age, vaccination interval, and severity of each AE. Results: The third dose of BNT162b2 was associated with significantly more frequent or milder AEs than the second dose. Logistic regression analyses detected significant differences in six items of AEs by age, three by sex, two by comorbidities, and zero by vaccination interval. Consistently, the risk of AEs was greater among younger persons, females, and those without comorbidities. Significant negative correlations were detected between age and vaccination interval, and between age and the severity of most AEs. Conclusions: Young, female, and having no comorbidities are risk factors for AEs after the third dose of BNT162b2, while vaccination interval is not

A patient with levator dysfunction resulting from slight blunt trauma

In clinical practice of plastic surgery, patients with palpebral/orbital swelling/hematoma due to facial bruise/fracture who can not open their eyelids are often encountered. However, most patients can open their eyelids after a few days with improvement in swelling/hematoma, and few develop blepharoptosis as a sequela. We reported a very rare patient with blepharoptosis due to slight blunt trauma without an open wound of the eyelid who did not show recovery in levator function. In this patient, paralytic blepharoptosis due to oculomotor injury caused by blunt trauma in a very localized area was considered