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The aim of this study was to characterize ankle stability of total talar prosthesis (TTP) and to determine the effect of implant sizes on stability as well as the resistance to TTP dislocation. Twelve below-knee cadaveric specimens were divided into two groups. Group 1 received a size matched implant and Group 2 received downsized implant by 5%. The stability assessment under fluoroscopy was performed for each cadaver in its native state. Following TTP insertion process, each then underwent evaluation of the TTP ankle stability. The stability of pre- and post-TTP was compared. (1) Anterior drawer distance. (2) Talar tilt angle under varus and valgus stress. (3) Subtalar tilt angle under varus stress was measured. Finally, the dislocation test was performed using the aforementioned testing conditions, then the stress force was slowly increased from 0 to 350 N, during which time it was observed on fluoroscopy all the time. Compared to pre TTP ankles, varus and anterior drawer stress showed significant instability (p < 0.001-0.031). Only anterior drawer stress in smaller sized implants showed significant instability when compared to identical sized implants (p = 0.008). No dislocation was seen under varus, valgus, and subtalar stress. However, anterior dislocation was observed in all cases of smaller size implant group (p = 0.045). TTP implant was stable under valgus and subtalar stress. However, clinicians should pay attention to anterior instability. Notably, downsized implants should be considered carefully to minimize the chance of anterior dislocation., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

RNA interference-based gene silencing drugs are attracting attention for treating various diseases. Lipid nanoparticles (LNPs) are carriers that efficiently deliver small interfering RNA (siRNA) to the cytoplasm of target cells. Recently, we developed potent and well-tolerated biodegradable LNPs with asymmetric ionizable lipids. Here, we evaluated the effect of LNPs on immune cells in mice. After intravenous administration, LNPs were efficiently incorporated into several tissue-resident macrophages, including liver macrophages, through an apolipoprotein E (ApoE)-independent mechanism. Administration of LNP-encapsulated siRNA against Irf5 , encoding the transcription factor critical for inflammatory responses, sharply reduced its expression in macrophages in vivo , and persisted for as long as 7 days. The therapeutic potential of Irf5 siRNA-loaded LNPs in inflammatory diseases was tested in a concanavalin A (Con A)-induced hepatitis model, whose pathogenic mechanisms are dependent on cytokine secretion from macrophages. We found that Con A-induced liver injury was significantly attenuated after LNP injection. Serum aspartate transaminase, alanine aminotransferase, and inflammatory cytokine levels were significantly reduced in mice injected with Irf5 siRNA-loaded LNPs compared to those injected with control siRNA-loaded LNPs. Our results suggest that administering biodegradable LNPs to deliver siRNA is a promising strategy for treating inflammatory disorders., Competing Interests: Y.S., H.I., and K.T. are employees of Eisai Co., Ltd. T. Tamura received a joint research fund from Eisai Co., Ltd. The remaining authors declare no competing interests., (© 2021 The Author(s).)

The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors., (© 2021. The Author(s).)

Objective: The correlation between enhancement of the vestibulocochlear nerves on gadolinium-enhanced magnetic resonance imaging (MRI) and vestibulocochlear functional deficits was examined in patients with Ramsay Hunt syndrome (RHS)., Methods: Nineteen patients with RHS who showed herpes zoster oticus, peripheral facial palsy, and vertigo were enrolled. Canal paresis (CP) in the caloric test, abnormal response to ocular and cervical vestibular myogenic potentials (oVEMP and cVEMP), and refractory sensorineural hearing loss were evaluated. MRI images perpendicular to the internal auditory canal were reconstructed to identify the superior (SVN) and inferior vestibular nerves (IVN) and the cochlear nerve (CV). The signal intensity increase (SIinc) of the four-nerve enhancement was calculated as an index., Results: Among RHS patients, 79%, 53%, 17% and 26% showed CP in the caloric test, abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, respectively. SIinc rates of the SVN were significantly increased in RHS patients with CP in the caloric test, and with abnormal responses to oVEMP and cVEMP. SIinc rates of the SVN tended to increase in RHS patients with refractory sensorineural hearing loss (p = 0.052). SIinc rates of the IVN were significantly increased in RHS patients with abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, but not in those with CP in the caloric test. SIinc rates of the CN were significantly increased in RHS patients with CP in the caloric test, abnormal response to oVEMP and refractory sensorineural hearing loss, but not in those with abnormal response to cVEMP., Conclusion: In patients with RHS, the origin of vertigo may be superior vestibular neuritis, which is affected by reactive varicella-zoster virus from the geniculate ganglion of the facial nerve through the faciovestibular anastomosis. The results also suggested that in some RHS patients, inferior vestibular neuritis contributes to the development of vertigo and that the origin of refractory sensorineural hearing loss is cochlear neuritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings. J. Med. Invest. 68 : 38-41, February, 2021.

We previously showed that chemotherapy-induced dysgeusia was associated with lingual taste receptor gene expression, and monosodium glutamate (MSG) improved dysgeusia by upregulating taste 1 receptor 3(T1R3) gene expression. In recent years, decreased taste sensitivity has also been reported in some young people, and these are partly due to their disordered eating habits. From these background, we investigated the effects of MSG supplementation on taste receptor expression and dietary intake in healthy females. Fifteen young healthy volunteers were enrolled for the present crossover study and divided in two groups (dietary supplementation with MSG at 2.7 g / day or 0.27 g / day). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative PCR analysis. Food intake was assessed by food frequency questionnaire (FFQg), and body composition was measured using Omron HBF-701. T1R3 expression levels in the tongue and taste sensitivity increased significantly in participants who consumed <10 g of MSG daily, whereas no alteration was observed in participants who consumed >10 g of MSG daily. Furthermore, protein, fat, and carbohydrate (PFC) balance and salt and sugar intake improved by MSG supplementation. In conclusion, MSG supplementation increased T1R3 expression in the tongue and improved dietary balance. J. Med. Invest. 68 : 315-320, August, 2021.

Objective : In the present study, an attempt was made to evaluate the acoustic characteristics of voice in pediatric patients with vocal nodules using acoustic analysis of voice. Methods : Thirty-five pediatric patients with vocal nodules and 32 control children without dysphonia were enrolled in this study. Their voice samples were analyzed using the Multi-Dimensional Voice Program. Acoustic parameters of voice, such as pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR), were measured. Results : In phonation at a loudness of over 80 dBA, the PPQ, APQ, and NHR values of the voice significantly increased in children with vocal nodules than in the control children without dysphonia. The sensitivities and specificities of PPQ, APQ, and NHR for prediction of vocal nodules in children were 62.86% and 84.38%, 74.29% and 75.00%, and 31.43% and 93.75%, respectively. Discussion : The present findings suggest that vocal nodules affect vocal fold vibration, resulting in impaired control of pitch and loudness leading to increased noise components. NHR could be used to evaluate the efficacy of treatment, such as voice rehabilitation, in pediatric patients with vocal nodules because of its high specificity for prediction of vocal nodules in children. J. Med. Invest. 68 : 276-279, August, 2021.

A novel polyomavirus (PyV) was identified in the intestinal contents of Japanese eastern bent-wing bats (Miniopterus fuliginosus) via metagenomic analysis. We subsequently sequenced the full genome of the virus, which has been tentatively named Miniopterus fuliginosus polyomavirus (MfPyV). The nucleotide sequence identity of the genome with those of other bat PyVs was less than 80%. Phylogenetic analysis revealed that MfPyV belonged to the same cluster as PyVs detected in Miniopterus schreibersii. This study has identified the presence of a novel PyV in Japanese bats and provided genetic information about the virus.

Background: Since the introduction of the guideline for the diagnosis and treatment of esophageal carcinoma in 2007, the indication for placing an esophageal stent has changed, especially with respect to the treatment of esophageal stricture after chemoradiotherapy(CRT). For CRT cases, irradiation after stent placement and stent placement after CRT are not recommended due to the risk of perforation., Methods: Thirty-eight patients who underwent esophageal stenting in our department between January 2007 and December 2018 and who were diagnosed with thoracic esophageal cancer were included in this study. We retrospectively examined the safety and treatment effect of esophageal stent placement., Results: Prior cancer therapy was observed in 16 cases(8 cases of chemotherapy and 8 cases of CRT). In the no prior therapy group, 13 cases were treated with BSC and 9 cases with chemotherapy. Esophageal stent placement after CRT was performed in 8 cases. Esophageal stent was placed 9(6-14)months after CRT. The stent patency period was 5(1-11)months, and the survival period after stent placement was 6(1-12)months. There was no difference in the frequency of complications and treatment outcomes of the CRT group compared with the non-CRT group., Conclusion: Cases undergoing esophageal stent placement after CRT can expect therapeutic effects similar to those of other cases. However, complications such as perforation can be fatal; thus, careful consideration should be given to each individual case for esophageal stent placement after CRT.

The purpose of this study is to examine the effect of intranasal corticosteroid (INCS) administration on histamine H1 receptor (H1R) gene expression in the nasal mucosa of healthy participants and the effects of dexamethasone on basal and histamine-induced H1R mRNA expression, and histamine-induced phosphorylation of extracellular signal-regulated kinase (ERK) in HeLa cells. Sixteen healthy participants were given INCS once daily for a week. After pretreatment of dexamethasone, HeLa cells were treated with histamine. Levels of H1R mRNA and phosphorylation of ERK were measured using real time PCR and immunoblot analysis, respectively. Levels of H1R mRNA in the nasal mucosa of healthy participants receiving INCS was significantly decreased. Dexamethasone suppressed basal levels of H1R mRNA, and histamine-induced up-regulation of H1R mRNA and ERK phosphorylation in HeLa cells. These data suggested that corticosteroid inhibited both basal transcription and histamine-induced transcriptional activation of H1R through its suppression of ERK phosphorylation in the signaling pathway involved in H1R gene transcription. It is further suggested that pre-seasonal prophylactic administration of INCS suppresses both basal and pollen-induced upregulation of H1R gene expression in the nasal mucosa of patients with pollinosis, leading to prevention of the exacerbation of nasal symptoms during peak pollen season. J. Med. Invest. 67 : 311-314, August, 2020.

The objective of this study is to clarify when facial palsy patients with lower value of Electroneurography (ENoG) should begin the rehabilitation to prevent the development of facial synkinesis. For this purpose, we examined the relationship between the value of ENoG measured 10-14 days after facial palsy onset and the onset day of the development of oral-ocular synkinesis. Sixteen patients with facial palsy including 11 with Bell's palsy and 5 with Ramsay Hunt syndrome (7 men and 9 women ; 15-73 years old ; mean age, 41.6 years) were enrolled in this study. There was no correlation between ENoG value and the onset day of the development of oral-ocular synkinesis (ρ = .09, p = .73). Oral-ocular synkinesis began to develop in 4.0 ± 0.7 months (mean ± SD ; range : 3.1-5.0 months) after facial palsy onset regardless of ENoG value. In conclusion, ENoG value cannot predict when facial synkinesis develops in patients with facial palsy. We recommend that facial palsy patients with a high risk for the development of synkinesis begin the biofeedback rehabilitation with mirror to prevent the development of facial synkinesis 3 months after facial palsy onset. J. Med. Invest. 67 : 87-89, February, 2020.

Background: Regarding the relationship between psychiatric disorders and dizziness, anxiety is the most frequently seen psychiatric disorder in dizzy patients. Objective: We compared the effects of anti-anxious benzodiazepines (loflazepate) and anti-vertiginous cholinergic antagonist (diphenidol) on the subjective symptoms in chronic vestibular patients with secondary anxiety. Methods: Forty-three patients who had chronic dizziness lasting more than three months due to organic vestibular diseases with secondary anxiety. Anxiety was evaluated by the State-Trait Anxiety Inventory (STAI). Subjective handicaps due to dizziness were assessed by the validated questionnaire consisted of 14 questions that were categorized into two physical and three emotional factors. During the initial six months of the study, 21 patients were treated by anti-anxious benzodiazepines (loflazepate, 2 mg/day) for four weeks, whereas anti-vertiginous cholinergic antagonist (diphenidol, 75 mg/day) was used for four weeks for other 22 patients during the later six months-period. Subjective handicaps and STAI were compared between pre- and post-treatment. Results: Loflazepate improved not only three emotional factors and state anxiety but also one of the physical factors. Diphenidol improved two physical factors but no emotional factors nor state and trait anxiety. Conclusions: Targeting for comorbid anxiety was beneficial for subjective symptoms of chronic dizziness with secondary anxiety.

A 73-year-old man was admitted to our hospital with anal pain. The 10 cm tumor was observed externally at the 3 o' clock side of his anus. He was unable to maintain the sitting position because of pain and had fecal incontinence and erosive skin inflammation. We identified this anal stenosis as anal canal adenocarcinoma(moderately differentiated). Thereby, no distant metastasis was found; we decided to treat the patient with conventional therapy. We made a double-hole colostomy in the sigmoid colon, and then the patient received preoperative chemoradiotherapy(CRT). Radiation therapy(RT)was adminis- tered at 40 Gy/20 Fr and oral capecitabine of 825mg/m / 2/time was administered twice a day on the RT days. The tumor shrinkage was good, and then we performed a laparoscopy-assisted abdominoperineal resection of the rectum. Pathologically therapeutic effect was Grade 1b. His activity of daily living was dramatically improved, and he can now main tan the sitting position. Twelve months postoperatively, he has no sign of recurrence. In this case, we experienced an anal canal adenocarcinoma that was possibly locally controlled by preoperative CRT and rectal amputation.

A 94-year-old woman, who had been treated for multiple colon cancers 4 years ago, complained of umbilicus induration and had been followed up in a previous hospital with a diagnosis of periumbilical inflammation. Four years and 3 months postoperatively, the umbilical induration was enlarged, and umbilical metastasis of adenocarcinoma was diagnosed on biopsy. Umbilical resection was performed, and multiple peritoneal metastases were revealed. Umbilical metastases may worsen the patient's quality of life; thus, local resection was recommended positively.

Rats are the most commonly used species in the neurosciences; however, little is known about the effects of selective electrical stimulation of individual vestibular sensors, on their eye movements. This limits their use to study the effects of vestibular stimulation on the brain, and their use in further exploring novel technologies such as artificial vestibular implants. We describe the effects of electrical stimulation of each vestibular sensor on vestibular-related eye movement in rats and compared the results to other species. We demonstrated that each sensor is responsible for specific bilateral eye movements. We found that the eye movements in rats differed from other species. Although the results were similar when stimulating the horizontal canal ampulla, differences appeared when stimulating the vertical canal sensors. During utricular stimulation, the ipsilateral eye moved dorsally in most cases, while the contralateral eye usually moved either caudally, or in extorsion. Saccular stimulation usually moved the ipsilateral eye dorsally or ventrally, while the contralateral eye usually moved ventrally or caudally. This study provides the first data on the application of selective electrical vestibular stimulation in the rat to the study of vestibular-related eye movements.

A novel cyclovirus was identified in the intestinal contents of Taiwan squirrels (Callosciurus erythraeus thaiwanensis) collected in Kanagawa prefecture, Japan, by metagenomic analysis, and was named Taiwan squirrel cyclovirus-1 (TsCyV-1). Phylogenetic analysis showed that TsCyV-1 formed a branch separate from other representative cyclovirus strains. TsCyV-1 is considered to be a new species in the genus Cyclovirus because the criteria for demarcation of cyclovirus species is proposed as nucleotide identities <80 %.