Whole-genome analysis of human group A rotaviruses in 1980s Japan and evolutionary assessment of global Wa-like strains across half a century.

Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like strains has been increasingly reported, indicating a shift in the molecular epidemiology of RVA. Although understanding RVA evolution requires the analysis of both current and historical strains, comprehensive pre-1980's sequencing data are scarce globally. We determined the whole-genome sequences of representative strains from six RVA gastroenteritis outbreaks observed at an infant home in Sapporo, Japan, between 1981 and 1989. These outbreaks were mainly caused by G1 or G3 Wa-like strains, resembling strains from the United States in the 1970s-1980s and from Malawi in the 1990s. Phylogenetic analysis of these infant home strains, together with Wa-like strains collected worldwide from the 1970s to 2020, revealed a notable trend: pre-2010 strains diverged into multiple lineages in many genomic segments, whereas post-2010 strains tended to converge into a single lineage. However, Bayesian skyline plot indicated near-constant effective population sizes from the 1970s to 2020, and selection pressure analysis identified positive selection only at amino acid 75 of NSP2. These results suggest that evidence supporting the influence of rotavirus vaccines, introduced globally since 2006, on Wa-like RVA molecular evolution is lacking at present, and phylogenetic analysis may simply reflect natural fluctuations in RVA molecular evolution. Evaluating the long-term impact of RV vaccines on the molecular evolution of RVA requires sustained surveillance.

Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1.

OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications. DESIGN, PATIENTS AND MESUREMENT: A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ2 tests, were employed for survival analysis and gene mutation comparisons. RESULTS: Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data. CONCLUSIONS: Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.

Swallowing improvement surgeries.

PURPOSE: To discuss the different swallowing improvement surgeries that address one or more dysfunctional pharyngolaryngeal structures causing dysphagia. These surgeries reduce the risk of aspiration without sacrificing vocal function. METHODS: We searched the PubMed database and used Google Scholar search engine to find studies discussing the different swallowing improvement surgeries. A manual search of references in selected articles and reviews was done as well. No chronologic limitation was set for the studies; however, only articles written in English and Japanese were considered. Due to the nature of this article, no particular inclusion or exclusion criteria were set when searching for studies to be used as references; however, all relevant studies were reviewed and agreed upon by the authors for inclusion in this review article. RESULTS/DISCUSSION: Surgeries to improve swallowing function can be categorized into those that reinforce nasopharyngeal closure or pharyngeal contraction, improve laryngeal elevation or pharyngoesophageal segment opening, and those that improve vocal fold closure to protect the airway during swallowing. They are an effective alternative treatment that may significantly improve these patients' quality of life. Swallowing rehabilitation with the altered pharyngolaryngeal structures is required post-operatively to significantly improve patients' dysphagia. CONCLUSIONS: Surgeries to improve swallowing function address specific dysfunctional sites involved in the swallowing mechanism. Choosing the most appropriate surgery for each patient requires knowledge of the pathophysiology for their dysphagia and detailed pre-operative work-up.

Differences in residual volume above different tracheostomy tube cuffs depending on tube structure, tube tilt angle, and liquid viscosity.

INTRODUCTION: Proper management of aspirated material above the tracheostomy tube cuff is crucial to prevent complications, such as aspiration pneumonia. This study aimed to thoroughly examine the effects of aspirated liquid viscosity, suction port positioning, and tube tilt angle on residual volume above the cuff (RVAC). METHODS: Five types of tracheostomy tubes (approximately 9 mm outer diameter) were placed through a transparent cylinder with an inner diameter of 18 mm. The cuff was inflated to completely seal the interior of the cylinder. Four liquids with different viscosities were poured onto the cuff, and the liquid above the cuff was suctioned from the side port. The cylinder was angled at 90° and 20°, and each test was performed thrice to determine the average RVAC. RESULTS: After side-port suctioning, some liquid residue was observed on the cuff of all tracheostomy tubes. The RVAC increased with higher liquid viscosity. The tubes with a longer distance from the suction port opening to the cuff top exhibited more RVAC. Moreover, the RVAC was almost the same regardless of the cylinder angle for tubes with a suction port on the lateral side. However, tubes with backside ports showed a decreased RVAC with cylinder tilt. CONCLUSIONS: This study underscores the persistence of residual material on cuffed tracheostomy tubes even with regular subglottic secretion drainage. This emphasizes the need for specialized tracheostomy tube development aimed at reducing post-suction RVAC. Improved designs can potentially minimize complications associated with residue accumulation.

The morphometrical evaluation after uvulopalatopharyngoplasty.

OBJECTIVES: The aim of this study was to evaluate the efficacy of uvulopalatopharyngoplasty (UPPP) and the corresponding postoperative morphometrical changes. METHODS: Patients diagnosed with obstructive sleep apnea syndrome who complained of snoring and apnea were enrolled in this study. Pre- and postoperative tests, including CTs, pharyngeal volume (PV), cross-sectional area (CSA), and six-category morphometrical studies, were performed. RESULTS: Of 11 patients included, 10 showed improvement of symptoms. BMI correlated with the respiratory event index (REI). In terms of PV, there was a significantly wider postoperative area. The rate of change between preoperative REI and postoperative REI (ΔREI) correlated with the amount of change of PV between preoperative PV and postoperative PV (ΔPV). CSA increased postoperatively and correlated with REI. Uvula space (UV) and distance between the hyoid bone and the base of the tongue (HB) increased postoperatively, and posterior airway space (PAS) and epiglottic space (Epi) decreased postoperatively. UV and PAS were significant (p = 0.046, 0.014). UV was related to REI. CONCLUSION: Widening the PV, increasing CSA, and the posterior movement of the tongue base after UPPP surgery were found. The improvement of REI did not depend only on volume. These results suggest that it was important not only to widen the PV but also to improve the shape of the pharynx.

Effects of jaw movement in bimaxillary orthognathic surgery on the upper airway: Computational fluid dynamics analysis.

Maxillomandibular repositioning in orthognathic surgeries has both morphologic and functional effects. These surgeries are thought to change the pharyngeal space and cause obstructive sleep apnoea syndrome, however. The primary purpose of this study is to evaluate the effects of jaw movement in bimaxillary orthognathic surgery on airway function and to identify the morphometric factors that can predict postoperative airway function. The subjects were 11 males and 12 females who had undergone orthognathic surgeries of the maxilla and mandible. The results of cephalometric analysis, cross-sectional area of the pharynx (CSA), pharyngeal volume and computational fluid dynamics (CFD) were compared. The CSA of the nasal (CSA1), total volume and total nasal volume decreased after surgery with statistical significance. Velocity at the oropharyngeal space (V2) increased after surgery with statistical significance. V2, CSA of the oropharyngeal space (CSA2) and PV were correlated with the horizontal posterior movement of point B, point Menton and overjet. V2 and CSA2 were correlated with SNB before and after surgery in all 46 analyses. Changes in pharyngeal airflow were more affected by pressure drop in the pharyngeal space (ΔPp) than by pressure drop in the nasal space (ΔPn). The relationship between the actual amount of change in the cephalometric reference point and the airway function is evident. CFD may thus be very useful as morphological analysis in preoperative treatment decision making.

Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation.

BACKGROUND: Postviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated. METHODS: A murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic-polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue. CONCLUSIONS: Taken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.

Stereotactic radiosurgery ensures an effective and safe long-term control of Koos grade IV vestibular schwannomas: a single-center, retrospective, cohort study.

PURPOSE: Stereotactic radiosurgery (SRS) is a standard treatment modality for vestibular schwannomas (VSs). However, there is a paucity of data on tumor control and neurological preservation for larger VSs. We aimed to investigate the long-term effectiveness of SRS for Koos grade IV compared with I-III VSs. METHODS: We included 452 patients with VSs (50 Koos grade IV and 402 Koos grade I‒III) who were treated with SRS at our institution from 1990 to 2021. Tumor control and functional preservation were calculated using the Kaplan-Meier method and compared between groups with the log-rank test. RESULTS: The median post-SRS follow-up period was 68 months. Progression-free survival rates were 91% at 5 and 10 years for Koos grade IV VSs, and 95% and 92%, respectively, for Koos grade I‒III VSs (p = 0.278). In Koos grade IV VSs, functional preservation rates of the facial and trigeminal nerves were both 96% at 5 years (both 98% for Koos grade I‒III VSs; facial, p = 0.410; trigeminal, p = 0.107). Hearing preservation rates were 61% at 5 years for Koos grade IV VSs and 78% for Koos grade I-III VSs (p = 0.645). Symptomatic transient tumor expansion was more common with Koos grade IV VSs (8.0% vs. 2.5%, p = 0.034), although all related symptoms diminished in accordance with tumor shrinkage. CONCLUSION: SRS may contribute to long-term tumor control and adequate neurological preservation in the treatment of Koos grade IV VSs, comparable to those in the treatment of Koos grade I‒III VSs.

Filtration-processed biomass nanofiber electrodes for flexible bioelectronics.

An increasing demand for bioelectronics that interface with living systems has driven the development of materials to resolve mismatches between electronic devices and biological tissues. So far, a variety of different polymers have been used as substrates for bioelectronics. Especially, biopolymers have been investigated as next-generation materials for bioelectronics because they possess interesting characteristics such as high biocompatibility, biodegradability, and sustainability. However, their range of applications has been restricted due to the limited compatibility of classical fabrication methods with such biopolymers. Here, we introduce a fabrication process for thin and large-area films of chitosan nanofibers (CSNFs) integrated with conductive materials. To this end, we pattern carbon nanotubes (CNTs), silver nanowires, and poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) by a facile filtration process that uses polyimide masks fabricated via laser ablation. This method yields feedlines of conductive material on nanofiber paper and demonstrates compatibility with conjugated and high-aspect-ratio materials. Furthermore, we fabricate a CNT neural interface electrode by taking advantage of this fabrication process and demonstrate peripheral nerve stimulation to the rapid extensor nerve of a live locust. The presented method might pave the way for future bioelectronic devices based on biopolymer nanofibers.

Efficacy of preoperative autologous blood storage in one-stage bilateral total knee arthroplasty.

BACKGROUND: One-stage bilateral total knee arthroplasty (TKA) has the advantages of a single hospital stay, shorter rehabilitation, and reduced financial burden on patients. However, perioperative bleeding is greater with one-stage bilateral TKA than with unilateral TKA and is more likely to require allogeneic blood transfusion. At our hospital, we normally store autologous blood about 1 month before surgery to reduce the need for allogeneic blood transfusion and avoid its adverse reactions as much as possible. The purpose of this study was to determine the efficacy of preoperative autologous blood storage for patients undergoing one-stage bilateral TKA. METHODS: We retrospectively examined the allogeneic blood transfusion avoidance rate and the perioperative decrease in hemoglobin (Hb) level in 166 patients according to whether or not they had preoperative autologous blood stored. The patients for whom blood was stored were then subdivided according to whether the amount of blood stored was 400 mL or 200 mL. RESULTS: Excluding allogeneic transfusion cases, the mean perioperative decrease in Hb was significantly lower in the patients with stored blood than in those without stored blood (3.5 g/dL vs 4.4 g/dL, p < 0.001). The allogeneic blood transfusion avoidance rate was significantly higher in the group with stored blood (98.5% vs 86.7%, p < 0.01). In the group with stored blood, the transfusion avoidance rate was higher, but not significantly, in the subgroup with 400 mL of blood stored than in those with 200 mL of blood stored (100% vs 97.5%) and the mean perioperative decrease in Hb was 3.5 g/dL in both blood storage volume groups. CONCLUSIONS: Preoperative autologous blood storage can help increase the likelihood of avoiding allogeneic blood transfusion in patients undergoing one-stage bilateral TKA.

Molecular characterization of the first human G15 rotavirus strain of zoonotic origin from the bovine species.

Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.

Molecular and clinical characterization of the equine-like G3 rotavirus that caused the first outbreak in Japan, 2016.

Since 2013, equine-like G3 rotavirus (eG3) strains have been detected throughout the world, including in Japan, and the strains were found to be dominant in some countries. In 2016, the first eG3 outbreak in Japan occurred in Tomakomai, Hokkaido prefecture, and the strains became dominant in other Hokkaido areas the following year. There were no significant differences in the clinical characteristics of eG3 and non-eG3 rotavirus infections. The eG3 strains detected in Hokkaido across 2 years from 2016 to 2017 had DS-1-like constellations (i.e. G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2), and the genes were highly conserved (97.5-100 %). One strain, designated as To16-12 was selected as the representative strain for these strains, and all 11 genes of this strain (To16-12) exhibited the closest identity to one foreign eG3 strain (STM050) seen in Indonesia in 2015 and two eG3 strains (IS1090 and MI1125) in another Japanese prefecture in 2016, suggesting that this strain might be introduced into Japan from Indonesia. Sequence analyses of VP7 genes from animal and human G3 strains found worldwide did not identify any with close identity (>92 %) to eG3 strains, including equine RV Erv105. Analysis of another ten genes indicated that the eG3 strain had low similarity to G2P[4] strains, which are considered traditional DS-1-like strains, but high similarity to DS-1-like G1P[8] strains, which first appeared in Asia in 2012. These data suggest that eG3 strains were recently generated in Asia as mono-reassortant strain between DS-1-like G1P[8] strains and unspecified animal G3 strains. Our results indicate that rotavirus surveillance in the postvaccine era requires whole-genome analyses.

A murine model of eosinophilic chronic rhinosinusitis using the topical application of a vitamin D3 analog.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS. METHODS: In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. CONCLUSIONS: Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.

Rotavirus vaccination in Japan: Efficacy and safety of vaccines, changes in genotype, and surveillance efforts.

In Japan, a monovalent rotavirus vaccine (RV1) and a pentavalent rotavirus vaccine (RV5) were launched as voluntary vaccinations in November 2011 and July 2012, respectively. Rotavirus (RV) vaccine coverage in Japan increased from 30.0% in 2012 to 78.4% in 2019. The number of RV gastroenteritis hospitalizations decreased after 2014 in Japan, and is expected to decrease further following the introduction of RV vaccines into the national immunization program in October 2020. The incidence rates of intussusception (IS) among children aged <1 year were 102.8 and 94.0 per 100,000 person-years in the pre-vaccine (2007-2011) and post-vaccine (2012-September 2014) eras, respectively. IS incidence did not increase following RV vaccine introduction in Japan. The efficacy and safety of RV vaccination were both documented in Japan. To reduce the risk of IS following RV vaccination, it is important that children receive a first dose of RV vaccine at age <15 weeks, preferably at age 2 months. Some strains that have emerged since RV vaccine introduction, such as DS-1-like G1P[8], eG3, and G8P[8], have spread nationwide. These three emerging genotypes did not affect the severity of the RV infection. Continuous city-level surveillance, using analysis of all 11 RV genome segments, is necessary to elucidate the genetic characteristics of prevalent RV strains. These efforts would also clarify the influence of vaccination on genetic changes of RV strains and the emergence of new genotypes.

Loss of Smell and Taste in Patients With Suspected COVID-19: Analyses of Patients' Reports on Social Media.

BACKGROUND: The year 2020 was the year of the global COVID-19 pandemic. The severity of the situation has become so substantial that many or even most of the patients with mild to moderate symptoms had to self-isolate without specific medical treatments or even without being tested for COVID-19. Many patients joined internet membership groups to exchange information and support each other. OBJECTIVE: Our goal is to determine the benefits and limits of using social media to understand the symptoms of patients with suspected COVID-19 with mild to moderate symptoms and, in particular, their symptoms of anosmia (loss of the sense of smell) and ageusia (loss of the sense of taste). The voluntary reports on an internet website of a membership group will be the platform of the analyses. METHODS: Posts and comments of members of an internet group known as COVID-19 Smell and Taste Loss, founded on March 24, 2020, to support patients with suspected COVID-19 were collected and analyzed daily. Demographic data were collected using the software mechanism called Group Insights on the membership group website. RESULTS: Membership groups on social media have become rare sources of support for patients with suspected COVID-19 with mild to moderate symptoms. These groups provided mental support to their members and became resources for information on COVID-19 tests and medicines or supplements. However, the membership was voluntary, and often the members leave without notification. It is hard to be precise from the free voluntary reports. The number of women in the group (6995/9227, 75.38% as of October 12, 2020) was about three times more than men (2272/9227, 24.62% as of October 12, 2020), and the peak age of members was between 20-40 years in both men and women. Patients who were asymptomatic other than the senses comprised 14.93% (53/355) of the total patients. Recovery of the senses was higher in the patients who were asymptomatic besides having anosmia and ageusia. Most (112/123, 91.06%) patients experienced other symptoms first and then lost their senses, on average, 4.2 days later. Patients without other symptoms tended to recover earlier (P=.02). Patients with anosmia and ageusia occasionally reported distorted smell and taste (parosmia and dysgeusia) as well as experiencing or perceiving the smell and taste without the sources of the smell or taste (phantosmia and phantogeusia). CONCLUSIONS: Our analysis of the social media database of suspected COVID-19 patients' voices demonstrated that, although accurate diagnosis of patients is not always obtained with social media-based analyses, it may be a useful tool to collect a large amount of data on symptoms and the clinical course of worldwide rapidly growing infectious diseases.

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.

[SURVEY OF PATIENTS' PERSPECTIVE ON SURGERY FOR CHRONIC RHINOSINUSITIS WITH NASAL POLYPS].

OBJECTIVE: To ensure that the best possible information is available for selecting treatment options in patients who have chronic rhinosinusitis with nasal polyps (CRSwNP), it is necessary to assess experiences with surgical procedures in real-world clinical practice. METHODS: We used an internet questionnaire to survey 300 patients who had a history of CRSwNP surgery or had been recommended for such surgery. RESULTS: The patients who underwent surgery showed high satisfaction with the effectiveness of the surgery. However between 20% and 30% were notably dissatisfied with the safety of the procedure, its effects on quality of life (QOL), its economic impact, and its influence on societal activities, such as attendance at work or school. This dissatisfaction tended to be particularly pronounced among older patients and those who had multiple surgeries. The primary reasons given for avoiding surgery were "afraid of surgery," "no time for hospitalization and treatment," and "surgery is too expensive." CONCLUSION: Our research indicates that, although recipient patients are highly satisfied with the effectiveness of surgery for CRSwNP, a number of patients hesitate because of concerns about safety, cost, and societal activities such as work and school attendance. These findings suggest that treatment in a clinical setting should consider not only therapeutic effects but also the patient's attitude and situation.

Rotavirus genotype and Vesikari score of outpatients in Japan in the vaccine era.

BACKGROUND: Group A rotaviruses (RVs) are a major cause of severe gastroenteritis among infants and young children. In Japan, RV vaccines were introduced in 2011, leading to a reduction in severe gastroenteritis cases. Studies are required to assess the effectiveness of the vaccines and their effect on the prevalence of RV genotypes. METHODS: Fecal samples were collected from outpatients with RV gastroenteritis in a pediatric clinic in Sapporo, Japan, from 2010 to 2016. GPI genotypes were determined using reverse-transcription polymerase chain reaction. Clinical information and immunization records were obtained from outpatients after 2013. GPI genotypes and clinical features were compared between patients with and without a RV vaccine history. RESULTS: In total, 270 cases were genotyped. G1P[8]I1 (Wa-like G1P[8]) strains were dominant from 2010 to 2012. G1P[8]I2 (DS-1-like G1P[8]) strains appeared in 2012 and dominated in 2013 to 2015. G2P[4]I2 and G9P[8]I1 strains increased every 3 years (G2P[4]I2: 2011 and 2014, G9P[8]I1: 2010, 2013 and 2016). After the 2013 season, 137 cases were collected, 24 of which were vaccinated. Cases requiring drip infusion were fewer in the vaccination group than in the non-vaccination group (16.7% vs 52.2%). No patients required hospitalization in the vaccination group compared with 10.6% in the non-vaccination group. A severe Vesikari score was less common in the vaccination group than in the non-vaccination group (33.3% vs 78.8%). There was no significant difference in the GPI genotype distribution between the two groups. CONCLUSION: Rotaviruses vaccine effectiveness, regardless of GPI genotype, was confirmed in terms of alleviation of disease severity.

Strategic Outlook toward 2030: Japan's research for allergy and immunology - Secondary publication.

Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.

Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa.

The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.