Olfactory and taste dysfunctions caused by COVID-19: a nationwide study.

BACKGROUND: Olfactory dysfunctions (OD) and taste dysfunctions (TD) are widely recognized as characteristic symptoms of COVID-19; however, the frequency and mode of occurrence has varied depending on the viral mutation. The prevalence and characteristics of OD/TD in Japan have not been definitively investigated. The purpose of this study is to assess the prevalence of OD/TD in Japan during the Alpha variant epidemic, and measure symptom prolongation at 6 months and 1 year later following initial infection. METHODS: Patients treated for COVID-19 between February to May 2021 were evaluated for OD/TD symptoms and provided with a QOL questionnaire. Olfactory tests and taste tests were performed using Open Essence and Taste Strips, respectively. RESULTS: Among the 251 COVID-19 patients who participated, 119 underwent both olfactory and taste tests. Prevalence of subjective OD and TD at the time of survey was 57.8% and 40.2%, respectively. After 12 months, the prevalence fell to 5.8% for OD and 3.5% for TD. Among the OD/TD patients, 36.6% experienced parosmia, and 55.4% experienced parageusia. Prevalence of parosmia and parageusia was higher at 6 and 12 months than at the time of survey. Patients with long-lasting disease reported qualitative dysfunctions and scored significantly higher in food-related QOL problems. Most patients who were aware of their hyposmia had low scores on the olfactory test (83.1%). In contrast, only 26.7% of patients who were aware of their hypogeusia had low scores on the taste test. CONCLUSIONS: The prevalence of COVID-19-related OD and TD at the time of survey was 57.8% and 40.2%, respectively. Subjective symptoms of OD and TD persisted for one year in 5.8% and 3.5% of patients, respectively. More than half of the patients with OD or TD complained of qualitative dysfunction and a decrease in their QOL related to eating and drinking. Most patients with TD did not have true TD, but rather developed flavour disorders associated with OD. This conclusion is supported by the finding that patients with subjective OD had low scores on the olfactory test, whereas most patients with subjective TD had normal scores on the taste test.

Factors associated with COVID-19 booster vaccine hesitancy: a nationwide, cross-sectional survey in Japan.

OBJECTIVES: COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese public. STUDY DESIGN: This was a cross-sectional study. METHODS: This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed. RESULTS: In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18-29 years; adjusted odds ratio [aOR]: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77). CONCLUSIONS: Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Potential treatments for genetic hearing loss in humans: current conundrums.

Genetic defects are a major cause of hearing loss in newborns. Consequently, hearing loss has a profound negative impact on human daily living. Numerous causative genes for genetic hearing loss have been identified. However, presently, there are no truly curative treatments for this condition. There have been several recent reports on successful treatments in mice using embryonic gene therapy, neonatal gene therapy and neonatal antisense oligonucleotide therapy. Herein, we describe state-of-the-art research on genetic hearing loss treatment through gene therapy and discuss the obstacles to overcome in curative treatments of genetic hearing loss in humans.

4ß-Hydroxywithanolide E isolated from Physalis pruinosa calyx decreases inflammatory responses by inhibiting the NF-κB signaling in diabetic mouse adipose tissue.

BACKGROUND: Chronic inflammation in adipose tissue together with obesity induces insulin resistance. Inhibitors of chronic inflammation in adipose tissue can be a potent candidate for the treatment of diabetes; however, only a few compounds have been discovered so far. The objective of this study was to find a novel inhibitor that can suppress the inflammatory response in adipose tissue and to elucidate the intracellular signaling mechanisms of the compound. METHODS: To find the active compounds, we established an assay system to evaluate the inhibition of induced MCP-1 production in adipocyte/macrophage coculture in a plant extract library. The active compound was isolated by performing high-performance liquid chromatography (HPLC) and was determined as 4ß-hydroxywithanolide E (4ßHWE) by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) spectral analyses. The effect of 4ßHWE on inflammation in adipose tissue was assessed with adipocyte culture and db/db mice. RESULTS: During the screening process, Physalis pruinosa calyx extract was found to inhibit production of MCP-1 in coculture strongly. 4ßHWE belongs to the withanolide family of compounds, and it has the strongest MCP-1 production inhibitory effect and lowest toxicity than any other withanolides in coculture. Its anti-inflammatory effect was partially dependent on the attenuation of NF-κB signaling in adipocyte. Moreover, in vivo experiments showed that the oral administration of 4ßHWE to db/db mice resulted in the inhibition of macrophage invasion and cytokine expression in adipose tissue after 2 weeks of treatment; improved the plasma adiponectin, non-esterified fatty acids and MCP-1 concentrations; and increased glucose tolerance after 3 to 4 weeks of treatment. CONCLUSIONS: These results suggest that 4ßHWE has anti-inflammatory effect via inhibition of NF-κB activation in adipocyte. Moreover, the attenuation of inflammation in adipocyte has an effect on the inhibition of macrophage accumulation in obese adipose tissue. Consequently, 4ßHWE improves impaired glucose tolerance. Thus, 4ßHWE is a useful natural anti-inflammatory compound to attenuate progression of diabetes and obesity.

Thermoresponsive chitosan/N-isopropylacrylamide copolymer through atom transfer radical polymerization.

Regioseletive copolymerization of N-isopropylacrylamide (NIPAM) onto chitosan was achieved by atom transfer radical polymerization (ATRP) by using a regioselective 3,6-di-O-bromoisobutyryl-2-N-phthaloyl chitosan as a macroinitiator. The degree of polymerization (DP) of polyNIPAM onto the chitosan derivative changed by varying the ratio between NIPAM monomer, macroinitiator, ligand, and transition metal. ATRP successfully proceeded and a DP of polyNIPAM up to 110.5 was obtained. The thermal decomposition temperature of the 3,6-di-O-bromoisobutyryl-2-N-phthaloyl chitosan was significantly improved by increasing the DP of the NIPAM component. The polyNIPAM-g-chitosan derivative showed a thermoresponsive property. Although it formed a stable suspension in water at room temperature, it caused a hydrophilic-to-hydrophobic transition at around 32°C, resulting in precipitate formation.

Preliminary results on the reproduction of a deep-sea snailfish Careproctus rhodomelas around the active hydrothermal vent on the Hatoma Knoll, Okinawa, Japan.

Deep-sea snailfish Careproctus rhodomelas were collected from an active hydrothermal vent using a remotely operated vehicle (R.O.V. Hyper-dolphin) and a pressurized device (Deep-Aquarium). Careproctus rhodomelas exhibited a cystovarian-type ovary containing a small number of developing oocytes at different stages, suggesting that the fish is a batch-spawner that spawns large eggs (c. 6·0 mm) several times within its life span. In vitro culture of the oocytes in the presence of human chorionic gonadotropin showed that oestradiol-17ß production fluctuated with oocyte development, suggesting that the oocytes were at the vitellogenic stage.

Potential risk of thermal damage to cervical nerve roots by a high-speed drill.

Using the transverse processes of fresh porcine lumbar spines as an experimental model we evaluated the heat generated by a rotating burr of a high-speed drill in cutting the bone. The temperature at the drilled site reached 174 degrees C with a diamond burr and 77 degrees C with a steel burr. With water irrigation at a flow rate of 540 ml/hr an effective reduction in the temperature was achieved whereas irrigation with water at 180 ml/hr was much less effective. There was a significant negative correlation between the thickness of the residual bone and the temperature measured at its undersurface adjacent to the drilling site (p < 0.001). Our data suggest that tissues neighbouring the drilled bone, especially nerve roots, can be damaged by the heat generated from the tip of a high-speed drill. Nerve-root palsy, one of the most common complications of cervical spinal surgery, may be caused by thermal damage to nerve roots arising in this manner.

Unsteady flow field around a human hand and propulsive force in swimming.

Much effort has been undertaken for the estimation of propulsive force of swimmers in the front crawl. Estimation is typically based on steady flow theory: the so-called quasi-steady analysis. Flow fields around a swimmer, however, are extremely unsteady because the change direction of hand produces unsteady vortex motions. To evaluate the force correctly, it is necessary to know the unsteady properties determined from the vortex dynamics because that unsteadiness is known to make the force greater. Unsteady flow measurements were made for this study using a sophisticated technique called particle image velocimetry (PIV) in several horizontal planes for subjects swimming in a flume. Using that method, a 100 time-sequential flow fields are obtainable simultaneously. Each flow field was calculated from two particle images using the cross-correlation method. The intensity of vortices and their locations were identified. A strong vortex was generated near the hand and then shed by directional change of the hand in the transition phase from in-sweep to out-sweep. When the vortex was shed, a new vortex rotating in the opposite direction around the hand was created. The pair of vortices induced the velocity component in the direction opposite to the swimming. Results of this study show that the momentum change attributable to the increase in this velocity component is the origin of thrust force by the hand.

Identification of six new photoactive yellow proteins--diversity and structure-function relationships in a bacterial blue light photoreceptor.

Photoactive yellow proteins (PYP) are bacterial photoreceptors with a Per-Arnt-Sim (PAS) domain fold. We report the identification of six new PYPs, thus nearly doubling the size of this protein family. This extends the taxonomic diversity of PYP-containing bacteria from photosynthetic to nonphotosynthetic bacteria, from aquatic to soil-dwelling organisms, and from Proteobacteria to Salinibacter ruber from the phylum Bacteriodetes. The new PYPs greatly increase the sequence diversity of the PYP family, reducing the most prevalent pair-wise identity from 45% to 25%. Sequence alignments and analysis indicate that all 14 PYPs share a common structure with 13 highly conserved residues that form the chromophore binding pocket. Nevertheless, the functional properties of the PYPs vary greatly--the absorbance maximum extends from 432 to 465 nm, the pK(a) of the chromophore varies from pH 2.8 to 10.2, and the lifetime of the presumed PYP signaling state ranges from 1 ms to 1 h. Thus, the PYP family offers an excellent opportunity to investigate how functional properties are tuned over a wide range, while maintaining the same overall protein structural fold. We discuss the implications of these results for structure-function relationships in the PYP family.

Olfactory schwannoma.

We report a case of olfactory schwannoma with calcification. Intraoperative findings indicated that the tumour originated from the olfactory groove. Intraoperative findings of previous studies have not indicated a clear relationship between subfrontal schwannoma and the olfactory nerve, which seems strange, given the association between tumours and cranial nerves at other sites. We suggest this observation has not been reported because the growing olfactory schwannoma changes the local morphology, affecting the appearance of the olfactory nerve.

Cortical dipole imaging of movement-related potentials by means of parametric inverse filters incorporating with signal and noise covariance.

OBJECTIVE: The objective of this study is to explore suitable spatial filters for inverse estimation of cortical equivalent dipole layer imaging from the scalp electroencephalogram. We utilize cortical dipole source imaging to locate the possible generators of scalp-measured movement-related potentials (MRPs) in human. METHODS: The effects of incorporating signal and noise covariance into inverse procedures were examined by computer simulations and experimental study. The parametric projection filter (PPF) and parametric Weiner filter (PWF) were applied to an inhomogeneous three-sphere head model under various noise conditions. RESULTS: The present simulation results suggest that the PWF incorporating signal information provides better cortical dipole layer imaging results than the PPF and Tikhonov regularization under the condition of moderate and high correlation between signal and noise distributions. On the other hand, the PPF has better performance than other inverse filters under the condition of low correlation between signal and noise distributions. The proposed methods were applied to self-paced MRPs in order to identify the anatomic substrate locations of neural generators. The dipole layer distributions estimated by means of PPF are well-localized as compared with blurred scalp potential maps and dipole layer distribution estimated by Tikhonov regularization. The proposed methods demonstrated that the contralateral premotor cortex was preponderantly activated in relation to movement performance. CONCLUSIONS: In cortical dipole source imaging, the PWF has better performance especially when the correlation between the signal and noise is high. The proposed inverse method was applicable to human experiments of MRPs if the signal and noise covariances were obtained.

Characterization of a proteolytic enzyme derived from a Bacillus strain that effectively degrades prion protein.

AIMS: The purpose of this paper was to screen candidate bacterial strains for the production of proteases suitable for application to the degradation of pathogenic forms of prion protein (PrP(Sc)). This paper describes the biochemical characteristics and proteolytic activity of the isolated protease. METHODS AND RESULTS: After screening more than 200 bacterial proteases for keratinolytic activity, we identified a Bacillus stain that produced a protease exhibiting high-degradation activity against a scrapie PrP(Sc). Sequence analysis indicated that this serine-protease belonged to the Subtilisin family and had optimum pH and temperature ranges of 9-10 and 60-70 degrees C. Western blotting analysis revealed that the protease was also capable of decomposing bovine spongiform encephalopathy-infected brain homogenate. In addition, the protease was demonstrated to degrade dried PrP(Sc) that had become firmly attached to a plastic surface considerably more effectively than proteinase K or PWD-1, a previously reported keratinase. CONCLUSIONS: These results indicate that the isolated protease exhibited higher activity for PrP(Sc) degradation compared with other proteases examined. SIGNIFICANCE AND IMPACT OF THE STUDY: This protease could be used under moderate conditions for the decontamination of precision instruments that are susceptible to PrP(Sc) contamination.

Cricoid ossification mimicking an impacted foreign body.

A 54-year-old man complained of severe throat pain and showed subglottic oedema on fibre-optic endoscopy with a distinctly narrowed subglottic space on anteroposterior radiography of the neck and dense linear opacity at the level of the cricoid cartilage on lateral plain radiography. These findings suggested a foreign body just posterior to the cricopharyngeus, but a computed tomography (CT) scan demonstrated a dense calcified ridge on the posterior lamina of the cricoid cartilage but no foreign body.The patient improved symptomatically with systemic antibiotics and topical steroids, and gastrointestinal endoscopy did not detect any foreign body. This is a rare case of vertical ossification of the cricoid lamina masquerading as a foreign body.

Comparison of the LMA-ProSeal and LMA-Classic in children.

BACKGROUND: The LMA-ProSeal is a new laryngeal mask airway with a rear cuff and drainage tube that allows a higher seal pressure than the LMA-Classic for the same intra-cuff pressure, and it permits drainage of gastric secretions and access to the alimentary tract. The LMA-ProSeal can be used in children but it does not have a rear cuff. This study compared the LMA-ProSeal and the LMA-Classic in children for ease of insertion, airway sealing pressure and fibre-optic visualization. METHODS: Sixty ASA I-II children undergoing herniorrhaphy, orchiopexy or myringotomy were included. The patients were randomly assigned to size 2 LMA-Classic trade mark or size 2 LMA-ProSeal groups for airway management. We assessed success rates at first attempt of insertion, airway sealing pressure, fibre-optic position, success rates of gastric tube placement and postoperative blood staining of the device, tongue-lip-dental trauma and hoarseness. RESULTS: There was no statistical difference between the two groups for the success rates at first attempt of insertion, airway sealing pressure and fibre-optic position. Gastric tube insertion was successful in 90% of cases in the LMA-ProSeal group. The LMA-Classic had a higher rate of postoperative blood staining, but there was no tongue-lip-dental trauma or hoarseness in either group. CONCLUSION: We conclude that ease of insertion and airway sealing pressure are similar between the LMA-ProSeal and the LMA-Classic in children.

Escherichia coli cells penetrated by chrysotile fibers are transformed to antibiotic resistance by incorporation of exogenous plasmid DNA.

A suspension of recipient Escherichia coli cells in stationary phase, chrysotile asbestos, and pUC18 donor DNA spread over the surface of a Luria-Bertani agar plate using a streak bar several times, resulted in intracellular uptake of the plasmid DNA by the E. coli cells. The transformation efficiency was highest with a duration of cell exposure to chrysotile of more than 60 s and an agar concentration of 2%. To improve chrysotile-mediated transformation efficiency, we systematically optimized various conditions and parameters. In comparison to chrysotile exposure without cations, exposure with cations produced up to 100-fold more transformants. Optimized conditions resulted in 10(6) transformants/ micro g pUC18 DNA. The drastic physical change due to 'quick drying on the surface of the agar plate' when cells were exposed to chrysotile, was essential for chrysotile-mediated transformation. We suggest that DNA uptake mediated by chrysotile asbestos is the result of a mechanical physical transformation of E. coli, since the E. coli cells are not chemically competent. Electron microscopy of cells exposed to chrysotile suggested penetration of the E. coli membrane by chrysotile fibers. It is suggested that E. coli transformation by the plasmid DNA was the result of penetration by chrysotile fibers to which plasmid DNA is bound or adsorbed.