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.

Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery.

OBJECTIVE: This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. METHOD: Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. RESULTS: Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). CONCLUSION: These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

Odontogenic chronic rhinosinusitis patients undergoing tooth extraction: oral surgeon and otolaryngologist viewpoints and appropriate management.

OBJECTIVE: This study aimed to propose appropriate management for odontogenic chronic rhinosinusitis. METHOD: Thirty-one adult patients with odontogenic chronic rhinosinusitis undergoing maxillary extraction were retrospectively analysed. Patients with (n = 21) and without (n = 10) oroantral fistula on computed tomography were classified. Functional endoscopic sinus surgery was performed when sinusitis did not improve after extraction. The critical indicators for surgical requirement in the management of odontogenic chronic rhinosinusitis were analysed. RESULTS: Sinusitis significantly improved after extraction in both groups. Patients without oroantral fistula had significantly more severe remnant sinusitis than those with oroantral fistula after extraction on computed tomography (p = 0.0037). The requirement for functional endoscopic sinus surgery was statistically significant for patients without orofacial fistula over those with orofacial fistula (p < 0.0001). The surgical improvement ratio was 93 per cent. CONCLUSION: The absence of oroantral fistula and severe sinusitis can be critical indicators for the requirement of functional endoscopic sinus surgery after extraction in the management of odontogenic chronic rhinosinusitis.

Predictors of disease progression after endoscopic sinus surgery in patients with chronic rhinosinusitis.

OBJECTIVE: This study aimed to determine the predictors of disease progression after functional endoscopic sinus surgery in patients with chronic rhinosinusitis. METHOD: A total of 281 adult chronic rhinosinusitis patients who underwent primary bilateral functional endoscopic sinus surgery between 2007 and 2017 and had at least 12 months of follow-up endoscopic evaluation were examined. Patients were divided into eosinophilic (n = 205) and non-eosinophilic chronic rhinosinusitis groups (n = 76). In order to determine adverse factors, post-operative endoscopic appearance scores were analysed in relation to the pre- and intra-operative findings using multiple regression analyses. RESULTS: The post-operative course of eosinophilic cases deteriorated over time, like the early period for non-eosinophilic cases. Frontal sinus polyps recurred early in eosinophilic chronic rhinosinusitis. Multivariate analyses indicated young adulthood, asthma, high computed tomography score and frontal sinus polyps as significant adverse predictors. CONCLUSION: Early, appropriate estimation of sinonasal conditions appears to be crucial for successful surgical management of chronic rhinosinusitis.

Post-operative course prediction during endoscopic sinus surgery in patients with chronic rhinosinusitis.

OBJECTIVE: This study aimed to analyse findings of functional endoscopic sinus surgery to estimate the post-operative course of patients with chronic rhinosinusitis. METHODS: From 2007 to 2015, 291 adult patients with bilateral chronic rhinosinusitis, divided into eosinophilic chronic rhinosinusitis (n = 210) and non-eosinophilic chronic rhinosinusitis (n = 81) groups, who underwent primary functional endoscopic sinus surgery were enrolled. Functional endoscopic sinus surgery findings, scored as operating score, were analysed in relation to pre-operative olfactory recognition threshold and sinonasal computed tomography imaging score, as well as post-operative endoscopic appearance. RESULTS: Operating scores in eosinophilic chronic rhinosinusitis were significantly worse than those in non-eosinophilic chronic rhinosinusitis. The anterior ethmoid sinus and superior meatus were predominantly inflamed. Operating score significantly correlated with pre-operative olfaction recognition threshold, computed tomography score and pre-operative endoscopic appearance score. In eosinophilic chronic rhinosinusitis, higher operating scores were related to post-operative deterioration of endoscopic appearance score. CONCLUSION: The operating score reflects the course following functional endoscopic sinus surgery. Patients with more severe operative findings require longer post-operative treatment.

Influence of opacification in the frontal recess on frontal sinusitis.

OBJECTIVES: This study aimed to radiologically evaluate the influence of inflammatory changes in frontal recess cells on frontal sinusitis. METHODS: A total of 93 patients (186 sides) who underwent primary sinonasal surgery at Hyogo College of Medicine were enrolled in 2015 and 2016. Opacification of agger nasi, fronto-ethmoidal, ethmoid bulla, suprabullar and frontal bulla cells was determined by pre-operative computed tomography and its influence on frontal sinusitis was investigated. RESULTS: In all, 42 per cent of 186 sides were affected by frontal sinusitis. Agger nasi, ethmoid bulla, fronto-ethmoidal, suprabullar and frontal bulla cells were identified in 99 per cent, 100 per cent, 38 per cent, 69 per cent, and 16 per cent of sides, respectively. The presence of frontal recess cells and frontal ostium size did not significantly influence frontal sinusitis development. However, opacification of agger nasi, type 1 fronto-ethmoidal and suprabullar cells significantly influenced frontal sinusitis development. CONCLUSION: Frontal sinusitis is caused by inflammatory changes in frontal recess cells.

Inverted papilloma with osteogenesis in the anterior ethmoid and frontal sinuses.

OBJECTIVE: We report a rare case of new bone formation (osteogenesis) within an inverted papilloma, occurring in the ethmoid and frontal sinuses. METHOD: The histopathological and radiological findings, differential diagnosis, and treatment of tumour-induced osteogenesis are discussed. RESULTS: A 68-year-old man complained of headache and left-sided, purulent rhinorrhoea of five years' duration. On nasal endoscopy, lesions similar to inflammatory nasal polyps were seen. Pre-operative radiological images demonstrated opacification of the left nasal cavity and anterior ethmoid and frontal sinuses, plus a bone-density lesion. The mass with bony lesion was completely removed endoscopically. The mass was histopathologically diagnosed as an inverted papilloma surrounding bony tissue. Furthermore, the histopathological findings (including immature bony tissue rimmed by osteoblasts) indicated an extremely rare case of inverted papilloma induced osteogenesis. Six months after surgery, no recurrence was detected. CONCLUSION: This case highlights the importance of clinical awareness of tumour-induced osteogenesis.

Observation of nonlinear coupling between small-poloidal wave-number potential fluctuations and turbulent potential fluctuations in Ohmically heated plasmas in the JFT-2M tokamak.

Two types of electrostatic modes with small-poloidal wave numbers (approximately 1 and 10-15 kHz) are observed in the edge region of Ohmically heated plasmas in the JFT-2M tokamak. The envelope of the higher frequency coherent mode is modulated at the frequency of the lower frequency mode. A bispectral analysis revealed that a significant nonlinear coupling among the two types of fluctuations and the broadband background turbulent potential fluctuations occurs inside the last closed magnetic flux surface, suggesting that a nonlinear process such as the parametric-modulational instability is involved.

Heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor.

Until now, there has not been enough information on how androgens or androgen deprivation may influence the response of cancer cells to radiation. In this study, the effect of dihydrotestosterone (DHT) on cellular proliferative activity and radiosensitivity was examined in a hormone-sensitive human prostate cancer cell line, LNCaP. In addition, the study also examined how a heat shock protein 90 (Hsp90) chaperone complex inhibitor modified the effect of DHT on the radiosensitivity of the cells, because binding of the androgen receptor (AR) to Hsp90 is required to maintain the stability and functioning of AR. The hormone-sensitive human prostate cancer cell line, LNCaP, was used. Radicicol was used as one of the known Hsp90 chaperone complex inhibitors, and the cells were incubated in the presence of this compound at a concentration of 500 nM. Cellular radiosensitivity was determined by the clonogenic assay; the changes in the protein expression were examined by Western blotting or immunofluorescence. DHT at a concentration of 1 nM caused enhancement of the proliferative activity and reduction of the radiosensitivity of the cells. Radicicol at a concentration of 500 nM abolished the DHT-induced decrease in cellular radiosensitivity and potentiated the radiation-induced cell killing synergistically. Consistent with the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and HER2/neu via reduced binding of AR to Hsp90, although selective degradation of HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect the cellular radiosensitivity. The results suggest that the Hsp9O chaperone complex may be a potential molecular target for potentiation of radiation-induced cell killing in a hormone-sensitive prostate cancer cell line.

Effects of mild heat exposure on sleep stages and body temperature in older men.

The purpose of this study was to examine the effects of mild heat exposure on sleep stages and body temperature in older men. Ten healthy male volunteers with a mean age of 69.2 +/- 1.35 years served as subjects. The experiments were carried out under two different sets of conditions: 26 degrees C 50% relative humidity (RH) and 32 degrees C 50% RH. The subjects slept from 2200 hours to 0600 hours with a cotton blanket and wearing short-sleeve pajamas and shorts on a bed covered by a sheet. Electroencephalogram, electro-occulogram and mental electromyogram recordings were made through the night. Rectal and skin temperatures were measured continuously. No significant differences were observed in sleep onset latency. In time spent in each sleep stage, wakefulness was significantly increased at 32 degrees C than at 26 degrees C. The total amount of wakefulness increased and rapid eye movement sleep (REM) decreased at 32 degrees C compared to 26 degrees C. The fall in rectal temperature was significantly suppressed and the mean skin temperature was significantly higher at 32 degrees C than at 26 degrees C. These results suggest that, for older men, even mild heat exposure during the nighttime sleep period may increase thermal load, suppress the decrease of rectal temperature, decrease REM, and increase wakefulness and whole-body sweat loss.

Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs.

Nipradilol is an alpha(1), beta-blocker with milder side effects than other beta-blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C-value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C-value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing beta-adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.

A prospective trial of steroid withdrawal after renal transplantation in children: results obtained 1990 and 2002.

Ten-year graft survival rate was 89% after immunosuppressive therapy with cyclosporine, methylprednisolone, and mizoribine in pediatric renal transplant recipients enrolled in our multicenter study. Adrenocorticosteroids, which cause growth retardation, were reduced by administration on alternate days in 67% and withdrawn in 23% of recipients. Acute rejection episodes occurred in 30% of patients after withdrawal of steroids. Graft function returned to prerejection levels after treatment with high-dose methylprednisolone. Catch-up growth occurred after alternate day administration and steroid withdrawal. Twenty-eight of 94 patients reached the final height of 156 cm in boys and 145 cm in girls, because of the gradually reduced growth rate. Management of growth retardation before transplantation, especially in patients with congenital renal diseases, and early reduction of the steroid dose after transplantation will increase the final height of children with chronic renal failure.

Nephropathy of cyanotic congenital heart disease: clinical characteristics and effectiveness of an angiotensin-converting enzyme inhibitor.

AIMS: Nephropathy has long been recognized as a potential complication of cyanotic congenital heart disease (CCHD). There have been few large-scale studies or clinical reports on renal impairment in patients with CCHD; similarly, very few studies have examined the drug treatment of nephropathy in CCHD. We examined the clinical characteristics and effectiveness of enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), in patients with CCHD complicated with significant proteinuria. MATERIALS AND METHODS: The clinical records of 37 patients with CCHD were evaluated; all were older than 10 years of age (median 19, range from 10 to 27) and had regular check-ups, including urinalysis. The treatment criteria for enalapril administration included significant proteinuria (urinary excretion > 1.0 g/24 h), stable cardiac condition and blood pressure within the normal range. RESULTS: Eleven patients (29.7%) had persistent proteinuria, 6 patients met the enalapril treatment criteria and 5 patients were treated for more than 12 months. Enalapril apparently reduced the urinary protein excretion in 4 of the 5 patients (80%). No consistent improvement of renal function, as evidenced in the glomerular filtration rate (GFR), renal plasma flow (RPF) or filtration fraction (FF) was found in these patients, but neither were any significant adverse effects noted. CONCLUSION: The incidence of nephropathy among patients with CCHD was about 30%, which was consistent with previous studies. It is worth considering the use of ACE-I when nephropathy accompanies CCHD.

Triterpenoids from Adiantum caudatum.

Three triterpenoids, 8alpha-hydroxyfernan-25,7beta-olide, 3alpha-hydroxy-4alpha-methoxyfilicane and 19alpha-hydroxyferna-7,9(11)-diene were isolated from the fresh fronds of Adiantum caudatum. Their structures were elucidated by spectroscopic techniques. Thirteen known triterpenoids were also identified from this fern.

Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis.

BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Chemical oxidation of organic matter in secondary-treated municipal wastewater by using methods involving ozone, ultraviolet radiation and TiO2 catalyst.

The efficiencies of chemical oxidation of organic matter in genuine secondary-treated municipal wastewater by using O3, O3/UV, O3/TiO2, UV/TiO2 and O3/UV/TiO2 methods were compared experimentally. Effects of carbonates on these efficiencies were also investigated. Elimination of carbonates from the water increased TOC reduction efficiency of all the methods. The effect of the carbonates on the O3 method was less significant than that on the other methods. The O3/UV method was the most effective for reducing TOC under both carbonate-present and decarbonated conditions. The catalytic ozone process (O3/TiO2) showed a tendency to increase the ozonation efficiency at the beginning of the reaction under the decarbonated condition, but the addition of the TiO2 catalyst inhibited the ozonation under the carbonate-present condition. The photocatalytic oxidation process (UV/TiO2) did not reduce TOC as much as the other methods, but it could reduce TOC over a long time. And the O3/UV/TiO2 method did not show a synergistic effect of ozonation and photocatalytic oxidation. Furthermore, zonation prior to coagulation increased TOC reduction efficiency of coagulation, but this effect was also affected by the carbonates in water.

Absolute quantification of AMPA receptor subunit mRNAs in single hippocampal neurons.

alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit (GluR1-4) mRNAs expressed by single neurons in rat hippocampal cultures were quantified by single-cell RT-PCR using an internal standard RNA after whole-cell patch-clamp recording. The internal standard RNA, derived from GluR2 with a single nucleotide substitution, was reverse-transcribed and PCR-amplified with the same efficiency as GluR1-4 mRNAs. The mean mRNA numbers harvested in vitro from pyramidal-like neurons on day 9 were 1150 +/- 324 molecules of GluR1, 1080 +/- 273 molecules of GluR2, 100 +/- 20 molecules of GluR3, and 50 +/- 10 molecules of GluR4 (mean +/- SEM, n = 12). In a non-pyramidal neuronal population that expresses AMPA receptors characterized by high Ca(2+) permeability, the numbers of GluR1, GluR3 and GluR4 mRNA molecules harvested per cell were 354 +/- 64, 25 +/- 17 and 168 +/- 36, respectively (n = 8). The GluR2 mRNA was not detected in this cell type. The calculated ratio of AMPAR mRNA molecules per total mRNA molecules was 1/240 in pyramidal-like neurons (1/500 for GluR2), being in the range obtained with total RNA from rat forebrain and cerebellum (1/170 and 1/380, respectively). Finally, our results indicated that the proportion of GluR1-4 mRNA located in neurites reached approximately 60% in pyramidal-like neurons. However, we found no evidence of preferential subcellular distribution of a given subunit.

Glia-synapse interaction through Ca2+-permeable AMPA receptors in Bergmann glia.

Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial cells in the cerebellum have Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) assembled without the GluR2 subunit. To elucidate the role of these Ca2+-permeable AMPARs, we converted them into Ca2+-impermeable receptors by adenoviral-mediated delivery of the GluR2 gene. This conversion retracted the glial processes ensheathing synapses on Purkinje cell dendritic spines and retarded the removal of synaptically released glutamate. Furthermore, it caused multiple innervation of Purkinje cells by the climbing fibers. Thus, the glial Ca2+-permeable AMPARs are indispensable for proper structural and functional relations between Bergmann glia and glutamatergic synapses.

Sindbis viral-mediated expression of Ca2+-permeable AMPA receptors at hippocampal CA1 synapses and induction of NMDA receptor-independent long-term potentiation.

Gene manipulation in order to artificially express a particular gene in neurons in the central nervous system is a powerful tool for the analysis of brain function. Sindbis viral vectors have been developed to express high levels of foreign genes in postmitotic brain neurons with little transfection of glial cells. In this study, we expressed the gene encoding the unedited GluR2 (GluR-B) subunit of the AMPA-type glutamate receptor that forms inwardly rectifying and Ca2+-permeable channels, in rat CA1 hippocampal neurons in slice cultures using Sindbis viral vectors. The pyramidal cell layer of the CA1 region was injected with recombinant Sindbis viruses encoding both enhanced green fluorescent protein (GFP) and unedited GluR2. The GFP fluorescence from CA1 neurons could be detected as early as 6 h and reached a maximal level about 48 h postinfection. The inwardly rectifying and Ca2+-permeable AMPA receptors were expressed in most CA1 pyramidal cells expressing GFP. These AMPA receptors expressed by gene transfer were involved in fast excitatory neurotransmission elicited by electrical stimulation of the Schaffer collaterals in the stratum radiatum. Tetanic stimulation of Schaffer collaterals induced NMDA receptor-independent, long-term potentiation due to Ca2+ influx through the newly expressed AMPA receptors in the area densely stained with GFP. Thus, the combined use of Sindbis viral vectors with the GFP reporter allowed physiological examination of the roles of a specific gene product in synaptic function in well-characterized brain neurons.

Algae-removal performance of a fluidized-bed biofilm reactor system for lake water treatment.

The algae removal efficiency of a pilot plant--based on a fluidized-bed biofilm reactor system for treating--was investigated. This system does not require back-washing because the fluidized-bed suffers no clogging. Moreover, the system uses dissolved oxygen in the influent water for aerobic biological treatment without the need for additional aeration equipment. This, it is an easy-maintenance, low-energy system for purifying eutrophic lake water. The system was operated continuously at a flow rate of 1500 m3/d for nine months at Tsuchiura Port in Lake Kasumigaura. And concentrations of chlorophyll-a and dissolved oxygen in both the influent and effluent water were continuously monitored. In summer (August to September) when water bloom occurred, the average efficiency of chlorophyll-a removal was 64% at an average influent chlorophyll-a concentration of 137.8 micrograms/L. Over the entire experimental period of nine months, the average daily amount of removed chlorophyll-a was 40.3 g/d at an average influent chlorophyll-a concentration of 89.5 micrograms/L. By analyzing the relationship between the amount of removed chlorophyll-a and the consumption of dissolved oxygen, it was estimated that almost all of the algae trapped in the reactor was biologically degraded.