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.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium WST-1.

Rapid susceptibility testing for slowly growing nontuberculous mycobacteria (NTM) using a colorimetric microbial viability assay based on the reduction of the water-soluble tetrazolium salt {2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1)} using 2,3,5,6-tetramethyl-1,4-benzoquinone as an electron mediator was developed. Using the Clinical and Laboratory Standards Institute (CLSI) method, a long-term incubation time (7-14 days) was required to determine the minimum inhibitory concentrations (MICs) of the slowly growing NTM. The MICs for a variety of different antibiotics against the slowly growing NTM were determined by the WST-1 colorimetric method and compared with those obtained using the broth microdilution methods approved by the CLSI. Good agreement was found between the MICs determined after 3-4 days using the WST-1 colorimetric method and those obtained after 10-14 days using the broth microdilution method. The results suggest that the WST-1 colorimetric assay is a useful method for the rapid determination of the MICs for the slowly growing NTM.

A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay.

UNLABELLED: A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay based on the reduction in a tetrazolium salt 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) with 2-methyl-1,4-napthoquinone as the electron mediator was developed. The proposed method was useful to measure the proliferation of 18 kinds of moulds and seven kinds of yeasts, including representative pathogens such as Aspergillus spp., Candida spp. and Cryptococcus spp. Linear relationships between the absorbance and viable fungal cell density were obtained for all fungi, suggesting that the absorbance change reflected the fungal proliferation. In addition, the minimum inhibitory concentrations (MICs) against a variety of different pathogenic moulds and yeasts for amphotericin B, itraconazole and 5-flucytosine were determined by susceptibility testing using the proposed method and compared with those obtained using the conventional broth microdilution method. There was an excellent agreement between the results obtained using the WST-8 colorimetric method and those obtained using the conventional Clinical and Laboratory Standard Institute method. The WST-8 colorimetric assay is a useful method for rapid determination of accurate MICs for a variety of different fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: A rapid microplate method for the proliferation assay of fungi and the antifungal susceptibility testing using the colorimetric microbial viability assay based on reduction in a tetrazolium salt (WST-8) was developed. The WST-8 colorimetric method was useful to measure the proliferation of a variety of different fungi. In the antifungal susceptibility testing, there was a good agreement between the MICs determined after 24 h using the WST-8 colorimetric method and those obtained after 48-96 h using the broth microdilution method. The proposed method was superior to conventional methods in terms of its rapidity towards a variety of different fungi.

Evaluation of the national health policy of thalassaemia screening in the Islamic Republic of Iran.

We reviewed the medical and economic burden of thalassaemia major with emphasis on prenatal diagnosis for disease prevention as the most economic health care policy approach. The current programme in the Islamic Republic of Iran screens couples just before marriage, identifies carriers and refers them for genetic counselling. We searched the current literature for a refined model and enquired into compliance issues in interviews with physicians, couples and families with affected children. The programme was unsatisfactory in comparison with comparable programmes in the Mediterranean region. We devised a simple decision tree that incorporates cost-effectiveness and technical, methodological and social issues that affect compliance. While revisions to the policy could improve efficiency, follow-up is needed, especially to provide prenatal diagnosis for carrier couples.

Evaluation of the national health policy of thalassaemia screening in the Islamic Republic of Iran

We reviewed the medical and economic burden of thalassaemia major with emphasis on prenatal diagnosis for disease prevention as the most economic health care policy approach. The current programme in the Islamic Republic of Iran screens couples just before marriage, identifies carriers and refers them for genetic counselling. We searched the current literature for a refined model and enquired into compliance issues in interviews with physicians, couples and families with affected children. The programme was unsatisfactory in comparison with comparable programmes in the Mediterranean region. We devised a simple decision tree that incorporates cost-effectiveness and technical, methodological and social issues that affect compliance. While revisions to the policy could improve efficiency, follow-up is needed, especially to provide prenatal diagnosis for carrier couples

Cell death of olfactory receptor neurons in a rat with nasosinusitis infected artificially with Staphylococcus.

Nasosinusitis is a common cause of acquired hyposmia or anosmia. To study the apoptotic death of olfactory receptor neurons in nasosinusitis, we made an inflammation model in rat infected with Staphylococcus. The histochemical changes in olfactory epithelium were examined using antibodies against protein gene product 9.5 (PGP 9.5), single-strand DNA (ssDNA), Bcl-2 and Bax that might be involved in the apoptosis of olfactory receptor neurons. The thickness of olfactory epithelium and the number of ssDNA-labeled cells were evaluated in each post-treatment group and the results were analyzed by two-way analysis of variance (ANOVA) and post hoc tests. Hematoxylin-eosin staining showed that a severe inflammatory reaction had occurred on the infected side of the nasal cavity and sinus, but not on the non-infected side. However, apoptosis of olfactory receptor neurons occurred on both sides; the apoptosis on the non-infected side started later and behaved like a shadow curve similarly to the infected side. Repeated measures ANOVA showed significant differences of both the thickness of olfactory epithelium (P < 0.0001) and the number of ssDNA-labeled cells (P = 0.0339) in the epithelium between the infected side and non-infected side comparing treatment, time and their interactions. Bcl-2 and Bax were detected only on the infected side in the early stages. Thus, nasosinusitis induced the apoptosis of olfactory receptor neurons. However, the apoptosis occurred not only on the infected side, but also on the non-infected side with no significant inflammation. The Bcl-2/Bax family seems to play an important role in the apoptosis induced by infection, but not in the apoptosis on the non-infected side. The results suggest that mechanisms of apoptosis of olfactory receptor neurons on the infected side may differ from those on the non-infected side.

Impact of olfactory impairment on quality of life and disability.

OBJECTIVE: To determine whether olfactory loss affects patients' quality of life or level of disability. DESIGN: Retrospective survey using questionnaire data and clinic database review. SETTING: Two university medical center smell and taste clinics. PATIENTS: A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). MAIN OUTCOME MEASURES: Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and 0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the most common cited impairments were ability to detect spoiled food (impaired vs improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P < .001). Differences in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported by 87% of the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS: Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.

Zinc modulates the electro-olfactogram of the frog.

OBJECTIVE: Zinc is considered an important element in olfaction, however, its exact role is still unclear. A large amount of zinc is contained in the olfactory mucosa, so Zn(2+) may behave as a neuromodulator, as in the hippocampus. To reveal the acute effects of Zn(2+) on olfactory mucosa, electro-olfactograms (EOG) were recorded with or without Zn(2+). METHODS: The isolated olfactory mucosa of a bullfrog (Rana catesbiana) was set in an EOG recording chamber and bathed in Ringer's solution. Effects of ZnSO(4) (25 microM) on EOGs were examined. Four types of stimulants, n-amyl acetate (200 microM), menthone (10 microM), forskolin (2 microM), and 3-isobutil-methylxisanthine (IBMX, 100 microM) were tested. RESULTS: Zn(2+) (25 microM) charged with the ciliated surface of the olfactory mucosa attenuates EOGs which were produced not only by odorants but also by forskolin and IBMX. The attenuating ratios of EOGs for stimulants were as follows; n-amyl acetate (0.51+/-0.18, n=4), menthone (0.48+/-0.28, n=4), forskolin (0.61+/-0.16, n=4), and IBMX (0.68+/-0.19, n=4); (mean+/-S.D.). These attenuations were reversible. The results indicate that Zn(2+) may block the c-AMP dependent transduction channels of the olfactory cells. CONCLUSION: Micro molar Zn(2+) attenuates EOG of the frog. Zn(2+) may be thought to behave as one of the modulators in olfactory reception.

Enzymatic Quantification of L-Tartrate in Wines and Grapes by Using the Secondary Activity of D-Malate Dehydrogenase.

L-Tartrate in wines and grapes was enzymatically quantified by using the secondary activity of D-malate dehydrogenase (D-MDH). NADH formed by the D-MDH reaction was monitored spectrophotometrically. Under the optimal conditions, L-tartrate (a 1.0 mM sample solution) was fully oxidized by D-MDH in 30 min. A linear relationship was obtained between the absorbance difference and the L-tartrate concentration in the range of a 0.02-1.0 mM sample solution with a correlation coefficient of 0.9991. The relative standard deviation from ten measurements was 1.71% at the 1.0 mM sample solution level. The proposed method was compared with HPLC, and the values determined by both methods were in good agreement.

Residual radioactivity in the soil of the Semipalatinsk Nuclear Test Site in the former USSR.

This paper deals with our efforts to survey residual radioactivity in the soil sampled at the Semipalatinsk Nuclear Test Site and at off-site areas in Kazakhstan. The soil was sampled at the hypocenter where the first Soviet nuclear explosion was carried out on 29 August 1949, and at the bank of the crater called "Bolapan," which was formed by an underground nuclear detonation on 15 January 1965 along the Shagan River. As a comparison, other soil was also sampled in the cities of Kurchatov and Almaty. These data have allowed a preliminary evaluation of the contemporary radioactive contamination of the land in and around the test site. At the first nuclear explosion site and at Bolapan, higher than background levels of 239,240Pu with weapons-grade plutonium were detected together with fission and activation products such as 137Cs, 60Co, 152Eu, and 154Eu.

Measurement of L-Malate Using Immobilized Enzyme Reactors: Comparison of Results Obtained with Four Different Enzymatic Systems.

For the measurement of malate by an enzyme sensor, we did a comparative study using malate dehydrogenase (MDH) alone, MDH and glutamate oxaloacetate transaminase (GOT) together, a malic enzyme (ME) that requires NADP as a cofactor, and MDH and NADH oxidase together. With respect to the response of each reactor to 0.5 mM L-malate, the systems using ME alone and MDH plus NADH oxidase gave high values. The ranges of measurements were 0.05-1.00 mM (MDH alone), 0.01-0.05 mM (MDH plus GOT), 0.01-0.50 mM (ME alone) and 0.02-1.00 mM (MDH plus NADH oxidase). In the system with MDH alone, however, reducing sugars in the sample interfered with measurements and it was impossible to use this system for practical analysis of fruit samples. By contrast, the systems using ME alone or MDH plus NADH oxidase were unaffected by the presence of reducing sugars and were suitable for analysis of samples. Thus, the MDH-NADH oxidase system is recommended for practical analyses of samples.

Bulbar morphology and expression of bulbar dopamine and parvalbumin in experimentally-induced anosmic rats.

Morphological study was carried out in rats with olfactory dysfunction induced by deafferentation of serotonergic fibers in the olfactory bulb. With a computer capable of area measurements, olfactory bulbs of the anosmic rats were found to be decreased in size to 61% of control bulbs, and all bulbar layers were involved in the bulbar shrinkage. Given areas of each bulbar layer in control bulbs to be 100%, percentages of each bulbar layer in the anosmic rats were 23% in the olfactory nerve layer, 54% in the glomerular layer, 63% in the external plexiform layer, 83% in the internal plexiform layer and 81% in the granule cell layer. Dopamine-and parvalbumin-containing neurons were examined immunohistochemically in the experimentally-induced anosmic rats. As a result, immunoreactive neurons for these two chemical substances were significantly decreased in number (dopamine, 33% of control value; parvalbumin, 46% of control value). The present study, using an animal model of anosmia, provided quantitative data on the bulbar atrophy and showed effects of anosmia on expression of dopamine and parvalbumin in the bulb.

Olfactory disturbance induced by deafferentation of serotonergic fibers in the olfactory bulb.

The serotonergic neurons of the brain stem project widely throughout the central nervous system, and the olfactory bulb is one of the major forebrain targets of the ascending serotonin pathway. According to physiological studies, neurons of the olfactory bulb were found to reduce their spontaneous discharge rates by electrophoretically applied serotonin. However, roles of the bulbar serotonin in the sense of smell remain unanswered. In the present study, using 5,7-dihydroxytryptamine, a specific neurotoxin for serotonin, we found that the conditioned rats who learned to avoid a repellent by olfaction lost ability of discrimination by deafferentation of the bulbar serotonergic fibers. Such olfactory dysfunction did not occur in the early stage (three days after injection of the toxin) when the serotonergic fibers disappeared in the bulb, but developed a few weeks later. Interestingly, histological examination revealed marked shrinkage of the bulbar glomerulus which is a major termination site of the bulbopetal serotonergic fibers, and also a synaptic site of olfactory receptor cells and bulbar output neurons. The results indicate that depletion of the serotonergic fibers in the olfactory bulb causes glomerular atrophy and olfactory disturbance in the rat.

Current problems and prospects with the Japanese compensation system for pollution-related health damage.

The Japanese compensation system for pollution-related health damage, which resulted from experiences in the 1960s and 1970s with severe cases of environmental pollution, has recently come to a crisis. This article presents scientific evidence associated with the establishment of the system and analyzes the polluters' criticism of the system. The current controversy illustrates the difficulty of applying epidemiological methods to nonspecific health effects and demonstrates the strength of industrial resistance against environmental policy in Japan.

Theory of air pollution damage on human populations.

Existing ideas of dose or exposure are discussed and criticized from the view point of the health damage caused by time dependent air pollutant concentrations. The idea of "dosage" is introduced and some of its mathematical properties are shown and illustrated. The problem of whether or not there exists threshold concentration in air pollution, as well as that of the relation between equi-exposure and equi-damage, is then discussed by making use of the ideas of dosage and healing power of the population. The assumption of this discussion is that the statistical distribution of air pollutant concentrations is log-normal, and that its time series is stationary.