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.

2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam.

Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (⩾3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)--the toxic equivalents (TEQ) levels⩾17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment.

OBJECTIVES: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. METHODS: A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary beta2-MG (microglobulin) > or =1000 microg/gCr. Mortality risk analysis was performed using Cox's proportional model to compare mortality between subjects with urinary beta2-MG > or =1000 and <1000 microg/gCr, and to investigate the relationship between the degree of urinary beta2-MG and mortality. RESULTS: Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary beta2-MG > or =1000 microg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary beta2-MG > or =1000 microg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary beta2-MG > or =1000 microg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary beta2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary beta2-MG > or =10000 microg/gCr in both sexes. CONCLUSION: Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Plasma insulin and blood pressure in normotensive Japanese men with normal glucose tolerance.

OBJECTIVE: To determine whether blood pressure within the normal range is associated with plasma insulin concentration in a Japanese population with normal glucose tolerance. METHODS: We studied 491 normotensive Japanese men with normal glucose tolerance, who had never been treated with antihypertensive medications. Plasma glucose and insulin response during a 75-g oral glucose-tolerance test, blood pressure, body mass index, serum lipids, alcohol consumption and smoking status were obtained. The subjects were divided into quartiles according to mean blood pressure level (< 79, 79-84, 85-91 and > or = 92 mmHg). To eliminate possible confounding factors, analysis of covariance was also performed. RESULTS: In univariate analyses the plasma insulin response after an oral glucose load, especially after 60 min, was significantly related to blood pressure level. Plasma glucose was related to blood pressure level only at fasting. When adjusted for age, body mass index, plasma glucose response and alcohol consumption, plasma insulin concentrations after 30 and 60 min in the highest quartile were significantly higher than those in the lowest quartile. CONCLUSIONS: Blood pressure was significantly and independently related to plasma insulin level after an oral glucose load in normotensive Japanese men with normal glucose tolerance. The results suggest that the relationship between blood pressure and insulin resistance already exists in a prehypertensive state even in a lean Asian population.

Microalbuminuria and hypertension in nondiabetic Japanese men.

To investigate the relationship between microalbuminuria and hypertension in nondiabetic subjects, we selected 245 Japanese men aged 35 to 69 years on the basis of the results of a 75 g oral glucose tolerance test. Prevalence of hypertension (blood pressure levels > or =140/90 mm Hg or treatment of hypertension) in microalbuminuria-positive (0.03 to 0.3 g/d) subjects was significantly higher than that in microalbuminuria-negative (<0.03 g/day) subjects. Also, the significant increase of levels of triglycerides, serum uric acid, and area of plasma insulin were recognized in microalbuminuria-positive subjects. Urinary albumin was significantly related to both systolic and diastolic blood pressure in a manner independent of these relevant factors, including area of insulin. With regard to renal functions, creatinine clearance of microalbuminuria positive subjects was significantly increased and fractional excretion of sodium of microalbuminuria-positive subjects was significantly decreased as compared with those of microalbuminuria-negative subjects. In normotensive subjects, serum uric acid, which is known to be related to sodium handling at renal tubules of microalbuminuria-positive subjects, was significantly higher than those of microalbuminuria negative subjects as well as triglycerides and area of insulin, without the differences of the levels of blood pressure and BMI. Therefore, it is suspected that microalbuminuria is a renal facet of insulin resistance, and a predictor value of hypertension.

Exercise blood pressure in young adults as a predictor of future blood pressure: a 12-year follow-up of medical school graduates.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P<0.001), and exercise SBP was not significant predictor. For DBP in women, any DBP at rest or after exercise was not significantly related to DBP at follow-up. In young adult men, SBP and DBP immediately after exercise would be a stronger predictor of future SBP and DBP rather than BP at rest. However, in young adult women, resting SBP rather than exercise SBP would be better to predict future SBP.

Relationship between urinary cadmium and mortality among inhabitants living in a cadmium polluted area in Japan.

A 15 year follow-up study of 3119 inhabitants living in a cadmium polluted area was conducted to investigate the influence of environmental cadmium exposure on the mortality. The cumulative survival curves of the subjects with urinary cadmium concentration > or = 10 microg/g creatinine was lower than that of the subjects with < 10 microg/g creatinine in the men aged 50-59 and 60-69 years and in the women aged 60-69 and 70-79 years. In the men aged 50-69 years and the all aged women, the cumulative survival curves became lower in proportion to the increase of urinary cadmium concentration, when the subjects were divided into four groups according to the amount of urinary cadmium concentration (< 5, 5-9.9, 10.1-19.9, > or = 20 microg/g creatinine). These results suggested a dose response relationship between cadmium exposure and mortality.

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium.

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

Dust exposure and lung cancer mortality in tunnel workers.

The eastern part of the Toyama Prefecture in Japan is one of the high-incidence areas of silicosis due to tunnel construction. In 1977 and 1978, we conducted a questionnaire survey primarily concerning the occupational history of all male inhabitants over 30 years of age living in five villages in this area and found 603 tunnel workers and inhabitants without dust history. These workers have been followed up to 1994 for about 17 to 18 years to clarify the relationship between tunnel work and lung cancer mortality. The SMR's of workers with dust exposure for all causes and for lung cancer was 120 and 188, respectively, which was significantly higher than those of the Japanese general population. After adjustment for age and smoking habits using Cox's proportional hazard model, tunnel work showed a significant relationship to mortality. Mortality risk ratio of tunnel workers was 2.15 compared with that of inhabitants without dust exposure history.

Relationship between shift work and onset of hypertension in a cohort of manual workers.

OBJECTIVES: This study investigated the possibility of a relationship between blood pressure level and rotating 3-shift work in a prospective follow-up of workers in a zipper and aluminum sash factory in Japan. METHODS: Altogether 1551 men aged 18-49 years were followed prospectively for 5 years, and the cumulative incidence of hypertension among 3-shift workers was compared with that of day workers. A multiple logistic analysis was used for adjusting for base-line characteristics such as age, body mass index, blood pressure, and drinking habit. RESULTS: In the younger age group, the relative risk of the rotating 3-shift workers during the observational period was increased compared with that of day workers after adjustment for the confounding factors. In the older group, the cumulative incidence of hypertension was not higher for workers who had continued shift work. However, a relatively high risk of hypertension was found for workers who converted from 3-shift work to day work when compared with those who remained on shift work and day work. CONCLUSIONS: It is suggested that there is an association between 3-shift work and blood pressure.

Urinary beta 2-microglobulin concentration and mortality in a cadmium-polluted area.

A 9-y follow-up study of 3,178 persons who lived in a cadmium-polluted area was conducted to assess the influence of environmental cadmium exposure on long-term outcome. The standardized mortality ratios of the urinary beta 2-microglobulin-positive subjects (> 1,000 micrograms/g creatinine) of both sexes were higher than those of the general Japanese population, whereas the cumulative survival curves were lower than those of the urinary beta 2-microglobulin-negative group. A significant association was also found between urinary beta 2-microglobulin and mortality, using a Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary beta 2-microglobulin excreted. These results suggest that the prognosis for cadmium-exposed subjects with proximal tubular dysfunction is unfavorable. The mortality rate tended to become higher as the severity of renal dysfunction progressed.

[The development of the Japanese version of the Maslach Burnout Inventory and the examination of the factor structure].

This article presents an evaluation of the factor structures of the Japanese version of the Maslach Burnout Inventory (MBI). The MBI is a widely used psychometric instrument for measuring 'burnout' developed by Maslach and her co-workers. The MBI consists of four subscales: Emotional Exhaustion, Personal Accomplishment, Depersonalization, and Involvement. The MBI was translated into Japanese along with a back-translation and was administered to a sample of 267 nurses. Various psychometric analyses showed that the Japanese version of the MBI has high reliability for the 22 items scored for the frequency dimension. The factor analysis using principal factoring with an oblique rotation resulted in three factor structures that had different implications from the MBI: Emotional Exhaustion/Depersonalization, Personal Accomplishment, and Physical Exhaustion. The correlationship between the MBI and the General Health Questionnaire (GHQ), measures of depression, showed that burnout was a unique phenomenon.

Comparative study on mortality patterns in Japan and China.

On the basis of the 1990 Chinese death notice data and 1990 Japanese populations vital statistical materials, the mortality patterns and proportions of individual causes of death in the two countries were compared. In both sexes, the mortality rates were the highest in almost all age groups in Chinese rural areas followed by urban areas and Japan. In Japan and in Chinese urban areas, malignant neoplasms cardiovascular diseases and cerebrovascular diseases were the major causes of death, with these three making up about 60% of the total. In Chinese rural areas, these three conditions were responsible for 43% of all deaths, a considerably lower figure as compared to those in the other two areas, and the mortality rates for infectious diseases and accident/suicide were higher than those in the other two areas. Of the three major adult diseases, cerebrovascular diseases were found to be especially frequent in both Chinese urban and rural areas. On the other hand, ischemic heart disease was found at comparable levels in Japan and China and the rate was lower than in other developed countries. Site-specific mortality rates for malignant neoplasms were characterized by high rates for lung, liver and esophageal cancers in China. The mortality rates for bronchitis in both Chinese urban and rural areas were markedly higher than those in Japan These differences in mortality rates and proportions of individual causes of death between China and Japan are thought to be attributable to the differences in medical services and the level of risk factors for each disease.

Potassium/energy and phosphorus/calcium ratios reflect the quality of nutrition.

A nutritional survey and questionnaire regarding dietary habits were administered to 649 men ranging in age from 35 to 64 years receiving a one-day health screening examination. First, comparisons of nutrient intake based on the nutrient rate of the Recommended Dietary Allowances for Japanese (RDA), and the total score on the questionnaire regarding dietary habits according to the RDA rates of total energy and calcium (Ca) were investigated. Then, the comparisons of intake of food groups, intake of nutrients and the total score on the questionnaire regarding dietary habits according to potassium/energy (K/E) ratio and phosphorus/calcium (P/Ca) ratio were determined. Last, differences between comparisons with the nutrient rates of RDA and comparisons with K/E ratio and P/Ca ratio were investigated. The following results were obtained: 1. Even in the group with RDA rates of total energy or Ca of > or = 90% and < or = 110% the RDA rates of some other nutrients were out-side the appropriate range. 2. In the group with high K/E ratios, as compared to the group with low ratios, the intake of potatoes, pulses, fruits, green/yellow vegetables, other vegetables, soy sauce, other beverages, fish/shellfish, and milk products showed high values, while cereals and fats/oils showed low values. For this reason, in the former group as compared to the latter, the intake and RDA total energy rate showed low values whereas the intake and RDA rates of nutrients such as Ca, Fe, and vitamin A were low. 3. In the group with high P/Ca ratios, as compared to the group with low ratios, the intake of beer and meats showed high values while that of pulses, green/yellow vegetables, and milk products showed low values. For this reason, in the former group as compared to the other groups, despite the fact that the intake and RDA total energy rate tended to be higher, the intake of nutrients such as Ca, P, K, and vitamin A showed lower values. 4. The RDA rates of all of the nutrients of group with a high K/E ratio and the group with a low P/Ca ratio generally showed largely appropriate values. 5. These results suggest that indices reflecting the balance of minerals such as the K/E and P/Ca ratios more objectively reflect the quality of nutrition than comparisons based on the RDA rates of total energy and specific-nutrient.

[A study of thyroid hormone levels of inhabitants of the cadmium-polluted Kakehashi River basin].

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.

[Study of an outbreak of itai-itai disease].

We studied an outbreak of itai-itai disease in the Jinzu River basin, in Toyama, Japan. One hundred and fifty females recognized as itai-itai disease patients till by 1990 were studied for the ages and years of onset and residence in the cadmium-polluted area. 1. Cases were recognized from as early as 1929, increased gradually to the peak of 1955-1959 and rapidly decreased up to the 1970s. 2. It was found that the later the patients was born, the younger the age of onset, though there was no difference of ages of onset between the cases born in the 1910s and the cases born from 1920. 3. The onset of itai-itai disease was most frequently seen at 50-59 years of residence in the cadmium-polluted area. It was found that the later a person started to inhabit the cadmium-polluted area, the shorter the period of residence in the cadmium-polluted area up to onset of itai-itai disease. 4. Comparing the patients who inhabited the cadmium-polluted area from birth and those who had moved there from non-polluted areas, the age of onset was higher in the latter, but there were no significant differences in the period of residence up to onset. From these findings, it appeared that itai-itai disease was not caused by aging, but by cadmium exposure starting from the 1910s.

Effects of maternal exposure to cadmium on pregnancy outcome and breast milk.

OBJECTIVE: The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated. METHODS: Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated. RESULTS: The rate of perterm deliveries of mothers with higher urinary Cd (> or =2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk. CONCLUSION: Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.