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.

Maturation of odour identification ability and related factors in children.

BACKGROUND: Olfaction plays an important role in our daily and social lives, both as adults and as children. This study assessed whether the ability to identify odours increases with age, as well as the ability in various age groups and the factors involved. METHODS: The survey was performed in 2017 on 697 Japanese children (366 girls and 331 boys) aged 6â€"18 years who lived in Tsunan, Niigata Prefecture, Japan by using the 'Open Essence', a card-type odour identification test. We collected information regarding age, sex, and physical characteristic. We also inquired whether participants had siblings or if members of the family smoked, and whether they had conversations about odour at home. Statistical analysis was performed to evaluate the factors affecting odour identification abilities. RESULTS: The results showed that the odour identification abilities of children increase with age, and children who have daily conversations about odours at home have better odour identification abilities. CONCLUSIONS: Odour identification ability increases with age. In addition, our findings suggest that conversation may positively affect odour identification. Hence, it is important for children to be exposed to an environment where they develop an interest in smells for better growth of their olfactory identification ability.

Measurement of axial phase difference of density fluctuations owing to spontaneously excited waves by using microwave reflectometer on GAMMA 10/PDX.

In the GAMMA 10/PDX tandem mirror, plasma with strong ion-temperature anisotropy is produced by using the ion cyclotron range of frequency waves. This anisotropy of ion temperature causes several Alfvén-Ion-Cyclotron (AIC) waves to spontaneously excite in the frequency range just below the ion cyclotron frequency. In addition, difference-frequency (DF) waves are excited in the radial inner region of the plasma by wave-wave coupling among the AIC waves. The radial density profiles were measured at multi-axial positions using a frequency-modulation reflectometer with an axial array of microwave antennas, and an axial variation of the density was found to be significant. In addition, a relative phase difference of the DF wave between axially separated two points was first obtained by finely choosing the probing frequency of the reflectometers with a maximum coherence used as a measure, indicating that the DF wave is a propagating wave, while the pump AIC waves are standing waves in the axial region of measurement.

Analytical characterisation of nanoscale zero-valent iron: A methodological review.

Zero-valent iron nanoparticles (nZVI) have been widely tested as they are showing significant promise for environmental remediation. However, many recent studies have demonstrated that their mobility and reactivity in subsurface environments are significantly affected by their tendency to aggregate. Both the mobility and reactivity of nZVI mainly depends on properties such as particle size, surface chemistry and bulk composition. In order to ensure efficient remediation, it is crucial to accurately assess and understand the implications of these properties before deploying these materials into contaminated environments. Many analytical techniques are now available to determine these parameters and this paper provides a critical review of their usefulness and limitations for nZVI characterisation. These analytical techniques include microscopy and light scattering techniques for the determination of particle size, size distribution and aggregation state, and X-ray techniques for the characterisation of surface chemistry and bulk composition. Example characterisation data derived from commercial nZVI materials is used to further illustrate method strengths and limitations. Finally, some important challenges with respect to the characterisation of nZVI in groundwater samples are discussed.

Non-labile silver species in biosolids remain stable throughout 50 years of weathering and ageing.

Increasing commercial use of nanosilver has focussed attention on the fate of silver (Ag) in the wastewater release pathway. This paper reports the speciation and lability of Ag in archived, stockpiled, and contemporary biosolids from the UK, USA and Australia, and indicates that biosolids Ag concentrations have decreased significantly over recent decades. XANES revealed the importance of reduced-sulfur binding environments for Ag speciation in materials ranging from freshly produced sludge to biosolids weathered under ambient environmental conditions for more than 50 years. Isotopic dilution with (110 m)Ag showed that Ag was predominantly non-labile in both fresh and aged biosolids (13.7% mean lability), with E-values ranging from 0.3 to 60 mg/kg and 5 mM CaNO3 extractable Ag from 1.2 to 609 µg/kg (0.002-3.4% of the total Ag). This study indicates that at the time of soil application, biosolids Ag will be predominantly Ag-sulfides and characterised by low isotopic lability.

Speciation and lability of Ag-, AgCl-, and Ag2S-nanoparticles in soil determined by X-ray absorption spectroscopy and diffusive gradients in thin films.

Long-term speciation and lability of silver (Ag-), silver chloride (AgCl-), and silver sulfide nanoparticles (Ag2S-NPs) in soil were studied by X-ray absorption spectroscopy (XAS), and newly developed "nano" Diffusive Gradients in Thin Films (DGT) devices. These nano-DGT devices were designed specifically to avoid confounding effects when measuring element lability in the presence of nanoparticles. The aging profile and stabilities of the three nanoparticles and AgNO3 (ionic Ag) in soil were examined at three different soil pH values over a period of up to 7 months. Transformation of ionic Ag, Ag-NP and AgCl-NPs were dependent on pH. AgCl formation and persistence was observed under acidic conditions, whereas sulfur-bound forms of Ag dominated in neutral to alkaline soils. Ag2S-NPs were found to be very stable under all conditions tested and remained sulfur bound after 7 months of incubation. Ag lability was characteristically low in soils containing Ag2S-NPs. Other forms of Ag were linked to higher DGT-determined lability, and this varied as a function of aging and related speciation changes as determined by XAS. These results clearly indicate that Ag2S-NPs, which are the most environmentally relevant form of Ag that enter soils, are chemically stable and have profoundly low Ag lability over extended periods. This may minimize the long-term risks of Ag toxicity in the soil environment.

Nutrition-related status and granulation tissue colour of pressure ulcers evaluated by digital image analysis in older patients.

OBJECTIVE: Granulation tissue colour may be an indicator for nutritional assessment in pressure ulcer (PU) care. This study evaluated the relationship between nutritional status, anaemia and diabetes, and granulation tissue colour of PUs by colour analysis of digital photographs in the clinical setting. METHOD: The cross-sectional study included 42 older patients with 51 full-thickness PUs from 10 institutions. Patient demographics, wound status, nutritional status and dietary intakes were obtained from medical charts. From a wound image, the granulation red index was processed by computer software and the proportion of pixels exceeding the threshold intensity of 80 for the granulation tissue surface (%GRI80) was calculated. RESULTS: Haemoglobin levels were positively associated with %GRI80 levels (p=0.007) in the crude model, but not in the adjusted model (p=0.260). The interaction term between diabetes and protein intake was significantly associated with %GRI80 levels in the adjusted models (p=0.010). At protein intakes of 0.95 g/kg or higher, diabetic wounds exhibited lower %GRI80 levels than non-diabetic wounds (p=0.002). At protein intakes of less than 0.95 g/kg, %GRI80 levels did not differ between diabetic and non-diabetic patients (p=0.247). Protein intakes of 0.95 g/kg or higher were associated with higher %GRI80 levels in non-diabetic patients (p=0.015), but not in diabetic patients (p=0.127). CONCLUSION: Granulation tissue colour, evaluated by the objective and quantitative analysis of digital photography, is related to haemoglobin level, diabetes and dietary intakes in clinical settings.

[Reusable imaging plate (IP) for swift and automatic measurement of X-ray CT dose profiles].

PURPOSE: In multi-slice CT, over beaming by penumbra effect has been reported, and measurements of X-ray CT beam profiles are very important for accurate performance assessment. This study was conducted in order to facilitate and economize on the measurement of CT dose profiles. METHODS: The imaging plate (IP: HR-V type, Fuji) was placed in its case, X-rayed, and then read with a digital IP reader, which then erased the data in preparation for reuse. The values were then compared with the values obtained with the standard one-use imaging film. The CT scanner used was a Toshiba Aquilion Multi (4 rows). RESULTS: The shape of the beam profile obtained using the IP method was for all practical purposes identical to that obtained using the film method. The FWHM values for 2.0, 4.0, 8.0, 12.0, 16.0, 20.0 and 32-mm beam were 4.88, 6.61, 10.2, 14.9, 18.2, 22.4 and 35.0 mm for the IP method and 4.81, 6.66, 10.2, 14.7, 18.1, 22.3 and 34.8 mm for the film method. In addition, in the IP method, the results obtained for the shape of the beam profile and the FWHM were found to be extremely similar irrespective of the X-ray tube used or individual differences between IPs. CONCLUSION: We have developed a new X-ray CT beam profile measurement system using an IP. This IP method permits data processing to be performed entirely in the digital domain, allowing high-precision measurements to be obtained with ease.

[The techniques to identify the epidural space do not influence the success rate in combined spinal-epidural anesthesia: a comparison between loss-of-resistance and hanging-drop].

The hanging-drop (HD) technique has been attributed to a negative epidural pressure induced by making a tent of the dura by the Tuohy needle. We, therefore, hypothesized that the HD technique would result in more successful intrathecal placement of the spinal needle in combined spinal-epidural anesthesia (CSEA) compared with the loss-of-resistance (LR). Seventy patients received CSEA using the needle-through-needle method with a spinal needle extending 9 mm beyond the Tuohy needle. Success rate in obtaining cerebrospinal fluid (CSF) at the first attempt was considerably low; 60% in HD and 57% in LR, which was not significantly different. Failure to obtain CSF after 3 attempts was not significantly different between the two techniques; 26% and 31% in HD and LR, respectively. In conclusion, there was no advantage of the HD technique for obtaining CSF in CESA compared with the LR. It seems that spinal needle length beyond the Tuohy needle should be more than 9 mm.

Synthesis and structure-activity relationship of diarylamide derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells.

A series of diarylamide derivatives were synthesized and evaluated for their inhibitory activities against human coronary artery smooth muscle cells (SMCs) and human coronary artery endothelial cells (ECs). Compound 2w was superior to the lead compound, Tranilast, in terms of the potency of the activity and cell selectivity.

Fatal hepatic failure caused by chemotherapy-induced reactivation of hepatitis B virus in a patient with hematologic malignancy.

A patient with hematologic malignancy and hepatitis B virus (HBV) infection received chemotherapy containing a glucocorticoid. The patient developed severe hepatitis after chemotherapy and, despite achieving complete remission of the malignancy, died of hepatic failure. We carried out a retrospective study of changes in the serological markers of HBV in this patient. Both serum hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) were negative on admission. During the course of chemotherapy, HBsAg gradually became positive, but no liver dysfunction was apparent until after completion of the chemotherapy. The patient showed no initial evidence of being a latent HBV carrier. Therefore, we believe that screening for HBsAg is insufficient for detecting latent HBV carriers, and that investigation for hepatitis B core antibody (HBcAb) is essential.

Xenopus msx-1 regulates dorso-ventral axis formation by suppressing the expression of organizer genes.

We demonstrated previously that Xmsx-1 is involved in mesoderm patterning along the dorso-ventral axis, under the regulation of BMP-4 signaling. When Xmsx-1 RNA was injected into the dorsal blastomeres, a mass of muscle tissue formed instead of notochord. This activity was similar to that of Xwnt-8 reported previously. In this study, we investigated whether the activity of Xmsx-1 is related to the ventralizing signal and myogenesis promoting factor, Xwnt-8. Whole-mount in situ hybridization showed that Xmsx-1, Xwnt-8, and XmyoD were expressed in overlapping areas, including the ventro-lateral marginal zone at mid-gastrula stage. The expression of XmyoD was induced by the ectopic expression of either Xmsx-1 or Xwnt-8 in dorsal blastomeres, and Xwnt-8 was induced by the ectopic expression of Xmsx-1. On the other hand, the expression of Xmsx-1 was not affected by the loading of pCSKA-Xwnt-8 or dominant-negative Xwnt-8 (DN-Xwnt-8) RNA. In addition, Xmsx-1 RNA did not abrogate the formation of notochord if coinjected with DN-Xwnt-8 RNA. These results suggest that Xmsx-1 functions upstream of the Xwnt-8 signal. Furthermore, the antagonistic function of Xmsx-1 to the expression of organizer genes, such as Xlim-1 and goosecoid, was shown by in situ hybridization analysis and luciferase reporter assay using the goosecoid promoter construct. Finally if Xmsx-1/VP-16 fusion RNA, which was expected to function as a dominant-negative Xmsx-1, was injected into ventral blastomeres, a partial secondary axis formed in a significant number of embryos. In such embryos, the activity of luciferase, under the control of goosecoid promoter sequence, was significantly elevated at gastrula stage. These results led us to conclude that Xmsx-1 plays a central role in establishing dorso-ventral axis in gastrulating embryo, by suppressing the expression of organizer genes.

[Induction of anesthesia with propofol injected through a central venous catheter].

We compared propofol injected through a central venous catheter with that through a peripheral cannula from the standpoint of injection pain, induction time and hemodynamic changes. Thirty-nine patients about to receive abdominal surgery, who had central venous catheters inserted via the subclavian vein, were included in this study. General anesthesia was induced with a loading dose of propofol 1 mg.kg-1 followed by an infusion of 10 mg.kg-1.hr-1 into the central vein without carrier intravenous fluid (group A, n = 13), the peripheral vein without carrier intravenous fluid (group B, n = 13) or the peripheral vein with rapid infusion of acetated Ringer's solution (group C, n = 13). After endotracheal intubation, anesthesia was maintained with propofol 4 mg.kg-1.hr-1. The incidence of injection pain was 53% in group B and 76% in group C, whereas none of the patients in group A felt discomfort or pain during propofol injection. The mean induction time was significantly shorter in group A (43 +/- 12 sec) than group B (66 +/- 16 sec) or group C (57 +/- 11 sec). There were no differences between each group in hemodynamic changes during induction of anesthesia. Propofol injection via central venous catheter can avoid the injection pain and shorten the induction time.

Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo.

This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4). Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues.

Structure and Bond Nature of the UF(5) Monomer.

The structure and bond nature for the ground state of the UF(5) monomer have been investigated by means of relativistic and nonrelativistic discrete-variational (DV) Xalpha molecular orbital (MO) methods. It is found that the nonrelativistic calculation provides only less than half of the U-F bond overlap population obtained by the relativistic calculation for the monomer with the C(4)(v)() geometry which was determined experimentally. Comparison of the U-F bond overlap population and valence level structures between the C(4)(v)() and D(3)(h)() geometries indicates that the stability of the D(3)(h)() monomer is almost equal to that of the C(4)(v)() one. Furthermore, it is confirmed that an intermediate structure (C(2)(v)()) between the two geometries shows similar values of effective charge, orbital, and bond overlap populations. This suggests that the energy barrier between the D(3h) and C(4)(v)() geometries is very small and the geometry of the UF(5) monomer is fluxional between the C(4)(v)() and D(3)(h)() symmetries. This is consistent with the previous results reported by the Hartree-Fock method with relativistic effective core potentials [Wadt, W. R.; Hay, P. J. J. Am. Chem. Soc. 1979, 101, 5198]. The flexibility of the UF(5) structure originates from the fact that the U 5f atomic orbitals, which play a major role in the U-F bonding interactions, spread with wide angular distributions of the electrons in hybridization with the U 6d atomic orbital.

Elevation of serum creatine kinase during treatment with antithyroid drugs in patients with hyperthyroidism due to Graves disease. A novel side effect of antithyroid drugs.

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element.

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3'-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the 32P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR.RXR heterodimers are potential competitors with PPAR.RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

3,5,3'-Triiodo-L-thyronine potentiates all-trans-retinoic acid-induced apoptosis during differentiation of the promyeloleukemic cell HL-60.

Although the programmed cell death mediated by thyroid hormone is not well evaluated in mammalian cells, thyroid hormone plays a crucial role in differentiation of the cells during the metamorphosis of Xenopus, suggesting that thyroid hormone has the potential ability to induce the apoptosis. To investigate the thyroid hormone-inducible apoptosis, we cultured HL-60 cells with various amounts of all-transretinoic acid (RA) and L-T3. T3 alone did not induce the apoptosis of the cells. T3, however, suppressed the proliferation of cells in the presence of RA. DNA ladder and microscopical examination showed that the reduction of cell number was due to the apoptosis induced by RA. These findings suggested that T3 affects the apoptotic process during the differentiation of HL-60 cells by RA. T3-inducible apoptosis may require the factors augmented by RA in HL-60 cells.