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.

Extremely small-diameter, high-density, radio frequency, plasma sources and central gas feeding for next-generation electrodeless plasma thrusters.

Radio frequency (RF) waves including helicon waves can readily produce high-electron-density (ne up to 1013 cm-3) plasmas with a broad range of external operating parameters. Various featured RF and helicon sources in a wide range of scales are suitable for plasma propulsion schemes. Electrodeless RF plasmas have no direct contact between electrodes and antennas, which enables long-life operation. However, one of the crucial problems is to reduce the plasma size for future applications in nano- and pico-satellites. Diagnostics of the plasma parameters in a small area should also be improved. Furthermore, to increase plasma performance, it is important to consider the radial electron density (ne) profile with an increasing upper limit, observed in high-density helicon sources due to the depletion of neutrals. This problem may be controlled by the location of neutral gas feeding and knowledge of the gas pressure distribution. Here, production of RF plasmas, with extremely small diameters from 3-mm down to 0.5-mm including 1-mm, was demonstrated, and characterization of ne and the electron temperature was performed with a collisional radiative model. Finally, to improve plasma performance such as ne and the thrust force, internal gas feeding was demonstrated using a developed Pirani gauge to measure neutral density.

Tranexamic acid blocks the thrombin-mediated delay of epidermal permeability barrier recovery induced by the cedar pollen allergen, Cry j1.

We previously demonstrated that Cry j1, the major pollen allergen of Cryptomeria japonica (Japanese cedar), transiently increases protease activity and intracellular Ca2+ concentration in cultured human keratinocytes, and delays recovery after stratum corneum barrier disruption in human skin ex vivo. Topical application of tranexamic acid or trypsin-type serine protease inhibitors accelerates barrier recovery. We hypothesized that tranexamic acid might prevent the transient protease activity increase and the barrier recovery delay induced by Cry j1. Here, we tested this hypothesis and examined the mechanism involved. In cultured human keratinocytes, knock-down of protease-activated receptor 1 (PAR-1) reduced the transient increase of calcium induced by Cry j1, whereas knock-down of PAR-2 did not. Knock-down of thrombin significantly reduced the transient increases of calcium concentration and protease activity. Tranexamic acid, soybean trypsin inhibitor, or bivalirudin (a thrombin inhibitor) also reduced the calcium elevation induced by Cry j1 and/or thrombin. Co-application of tranexamic acid or bivalirudin with Cry j1 to human skin ex vivo blocked the delay of barrier recovery. These results suggest that thrombin and PAR-1 or PAR-1-like receptor might mediate the adverse effects of Cry j1 on human epidermal keratinocytes, and could open up a new strategy for treating inflammatory skin diseases.

Durability of protective effect of dulaglutide on pancreatic ß-cells in diabetic mice: GLP-1 receptor expression is not reduced despite long-term dulaglutide exposure.

AIMS: It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. METHODS: Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks. Various metabolic parameters, such as glucose-stimulated insulin secretion (GSIS), insulin and TG content in islets, were evaluated after the intervention. ß-cell-related gene expression was also analyzed by real-time RT-PCR. RESULTS: In db/m mice, GLP-1R expression in ß-cells did not decrease, not even after long-term administration of Dula, compared with control mice, while GLP-1R expression in 24-week-old db/db mice treated with Dula was augmented, rather than downregulated, compared with 24-week-old CTL db/db mice. This was probably due to improved glycaemic control. In db/db mice treated with Dula, food intake and blood glucose levels were significantly decreased up to 24 weeks of age compared with CTL db/db mice, and their expression levels of various ß-cell-related genes, insulin content and GSIS were also enhanced. In contrast, oxidative and endoplasmic reticulum stress, inflammation, fibrosis and apoptosis were suppressed with Dula treatment. CONCLUSION: Dula exerts beneficial effects on glycaemic control and has long-lasting protective effects on pancreatic ß-cells. GLP-1R expression levels were not reduced at all in non-diabetic as well as diabetic mice despite long-term dulaglutide exposure.

Observations of cavity polaritons in one-dimensional photonic crystals containing a liquid-crystalline semiconductor based on perylene bisimide units.

We investigated the optical transmission properties of one-dimensional photonic crystal (1D-PC) microcavity structures containing the liquid-crystalline (LC) perylene tetracarboxylic bisimide (PTCBI) derivative. We fabricated the microcavity structures for this study by two different methods and observed the cavity polaritons successfully in both samples. For one sample, since the PTCBI molecules were aligned in the cavity layer of the 1D-PC by utilizing a friction transfer method, vacuum Rabi splitting energy was strongly dependent on the polarization of the incident light produced by the peculiar optical features of the LC organic semiconductor. For the other sample, we did not utilize the friction transfer method and did not observe such polarization dependence. However, we did observe a relatively large Rabi splitting energy of 187 meV, probably due to the improvement of optical confinement effect.

Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588(®) (CBM 588(®)), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, ß, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.

Comparison of antibiotic susceptibility in viridans group streptococci in low and high antibiotic-prescribing General Practices.

WHAT IS KNOWN AND OBJECTIVE: Antibiotic resistance has become a global public health issue. Most antibiotics are prescribed in the community, although there is less stewardship of such agents in the community compared to secondary and tertiary care. Few studies have attempted to examine the prescribing practices in General Practice and its impact on antibiotic resistance and, therefore, a study was performed in order to compare antibiotic susceptibilities of commensal viridans group streptococci (VGS) obtained from patient cohorts in General Practices (GP), who were high and low prescribers of oral antibiotics. METHOD: Sixty-five patients (<1 month-81 years; 77% female: 23% male) were enrolled onto the study, and viridans group streptococci (n = 5/patient) were collected from each patient's nasal passages and oropharynx region and tested for antibiotic susceptibility against (i) tetracyclines (doxycycline); (ii) macrolides (erythromycin); (iii) ß-lactams (penicillin G); and (iv) fluoroquinolones (ofloxacin & levofloxacin). RESULTS AND DISCUSSION: There were no significant differences in MICs between high and low GP prescribers with doxycycline (P = 0·094), erythromycin (P = 0·122), ofloxacin (P = 0·193) and levofloxacin (P = 0·058). However, there was a significant difference between high and low GP practices with regard to penicillin G (P = 0·031). This finding is important as the ß-lactams are the most commonly prescribed oral antibiotic in the community. WHAT IS NEW AND CONCLUSION: This study demonstrates that high prescribing practices may lead to an altered (higher) level of resistance to these agents in the commensal VGS population, which may be important as reservoirs of antibiotic resistance determinants in subsequent horizontal gene transfer events, particularly with newly colonizing pathogens, including pneumococci. Primary care physicians should be aware that increased prescribing of antibiotics may led to increased level of penicillin resistance.

Distinct dopaminergic control of the direct and indirect pathways in reward-based and avoidance learning behaviors.

The nucleus accumbens (NAc) plays a pivotal role in reward and aversive learning and learning flexibility. Outputs of the NAc are transmitted through two parallel routes termed the direct and indirect pathways and controlled by the dopamine (DA) neurotransmitter. To explore how reward-based and avoidance learning is controlled in the NAc of the mouse, we developed the reversible neurotransmission-blocking (RNB) technique, in which transmission of each pathway could be selectively and reversibly blocked by the pathway-specific expression of transmission-blocking tetanus toxin and the asymmetric RNB technique, in which one side of the NAc was blocked by the RNB technique and the other intact side was pharmacologically manipulated by a transmitter agonist or antagonist. Our studies demonstrated that the activation of D1 receptors in the direct pathway and the inactivation of D2 receptors in the indirect pathway are key determinants that distinctly control reward-based and avoidance learning, respectively. The D2 receptor inactivation is also critical for flexibility of reward learning. Furthermore, reward and aversive learning is regulated by a set of common downstream receptors and signaling cascades, all of which are involved in the induction of long-term potentiation at cortico-accumbens synapses of the two pathways. In this article, we review our studies that specify the regulatory mechanisms of each pathway in learning behavior and propose a mechanistic model to explain how dynamic DA modulation promotes selection of actions that achieve reward-seeking outcomes and avoid aversive ones. The biological significance of the network organization consisting of two parallel transmission pathways is also discussed from the point of effective and prompt selection of neural outcomes in the neural network.

Single-shot detection of mid-infrared spectra by chirped-pulse upconversion with four-wave difference frequency generation in gases.

Single-shot detection of ultrabroadband mid-infrared spectra was demonstrated by using chirped-pulse upconversion technique with four-wave difference frequency generation in gases. Thanks to the low dispersion of the gas media, the bandwidth of the phase matching condition of the upconversion process becomes very broad and the entire mid-infrared spectrum spanning from 200 to 5500 cm(-1) was upconverted by using a 10 ps chirped pulse to visible wavelength radiation, which was detected with a conventional visible dispersive spectrometer. This method was demonstrated by the successful measurement of infrared absorption spectra of organic polymer films.

Construction, expression and characterisation of recombinant molecules of the urease gene operon from a urease-positive thermophilic Campylobacter (UPTC) isolate.

A recombinant molecule of the full-length urease gene operon was constructed in vitro from the Japanese urease-positive thermophilic Campylobacter (UPTC) CF89-12 isolate and expressed in Escherichia coli cells. Several large deletion recombinant variants of urease subunit genes were also constructed and expressed in E. coli cells. A positive urease reaction with the log-phase cultured E. coli JM109 cells in the NiCl2-containing medium transformed with pGEM-T vector carrying the recombinant molecule of the full-length operon was detected with isopropyl-beta-D-thiogalactoside. Among the several deletion recombinant variants, each ureA-, ureB-, ureE-, ureF-, ureG- and ureH-large deficient, only ureE-large deletion variant (63% deficient) showed a positive urease reaction (approximately 15-fold). In addition, a ureE-complete deletion recombinant variant (100% deficient) constructed also showed a positive reaction of urease (approximately 18-fold). Recombinant urease subunits A and B were immunologically identified by Western blot analysis with anti-urease alpha (A) and beta (B) raised against Helicobacter pylori.

Alterations of body mass index and body composition in atomic bomb survivors.

OBJECTIVE: Obesity, underweight, sarcopenia and excess accumulation of abdominal fat are associated with a risk of death and adverse health outcomes. Our aim was to determine whether body mass index (BMI) and body composition, assessed with dual-energy X-ray absorptiometry (DXA), are associated with radiation exposure among atomic bomb (A-bomb) survivors. DESIGN: This was a cross-sectional study conducted in the Adult Health Study of the Radiation Effects Research Foundation. SUBJECTS: We examined 2686 subjects (834 men and 1852 women), aged 48-89 years (0-40 years at A-bomb exposure), for BMI analysis. Among them, 550 men and 1179 women underwent DXA in 1994-1996 and were eligible for a body composition study. RESULTS: After being adjusted for age and other potential confounding factors, A-bomb radiation dose was associated significantly and negatively with BMI in both sexes (P=0.01 in men, P=0.03 in women) and appendicular lean mass (P<0.001 in men, P=0.05 in women). It was positively associated with trunk-to-limb fat ratio in women who were less than 15 years old at the time of exposure (P=0.03). CONCLUSIONS: This is the first study to report a significant dose response for BMI and body composition 50 years after A-bomb radiation exposure. We will need to conduct further studies to evaluate whether these alterations affect health status.

Molecular analysis of the 16S-23S rDNA internal spacer region (ISR) and truncated tRNA(Ala) gene segments in Campylobacter lari.

Following PCR amplification and sequencing, nucleotide sequence alignment analyses demonstrated the presence of two kinds of 16S-23S rDNA internal spacer regions (ISRs), namely, long length ISRs of 837-844 base pair (bp) [n = six for urease-negative (UN) Campylobacter lari isolates, UN C. lari JCM2530(T), RM2100, 176, 293, 299 and 448] and short length ISRs of 679-725 bp [n = six for UN C. lari: n = 14 for urease-positive thermophilic Campylobacter (UPTC) isolates]. The analyses also indicated that the short length ISRs mainly lacked the 156 bp sequence from the nucleotide positions 122-277 bp in long length ISRs for UN C. lari JCM2530(T). The 156 bp sequences shared 94.9-96.8 % sequence similarity among six isolates. Surprisingly, atypical tRNA(Ala) gene segment (5' end 35 bp), which was extremely truncated, occurred within the 156 bp sequences in the long length ISRs, as an unexpected tRNA(Ala) pseudogene. An order of the intercistronic tRNA genes within the short nucleotide spacer of 5'-16S rDNA-tRNA(Ala)-tRNA(Ile)-23S rDNA-3' occurred in all the C. lari isolates examined.

Biochemical characterisation of urease from urease-positive thermophilic campylobacter (UPTC).

This study aims to characterise biochemically urease from an atypical Campylobacter lari, namely urease-positive thermophilic Campylobacter (UPTC). Urease was purified from cells of a Japanese UPTC isolate (CF89-12) using phenyl-Sepharose chromatography. Two protein components (estimates molecular masses 24 kDa and 61 kDa) were obtained that appeared to be structural proteins of urease (subunits A and B), and these were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (PAGE). The native molecular weight for the final purified UPTC urease was estimated to be approximately 186,000 Da which is close to the calculated molecular weight (182,738 Da) based on all six open reading frames of UPTC CF89-12 urease genes (ureA, B, E, F, G and H), as described previously. Moreover, an active band was observed on phenol red staining after a nondenaturing native PAGE of the crude extract from the UPTC cells. In addition, the purified urease of UPTC CF8912 showed enzyme activity over a broad pH range (pH 6-10), with maximal activity at pH 8.0. The urease was also stable against heat treatment, with almost no loss of enzyme activity seen following 60-min incubation at temperatures of 20-60 degrees C. Urease subunits A and B were identified immunologically by Western blot analysis with rabbit anti-urease alpha (A) and beta (B) raised against Helicobacter pylori.

Influence of adrenal subclinical hypercortisolism on hypertension in patients with adrenal incidentaloma.

OBJECTIVE: The purpose of our study was to clarify whether subtle cortisol-producing tumors, such as not only subclinical Cushing's syndrome (SubCS) but also subclinical hypercortisolism (SH), influence the prevalence of hypertension, since numerous basic research studies have noted that glucocorticoid excess influences blood pressure. METHODS: 80 patients with adrenocortical adenomas (39 women and 41 men; mean age 62.1 years) were enrolled. SubCS was diagnosed using a diagnostic criteria, and SH was diagnosed as the presence of a serum cortisol level greater than 50 nmol/L following 1-mg dexamethasone suppression test (DST). RESULTS: SubCS, SH, or non-functioning adrenocortical adenoma (NF) was diagnosed in 14, 13, or 53 patients, respectively. The prevalence of hypertension differed significantly among the diagnoses (SubCS, 78.6%; SH, 84.6%; NF, 39.6%; P=0.002), whereas no differences in other clinical characteristics such as age, sex, or waist girth were observed. The patients with SH had an 11.7-fold increased risk (95% confidence interval: 1.9-72.7, P=0.009) and those with SubCS had a 9.5-fold increased risk (95% confidence interval: 1.9-48.3, P=0.007) for hypertension compared to those with NF using a multivariate analysis. CONCLUSION: We demonstrated that subtle cortisol-producing tumors, such as SH as well as SubCS, were an independent risk factor for hypertension. The cut-off value of the 1-mg DST would be appropriate to predict the development of hypertension.

Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated with renal hypouricemia.

Renal hypouricemia is a clinical disorder attributed to an increased renal urate excretion rate and is well known to involve a high risk of urolithiasis and exercise-induced acute kidney injury (AKI). This report concerns two interesting cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia. A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively), oliguria and NS. They were treated with prednisolone and temporary hemodialysis. Renal function improved, but hypouricemia persisted during hospitalization. Histological findings in both cases led to a diagnosis of minimal change nephrotic syndrome and identification of the diuretic phase of tubulointerstitial damage because of findings such as acute tubular necrosis. Furthermore, distal tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal. Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a homozygous mutation in exon 4 (W258stop) of each one. Our cases show that patients with renal hypouricemia may be susceptible to AKI without involvement of exercise if they possess some facilitators. Renal hypouricemic patients should therefore be carefully examined for all complications from renal hypouricemia because of high risk of AKI.

Reliability of nucleotide sequence information of full-length flagellin A gene (flaA) and flaA short variable region (SVR) for molecular discrimination of Campylobacter lari organisms.

We aimed to clarify if the thermophilic Campylobacter lari organisms including urease-negative (UN) C. lari and urease-positive thermophilic Campylobacter (UPTC) can be differentiated at the species and/or subspecies levels by employing the full-length flaA gene and flaA short variable region (SVR) nucleotide sequence information or not. Thermophilic Campylobacter isolates (n = 45) including UN C. lari (n = 17), UPTC (n = 18), and Campylobacter jejuni (n = 10) were well discriminated at the isolate level by the unweighted pair group method using arithmetic means analysis and neighbor joining procedures constructed based on the full-length flaA gene and flaA SVR nucleotide sequence information. Thus, these procedures may possibly be useful for epidemimological studies for C. lari and C. jejuni.

Low serum levels of total and high-molecular-weight adiponectin predict the development of metabolic syndrome in Japanese-Americans.

BACKGROUND: Adiponectin is thought to play a significant role in the development of both insulin resistance and metabolic syndrome. Yet, there is very few evidence about the association plasma adiponectin and metabolic syndrome in the prospective study. Adiponectin exists as multimers in serum, and high-molecular-weight (HMW) adiponectin is particularly considered to be the active form of the protein. AIM: We investigated whether serum HMW adiponectin as well as total adiponectin is associated with the development of metabolic syndrome in a longitudinal study. SUBJECTS AND METHODS: We enrolled 224 men and 312 women of Japanese- Americans without metabolic syndrome at baseline who were followed for an average of 3.2 yr. The association of plasma total and HMW adiponectin with a progression to metabolic syndrome was examined. RESULTS: Subjects who developed metabolic syndrome had significantly lower plasma total and HMW adiponectin levels at baseline than those who did not develop metabolic syndrome. In a Cox proportional hazards model, lower total and HMW adiponectin levels were independent risk factors for the development of metabolic syndrome after adjusting for age, body mass index, classification of 75-g glucose tolerance test, and homeostasis model assessment (hazards ratio: total, 0.684, p=0.017, in men; 0.606, p=0.003, in women; HMW, 0.687, p=0.014, in men; 0.704, p=0.029, in women, respectively). CONCLUSIONS: Low circulating levels of total and HMW adiponectin may be a possible predictor for the development of metabolic syndrome.