Characterization of rosacea patients in Tohoku area of Japan: Retrospective study of 340 rosacea cases.

Rosacea is a chronic inflammatory skin disease with facial redness and acne-like papules and pustules. The characteristics and background of rosacea patients in Japan have not been well documented. In this study, we retrospectively collected the medical information of rosacea patients, and investigated the background, complications, exacerbating factors, and status of allergy. Between January 2010 and December 2020, 431 cases were diagnosed as rosacea or rosacea-like dermatitis. We selected 340 patients, in which we could confirm telangiectasia on facial skin. Females and males numbered 266 and 74, respectively. The average age of the first visit was 51.5 years, and the youngest and oldest were 11 and 88 years old. Among 340 cases, 323 had erythematotelangiectatic rosacea, 97 papulopustular rosacea, 20 phymatous rosacea presenting as rhinophyma, and four had symptoms of ocular rosacea. The most common complication was hay fever (93 individuals, 27.4%), and 66 (19.4%) had a medical history of contact dermatitis. Temperature differences (141 individuals, 41.5%) were the most common exacerbating factor followed by sunlight exposure (60 individuals, 17.6%). Seventy-eight individuals received allergen-specific immunoglobulin (Ig)E tests, and IgE for cedar was the most frequently observed (46 individuals, 59.0%). High frequencies of IgE for Dermatophagoides pteronyssinus or D. farinae (33 individuals, 42.3%) and house dust I (31 individuals, 39.7%) suggested that environmental conditions at home would affect rosacea symptoms. Since the facial skin is exposed to environmental stimuli every moment, this retrospective observation suggested the importance of the daily lifestyle guidance as well as medical treatments.

Phase equilibrium and dielectric relaxation in mixture of 5CB with dilute dimethyl phthalate: effect of coupling between orientation and composition fluctuations on molecular dynamics in isotropic one-phase state.

Phase equilibrium and dielectric relaxation were examined for mixtures of liquid-crystalline (LC)-forming 4-cyano-4'-pentylbiphenyl (5CB) with dilute dimethyl phthalate (DMP). The mixtures were in an isotropic one-phase state at high temperatures T but were separated into nematic and isotropic phases at low T < TIN (isotropic-to-nematic transition temperature), and the isotropic phase disappeared and a nematic one-phase state was realized on a further decrease of T below another transition temperature . These TIN and data (phase diagram) were described considerably well by a simple model of free energy contributed from a Flory-Huggins type mixing entropy (no enthalpic contribution) and a Landau-de Gennes type nematic interaction. This success of the model, not expected for ordinary (not LC-forming) components exhibiting enthalpically-driven phase separation, suggested that the phase separation in the DMP/5CB mixtures was triggered by the nematic transition of 5CB (possibly governed by the packing entropy) and thus the orientation fluctuation of 5CB molecules was coupled with the composition fluctuation. This coupling was expected to affect the dielectric relaxation detecting the rotational dynamics of 5CB molecules, the major component in the mixtures. This expectation was examined for a representative mixture having the DMP content of wDMP = 3.1 wt% and TIN ≅ 27.0 °C. In a high-T asymptote (T > TIN + 10 °C), the dielectric relaxation of this mixture was close to that of pure 5CB, which suggested no significant effect of the above coupling on 5CB dynamics in the mixture at such high T. Nevertheless, in a significantly wide range of T between TIN and TIN + 10 °C, the dielectric relaxation time τε of the isotropic one-phase mixture increased on cooling much more significantly compared to τε in that high-T asymptote. The kinematic viscosity ν of the mixture exhibited a qualitatively similar increase in the same range of T, but this increase was weaker than that of τε. This difference between the dielectric τε and the rheological ν was attributed to coupling of the orientation and the composition fluctuations mentioned above. Namely, the composition fluctuation enhances the orientation fluctuation in the mixture thereby providing τε (reflecting the orientation fluctuation) with an extra increase. Pure 5CB exhibited similar increases of τε and ν (stronger for the former) but only in a close vicinity of (within 2-3 °C), because the orientation fluctuation in pure 5CB is coupled with the density fluctuation, not with the composition fluctuation being absent in the pure 5CB system. This behavior of pure 5CB in turn suggests an importance of the coupling of orientation and composition fluctuations in the mixture.

Effect of interleukin-17A inhibitor in Japanese patients with psoriatic arthritis compared with tumor necrosis factor-alpha inhibitor.

OBJECTIVES: The patient of severe psoriatic arthritis (PsA) is mainly treated with oral methotrexate, ciclosporin, and anti-tumor necrosis factor-alpha inhibitors (TNFi). Recently, anti-interleukin-17A inhibitors (IL-17Ai) have been used in the treatment of PsA. This study aimed to evaluate the efficacy and safety of IL-17Ai in Japanese patients with PsA compared with those of TNFi. METHODS: This was a longitudinal and retrospective study. The study population included 31 Japanese patients with PsA. All enrolled patients fulfilled the Classification Criteria for Psoriatic Arthritis. All patients were treated with TNFi or IL-17Ai. The assessed clinical manifestations were C-reactive protein (CRP)-based Disease Activity Score in 28 Joints (DAS28-CRP), disease activity in psoriatic arthritis (DAPSA), 20% achievement of American College of Rheumatology core set, swollen joint count (SJC), tender joint count (TJC), and visual analog scale (VAS). Functional ability of patients with PsA was analyzed using the modified health assessment questionnaire (mHAQ) score. We evaluated the parameters at baseline and weeks 12, 24, and 52. RESULTS: The change in SJC, TJC, VAS, mHAQ, and DAPSA had no significant difference at weeks 12, 24, and 52. The improvements of CRP and DAS28-CRP were significantly higher in TNFi group only at week 12. The biologics retention rate was significantly higher in TNFi group by the log-rank test. No critical adverse events occurred. CONCLUSIONS: Our study presented that IL-17Ai had treatment effects comparable to TNFi. IL-17Ai might have the potential to become an alternative to the previous drug, but more large-scale studies are expected.

Soybean amplifies the hypohomocysteinemic effect of betaine and improves its hypercholesterolemic effect.

We examined whether soybean (SB) and soy protein isolate (SPI) can prevent the betaine-induced elevation of plasma cholesterol as well as maintain the betaine-induced reduction of plasma Hcy concentration. Rats were fed casein-, SB-, or SPI-based diet with or without betaine; SPI-based diet with betaine containing soybean fiber (SF) or soy lecithin (SL) or the combination of SF and SL. Plasma Hcy concentration was decreased by feeding betaine to rats fed the casein-, SB-, and SPI-based diets. Betaine-induced elevation of plasma cholesterol was decreased by feeding the SB-based diet compared with the casein-based diet, but was not decreased by feeding the SPI-based diet. In rats fed the SPI-based diet, the increased concentration of plasma cholesterol by betaine feeding was not prevented by independent addition of SL or SF, but was prevented by a combination of SL and SF, and was associated with increased fecal excretion of bile acids.

Competition Between Resonant Plasmonic Coupling and Electrostatic Interaction in Reduced Graphene Oxide Quantum Dots.

The light emission from reduced graphene oxide quantum dots (rGO-QDs) exhibit a significant enhancement in photoluminescence (PL) due to localized surface plasmon (LSP) interactions. Silver and gold nanoparticles (NPs) coupled to rGO nanoparticles exhibit the effect of resonant LSP coupling on the emission processes. Enhancement of the radiative recombination rate in the presence of Ag-NPs induced LSP tuned to the emission energy results in a four-fold increase in PL intensity. The localized field due to the resonantly coupled LSP modes induces n-π* transitions that are not observed in the absence of the resonant interaction of the plasmons with the excitons. An increase in the density of the Ag-NPs result in a detuning of the LSP energy from the emission energy of the nanoparticles. The detuning is due to the cumulative effect of the red-shift in the LSP energy and the electrostatic field induced blue shift in the PL energy of the rGO-QDs. The detuning quenches the PL emission from rGO-QDs at higher concentration of Ag NPs due to non-dissipative effects unlike plasmon induced Joule heating that occurs under resonance conditions. An increase in Au nanoparticles concentration results in an enhancement of PL emission due to electrostatic image charge effect.

Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes.

In the present study, the effects of Euglena and paramylon on hyperglycemia were examined in Otsuka Long-Evans Tokushima fatty (OLETF; type 2 diabetes mellitus model) rats. OLETF rats were fed an AIN-93 M diet containing cellulose, Euglena, or paramylon for 10 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. An oral glucose-tolerance test (OGTT) was performed at 0 and 10 weeks. OLETF control rats were obese because of bulimia and showed abdominal fat accumulation and hyperglycemia. Euglena supplementation improved hyperglycemia and decreased food intake, body weight gain, and abdominal fat. However, there were no changes in the paramylon-supplemented group compared to the OLETF control group. Triglyceride concentrations in the serum and liver were lower in Euglena-supplemented rats than in OLETF control rats. There was a correlation between hepatic triglyceride concentration and the area under the curve (AUC) of OGTT at 10 weeks. This suggests that the improvement in glycemic control in the Euglena-supplemented group may depend on substances other than paramylon present in Euglena.

Effects of Biotin Deficiency on Biotinylated Proteins and Biotin-Related Genes in the Rat Brain.

Biotin is a water-soluble vitamin that functions as a cofactor for biotin-dependent carboxylases. The biochemical and physiological roles of biotin in brain regions have not yet been investigated sufficiently in vivo. Thus, in order to clarify the function of biotin in the brain, we herein examined biotin contents, biotinylated protein expression (e.g. holocarboxylases), and biotin-related gene expression in the brain of biotin-deficient rats. Three-week-old male Wistar rats were divided into a control group, biotin-deficient group, and pair-fed group. Rats were fed experimental diets from 3 wk old for 8 wk, and the cortex, hippocampus, striatum, hypothalamus, and cerebellum were then collected. In the biotin-deficient group, the maintenance of total biotin and holocarboxylases, increases in the bound form of biotin and biotinidase activity, and the expression of an unknown biotinylated protein were observed in the cortex. In other regions, total and free biotin contents decreased, holocarboxylase expression was maintained, and bound biotin and biotinidase activity remained unchanged. Biotin-related gene (pyruvate carboxylase, sodium-dependent multivitamin transporter, holocarboxylase synthetase, and biotinidase) expression in the cortex and hippocampus also remained unchanged among the dietary groups. These results suggest that biotin may be related to cortex functions by binding protein, and the effects of a biotin deficiency and the importance of biotin differ among the different brain regions.

P3N-PIPO, a Frameshift Product from the P3 Gene, Pleiotropically Determines the Virulence of Clover Yellow Vein Virus in both Resistant and Susceptible Peas.

UNLABELLED: Peas carrying the cyv1 recessive resistance gene are resistant to clover yellow vein virus (ClYVV) isolates No.30 (Cl-No.30) and 90-1 (Cl-90-1) but can be infected by a derivative of Cl-90-1 (Cl-90-1 Br2). The main determinant for the breaking of cyv1 resistance by Cl-90-1 Br2 is P3N-PIPO produced from the P3 gene via transcriptional slippage, and the higher level of P3N-PIPO produced by Cl-90-1 Br2 than by Cl-No.30 contributes to the breaking of resistance. Here we show that P3N-PIPO is also a major virulence determinant in susceptible peas that possess another resistance gene, Cyn1, which does not inhibit systemic infection with ClYVV but causes hypersensitive reaction-like lethal systemic cell death. We previously assumed that the susceptible pea cultivar PI 226564 has a weak allele of Cyn1 Cl-No.30 did not induce cell death, but Cl-90-1 Br2 killed the plants. Our results suggest that P3N-PIPO is recognized by Cyn1 and induces cell death. Unexpectedly, heterologously strongly expressed P3N-PIPO of Cl-No.30 appears to be recognized by Cyn1 in PI 226564. The level of P3N-PIPO accumulation from the P3 gene of Cl-No.30 was significantly lower than that of Cl-90-1 Br2 in a Nicotiana benthamiana transient assay. Therefore, Cyn1-mediated cell death also appears to be determined by the level of P3N-PIPO. The more efficiently a ClYVV isolate broke cyv1 resistance, the more it induced cell death systemically (resulting in a loss of the environment for virus accumulation) in susceptible peas carrying Cyn1, suggesting that antagonistic pleiotropy of P3N-PIPO controls the resistance breaking of ClYVV. IMPORTANCE: Control of plant viral disease has relied on the use of resistant cultivars; however, emerging mutant viruses have broken many types of resistance. Recently, we revealed that Cl-90-1 Br2 breaks the recessive resistance conferred by cyv1, mainly by accumulating a higher level of P3N-PIPO than that of the nonbreaking isolate Cl-No.30. Here we show that a susceptible pea line recognized the increased amount of P3N-PIPO produced by Cl-90-1 Br2 and activated the salicylic acid-mediated defense pathway, inducing lethal systemic cell death. We found a gradation of virulence among ClYVV isolates in a cyv1-carrying pea line and two susceptible pea lines. This study suggests a trade-off between breaking of recessive resistance (cyv1) and host viability; the latter is presumably regulated by the dominant Cyn1 gene, which may impose evolutionary constraints upon P3N-PIPO for overcoming resistance. We propose a working model of the host strategy to sustain the durability of resistance and control fast-evolving viruses.

Metallic Nanodroplet Induced Coulomb Catalysis for Off-Resonant Plasmonic Enhancement of Photoemission in Semiconductors.

The enhancement of light from semiconductors due to surface plasmons coupled resonantly to its emission is limited because of dissipation in the metal and is also restricted by the dielectric characteristics and homogeneity of the metal-semiconductor interface. We report a new mechanism based on electrostatic interactions of carriers and their image charges in metals to generate more photons from optical sources at frequencies that are off-resonant to the localized plasmon frequency. Coulomb catalysis of carrier accumulation resulting from the inhomogeneity of metal nanodroplets on a semiconductor's surface can result in an enhancement of light that is nondissipative and does not require resonant coupling of plasmons to the emission wavelength. The enhancement occurs because of an increase in the ratio of radiative to nonradiative recombination in the vicinity of metal nanoparticles. It is equally effective with any type of metal and enhances radiation at any frequency, a property that is of principal importance for the realization of widely tunable semiconductor emitters. This fundamental mechanism provides a new perspective for improving the efficiency of light emitters and controlling carrier concentration on the nanoscale. The structural characteristics of the hybrid metal-semiconductor emitters are studied using electron microscopy and atomic force microscopy. We demonstrate the electrostatic mechanism by studying steady-state and transient photoluminescence from two-dimensional semiconductors, such as GaAs/AlGAs quantum wells, and bulk semiconductors, such as ZnO thin films, emitting in the near-IR and UV wavelength regimes, respectively.

Dietary intake of high-dose biotin inhibits spermatogenesis in young rats.

To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats.

Rapid identification of strains belonging to the Mycobacterium abscessus group through erm(41) gene pyrosequencing.

Mycobacterium abscessus and Mycobacterium massiliense lung infections have different clarithromycin susceptibilities, making proper identification important; however, standard multi-gene sequencing in clinical laboratories is laborious and time consuming. We developed a pyrosequencing-based method for rapid identification of strains belonging to the M. abscessus group by targeting erm(41). We examined 55 isolates from new pulmonary M. abscessus infections and identified 28 M. abscessus, 25 M. massiliense, and 2 Mycobacterium bolletii isolates. Multi-gene sequencing of 16S rRNA, hsp65, rpoB, and the 16S-23S ITS region was concordant with the results of erm(41) pyrosequencing; thus, the M. abscessus group can be identified by single-nucleotide polymorphisms in erm(41). The method also enables rapid identification of polymorphic, inducible clarithromycin-resistant sequevars (T28 or C28). Pyrosequencing of erm(41) is a rapid, reliable, high-throughput alternative method for identifying and characterizing M. abscessus species. Further testing of a diverse collection of isolates is necessary to demonstrate the discriminatory power of erm(41) sequencing to differentiating species with this highly divergent group.

Enhanced photoluminescence emission from anthracene-doped polyphenylsiloxane glass.

Anthracene-doped polyphenylsiloxane (PPS) glass containing silver nanoparticles (AgNPs) of appropriate size was synthesized in a form of solid thin films for modifying light emission characteristics. The photoluminescence (PL) emission from the anthracene molecules at ~2.95 eV was resonantly coupled to the localized surface plasmon (LSP) polariton modes that were induced by the excitation of ~30 nm sized AgNPs. The increase in absorption of incident photons within a highly scattering medium, energy transfer from the localized excitons to the LSP modes, and the electrostatic Coulomb effects of the excitons in the presence of metal NPs all resulted in a significant enhancement of PL emission. The PL enhancement is dependent on the concentration of the anthracene molecules. The integrated PL intensity enhancement at the optimum concentration of anthracene molecules in the PPS glass with AgNPs is found to exceed 50.

Antitumor activity of the ß-glucan paramylon from Euglena against preneoplastic colonic aberrant crypt foci in mice.

In the present study, the effects of ß-glucans isolated from Euglena on the formation of preneoplastic aberrant crypt foci (ACF) in the colon were examined in mice. Mice were fed a semi-purified AIN-93M diet containing cellulose or the same diet but with the cellulose replaced with ß-glucans in the form of Euglena, paramylon, or amorphous paramylon, for 11 weeks. After consuming these dietary supplements for 8 days, half of the mice were intraperitoneally administered 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) body weight every week for 6 weeks. Among the DMH-treated groups, the paramylon- and amorphous paramylon-fed mice displayed a significantly lower number of ACF than the control group. Also, the liver weight of the paramylon group was markedly decreased compared with those of the control and Euglena groups, whereas the cecal content weight and fecal volume of the paramylon group were significantly increased. As for the levels of organic acids in the cecal contents, the paramylon group displayed significantly increased lactic acid levels compared with the control and Euglena groups. From these findings, although the mechanism of the ACF-inhibiting effects of paramylon remains unclear, it is considered that ß-glucans, such as paramylon and its isomer amorphous paramylon, have preventive effects against colon cancer and are more effective against the condition than Euglena.

Quantitative and qualitative involvement of P3N-PIPO in overcoming recessive resistance against Clover yellow vein virus in pea carrying the cyv1 gene.

In pea carrying cyv1, a recessive gene for resistance to Clover yellow vein virus (ClYVV), ClYVV isolate Cl-no30 was restricted to the initially infected cells, whereas isolate 90-1 Br2 overcame this resistance. We mapped the region responsible for breaking of cyv1-mediated resistance by examining infection of cyv1 pea with chimeric viruses constructed from parts of Cl-no30 and 90-1 Br2. The breaking of resistance was attributed to the P3 cistron, which is known to produce two proteins: P3, from the main open reading frame (ORF), and P3N-PIPO, which has the N-terminal part of P3 fused to amino acids encoded by a small open reading frame (ORF) called PIPO in the +2 reading frame. We introduced point mutations that were synonymous with respect to the P3 protein but nonsynonymous with respect to the P3N-PIPO protein, and vice versa, into the chimeric viruses. Infection of plants with these mutant viruses revealed that both P3 and P3N-PIPO were involved in overcoming cyv1-mediated resistance. Moreover, P3N-PIPO quantitatively affected the virulence of Cl-no30 in cyv1 pea. Additional expression in trans of the P3N-PIPO derived from Cl-no30, using White clover mosaic virus as a vector, enabled Cl-no30 to move to systemic leaves in cyv1 pea. Susceptible pea plants infected with chimeric ClYVV possessing the P3 cistron of 90-1 Br2, and which were therefore virulent toward cyv1 pea, accumulated more P3N-PIPO than did those infected with Cl-no30, suggesting that the higher level of P3N-PIPO in infected cells contributed to the breaking of resistance by 90-1 Br2. This is the first report showing that P3N-PIPO is a virulence determinant in plants resistant to a potyvirus.

Successful Treatment of MMP-9-Expressing Angiosarcoma with Low-Dose Docetaxel and Bisphosphonate.

We describe a 78-year-old Japanese patient with angiosarcoma on the scalp. Interestingly, immunohistochemical staining revealed this tumor as positive for matrix metalloproteinase 9 (MMP-9). After conventional therapy for angiosarcoma with surgical treatment and radiation therapy, we intravenously administered docetaxel at 40 mg/m(2) body surface area together with oral administration of 17.5 mg sodium risedronate hydrate. One and a half years after the standard treatment, there was no evidence of local recurrence or metastasis.

Involvement of the P1 cistron in overcoming eIF4E-mediated recessive resistance against Clover yellow vein virus in pea.

Two recessive genes (cyv1 and cyv2) are known to confer resistance against Clover yellow vein virus (ClYVV) in pea. cyv2 has recently been revealed to encode eukaryotic translation initiation factor 4E (eIF4E) and is the same allele as sbm1 and wlm against other potyviruses. Although mechanical inoculation with crude sap is rarely able to cause infection of a cyv2 pea, biolistic inoculation of the infectious ClYVV cDNA clone does. At the infection foci, the breaking virus frequently emerges, resulting in systemic infection. Here, a derived cleaved-amplified polymorphic sequence analysis showed that the breakings were associated with a single nonsynonymous mutation on the ClYVV genome, corresponding to an amino-acid substitution at position 24 (isoleucine to valine) on the P1 cistron. ClYVV with the point mutation was able to break the resistance. This is a first report demonstrating that P1 is involved in eIF4E-mediated recessive resistance.