Skin health survey on atopic dermatitis among Japanese children: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Precise skin phenotypic data are indispensable in accurately diagnosing atopic dermatitis (AD). Therefore, this study examined the interobserver concordance for AD and non-AD diagnoses between two dermatologists. AD prevalence determined by the self-reported physician diagnoses and the diagnoses determined from the United Kingdom (UK) diagnostic criteria were compared with the diagnoses made by the two dermatologists, using data from a skin health survey. METHODS: This study included 1,638 children that participated in the skin health survey, which was part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. AD was assessed using dermatologist assessments, self-reported physician diagnoses, and the UK diagnostic criteria. The concordance for diagnoses was evaluated using kappa. The sensitivity and specificity of the self-reported physician diagnoses and the UK diagnostic criteria were calculated by comparing them with the two dermatologists' diagnoses. RESULTS: Among the 1,638 children, 393 (24.0 %), 194 (11.9 %), and 597 (37.2 %) were diagnosed with AD by the two dermatologists, physicians, and the UK diagnostic criteria, respectively. The kappa (95 % CI) of the interobserver concordance for AD or non-AD diagnoses between the two dermatologists was 0.78 (0.75-0.81). The sensitivity and specificity of the self-reported physician diagnoses were 26.7 % and 94.1 %, respectively. The sensitivity and specificity of the UK diagnostic criteria were 85.0 % and 82.4 %, respectively. CONCLUSIONS: Interobserver concordance for AD or non-AD diagnoses between the two dermatologists was substantial. Self-reported physician diagnoses exhibited low sensitivity that potentially indicated underdiagnosis of AD, whereas the UK diagnostic criteria might overdiagnose AD.

In situthermal noise measurements under nanoindentation of suspended graphene.

We demonstrated thermal noise measurement under the nanoindentation of monolayer and bilayer graphene nanodrums. The resonant oscillation of the cantilever excited only by a thermal energy is detectable even in the case of contact with a suspended graphene. The contact resonance fRequency can be obtained in 1 millisecond intervals during the force curve measurement by optimizing the parameters of a real-time spectrum analyzer. The pretension value of the graphene nanodrum is evaluated by the minimum frequency just when the applied force of the cantilever becomes zero. The simultaneous measurement of the force and the resonant frequency with respect to the deformation of the graphene nanodrum enables us to determine the value of InvOLS (inverse optical lever sensitivity) more accurately in each measurement. From the analysis scheme, force curve measurements of the graphene nanodrums with the same diameters show good reproducibility. We also revealed that the effective spring constant of the graphene nanodrums consists of a weak sample-dependent pretension factor and a deformation-dependent factor proportional to the number of graphene layers.

Extension of Selection Time for the Emergency Destination of Patients with a Fever Due to the Coronavirus Disease 2019 Pandemic: A Difference-in-differences Analysis.

Objective During the coronavirus disease 2019 (COVID-19) pandemic period, an extended total activity time (TAT) in emergency cases has been reported, especially in febrile patients. A brief selection time (ST) regarding the transport of patients to designated hospitals is vital to achieving a good outcome. However, to our knowledge, no studies have reported the impact of the COVID-19 pandemic on the ST. We therefore examined the impact of a fever on the ST for the transportation of emergency patients during the COVID-19 pandemic. Methods We analyzed emergency medical services (EMS) data in Sapporo between January 2015 and December 2020. The primary outcome was the ST for the emergency destination of patients. The secondary outcomes were the number of inquiries, time from emergency call to arrival at the scene [call-to-scene time (CST)], time from arrival at the hospital to return base [arrival-to-return time (ART)], and TAT. We used a multivariable linear regression model to estimate the difference-in-differences effect. Results A total of 383,917 patients who were transported to the hospital were enrolled within the study period. The mean ST was 5.8 minutes in 2019 and 7.1 minutes in 2020. The difference-in-differences analyses showed that the mean ST increased by 2.52 minutes (p<0.001), the mean ART by 3.10 minutes (p<0.001), and the mean TAT by 7.27 minutes (p<0.001) for patients with a fever during the COVID-19 period. Conclusion This study showed that febrile patients had a longer ST, ART, and TAT during the 2020 COVID-19 period. Considering the COVID-19 pandemic and the threat of future pandemics, regional infection control and information-sharing should be conducted to reduce the EMS activity time.

Ferromagnetic metal conversion directly from two-dimensional nickel hydroxide.

We have demonstrated a direct metallic conversion from nickel hydroxide nanosheets to nickel metal nanostructures by thermal annealing in vacuum. The metal transition of the single-layer nanosheets deposited on a Si substrate was revealed by x-ray absorption near edge structure (XANES) measurements. The XANES signal significantly changed at annealing temperatures above 250 °C. The metal transition temperature coincides with the reported temperatures at which layered nickel hydroxide nanosheets are converted to nickel oxide nanosheets by calcination in air. Auger measurements confirmed that a dissociation of oxygen from the hydroxide nanosheet induces the metallic conversion. The converted nickel metallic structures exhibit ferromagnetic behavior revealed by x-ray magnetic circular dichroism (XMCD) measurement. Atomic force microscopy measurements indicate that diffusions of nickel atoms on the substrates leads to a structural change from a 2D-like structure to a particle-like structure.

Risk factors for malnutrition among school-aged children: a cross-sectional study in rural Madagascar.

BACKGROUND: For over 20 years, Madagascar has been challenged by continued high prevalence of stunting, underweight and wasting among children under 5 years of age. Yet, nutritional status of post-under-five age group has never been assessed in the country, despite its importance in relation not only to physical health but also to cognitive capacity and educational achievements of children. This study aims to estimate prevalence of malnutrition among schoolchildren aged 5-14 years in Madagascar. It further attempts to identify the possible risk factors for their malnutrition. This is the first study that estimates prevalence of malnutrition among school-aged children in Madagascar. METHODS: A cross-sectional household survey was conducted in Antananarivo-Avaradrano district, Analamanga region, Madagascar. The study targeted 393 first and second graders 5-14 years of age enrolled at 10 primary schools, where school-feeding was implemented. Data were collected from anthropometric measurements, their subsequent household structured interviews and observations. Bivariate (Chi-square test or Mann-Whitney's U test) and multivariable (logistic regression) analyses were performed, to identify the possible risk factors associated with malnutrition. RESULTS: The overall prevalence rates of stunting, underweight and thinness were 34.9%, 36.9% and 11.2%, respectively. Nineteen children (4.8%) suffered from all the three forms of undernutrition. Older schoolchildren had a significantly greater likelihood of being stunted, underweight and thin. The greater number of members a household had, the higher likelihood of being stunted and thin its schoolchild had. Children having lower Household Dietary Diversity Score were more likely to be underweight. Yet, 'Had lunch at school yesterday' was associated neither with being stunted nor with being underweight and thin. This implies room for improvement of the current school feeding program. CONCLUSIONS: Prevalence rates of stunting and underweight among 393 children examined were as high as the national averages among children under 5 years of age. Adequate food availability and dietary diversity over a sufficient period (incl. 5-14 years of age) are necessary for increasing likelihood of catch-up in height-for-age and weight-for-age, which are expectable during adolescence. To supplement inadequate household dietary diversity practices, school-feeding program may need to use more animal-protein ingredients.

The utility of body mass index as an indicator for lipid abnormalities in non-fasting children.

BACKGROUND: Many studies have reported the association between body mass index (BMI) and fasting lipid profiles in children. However, little information exists about the screening of dyslipidemia in the non-fasted state. This study assessed whether BMI can predict non-fasting lipid abnormalities in children. METHODS: Using gender-separated analysis, 3895 boys and 3866 girls (aged 11-12 years) were investigated. Total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL-C) were measured, and non-HDL-C (=TC-[HDL-C]) was calculated. A BMI z-score was employed as the weight status. Gender-specific 95th percentiles of TC, TG and non-HDL-C were defined as "elevated", with the 5th percentiles of HDL-C defined as "reduced". RESULTS: TG and non-HDL-C were positively, and HDL-C was negatively correlated with the BMI z-score in both genders. Both obese (2

Synthetic studies on and mechanistic insight into [W(CO)5(L)]-catalyzed stereoselective construction of functionalized bicyclo[5.3.0]decane frameworks.

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)(5)(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl-substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven-membered rings were present. The reaction of (Z)-enol silyl ethers proceeded through Cope rearrangement of cis-divinylcyclopropane intermediates, and that of (E)-enol silyl ethers by 1,4-addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.

Sialolipoma of the palate: a rare case and review of the literature.

Sialolipoma is a new variant of salivary gland lipoma, which was first described in 2001. We report a rare case of sialolipoma of the palate, and review another 10 cases affecting the minor salivary gland and 13 affecting the major salivary gland, together with details of the clinical and histopathological findings.

Spontaneous fluctuation of the resting membrane potential in Paramecium: amplification caused by intracellular Ca2+.

The ciliated protozoan Paramecium spontaneously changes its swimming direction in the absence of external stimuli. Such behavior is based on resting potential fluctuations, the amplitudes of which reach a few mV. When the resting potential fluctuation is positive and large, a spike-like depolarization is frequently elicited that reverses the beating of the cilia associated with directional changes during swimming. We aimed to study how the resting potential fluctuation is amplified. Simultaneous measurements of the resting potential and intracellular Ca(2+) ([Ca(2+)](i)) from a deciliated cell showed that positive potential fluctuations were frequently accompanied by a small increase in [Ca(2+)](i). This result suggests that Ca(2+) influx through the somatic membrane occurs during the resting state. The mean amplitude of the resting potential fluctuation was largely decreased by either an intracellular injection of a calcium chelater (BAPTA) or by an extracellular addition of Ba(2+). Hence, a small increase in [Ca(2+)](i) amplifies the resting potential fluctuation. Simulation analysis of the potential fluctuation was made by assuming that Ca(2+) and K(+) channels of surface membrane are fluctuating between open and closed states. The simulated fluctuation increased to exhibit almost the same amplitude as the measured fluctuation using the assumption that a small Ca(2+) influx activates Ca(2+) channels in a positive feedback manner.

Fibril formation of hsp10 homologue proteins and determination of fibril core regions: differences in fibril core regions dependent on subtle differences in amino acid sequence.

Heat shock protein 10 (hsp10) is a member of the molecular chaperones and works with hsp60 in mediating various protein folding reactions. GroES is a representative protein of hsp10 from Escherichia coli. Recently, we found that GroES formed a typical amyloid fibril from a guanidine hydrochloride (Gdn-HCl) unfolded state at neutral pH. Here, we report that other hsp10 homologues, such as human hsp10 (Hhsp10), rat mitochondrial hsp10 (Rhsp10), Gp31 from T4 phage, and hsp10 from the hyperthermophilic bacteria Thermotoga maritima, also form amyloid fibrils from an unfolded state. Interestingly, whereas GroES formed fibrils from either the Gdn-HCl unfolded state (at neutral pH) or the acidic unfolded state (at pH 2.0-3.0), Hhsp10, Rhsp10, and Gp31 formed fibrils from only the acidic unfolded state. Core peptide regions of these protein fibrils were determined by proteolysis treatment followed by a combination of Edman degradation and mass spectroscopy analyses of the protease-resistant peptides. The core peptides of GroES fibrils were identical for fibrils formed from the Gdn-HCl unfolded state and those formed from the acidic unfolded state. However, a peptide with a different sequence was isolated from fibrils of Hhsp10 and Rhsp10. With the use of synthesized peptides of the determined core regions, it was also confirmed that the identified regions were capable of fibril formation. These findings suggested that GroES homologues formed typical amyloid fibrils under acidic unfolding conditions but that the fibril core structures were different, perhaps owing to differences in local amino acid sequences.

Metabolic syndrome and age-related dementia: endocrinological aspects of adaptation to aging.

Metabolic syndrome is one of the determinants of lifespan in Japan. In order to prevent the acute vascular events, intervention is recommended. However, management of patients with this syndrome increased the number of patients with cognition decline and depressive state. Endocrinological studies with human and experimental animals showed that there is a negative relationship between progression of metabolic syndrome and occurrence of mental disorders. In this review, we summarize our clinical and experimental data, and discuss on the mechanism of the metabolic syndrome prevention of progression of age-related mental disorder.

[A successful treatment of percutaneous radio frequency ablation for advanced thyroid cancer].

The patient was a 69-year-old woman. She received chemotherapy and radiation for thyroid tumor (undifferentiated cancer) following an operation in 1998. The chemotherapy was regularly repeated for relapse. The tumor increased gradually and came to cause dysphagia. She initially rejected nutritional management that depends on intravenous hyper alimentation or gastrostomy. After receiving an informed consent, we performed percutaneous radio frequency ablation (RFA) for the tumor using a Cool-tip needle on April 2, 2003. The algorithm of RFA was 9 min: 30 --> 120 W, 12 min: 50 --> 110 W, 9 min: 50 --> 100 W. After 2 days, the covered stent was implanted in the esophagus and an oral intake was started. Although the operation for undifferentiated thyroid cancer is controversial, we performed RFA and esophageal stenting for improving of QOL. This is the first case report in Japan.

Tumor-specific gene therapy for undifferentiated thyroid carcinoma utilizing the telomerase reverse transcriptase promoter.

A tumor-specific targeting system for cancer gene therapy was studied using the human telomerase reverse transcriptase (hTERT) promoter. Telomerase activity is increased in most tumors but not detected in most normal cells. We developed the recombinant adenovirus, carrying human herpes simplex virus thymidine kinase gene under the control of the hTERT promoter (AdhTERTtk) to obtain restricted expression of a suicide gene only in tumor cells. We found that transcriptional activity of hTERT was 2- to 9-fold higher in undifferentiated thyroid carcinoma cell lines than that of the Simian virus 40 promoter in transient transfection assay. Undifferentiated thyroid carcinoma cell lines were infected with AdhTERTtk, and sensitivity to ganciclovir (GCV) was analyzed. Cell viability was decreased in a GCV dose-dependent manner after treatment with AdhTERTtk/GCV. The cell-killing ability of AdhTERTtk in all thyroid or nonthyroid carcinoma cell lines tested was similar to AdCMVtk, which carries herpes simplex virus thymidine kinase gene driven by the cytomegalovirus promoter. However, normal cell lines were largely unaffected by AdhTERTtk/GCV, whereas these cells were also sensitive to GCV after infection with AdCMVtk. A xenograft model was established by transplanting human differentiated or undifferentiated thyroid carcinoma cells into Balb-C nude mice. The injections of AdhTERTtk into tumors and ip administration of GCV showed significant inhibition of tumor growth, similar to AdCMVtk/GCV treatment. Systemic administrations of adenovirus and GCV to normal rats demonstrated remarkable increase of serum liver transaminase levels and severe hepatic damages in pathological examinations in AdCMVtk-injected rats but not in the AdhTERTtk group. These results indicate that the AdhTERTtk/GCV system is a promising therapy for undifferentiated thyroid carcinoma, which is one of the most malignant tumors, without damage to normal tissues.

Communication network in the follicular papilla and connective tissue sheath through gap junctions in human hair follicles.

Epithelial-mesenchymal interactions play a crucial role in the induction of life-long cyclic transformations of hair follicles. Many studies have already demonstrated several candidates for the soluble factors secreted from the mesenchymal components of the hair follicle, i.e. the follicular papilla (FP) and connective tissue sheath (CTS), which may be responsible for hair cycling. In this paper, we focused on cell-cell contact between FP cells (FPCs), between CTS cells (CTSCs), and between FPCs and CTSCs that may allow these mesenchymal components to function as a syncytium during hair cycling. Electron microscopic examination of the FP and the CTS obtained from human scalp revealed a tri-lamellar structure of the plasma membranes, which is a characteristic of gap junctions at the cell-cell contacting area. The immunohistochemical study with anticonnexin 43 Ab using a confocal laser scanning microscope demonstrated numerous spotted positive signals scattered throughout the FP. In the CTS, spotted positive signals were arranged linearly along the basement membrane of the hair follicle. In particular, these positive spots were aggregated in the transitional region between the FP and the CTS. By Western blot analysis of total protein extracts from the cultured FPCs and neonatal human dermal fibroblasts using anticonnexin 43 antibody, a positive band corresponding to connexin 43 was detected at 43 kDa on both the FPC lane and fibroblast lane. These findings suggest that the FP and the CTS form a communicating network through gap junctions, which may play a role in controlling the dynamic structural changes of hair follicles during hair cycling.

Macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 induces the differentiation of CD34+ hematopoietic progenitor cells into Langerhans cells under serum-free conditions without granulocyte-macrophage colony-stimulating factor.

Macrophage colony-stimulating factor has not been considered as a factor responsible for dendritic cell or Langerhans cell development from hematopoietic progenitor cells. In this study, we examined whether macrophage colony-stimulating factor could be used instead of granulocyte-macrophage colony-stimulating factor for the in vitro development of Langerhans cells from hematopoietic progenitor cells. We replaced granulocyte-macrophage colony-stimulating factor with macrophage colony-stimulating factor from a serum-free culture containing granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt3 ligand, tumor necrosis factor-alpha, and transforming growth factor-beta1. This serum-free culture medium containing macrophage colony-stimulating factor, but not granulocyte-macrophage colony-stimulating factor (macrophage colony-stimulating factor culture), could induce CD1a+ Birbeck granule+ Langerin+ E-cadherin+ factor-like XIIIa Langerhans cells. As a control, the culture of hematopoietic progenitor cells in this culture medium depleted of macrophage colony-stimulating factor or transforming growth factor-beta1 resulted in far fewer or null CD1a+ cells, respectively. Macrophage colony-stimulating factor increased the number of CD1a+ cells in a concentration-dependent fashion. These macrophage colony-stimulating factor-induced Langerhans cells were different from granulocyte-macrophage colony-stimulating factor-induced Langerhans cells in their decreased expression of CD11c and their immature phenotype. The decreased expression of CD11c, however, was recovered by culturing them with granulocyte-macrophage colony-stimulating factor, while they acquired a mature phenotype qby granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, interleukin-1alpha, or lipo-polysaccharide. Macrophage colony-stimulating factor-induced Langerhans cells could stimulate allogeneic T cells. Interestingly, we could keep the growth and immature phenotypes of macrophage colony-stimulating factor-induced Langerhans cells for at least 28 d of culture. These studies demonstrated that macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 could induce Langerhans cell development from hematopoietic progenitor cells in vitro without granulocyte-macrophage colony-stimulating factor, which suggests the possibility that macrophage colony-stimulating factor plays a part in the Langerhans cell development in vivo. In addition, the culture using macrophage colony-stimulating factor presents a novel culture system to enable a large-scale and long-term culture of immature Langerhans cells.

Plasma extravasation induced by dietary supplemented histamine in histamine-free mice.

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.

Cholinergic urticaria, a new pathogenic concept: hypohidrosis due to interference with the delivery of sweat to the skin surface.

BACKGROUND: Acetylcholine has been suspected to be a pathogenetic factor for cholinergic urticaria (CU), without definite evidence. In contrast, there are scattered reports of CU associated with acquired generalized hypohidrosis. We have recently examined 2 patients with CU in both of whom we noticed the presence of extensive hypohidrosis that occurred only in winter. OBJECTIVE: In these 2 patients, acquired hypohidrosis due to superficial obstruction of the acrosyringium was suspected as the cause. Both case 1, a 22-year-old Japanese man, and case 2, a 21-year-old Japanese man, began to have anhidrosis and numerous red macules on their body whenever they felt hot in winter. These symptoms ceased to appear in summer. METHODS: We studied histologically their lesional skin in addition to provocation tests for CU. RESULTS: The diagnosis of CU was confirmed by the provocation of typical wheals after physical exercise in both cases. Histological study revealed findings suggestive of the presence of occlusion of the superficial acrosyringium. CONCLUSION: We think that such a hypohidrosis due to occlusion of superficial sweat ducts may also play a role in many other patients with CU of unknown etiology that becomes exacerbated in winter when sweating is not a frequent event.