Impact of the Coronavirus Disease 2019 Outbreak on Activity and Exercise Levels among Older Patients.

OBJECTIVES: This study aimed to clarify the impact of the coronavirus disease 2019 outbreak on the levels of activity among older patients with frailty or underlying diseases. A total of 175 patients (79.0±7.0 years) undergoing outpatient or home-based rehabilitation, stratified into groups, based on frailty status. The percentage of patients who went out at least once a week decreased after the outbreak from 91% to 87%, from 65% to 46%, and from 47% to 36% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in exercise during the outbreak was 75%, 51%, and 41% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in voluntary exercise after instruction was lowest in the frail group (35%). Older patients with frailty are susceptible to the negative effects of refraining from physical activity and require careful management.

Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice.

Disrupted-in-schizophrenia 1 (Disc1) is a key molecular driver for the biology of mental diseases. In order to investigate its role in brain function, we previously generated mice lacking exons 2 and 3 of Disc1 on a C57BL/6J genetic background (Disc1Δ2-3/Δ2-3 mice), which have a deficiency of the full-length Disc1 protein. In the present study, we examined the role of Disc1 in cognitive function using a touchscreen-based visual discrimination (VD) task in which mice had to discriminate 1 of 2 stimuli simultaneously displayed on the screen and received a liquid reward. Disc1Δ2-3/Δ2-3 mice showed impaired performance in the VD task, and this was mainly attributed to the perseverative response being significantly stronger than that in wild-type (WT) mice. Furthermore, the numbers of marbles buried in the marble burying test and nestlets shredded in the nestlet shredding test by Disc1Δ2-3/Δ2-3 mice were significantly higher than those by WT mice, suggesting perseverative/compulsive behaviors by Disc1Δ2-3/Δ2-3 mice. A treatment with clozapine ameliorated behavioral deficits in the VD and marble burying tasks. c-Fos expression was significantly stronger in the dorsomedial striatum (DMS), but not the dorsolateral striatum (DLS) after the first VD session in Disc1Δ2-3/Δ2-3 mice than in WT mice. The treatment of mice that had previously expressed hM3Dq in the DMS with clozapine-N-oxide (CNO) impaired performance in the VD task. These results suggest that cognitive impairments accompanied by perseverative/compulsive behaviors in Disc1Δ2-3/Δ2-3 mice are associated with hyperactivity of the DMS.

Preliminary Study on Prevalence and Associated Factors with Sarcopenia in a Geriatric Hospitalized Rehabilitation Setting.

The reported prevalence of sarcopenia has shown a wide range, crucially based on the diagnostic criteria and setting. This cross-sectional study evaluated the prevalence of sarcopenia and sought to identify factors associated with sarcopenia on admission in a specialized geriatric rehabilitation setting based on the newly developed the Asian Working Group for Sarcopenia algorithm. Among 87 participants (mean age, 76.05 ± 7.57 years), 35 (40.2%) were classified as showing sarcopenia on admission. Prevalence was high, particularly among participants ≥80 years old, with tendencies toward lower body mass index, smoking habit, lower cognitive function, and greater functional impairment compared with the non-sarcopenic group. Identification of sarcopenia in elderly patients before rehabilitation and consideration of risk factors may prove helpful in achieving rehabilitation outcomes.

Transition of Akabane virus genogroups and its association with changes in the nature of disease in Japan.

Akabane virus (AKAV) is teratogenic to the foetus of domestic ruminants and causes a significant reproduction loss in cattle in Japan. In several past epizootics in cattle, AKAV was also associated with post-natal encephalomyelitis, mainly in calves and young stock. Previously analysed AKAV isolates in East Asia form two major clusters, genogroups I and II, with isolates involved in encephalomyelitis belonging mainly to the former. Between 2007 and 2013, AKAV epizootics were regularly observed in Japan during the summer/autumn season, and abnormal deliveries and post-natal encephalomyelitis caused by the virus in cattle were reported. During this period, 30 AKAV isolates were obtained from diseased and sentinel cattle, a piglet and Culicoides biting midges throughout Japan and were subjected to genetic comparison and phylogenetic analysis with previous isolates. In 2007, 2011 and 2013, AKAV belonging to genogroup I was identified in the central nervous systems of calves showing neurological disorders. Notably, a total of 165 cases of bovine encephalomyelitis were reported in 2011 and the isolated viruses from affected animals shared high genetic identities with a South Korean isolate that was associated with a large outbreak in 2010, suggesting some epidemiological linkage between these epizootics. Epizootics of genogroup II were observed in 2008 and 2010, but bovine post-natal encephalomyelitis cases rarely occurred. Our findings suggest that the frequent incursion of genogroup I isolates has increased the frequency of post-natal encephalomyelitis cases in Japan in recent years. Infection by genogroup I virus was also identified in piglets with neurological disorders or congenital malformations in 2011 and 2013. The aetiological role of AKAV in pigs should be elucidated in the future.

The Biomarker Salivary SP-D May Indicate Small Airway Inflammation and Asthma Exacerbation.

BACKGROUND: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. METHODS: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. RESULTS: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. CONCLUSIONS: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma.

Spatiotemporal treadmill gait measurements using a laser range scanner: feasibility study of the healthy young adults.

OBJECTIVE: Spatio-temporal parameters are typically used for gait analysis. Although these parameters are measured by sophisticated systems such as 3D motion capture system or optoelectronic bars, these systems cannot be deployed easily because of their high costs, large space requirements and elaborate set-up. The purpose of this study is to develope a system for measuring spatiotemporal gait parameters using a laser range scanner during treadmill gait. APPROACH: To calculate accurate spatiotemporal parameters, the differences between the laser range scanner measured values and the reference values obtained from a 3D motion capture system were investigated in thirty subjects. From measurements in time and position at foot contact/off, adjustments to compensate for the differences in time and position were derived. Then, to determine the validity of the proposed system, values from the proposed system and the reference system were compared in four additional subjects. MAIN RESULTS: The results indicate that the data from the laser range scanner demonstrate certain differences in time and position compared with reference values. However, when compensation values were introduced, each spatiotemporal parameter correlated well with the reference values. SIGNIFICANCE: This newer system is smaller, is easier to deploy and requires less training than the 3D motion capture system.

The biomarker salivary SP-D may indicate small airway inflammation and asthma exacerbation

Background: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. Methods: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. Results: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. Conclusion: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma (AU)

Antecedentes: El empleo de biomarcadores no invasivos es una buena herramienta para estudiar la fisiopatología de los diferentes fenotipos del asma infantil. Objetivo: El objetivo de este estudio fue examinar la utilidad de la proteína salival surfactante (SP) D en la evaluación de la fisiopatología del asma infantil. Métodos: Se midieron las concentraciones en la saliva de SP-D y se realizaron oscilometrías forzadas de impulsos (FOT) en 21 niños asmáticos y 19 controles sanos. Las ecuaciones de regresión para los valores predictivos de los índices FOT se generaron a partir de controles sanos. Se analizaron las correlaciones entre la concentración de SP-D salival y los porcentajes de los valores predictivos de los índices FOT, así como la gravedad de las exacerbaciones. Resultados: Se encontró que los niveles en la saliva de la SP-D fueron más elevados en los niños asmáticos en comparación con los controles sanos. En los niños asmáticos, los niveles de SP-D salival se correlacionaron con los porcentajes de las diferencias predichas en la resistencia entre 5Hz y 20Hz (% R5-R20), que representan la resistencia de las vías respiratorias periféricas y la gravedad de la exacerbación del asma. Conclusión: La SP-D salival puede reflejar la inflamación asmática en las vías respiratorias pequeñas y puede ser un marcador útil para monitorizar el grado de exacerbación en el asma infantil (AU)

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men.

The association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (ß = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels.

Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine.

The Fgf family comprises 22 members with diverse functions in development, repair, metabolism, and neuronal activities. Fgf10 mediates biological responses by activating Fgf receptor 2b (Fgfr2b) with heparin/heparan sulfate in a paracrine manner. Fgf10 and Fgfr2b are expressed in mesenchymal and epithelial tissues, respectively. Fgf10 is an epithelial-mesenchymal signaling molecule. Fgf10 knockout mice show severe phenotypes with complete truncation of the fore- and hindlimbs and die shortly after birth due to impaired lung development, indicating that Fgf10 serves as an essential regulator of lung and limb formation. Fgf10 also has roles in the development of white adipose tissue, heart, liver, brain, kidney, cecum, ocular glands, thymus, inner ear, tongue, trachea, eye, stomach, prostate, salivary gland, mammary gland, and whiskers. The diverse phenotypes of Fgf10 knockout mice are closely related to those of Fgfr2 knockout mice, suggesting that Fgf10 acts as a major ligand for Fgfr2b in mouse multi-organ development. Aplasia of lacrimal and salivary glands and lacrimo-auriculo-dento-digital syndrome are caused by Fgf10 mutations in humans. Variants in Fgf10 may be involved in an increased risk for limb deficiencies and cleft lip and palate. Patients with Fgf10 haploinsufficiency have lung function parameters indicating chronic obstructive pulmonary disease. Fgf10 induces migration and invasion in pancreatic cancer cells. Fgf10 signaling may be involved in an increased risk for breast cancer. Fgf10 also induces the differentiation of embryonic stem cells into a gut-like structure, cardiomyocytes, and hepatocytes. These findings indicate the crucial roles of Fgf10 in development, disease, and regenerative medicine.

Threshold levels for wettability in nano- and micro-meter periodic structures.

The purposes of this study are to clarify the relationship between surface wettability and the pitch and size of periodic structures on the surface and to determine the thresholds at which the wettability switches from being hydrophobic to hydrophilic. To this various nano- and micro-meter scale periodic structures were fabricated. By applying a fine periodic structure to the surface, the wettability can be controlled between + 50° (hydrophobic) and -55° (hydrophilic). The pitch of the periodic structure at which the wettability switches from hydrophilic to hydrophobic was found to between 500 and 1,000 nm. Additionally, the height of the periodic structure at which the wettability switches from hydrophobic to hydrophilic was found to between 300 and 700 nm.

Amorphous nanosilica particles induce ROS generation in Langerhans cells.

Generation of total intracellular reactive oxygen species (ROS) was measured in XS52 cells, a Langerhans cell-like line, treated with different sized amorphous silica particles. The results suggested that exposure to amorphous nanosilica particles (nSPs) with a particle size of 70 nm induced a higher level of ROS generation than did exposure to micron-sized amorphous silica particles. This finding means that it is essential to examine the biological effects of ROS generated after exposure to nSPs, which will provide useful information for hazard identification as well as the design of safer nanomaterials.

Dermal absorption of amorphous nanosilica particles after topical exposure for three days.

The skin penetration and cellular localization of well-dispersed amorphous nanosilica particles (nSPs) with a diameter of 70 nm was analyzed in mice. Our results suggest that after topical exposure for three days the particles penetrate the skin barrier and are transported to the lymph nodes. These findings underscore the need to examine biological effects following dermal exposure to nSPs for the development of safer use of nSPs.

Estimation of the kinetic-optimized stimulus intensity envelope for drop foot gait rehabilitation.

The purpose of present study is to estimate the optimal stimulus intensity envelope for drop foot rehabilitation based on a kinetic perspective. The voluntary and electric-stimulated elicited dorsiflexion torque responses of 11 healthy subjects were measured. During dorsiflexion, we recorded the tibialis anterior (TA) electromyography (EMG) or the stimulation intensity at four angles of the ankle joint. From these measurements, we derived two approximate equations that estimate dorsiflexion produced by either voluntary contraction or by electrical stimulation using a sigmoid function and a stepwise-regression analysis. We then tested the predictive capability of the model using Pearson correlation. Both equations indicated high correlation coefficients. Finally, we derived a relation between the TA EMG amplitude and stimulation intensity. From the obtained equation, we determined the optimal stimulus amplitude. We assume that the derived stimulus intensity envelope, calculated from EMG amplitude and angle of ankle joint, satisfies kinetic demand.

Size-dependent immune-modulating effect of amorphous nanosilica particles.

The immune-modulating effect following intradermal injection of various-sized amorphous silica particles was analyzed in terms of induction of ovalbumin-specific CD8+ T cells in vivo. IFN-gamma ELISPOT assays revealed that only nanosilica particles with a diameter of less than 100 nm significantly enhanced CD8+ T cell responses against ovalbumin. These results indicate that the size of nanomaterials is a critical determinant in terms of their safe use.

Detection of titanium dioxide particles on frozen tissue sections using synchrotron radiation X-ray fluorescence analysis.

Recent studies into the in vivo absorption and biological influence of particulate matter, especially nanomaterials (NMs), have raised worldwide concerns over their safety. However, it is often technically difficult to conduct these studies because NMs are too small to be observed by optical microscopy. Here, we attempted to establish a new method to visually detect NMs on tissue samples. Specifically, we have analyzed titanium dioxide particles with a diameter of 5 microm, which are widely used in cosmetics, using frozen tissue sections by synchrotron radiation X-ray fluorescence analysis.

Prevalence of intestinal parasites and genotyping of Giardia intestinalis in pet shop puppies in east Japan.

The current study examined the prevalence of intestinal parasites and genotypes of Giardia intestinalis in puppies from nine pet shops in east Japan. Fresh fecal samples from 1794 puppies (≦3 months old) were collected on one occasion. Giardia spp. was examined for specific coproantigen using ELISA kit (SNAP®Giardia, IDEXX Laboratories, Inc., USA). Other intestinal parasites were detected microscopically using the formalin-ethyl acetate sedimentation technique. Genotyping was determined for the random 29 stool samples identified as Giardia spp. positive using PCR and direct sequencing of the glutamate dehydrogenase (gdh) gene. Overall prevalence of protozoan Giardia spp. and Cystoisospora spp. revealed 23.4% and 11.3%, respectively. Prevalence of ascarids, Strongyloides spp. and hookworms were recorded 1.8%, 1.1% and 0.1%, respectively. Protozoan Giardia spp. and Cystoisospora spp., thus, represent important pathogens among pet shop puppies. All genotyped G. intestinalis isolates were belonged to assemblage C or D, identified as dog-specific genotypes. Zoonotic assemblage A and B were not demonstrated. The result suggests that the risk of zoonotic transmission of G. intestinalis from pet shops puppies to humans may be quite low in Japan.

Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV.

The development of a safe and effective mucosal vaccine adjuvant is a crucial step for the development of vaccines against human immunodeficiency virus type-1 (HIV). We have previously reported that a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, possessed strong mucosal vaccine adjuvant activities in mice. Here, we evaluated the potential of mTNF-K90R as a mucosal vaccine adjuvant for the induction of systemic and mucosal immune responses against HIV. Nasal immunization of BALB/c mice with 5 microg of an HIV gp120 env protein immunogen together with mTNF-K90R induced higher serum anti-HIV gp120 protein immunoglobulin G (IgG) responses than gp120 alone. Furthermore, mTNF-K90R induced anti-gp120 IgA responses in nasal as well as vaginal washes from immunized mice, although these were not administration sites. Again, responses with mTNF-K90R were higher than with gp120 alone. These results indicate that mTNF-K90R may be applicable as amucosal adjuvant for HIV vaccination to induce both systemic and mucosal immune responses.

Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells.

Amorphous silica nanoparticles (nSPs), are widely used in medicines, cosmetics and food. However, due to their reduced particle size they are suspected to pose new risks induced by changes in biological reactivity and kinetics, which differ from those of bulk materials. In a previous study, we showed that silica particles with a diameter of 70 nm penetrated the stratum corneum (SC) of mouse skin and were taken up by living cells such as keratinocytes and Langerhans cells. To clarify the relationship between particle size, distribution and cellular response, we have evaluated size-dependent intracellular localization and cytotoxicity of silica particles, using the mouse epidermal Langerhans cell line XS52. On treatment with silica particles of diameters 70, 300, and 1000 nm, cellular uptake and cytotoxicity increased with reduction in particle size. These results suggest that smaller sized silica particles induced greater cytotoxicity against Langerhans cells, which was correlated with the quantity of particle uptake into the cells.

Making tracks: electronic excitation roles in forming swift heavy ion tracks.

Swift heavy ions cause material modification along their tracks, changes primarily due to their very dense electronic excitation. The available data for threshold stopping powers indicate two main classes of materials. Group I, with threshold stopping powers above about 10 keV nm(-1), includes some metals, crystalline semiconductors and a few insulators. Group II, with lower thresholds, comprises many insulators, amorphous materials and high T(c) oxide superconductors. We show that the systematic differences in behaviour result from different coupling of the dense excited electrons, holes and excitons to atomic (ionic) motions, and the consequent lattice relaxation. The coupling strength of excitons and charge carriers with the lattice is crucial. For group II, the mechanism appears to be the self-trapped exciton model of Itoh and Stoneham (1998 Nucl. Instrum. Methods Phys. Res. B 146 362): the local structural changes occur roughly when the exciton concentration exceeds the number of lattice sites. In materials of group I, excitons are not self-trapped and structural change requires excitation of a substantial fraction of bonding electrons, which induces spontaneous lattice expansion within a few hundred femtoseconds, as recently observed by laser-induced time-resolved x-ray diffraction of semiconductors. Our analysis addresses a number of experimental results, such as track morphology, the efficiency of track registration and the ratios of the threshold stopping power of various materials.