Association of low back pain and sleep quality with presenteeism.

BACKGROUND: Low back pain (LBP) and poor subjective sleep quality (SSQ) are major risk factors for presenteeism. However, no studies have investigated whether combined LBP and poor SSQ are associated with presenteeism. AIMS: We aimed to examine whether a combination of LBP and poor SSQ is associated with presenteeism. METHODS: This cross-sectional study included 936 workers (median age, 38 years; men, 89%), with evaluated presenteeism using the work limitations questionnaire. We divided them into 'no presenteeism' and 'presenteeism' categories. The presence of LBP was defined as a numerical rating scale (NRS) score of ≥1 in current pain intensity. SSQ was assessed using a single question regarding whether the participants typically got enough sleep. We categorized the participants into four groups: (i) LBP + poor SSQ, (ii) non-LBP + poor SSQ, (iii) LBP + good SSQ and (iv) non-LBP + good SSQ. Logistic regression analysis was used to investigate the association between presenteeism and the presence of LBP and poor SSQ, adjusting for age, sex, work type, education, marital status, smoking status, body mass index and weekly working hours. RESULTS: The data from 533 participants were used for analysis (median age, 38 years; men, 90%, response rate, 66%). Combined LBP and poor SSQ were significantly associated with presenteeism (non-LBP + poor SSQ: adjusted odds ratio = 0.56, 95% CI 0.32-0.96; LBP + good SSQ: 0.33, 0.20-0.56; non-LBP + good SSQ: 0.29, 0.18-0.48). CONCLUSIONS: Evaluating both LBP and SSQ may be beneficial in considering presenteeism.

The motion and distribution of the gas in the central 300 pc of the galaxy as revealed by spectra of H3.

Spectroscopy of absorption lines of H3+ in the central molecular zone (CMZ) of the Galaxy show that a previously largely unknown component of the interstellar medium there, warm (T∼200 K) and diffuse (n ≲ 102 cm-3) gas, makes up a large fraction of the volume of the CMZ, and that this gas is moving radially outward from the centre. These discoveries upend the generally accepted understanding that the interstellar environment of the CMZ comprises almost entirely an ultra-hot plasma and dense molecular clouds. The radial momentum associated with the diffuse gas in the CMZ exceeds that of the ejecta of thousands of core-collapse supernovae and implies some extraordinary past activity in the centre, possibly associated with the supermassive black hole, Sgr A*. We speculate that within approximately 106 years, gravity could halt the expansion of the diffuse gas and that contraction towards the centre could then commence. This article is part of a discussion meeting issue 'Advances in hydrogen molecular ions: H3+, H5+ and beyond'.

Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment.

BACKGROUND: Interleukin (IL)-25 is a member of the IL-17 family, which can promote and augment T-helper (Th) type 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases. OBJECTIVES: To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL). METHODS: Expression and location of IL-25 in lesional skin was investigated with immunohistochemistry. The effect of various cytokines on IL-25 production from normal human epidermal keratinocytes was assessed by quantitative reverse-transcription real-time polymerase chain reaction. Serum IL-25 levels were measured by enzyme-linked immunosorbent assay. The direct effect of IL-25 on tumour cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in patients with Sézary syndrome. RESULTS: IL-25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL-4 and IL-13, and periostin induced IL-25 expression by normal human epidermal keratinocytes. Serum IL-25 levels were increased in patients with advanced CTCL and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL-25R and its expression was augmented by stimulation with IL-25. IL-25 enhanced IL-13 production from MyLa cells via phosphorylation of signal transducer and activator of transcription 6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL-25R and showed increase of IL-13 production by IL-25. CONCLUSIONS: Th2 cytokines highly expressed in CTCL lesional skin induce IL-25 production by epidermal keratinocytes, which may, in turn, lead to formation of a Th2-dominant microenvironment through the direct induction of IL-13 by tumour cells.

The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor: Outcomes and successful predictors of ITI treatment.

INTRODUCTION: Immune tolerance induction (ITI) was the primary therapeutic approach to eradicate inhibitors in haemophilia patients. Several large ITI registries had been reported, but successful predictors of ITI outcome are still debated. No reports are available on large ITI studies in non-caucasian countries. AIM: We designed a retrospective cohort study of ITI in Japanese haemophilia patients with inhibitor. METHODS: Retrospective data were collected from 155 haemophilia (H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITI outcome was centrally reviewed. We defined "success" as undetectable inhibitor after 2 consecutive measurements. RESULTS: The ITI success rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITI using von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITI was a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). CONCLUSION: The results provided potentially important information for improving future success rates for ITI in inhibitor patients.

Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma.

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.

Distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) in the human testis and in testicular germ cell tumors.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide expressed in the central nervous system and peripheral organs. Previous studies revealed the role and distribution of PACAP in the rodent testis, however, its presence in the human testis and in testicular germ cell tumors is not known. We used RT-PCR and immunohistological observations to investigate whether human testicular tissue and testicular germ cell tumors contain PACAP. The mRNAs for PACAP and its receptors were detected in total RNA extracted from human testes. PACAP immunoreactivity was observed in spermatogonia and spermatids from normal testes. In contrast, diffuse PACAP immunopositivity was observed in seminoma tumor cells, while only faint immunoreactivity was observed in embryonal carcinoma cells. Our data suggest that PACAP may play a role in human spermatogenesis and in testicular germ cell tumor development.

Possible involvement of A2A and A3 receptors in modulation of insulin secretion and ß-cell survival in mouse pancreatic islets.

Adenosine A1, A2A, A2B and A3 receptor mRNAs were found to be expressed in mouse pancreatic islets and Beta-TC6 cells but their physiological or pharmacological actions are not fully clarified. We showed that adenosine (100 µM) augmented insulin secretion by islets in the presence of either normal (5.5 mM) or a high concentration of glucose (20 mM). The augmentation of insulin secretion in the presence of high glucose was blocked by an A2A antagonist, but not by A2B and A3 antagonists, while an A1 antagonist potentiated the adenosine effect. An adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) as well as A1, A2A and A3 receptor agonists also produced stimulation. On the other hand, an A3 agonist markedly reduced Beta-TC6 cell proliferation and the islet cell viability, while adenosine and NECA did not. The effect of A3 agonist was partially blocked by the A3 antagonist. In addition, treatment with the A3 agonist produced a small but significant extent of apoptosis in Beta-TC6 cells as judged by terminal transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. These results combined together suggested that like the A1 receptor, activation of A2A receptors by adenosine results in augmented insulin secretion, while the A3 receptor is involved in modulation of the survival of pancreatic ß-cells.

Investigation of removal and inactivation efficiencies of human sapovirus in drinking water treatment processes by applying an in vitro cell-culture system.

Here, we examined the efficiencies of drinking water treatment processes for the removal and inactivation of human sapovirus (HuSaV). We applied a recently developed in vitro cell-culture system to produce purified solutions of HuSaV containing virus concentrations high enough to conduct virus-spiking experiments, to develop an integrated cell culture-polymerase chain reaction (ICC-PCR) assay to quantify the infectivity of HuSaV, and to conduct virus-spiking experiments. In virus-spiking coagulation-sedimentation-rapid sand filtration (CS-RSF) and coagulation-microfiltration (C-MF) experiments, HuSaV removals of 1.6-3.7-log10 and 1.2->4.3-log10, respectively, were observed. The removal ratios observed with CS-RSF were comparable and correlated with those of murine norovirus (MNV, a widely used surrogate for human noroviruses) and pepper mild mottle virus (PMMoV, a potential surrogate for human enteric viruses in physical and physicochemical drinking water treatment processes), and those observed with C-MF were higher than but still correlated with those of MNV and PMMoV, indicating that MNV and PMMoV are both potential surrogates for HuSaV in CS-RSF and C-MF. For astrovirus (AstV, a representative human enteric virus), removal ratios of 1.8-3.3-log10 and 1.1->4.0-log10 were observed with CS-RSF and C-MF, respectively. The removal ratios of AstV observed with CS-RSF were comparable and correlated with those of PMMoV, and those observed with C-MF were higher than but still correlated with those of PMMoV, indicating that PMMoV is a potential surrogate for AstV in CS-RSF and C-MF. When the efficacy of chlorine treatment was examined by using the developed ICC-PCR assay, 3.8-4.0-log10 inactivation of HuSaV was observed at a CT value (free-chlorine concentration [C] multiplied by contact time [T]) of 0.02 mg-Cl2·min/L. The infectivity reduction ratios of HuSaV were comparable with those of MNV. For AstV, 1.3-1.7-log10 and >3.4-log10 inactivation, as evaluated by ICC-PCR, was observed at CT values of 0.02 and 0.09 mg-Cl2·min/L, respectively. These results indicate that HuSaV and AstV are both highly sensitive to chlorine treatment and more sensitive than a chlorine-resistant virus, coxsackievirus B5 (1.3-log10 inactivation at a CT value of 0.4 mg-Cl2·min/L, as evaluated by the ICC-PCR assay).

Unpaired electron species in thin films of calf-thymus DNA molecules induced by nitrogen and oxygen K-shell photoabsorption.

The mechanism of DNA modification induced by K-shell photoabsorption of nitrogen and oxygen atoms was investigated by electron paramagnetic resonance and x-ray absorption near edge structure measurements of calf thymus DNA. A g factor of 2.000 for the unpaired electron species, which only arises during irradiation, was measured. The EPR intensities for DNA zwere twofold times larger than those estimated based on the photoabsorption cross section. This suggests that the DNA film itself forms unpaired electron species through the excitation of enhanced electron recapturing, known as the postcollision interaction process.

Antiferromagnetic spin fluctuations above the dome-shaped and full-gap superconducting states of LaFeAsO1-xFx revealed by (75)As-nuclear quadrupole resonance.

We report a systematic study by (75)As nuclear-quadrupole resonance in LaFeAsO(1-x)F(x). The antiferromagnetic spin fluctuation found above the magnetic ordering temperature T(N) = 58 K for x = 0.03 persists in the regime 0.04 ≤ x ≤ 0.08, where superconductivity sets in. A dome-shaped x dependence of the superconducting transition temperature T(c) is found, with the highest T(c) = 27 K at x = 0.06, which is realized under significant antiferromagnetic spin fluctuation. With increasing x further, the antiferromagnetic spin fluctuation decreases, and so does T(c). These features resemble closely the cuprates La(2-x)Sr(x)CuO(4). In x = 0.06, the spin-lattice relaxation rate (1/T(1)) below T(c) decreases exponentially down to 0.13T(c), which unambiguously indicates that the energy gaps are fully opened. The temperature variation of 1/T(1) below T(c) is rendered nonexponential for other x by impurity scattering.

An analysis of factors affecting the incidence of inhibitor formation in patients with congenital haemophilia in Japan.

Studies conducted in European and North American countries have demonstrated that various factors including races affect the frequency of inhibitor formation in haemophilia patients. The present study was undertaken to analyse factors affecting the incidence of inhibitor formation in Japanese haemophilia A and B patients. Analytical data were retrospectively collected from haemophilia A and B patients born after 1988, the year when monoclonal antibody-purified factor VIII products were first marketed in Japan. Various data were collected from 184 patients (153 cases of haemophilia A; 31 cases of haemophilia B). The sample size of haemophilia B cases was too small to reveal any significant differences between the inhibitor formation group and the inhibitor-free group in any of background variables. For patients with haemophilia A, on the other hand, univariate analysis identified the severity of haemophilia and a positive family history of inhibitor development as risk factors for the formation of inhibitors. In analyses of the clotting factor products used, the incidence of inhibitor formation did not differ significantly between the group treated with plasma-derived products (29.7%) and the group treated with recombinant products (25.0%). When background variables were compared, age was higher in the group treated with plasma-derived products but none of the other background variables differed between the two groups. These results suggest that in Japanese haemophilia patients, the type of clotting factor preparations used for therapy has not influenced the incidence of inhibitor formation.

Genetic diversity of genogroup IV noroviruses in wastewater in Japan.

AIMS: To investigate the prevalence, seasonality and genetic diversity of genogroup IV noroviruses (GIV NoVs) in wastewater in Japan. METHODS AND RESULTS: Untreated and treated wastewater samples were collected monthly for a year from a wastewater treatment plant in Japan. The concentrated wastewater samples were examined for the presence of GIV NoV genomes with seminested RT-PCR assay targeting partial capsid gene. Among 12 untreated and 12 treated wastewater samples tested, GIV NoV genomes were detected in three (25%) untreated and two (17%) treated wastewater samples with a high positive ratio in winter season. Genetic analysis revealed that the GIV NoVs in the wastewater samples were genetically diverse and were classified into three different genetic clusters. CONCLUSIONS: Frequent detection of GIV NoVs in winter season, which is a common epidemic period of human NoVs in Japan, indicates that GIV NoVs exhibit temporal trends similar to GI and GII NoVs. Based on the partial capsid gene sequences, we identified several unique GIV NoV strains belonging to the novel genetic cluster, demonstrating that GIV NoVs are more genetically diverse than previously appreciated. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings provide novel evidence of considerable genetic diversity among the GIV NoV strains.

HLA alleles and haplotypes distribution in Dai population in Yunnan province, Southwest China.

Human leukocyte antigen (HLA) analysis would be a useful tool to trace the origin of modern humans. In this study, we provided the first four digital HLA-A, -B, -C and -DRB1 allele and haplotype data in the Dai ethnic population, which is a unique and representative Kam-Tai-speaking ethnic minority living in the Yunnan province of Southwestern China. Our results showed that the Dai population has unique HLA characteristic that are most closely related to the Southeastern Asia group and similar to the Kam-Tai speaking populations in China and Thailand.

Developmental alterations in expression and subcellular localization of antizyme and antizyme inhibitor and their functional importance in the murine mammary gland.

Ornithine decarboxylase (ODC), antizyme (AZ), and antizyme inhibitor (AIn) play a key role in regulation of intracellular polyamine levels by forming a regulatory circuit through their interactions. To gain insight into their functional importance in cell growth and differentiation, we systematically examined the changes of their expression, cellular polyamine contents, expression of genes related to polyamine metabolism, and beta-casein gene expression during murine mammary gland development. The activity of ODC and AZ1 as well as putrescine level were low in the virgin and involuting stages, but they increased markedly during late pregnancy and early lactation when mammary cells proliferate extensively and begin to augment their differentiated function. The level of spermidine and expression of genes encoding spermidine synthase and AIn increased in a closely parallel manner with that of casein gene expression during pregnancy and lactation. On the other hand, the level of spermidine/spermine N(1)-acetyltransferase (SSAT) mRNA and AZ2 mRNA decreased during those periods. Immunohistochemical analysis showed the translocation of ODC and AIn between the nucleus and cytoplasm and the continuous presence of AZ in the nucleus during gland development. Reduction of AIn by RNA interference inhibited expression of beta-casein gene stimulated by lactogenic hormones in HC11 cells. In contrast, reduction of AZ by AZsiRNA resulted in the small increase of beta-casein gene expression. These results suggested that AIn plays an important role in the mammary gland development by changing its expression, subcellular localization, and functional interplay with AZ.

Genetic link among Hani, Bulang and other Southeast Asian populations: evidence from HLA -A, -B, -C, -DRB1 genes and haplotypes distribution.

Human leucocyte antigen (HLA) genetic characteristic of different ethnic minorities would be useful for tracing the origin of modern human HLA matching in transplantation and disease associations. In this study, we reported HLA-A, -B, -C and -DRB1 alleles and haplotypes in the Bulang and Hani populations of southwestern China using a high-resolution polymerase chain reaction-Luminex (PCR-Luminex) typing method. A total of nine HLA-A, 22 HLA-B, 13 HLA-C and 18 HLA-DRB1 alleles were identified in the Bulang population, and 11 HLA-A, 25 HLA-B, 14 HLA-C and 19 HLA-DRB1 alleles were in the Hani population. Compared with other populations, the predominant A*1101-B*1502-DRB1*1202 haplotype in the Bulang and Hani populations was also common in Jinuo, Wa, Dai, Maonan and Vietnamese populations. The distribution of HLA genes indicate that Bulang and Hani populations belong to the Southeast Asia group and they have maintained their original genetic characteristics and kept a long genetic distance from other populations owing to founder effects and subsequent geographic isolation. In addition, the close relationship among ethnic groups in Yunnan province and the Thai and Vietnamese populations were confirmed, whereas the Mon-Kmer-speaking populations shared other common HLA alleles and haplotypes compared with other linguistic groups.

Probing spin correlations using angle-resolved photoemission in a coupled metallic/Mott insulator system.

A nearly free electron metal and a Mott insulating state can be thought of as opposite ends of the spectrum of possibilities for the motion of electrons in a solid. Understanding their interaction lies at the heart of the correlated electron problem. In the magnetic oxide metal PdCrO2, nearly free and Mott-localized electrons exist in alternating layers, forming natural heterostructures. Using angle-resolved photoemission spectroscopy, quantitatively supported by a strong coupling analysis, we show that the coupling between these layers leads to an "intertwined" excitation that is a convolution of the charge spectrum of the metallic layer and the spin susceptibility of the Mott layer. Our findings establish PdCrO2 as a model system in which to probe Kondo lattice physics and also open new routes to use the a priori nonmagnetic probe of photoemission to gain insights into the spin susceptibility of correlated electron materials.