•Inactivation of AdV, CV, and PMMoV by heat and free chlorine was evaluated.•PMMoV showed high resistance to heat treatment, compared with AdV and CV.•PMMoV showed very high resistance to chlorine ...treatment, compared with AdV and CV.•PMMoV is a potential enteric virus surrogate for heat but not chlorine treatment.•PMAxx-Enhancer-PCR analysis best estimated viral disinfection efficacy.
Evaluating the efficacy of disinfection processes to inactivate human enteric viruses is important for the prevention and control of waterborne diseases caused by exposure to those viruses via drinking water. Here, we evaluated the inactivation of two representative human enteric viruses (adenovirus type 40 AdV and coxsackievirus B5 CV) by thermal or free-chlorine disinfection. In addition, we compared the infectivity reduction ratio of a plant virus (pepper mild mottle virus PMMoV, a recently proposed novel surrogate for human enteric viruses for the assessment of virus removal by coagulation‒rapid sand filtration and membrane filtration) with that of the two human enteric viruses to assess the suitability of PMMoV as a human enteric virus surrogate for use in thermal and free-chlorine disinfection processes. Finally, we examined whether conventional or enhanced viability polymerase chain reaction (PCR) analysis using propidium monoazide (PMA) or improved PMA (PMAxx) with or without an enhancer could be used as alternatives to infectivity assays (i.e., plaque-forming unit method for AdV and CV; local lesion count assay for PMMoV) for evaluating virus inactivation by disinfection processes. We found that PMMoV was more resistant to heat treatment than AdV and CV, suggesting that PMMoV is a potential surrogate for these two enteric viruses with regard to thermal disinfection processes. However, PMMoV was much more resistant to chlorine treatment compared with AdV and CV (which is chlorine-resistant) (CT value for 4-log10 inactivation: PMMoV, 84.5 mg-Cl2·min/L; CV, 1.15–1.19 mg-Cl2·min/L), suggesting that PMMoV is not useful as a surrogate for these enteric viruses with regard to free-chlorine disinfection processes. For thermal disinfection, the magnitude of the signal reduction observed with PMAxx-Enhancer-PCR was comparable with the magnitude of reduction in infectivity, indicating that PMAxx-Enhancer-PCR is a potential alternative to infectivity assay. However, for free-chlorine disinfection, the magnitude of the signal reduction observed with PMAxx-Enhancer-PCR was smaller than the magnitude of the reduction in infectivity, indicating that PMAxx-Enhancer-PCR underestimated the efficacy of virus inactivation (i.e., overestimated the infectious virus concentration) by chlorine treatment. Nevertheless, among the PCR approaches examined in the present study (PCR alone, PMA-PCR or PMAxx-PCR either with or without enhancer), PMAxx-Enhancer-PCR provided the most accurate assessment of the efficacy of virus inactivation by thermal or free chlorine disinfection processes.
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Here, we evaluated the efficacy of direct microfiltration (MF) and ultrafiltration (UF) to remove three representative human enteric viruses (i.e., adenovirus AdV type 40, coxsackievirus CV B5, and ...hepatitis A virus HAV IB), and one surrogate of human caliciviruses (i.e., murine norovirus MNV type 1). Eight different MF membranes and three different UF membranes were used. We also examined the ability of coagulation pretreatment with high-basicity polyaluminum chloride (PACl) to enhance virus removal by MF. The removal ratios of two bacteriophages (MS2 and φX174) and a plant virus (pepper mild mottle virus; PMMoV) were compared with the removal ratios of the human enteric viruses to assess the suitability of these viruses to be used as surrogates for human enteric viruses. The virus removal ratios obtained with direct MF with membranes with nominal pore sizes of 0.1–0.22 μm differed, depending on the membrane used; adsorptive interactions, particularly hydrophobic interactions between virus particles and the membrane surface, were dominant factors for virus removal. In contrast, direct UF with membranes with nominal molecular weight cutoffs of 1–100 kDa effectively removed viruses through size exclusion, and >4-log10 removal was achieved when a membrane with a nominal molecular weight cutoff of 1 kDa was used. At pH 7 and 8, in-line coagulation–MF with nonsulfated high-basicity PACls containing Al30 species had generally a better virus removal (i.e., >4-log10 virus removal) than the other aluminum-based coagulants, except for φX174. For all of the filtration processes, the removal ratios of AdV, CV, HAV, and MNV were comparable and strongly correlated with each other. The removal ratios of MS2 and PMMoV were comparable or smaller than those of the three human enteric viruses and MNV, and were strongly correlated with those of the three human enteric viruses and MNV. The removal ratios obtained with coagulation–MF for φX174 were markedly smaller than those obtained for the three human enteric viruses and MNV. However, because MS2 was inactivated after contact with PACl during coagulation pretreatment, unlike AdV, CV, MNV, and PMMoV, the removal ratios of infectious MS2 were probably an overestimation of the ability of coagulation–MF to remove infectious AdV, CV, and caliciviruses. Thus, PMMoV appears to be a suitable surrogate for human enteric viruses, whereas MS2 and φX174 do not, for the assessment of the efficacy of membrane filtration processes to remove viruses.
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•Removal of human enteric viruses by membrane filtration was evaluated.•Adsorptive interactions underlay human enteric virus removal by direct MF.•Direct UF and coagulation–MF removed 4-log10 of human enteric viruses.•Removal ratios of AdV, CV, HAV, and MNV were comparable.•PMMoV is a potential surrogate for human enteric viruses.
Here, we evaluated the removal of three representative human enteric viruses — adenovirus (AdV) type 40, coxsackievirus (CV) B5, and hepatitis A virus (HAV) IB — and one surrogate of human ...caliciviruses — murine norovirus (MNV) type 1 — by coagulation–rapid sand filtration, using water samples from eight water sources for drinking water treatment plants in Japan. The removal ratios of a plant virus (pepper mild mottle virus; PMMoV) and two bacteriophages (MS2 and φX174) were compared with the removal ratios of human enteric viruses to assess the suitability of PMMoV, MS2, and φX174 as surrogates for human enteric viruses. The removal ratios of AdV, CV, HAV, and MNV, evaluated via the real-time polymerase chain reaction (PCR) method, were 0.8–2.5-log10 when commercially available polyaluminum chloride (PACl, basicity 1.5) and virgin silica sand were used as the coagulant and filter medium, respectively. The type of coagulant affected the virus removal efficiency, but the age of silica sand used in the rapid sand filtration did not. Coagulation–rapid sand filtration with non-sulfated, high-basicity PACls (basicity 2.1 or 2.5) removed viruses more efficiently than the other aluminum-based coagulants. The removal ratios of MS2 were sometimes higher than those of the three human enteric viruses and MNV, whereas the removal ratios of φX174 tended to be smaller than those of the three human enteric viruses and MNV. In contrast, the removal ratios of PMMoV were similar to and strongly correlated with those of the three human enteric viruses and MNV. Thus, PMMoV appears to be a suitable surrogate for human enteric viruses for the assessment of the efficacy of coagulation–rapid sand filtration to remove viruses.
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•Removal of human enteric viruses by coagulation–sand filtration was evaluated.•Coagulation–sand filtration reduced human enteric viruses by about 1–3-log10.•PMMoV and human enteric virus removal ratios were comparable.•PMMoV was not inactivated by contact with PACl.•PMMoV is a potential surrogate for human enteric viruses.
Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate ...processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45μm particle size. The results show that a fully dense plate thinner than 1.8mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35–120MPa when the porosity was in the range 75–55%. Porous Ti metals fabricated by SLM were heat-treated at 1300°C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.
Summary Objective This study aimed to investigate alignment based on age in normal knees and alignment based on deformity in osteoarthritis (OA) knees using detailed radiographic parameters. Design ...Various parameters were measured from weight-bearing long leg radiographs of 1251 legs (797 normal and 454 OA knees) as a cross-sectional study. Normal knees were classified by age (young, middle aged, aged, and elderly) and symptomatic OA knees on the basis of the alignment (femorotibial angle (FTA): mild, moderate, severe and profound). The mean measurements in each group were calculated and compared within each group. Results The femoral shaft showed medially bowed curvature ( femoral bowing ) of approximately 2° in the young normal group, which shifted to lateral bowing with age. However, OA knees showed larger lateral bowing with OA grade, which might reduce the condylar-shaft angle and subsequently shifted the mechanical axis medially. Progression of mild to moderate OA might be associated with a decreasing condylar-shaft angle ( femoral condylar orientation ) and widening condylar-plateau angle ( joint space narrowing ) rather than decreasing tibial plateau flattering. Steeping of the tibial plateau inclination due to increasing tibial plateau shift ( tibial plateau compression ) rather than medial tibial bowing might be the main contributor to worsening of varus deformity in knees with severe and profound OA. Conclusions This cross-sectional study might provide the possibility of OA initiation and progression. The lateral curvature of the femoral shaft associated with aging may contribute to the initiation of varus-type OA of the knee. These changes in the femur may be followed by secondary signs of OA progression including varus femoral condylar orientation, medial joint space narrowing, and tibial plateau compression.
•Reduction of PMMoV and human enteric viruses in four full-scale DWTPs was evaluated.•The developed virus concentration method achieved high recovery (>30%) of PMMoV.•CS–RSF and C–MF reduced PMMoV by ...about 1–3-log10.•Low coagulant dosage led to low reduction ratios (1-log10) of PMMoV in C–MF.•Reduction ratios of EVs and HuNoV GII were higher than those of PMMoV in CS–RSF.
Here, we evaluated the reduction efficiencies of indigenous pepper mild mottle virus (PMMoV, a potential surrogate for human enteric viruses to assess virus removal by coagulation-sedimentation–rapid sand filtration CS–RSF and coagulation–microfiltration C–MF) and representative human enteric viruses in four full-scale drinking water treatment plants that use CS–RSF (Plants A and B) or C–MF (Plants C and D). First, we developed a virus concentration method by using an electropositive filter and a tangential-flow ultrafiltration membrane to effectively concentrate and recover PMMoV from large volumes of water: the recovery rates of PMMoV were 100% when 100-L samples of PMMoV-spiked dechlorinated tap water were concentrated to 20 mL; even when spiked water volume was 2000 L, recovery rates of >30% were maintained. The concentrations of indigenous PMMoV in raw and treated water samples determined by using this method were always above the quantification limit of the real-time polymerase chain reaction assay. We therefore were able to determine its reduction ratios: 0.9–2.7-log10 in full-scale CS–RSF and 0.7–2.9-log10 in full-scale C–MF. The PMMoV reduction ratios in C–MF at Plant C (1.0 ± 0.3-log10) were lower than those in CS–RSF at Plants A (1.7 ± 0.5-log10) and B (1.4 ± 0.7-log10), despite the higher ability of MF for particle separation in comparison with RSF owing to the small pore size in MF. Lab-scale virus-spiking C–MF experiments that mimicked full-scale C–MF revealed that a low dosage of coagulant (polyaluminum chloride PACl) applied in C–MF, which is determined mainly from the viewpoint of preventing membrane fouling, probably led to the low reduction ratios of PMMoV in C–MF. This implies that high virus reduction ratios (>4-log10) achieved in previous lab-scale virus-spiking C–MF studies are not necessarily achieved in full-scale C–MF. The PMMoV reduction ratios in C–MF at Plant D (2.2 ± 0.6-log10) were higher than those at Plant C, despite similar coagulant dosages. In lab-scale C–MF, the PMMoV reduction ratios increased from 1-log10 (with PACl basicity 1.5, as at Plant C) to 2–4-log10 (with high-basicity PACl basicity 2.1, as at Plant D), suggesting that the use of high-basicity PACl probably resulted in higher reduction ratios of PMMoV at Plant D than at Plant C. Finally, we compared the reduction ratios of indigenous PMMoV and representative human enteric viruses in full-scale CS–RSF and C–MF. At Plant D, the concentrations of human norovirus genogroup II (HuNoV GII) in raw water were sometimes above the quantification limit; however, whether its reduction ratios in C–MF were higher than those of PMMoV could not be judged since reduction ratios were >1.4-log10 for HuNoV GII and 2.3–2.9-log10 for PMMoV. At Plant B, the concentrations of enteroviruses (EVs) and HuNoV GII in raw water were above the quantification limit on one occasion, and the reduction ratios of EVs (>1.2-log10) and HuNoV GII (>1.5-log10) in CS–RSF were higher than that of PMMoV (0.9-log10). This finding supports the usefulness of PMMoV as a potential surrogate for human enteric viruses to assess virus removal by CS–RSF.
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•Removal/inactivation of HuSaV by drinking water treatment was successfully evaluated.•Integrated cell culture-PCR was developed to quantify infectious HuSaV.•Order of removal ratios by CS–RSF and ...C–MF was HuSaV = AstV ≥ MNV = PMMoV.•MNV and PMMoV are potential surrogates for HuSaV in CS–RSF and C–MF.•Order of resistance to free-chlorine disinfection was CV >> AstV > HuSaV = MNV.
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).
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•Differences in aluminum species in coagulant affected enterovirus removal.•High Alc content PACl with basicity 2.1 effectively removed enteroviruses.•Al30 species in PACl probably ...played a major role in enterovirus removal.•PV and CV removal ratios were almost the same during coagulation.•Viruses were removed mainly by coprecipitation into growing aluminum hydroxide.
We prepared different types of aluminum-based coagulants, consisting of mainly monomeric aluminum species, polymeric aluminum species, or colloidal aluminum species, to investigate the effect of aluminum hydrolyte species on the removal of two types of human enteroviruses, poliovirus (PV) type 1 and the free-chlorine-resistant virus coxsackievirus (CV) B5, from lake and river water samples during the coagulation process. We found that differences in the distribution of the aluminum hydrolyte species in the coagulant affected the removal of these enteroviruses during coagulation: the removal ratios of PV and CV observed with polyaluminum chloride (PACl) with a high colloidal aluminum content and a basicity of 2.1 (i.e., PACl-2.1c) were larger than those observed with high monomeric aluminum content coagulant (i.e., AlCl3 solution) and with high polymeric aluminum content coagulant PACl (PACl-2.1b). Unlike AlCl3 or PACl-2.1b, PACl-2.1c contains Al30 species, indicating that Al30 species probably play a major role in the removal of enteroviruses. The PV and CV removal ratios were almost identical, regardless of the coagulant type or viral quantification method used (plaque-forming unit method or real-time polymerase chain reaction method), suggesting that PV and CV behaved similarly during the coagulation process. We also experimentally confirmed that the main mechanism for virus removal was coprecipitation into growing aluminum hydroxide during charge neutralization; virus adsorption onto formed aluminum hydroxide flocs also contributed to virus removal, but played a limited role.
The apolipoprotein E (ApoE) gene is a genetic risk factor for late-onset Alzheimer's disease, in which ε4 allele carriers have increased risk compared to the common ε3 carriers. Cadmium (Cd) is a ...toxic heavy metal and a potential neurotoxicant. We previously reported a gene-environment interaction (GxE) effect between ApoE4 and Cd that accelerates or increases the severity of the cognitive decline in ApoE4-knockin (ApoE4-KI) mice exposed to 0.6 mg/L CdCl
through drinking water compared to control ApoE3-KI mice. However, the mechanisms underlying this GxE effect are not yet defined. Because Cd impairs adult neurogenesis, we investigated whether genetic and conditional stimulation of adult neurogenesis can functionally rescue Cd-induced cognitive impairment in ApoE4-KI mice. We crossed either ApoE4-KI or ApoE3-KI to an inducible Cre mouse strain, Nestin-CreER
:caMEK5-eGFP
(designated as caMEK5), to generate ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5. Tamoxifen administration in these mice genetically and conditionally induces the expression of caMEK5 in adult neural stem/progenitor cells, enabling the stimulation of adult neurogenesis in the brain. Male ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5 mice were exposed to 0.6 mg/L CdCl
throughout the experiment, and tamoxifen was administered once Cd-induced impairment in spatial working memory was consistently observed. Cd exposure impaired spatial working memory earlier in ApoE4-KI:caMEK5 than in ApoE3-KI:caMEK5 mice. In both strains, these deficits were rescued after tamoxifen treatment. Consistent with these behavioral findings, tamoxifen treatment enhanced adult neurogenesis by increasing the morphological complexity of adult-born immature neurons. These results provide evidence for a direct link between impaired spatial memory and adult neurogenesis in this GxE model.
Summary
Background
Antimelanoma differentiation‐associated protein (anti‐MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP‐ILD) in patients with clinically ...amyopathic dermatomyositis (CADM) or dermatomyositis (DM).
Objectives
We aimed to evaluate the relevance of monitoring anti‐MDA5 antibody levels for the management of RP‐ILD in patients with CADM or DM.
Methods
Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP‐ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti‐MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide.
Results
All patients achieved RP‐ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti‐MDA5 antibody levels at remission. Six (50%) patients became anti‐MDA5 antibody negative after therapy. After a mean follow‐up of 31 months, RP‐ILD relapse was observed in four (33%) patients in both the anti‐MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti‐MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti‐MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti‐MDA5 antibody exhibited symptoms of relapse during follow‐up. Therefore, reincrease in anti‐MDA5 antibody levels was associated with relapse.
Conclusions
The anti‐MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP‐ILD relapse in patients with CADM or DM.
What's already known about this topic?
Myositis‐specific autoantibodies are strongly associated with distinct clinical phenotypes; thus, they can be used to classify patients into groups with more homogeneous clinical features.
Antimelanoma differentiation‐associated protein (anti‐MDA)5 antibodies are specifically expressed in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM), and are associated with rapidly progressive interstitial lung disease (RP‐ILD).
What does this study add?
Anti‐MDA5 antibody levels correlate with disease activity.
Relapse is associated with a reincrease in anti‐MDA5 antibody levels.
What is the translational message?
Anti‐MDA5 antibody levels are a novel parameter for monitoring and a good predictor of RP‐ILD relapse in patients with CADM/DM.
Linked Comment: Jordan and Ghoreschi. Br J Dermatol 2017; 176:294–295.
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