Human T lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy, and adult T cell lymphoma/leukemia (ATL/L). Pulmonary complications such as alveolitis and bronchiectasis were found in individuals who develop TSP/HAM due to chronic inflammation. These individuals showed image anomalies in CT scans and changes in pulmonary function parameters distinctive of pulmonary disease. Furthermore, infected individuals have a greater susceptibility to pulmonary tuberculosis either due to changes in the innate immune response, in asymptomatic carriers, or to an opportunistic disease linked to immunodepression, in individuals who develop ATL/L. This summary addresses the general lack of knowledge regarding the relationship between HTLV-1 and pulmonary diseases and provides direction for future work. Human lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy, and adult T-cell lymphoma/leukemia (ATL/L) . VariousA relationship between HTLV-1 and pulmonary diseases was established with reports of individuals with TSP/HAM who exhibit pulmonary diseases with characteristics of lymphocytic inflammatory infiltrate  and lateDespite several studies linked HTLV-1 to pulmonary diseases, the scientific community still has several questions to solve about the physiopathology of HTLV-1 infection and understand why do some HTLV-1-infected individuals have pulmonary damage while others do not. A recent study in Australia related highest mortality rates among subjects infected with HTLV-1c subtype . AnotherThis study aims to improve the understanding of lung disease in patients infected with HTLV, through a review of publications on this neglected theme, gathering information from studies on the area including recent reports.Patients with HTLV-1 with pulmonary involvement exhibit an elevation of T lymphocytes in bronchoalveolar lavage fluid (BALF) and consequent pulmonary inflammation, which is mediated by a Th1 type immune response, characterized by the presence of soluble IL-2 receptors (IL-2R), increased levels of interleukins IL-2, IL-12, and interferon (IFN-γ) . An incrFigure 1).Another characteristic of pulmonary disorders in patients with HTLV-1 is the presence of alveolitis  and lymphocytosis (CD4+ and CD25+) , in anotA local production of ICAM-1, cytokines , and chemokines (CCL2 and CCL5) is believed to be induced by the NF-κβ and AP-1 pathways in HTLV-1-infected epithelial cells; this mechanism can explain, in part, the pathogenesis of HTLV-1-related lung diseases characterized by the production of inflammatory cytokines and chemokines, and expression of adhesion molecules by the infected cells . PatientTax and HBZ in BALF cells of patients with HTLV-1. Additionally, there is a positive correlation between high levels of Foxp3 mRNA and a high proportion of lymphocytes in BALF of patients with HTLV-1-related lung diseases. These findings suggest the involvement of regulatory T cells in the pathogenesis of pulmonary inflammation  induced by Tax, which is responsible for the activation and circulation of inflammatory cells and their recruitment to the lungs; and by ICAM, which promotes leukocyte adhesion to the pulmonary endothelium . Other fammation .There are findings showing that HTLV-1-specific CD8+ T cells accumulate in the BALF at a higher concentration than that in the peripheral blood of patients infected with HTLV-1, suggesting that selective infiltration occurs in the lungs and specific immune responses occur in lung tissues . This hyFigure 2B).Patients with HTLV-1-associated inflammatory diseases  exhibit more substantial lung tissue injury, as evidenced by the significantly increased levels of lymphocytes (CD4+ and CD25+), cytokines , and inflammatory chemokines (MIP-1α and IP-10) as well as cell adhesion molecules (ICAM-1) in the BALF compared to the levels observed in asymptomatic carriers , 2013. T> 1000 copies per 105 peripheral blood leukocytes) when compared to those infected with the same virus but with lower proviral load or uninfected subjects. This mortality was largely due to bronchiectasis-related deaths  , high morculosis .This was also demonstrated in the Northeast Region of Brazil  and in aA cohort study conducted in Salvador, Bahia, Brazil, found a higher incidence density of 3,3 per 1,000 people in an HTLV-1 infected group. The higher risk of PT was found mainly in individuals aged 31 to 50 years . In anotM. tuberculosis .The increased susceptibility to infection appears to be linked to a change in the innate immune response associated with HTLV-1, which facilitates the multiplication of the etiological agent of PT and leads to a more severe disease . HTLV-1 rculosis . Furtherividuals . The exaFigure 2A). It causes more susceptibility to this individuals develop opportunistic infections by several pathogens  express of FoxP3+ phenotype anti-inflammatory cytokines, such as IL-10, suggesting an immunoregulatory function leading to immunodeficiency   (n = 19) (Computed tomography (CT) abnormalities in patients with HTLV-1 are predominantly parenchymal, especially centrilobular nodules, thickening of bronchovascular bundles, ground-glass opacity, and bronchiectasis. There is an association between HTLV-1 infection and bronchiectasis . In a ca= 0.004) , and thi= 0.004) . In a st(n = 19) .In patients with HAM/TSP, combinations of alterations are frequently found in CT, including bronchiectasis and pleural thickening, bronchiectasis and parenchymal bands, bronchiectasis and interlobular septum thickening, bronchiectasis and centrilobular nodules, and centrilobular nodules and parenchymal bands, with some patients presenting three or more changes . Other iA study involving indigenous individuals in Australia (840 patients) shows higher rates of CT with bronchiectasis between the individuals infected with high proviral loads. All individuals were infected with HTLV-1c, and although HTLV-1 associated bronchiectasis affects diverse genetic backgrounds, the infected individuals in Japan use to have subclinical lung disorders. It was demonstrated that the HTLV-1 infected indigenous adults have more diffuse bronchiectasis and a higher HTLV-1c proviral load, which correlates with more extensive injuries and deaths due to bronchiectasis. The authors demonstrate that rates of bronchiectasis and bronchitis/bronchiolitis were significantly higher in this population than among the healthy individuals  they propose that this viral subtype is linked with major lung injury lesions between this population .Also, certain studies that try to correlate the CT image findings with alterations in the respiratory function. In a study with asymptomatic individuals, no difference in parameters of respiratory function was found when compared to those of a healthy control group. These results suggest that the HTLV associated pulmonary abnormalities previous described in CT images, cells, and BALF could not affect the pulmonary function, but in this study, the parameters were not evaluated in symptomatic individuals .1) (74.4% of predicted) and 64.1% forced expiratory volume in one second/forced vital capacity (FEV1/FVC)   due AdulEV1/FVC) .1, and maximum voluntary ventilation (MVV). Low VC is related to restrictive lung disease, a reduction of FEV1 is correlated with airway obstruction, and a reduction of MVV is related to both conditions and to reduced mobility. Therefore, it is possible that the lesions found in imaging studies associated with reduced mobility affecting patients with HAM/TSP play a key role in the development of obstructive or restrictive lung diseases , FEVdiseases . It is p1 in seropositive to seronegative patients. The reduction in the number of pulmonary CD4+ T lymphocytes reduces the ability to generate specific antigen responses, resulting in immunosuppression and therefore explaining the vulnerability to infections even in the presence of immunologic effectors. The early complement diagnostic of pulmonary function could inform an adequate intervention to avoid possible complications  and chemokines (MIP-1α and IP-10), which damage lung tissues via the infiltration of activated T CD8 + lymphocytes with an altered immune response pattern due to the expression of Tax and HBZ. HTLV-1 causes persistent inflammation in all organs in which it manifests. In the lungs, the characteristic fibrosis of these lesions is related to chronic inflammation, leading to the activation of pulmonary fibroblasts.M. tuberculosis.The HTLV-1 virus appears to have a peculiar tropism in relation to the lungs that is expressed by the pulmonary lesions found in individuals with HAM/TSP. In most cases, pulmonary symptomatology in patients with HTLV-1 is subclinical; however, further investigations are necessary to determine the evolution of the pathology in individuals with advanced pulmonary disease. The pulmonary inflammatory process related to HTLV-1, when associated with other inflammatory characteristics, may lead to a worse prognosis. Individuals infected with more aggressive viral subtypes and high proviral loads shows more severe lung injury, e.g., cases of Australian indigenous infected with HTLV-1c, ATL/L patients showed lung injury due to opportunistic infections, as Tuberculosis and Pneumonia caused by HTLV-1 infection induced immunodeficiency. On the other hand, the asymptomatic carriers seem to suffer from milder immunodeficiency due to the development of coinfection with The findings of lung lesions are more prominent in patients with some degree of clinical presentation (HAM/TSP), suggesting that lesions at the pulmonary level follow lesions in other organs, as well as the systemic inflammatory process. Accordingly, it may be appropriate to consider HTLV-1 infection as a systemic inflammatory disease of chronic evolution. Pulmonary lesions in asymptomatic individuals appear to be explained by an inaccurate classification, including in this category individuals with only one symptom. To better determine the course of the infection, well-defined classification criteria should be used. We believe that the most appropriate classification is the Many studies made until now still do not allow a comprehensive understanding of pathophysiological mechanisms and their links to specific clinical presentations of patients infected by HTLV-1. There are mainly observational studies, who did not characterize the various mechanisms involved in lung alterations associated with HTLV-1 infection, these studies have limited scope or describe only isolated clinical cases. They do not answer the question about the evolution and physiopathology of the HTLV-1 related pulmonary disease, which remains unclear. Prospective studies and case-control studies are required to understand these mechanisms better, properly characterize the pulmonary involvement associated with HTLV-1 infection and to design strategies for disease treatment or management. This review intends to contribute with this reflections and provides direction for the future investigations.LF, AF, JQ, and AD conceptualized and designed the study, contributed to data acquisition, data interpretation, drafting of the manuscript, final approval of the version to be published, and drawing the figures. LF, AF, VN, AD, and JQ contributed to data interpretation, drafting of the manuscript, provided study supervision, contributed to data interpretation, and provided critical revision of the manuscript for important intellectual content. LF and AD contributed to data acquisition or analysis and editing of the manuscript for intellectual content.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DG and handling Editor declared their shared affiliation at time of review.


Cryptosporidium spp. and Giardia duodenalis into humans varies according to species/genotypes of the pathogens. Although infections with both parasites are recorded in Egypt, few data are available on the distribution of Cryptosporidium species and G. duodenalis genotypes. The present study assessed the occurrence and genetic diversity of Cryptosporidium spp. and G. duodenalis in Egyptian children.The transmission of Cryptosporidium spp., respectively, whereas PCR and sequence analyses of the triose phosphate isomerase, glutamate dehydrogenase and β-giardin genes were used to detect and genotype Giardia duodenalis.In the present study, 585 fecal specimens were collected from children eight years old and younger in three provinces  during March 2015 to April 2016. PCR-RFLP analysis of the small subunit rRNA gene and sequence analysis of the 60 kDa glycoprotein gene were used to detect and subtype Cryptosporidium spp. and G. duodenalis were 1.4% and 11.3%, respectively. The Cryptosporidium species identified included C. hominis and C. parvum, each with three subtype families. The C. hominis subtypes were IbA6G3 (n = 2), IdA17 (n = 1), IdA24 (n = 1) and IfA14G1R5 (n = 1), while C. parvum subtypes were IIdA20G1 (n = 1), IIaA15G2R1 (n = 1), and IIcA5G3a (n = 1). The G. duodenalis identified included both assemblages A (n = 31) and B (n = 34). All G. duodenalis assemblage A belonged to the anthroponotic sub-assemblage AII, while a high genetic heterogeneity was seen within assemblage B.The overall infection rates of Cryptosporidium spp. and G. duodenalis in Egypt and the potential importance of anthroponotic transmission in the epidemiology of both pathogens.Data from this study are useful in our understanding of the genetic diversity of The online version of this article (10.1186/s13071-018-2981-7) contains supplementary material, which is available to authorized users. Cryptosporidium spp. and Giardia duodenalis are common etiological agents in humans and animals globally [Cryptosporidium is second only to rotavirus in causing diarrhea and death in children in developing countries, responsible for 2.9 million cases annually in children aged < 24 months in the sub-Saharan Africa [G. duodenalis is responsible for ~280 million cases of intestinal diseases per year worldwide [Cryptosporidium spp. and G. duodenalis are transmitted in humans through the fecal-oral route, either directly by person-to-person transmission or contact with infected animals or indirectly via food-borne or water-borne transmission following ingestion of contaminated food or water [Diarrhea is a worldwide public health issue, responsible for 2.3 billion sicknesses and 1.3 million deaths in 2015. It is the second most important cause of death among children under 5 years of age [orldwide . CryptosCryptosporidium species have been recognized, but humans are mostly infected with C. parvum and C. hominis [G. duodenalis genotypes (frequently referred as assemblages) identified using molecular tools, assemblages A and B are responsible for most human infections. Between them, assemblage A is also commonly seen in animals and thus could be responsible for zoonotic G. duodenalis infection [Currently, over 30  hominis  with the hominis . Similarnfection , 9.C. parvum are more frequently found in certain host species, such as IIa in cattle, IIc in humans, and IId in sheep and goats. While all three subtype families of C. parvum can infect humans, their distribution in humans differs geographically and socioeconomically, probably as a result of differences in the importance of various transmission routes [G. duodenalis assemblage A, with AI subtypes being more commonly found in domestic animals, AII subtypes mostly in humans, and AIII subtypes almost exclusively in wild ruminants [Cryptosporidium spp. and G. duodenalis at species and subtype levels are helpful in improving our understanding of cryptosporidiosis and giardiasis epidemiology [It has been noted that some subtype families of n routes . Similaruminants , 9. Thusemiology .Cryptosporidium and G. duodenalis genotypes and subtypes in humans in Egypt. Previous microscopic and serologic studies had shown a common occurrence of Cryptosporidium spp. and G. duodenalis in humans in the country [Cryptosporidium spp. and G. duodenalis in a small number of human clinical specimens [Cryptosporidium and G. duodenalis genotypes and subtypes in kindergarten age children (≤ 8 years) in order to improve our understanding of the transmission of these parasites in Egypt.Compared with other countries, few data exist on the occurrence of  country –12. Onlypecimens –18. The This study was conducted during March 2015 to April 2016 in El-Dakahlia, El-Gharbia, and Damietta provinces, Egypt  and manufacturer-recommended procedures. DNA was eluted in 100 μl molecular grade water and stored at -20 °C prior to molecular analyses.Cryptosporidium spp. using a nested polymerase chain reaction (PCR) targeting a ∼834 bp fragment of the small subunit rRNA (SSU rRNA) gene [C. parvum- and C. hominis-positive specimens were further analyzed by a nested PCR targeting a ∼850 bp fragment of the 60 kDa glycoprotein (gp60) gene [C. baileyi and C. parvum DNA as the positive control for SSU rRNA and gp60 PCR, respectively, and reagent-grade water as the negative control. Cryptosporidium species in the positive specimens were identified by RFLP analysis of the secondary SSU rRNA PCR products using restriction enzymes SspI  and VspI  as described [C. hominis and C. parvum subtypes were identified by bidirectional DNA sequence analysis of the secondary PCR products of the gp60 gene [All specimens were examined for NA) gene . C. parv60) gene . Each anescribed . C. homip60 gene .G. duodenalis using nested-PCR assays targeting 3 genetic loci, including triose phosphate isomerase (tpi) [bg) [gdh) [G. duodenalis-positive when the expected PCR product was obtained from at minimum one of the three loci. G. duodenalis genotypes and subtypes were identified by bidirectional DNA sequence analysis of the secondary PCR products.All 585 specimens were analyzed for se (tpi) , beta-gipi) [bg)  and glutg) [gdh)  genes. Swww.technelysium.com.au/ChromasPro.html). They were aligned against each other and reference sequences [http://www.clustal.org/) to identify Cryptosporidium subtypes and G. duodenalis assemblages and subtypes. Multilocus genotypes (MLGs) of G. duodenalis assemblage A were identified based on nucleotide sequences at the tpi, bg, and gdh loci, using the established nomenclature system [All positive secondary PCR products generated in the study were purified using Montage PCR filters  and sequenced in both directions on an ABI 3130 Genetic Analyzer . Nucleotide sequences generated were edited and assembled using the ChromasPro software , gender (boys and girls), residency , and children with and without gastrointestinal symptoms  or animal contact (with and without). The relationship between age and diarrhea was assessed using the nonparametric Kendall’s tau_b and Spearman’s rho tests. The statistical analysis was performed using the SPSS software version 20.0 . Differences were considered significant at P < 0.05.The Chi-square test was used to compare Cryptosporidium spp. and G. duodenalis, respectively. No concurrence of the two pathogens was detected in any of the specimens.Of the 585 fecal specimens examined in this study from kindergarten children, 8 (1.4%) and 66 (11.3%) were positive for Cryptosporidium (2.7%) and G. duodenalis (14.2%) infections were detected in children of age ≤ 3 years and 4 years, respectively; neither Cryptosporidium nor G. duodenalis were detected in children of 8 years in age  .By age, the highest rates of odenalis 4.2% infeCryptosporidium infection rate was 2.3% and 1.2 % in children with and without diarrhea, respectively . In contrast, the infection rate of G. duodenalis was significantly higher in diarrheic children (19.1%) than in non-diarrheic ones (9.9%) . There was also an insignificantly higher occurrence of Cryptosporidium spp. in children with abdominal pain (2.0%) than those without it (0.4%) . In contrast, G. duodenalis infection rates were similar between the two groups . The infection rates of Cryptosporidium and G. duodenalis were similar between children with  and without  animal contact . In addition, children in rural areas had Cryptosporidium and G. duodenalis infection rates  similar to those in urban areas  was higher than in El-Gharbia (1.1%) and Damietta (0.8%). In contrast, the infection rate of G. duodenalis was higher in El-Dakahlia (11.4%) and El-Gharbia (12.7%) than in Damietta .There was a significant negative correlation between age and diarrhea , Id (in two specimens) and If (in one specimen), while the C. parvum subtypes families included IIa, IIc, and IId (in one specimen each). There were two subtypes (IdA17 and IdA24) in the subtype family Id and one subtype each in subtype families Ib (IbA6G3 in two specimens) and If (IfA14G1R5 in one specimen). The C. parvum subtypes detected included IIaA15G2R1, IIdA20G1 and IIcA5G3a (in one specimen each).The RFLP analysis of the ns Table . Three sG. duodenalis-positive specimens, 56 were positive in tpi PCR, 48 in gdh PCR, and 55 in bg PCR. Among them, 31 (47.0%) had assemblage A and 34 (51.5%) had assemblage B, with one specimen (1.5%) being positive for both assemblages A and B  in GenBank  in GenBank, while at the bg locus, 22 were identical to the A3 subtype (AY072724), 4 were identical to the A2 subtype (AY072723), and 2 belonged to a new subtype A9 (MG746615). Among the assemblage A specimens, 4 and 18 specimens had MLGs AII-1 and AII-9, respectively. In addition, one new MLG AII-15 was identified in one specimen , JF918523 (n = 2), KT948107 (n = 2), KT948111 (n = 2), AB781127 (n = 1), AY368163 (n = 1), JF918519 (n = 1), KY696816 (n = 1) or KX468984 (n = 1), while 14 specimens generated sequences of one of the 10 new types (MG787950–MG787959). Similarly, of the 23 specimens that were positive for assemblage B at the gdh locus, 14 had sequences identical to either KY696804 (n = 4), KM190714 (n = 3), KP687771 (n = 3), U362955 (n = 2), EF507654 (n = 1) or KP687770 (n = 1), while the remaining nine specimens produced sequences of one of the eight new types (MG746604–MG746611). At the bg locus, 24 specimens generated sequences identical to either KU504732 (n = 6), KY696836 (n = 5), JF918485 (n = 3), KU504720 (n = 2), KU504707 (n = 2), MF169196 (n = 2), AB480877 (n = 1), KT948086 (n = 1), KU504731 (n = 1) or KY483962 (n = 1), whereas three specimens yielded sequences that belonged to one of the three new subtypes (MG746612–MG746614). Altogether, 44 specimens were successfully subtyped at all three genetic loci, forming 3 MLGs of assemblage A and 20 MLGs of assemblage B.Much higher genetic diversity was seen in assemblage B  was observed in children in China [Cryptosporidium spp. in this study might be due to the older age of children enrolled in this study. In developing countries, children under two years have the highest occurrence of Cryptosporidium spp. [. In addition, children participating in the study were healthy kindergartners rather than in-patients and outpatients in most previous studies. As expected, children with diarrhea had higher occurrence of both Cryptosporidium spp. and G. duodenalis in this and earlier studies [In the present study, the overall infection rates of ectively –27. A prectively , 17. In ectively . Similarin China , 30. Theium spp. . In addi studies . These aC. hominis and C. parvum in children. This is similar to results of other studies in Egypt [C. hominis in children in this and other African studies suggests that anthroponotic transmission is important in cryptosporidiosis epidemiology in this area, although the occurrence of zoonotic infections could not be fully excluded [C. parvum, which is considered a human-adapted C. parvum subtype [C. parvum in children, which were only identified in two of the eight cryptosporidiosis cases in this study [Cryptosporidium spp. in Egyptian children.In our study, we identified only in Egypt , 14, 32.excluded , 32–35.  subtype . In contis study –40. The Cryptosporidium spp. were detected in only a few specimens in the study, we recorded seven subtypes in six families, including Ib, Id and If subtype families of C. hominis and IIa, IIc, and IId subtype families of C. parvum. This indicates that the transmission of Cryptosporidium in the study area is intensive. It has been reported that subtype families Ia, Ib, Id and Ie are common in children in developing countries [C. hominis subtype families [C. hominis transmission in Egypt is probably autochthonous in nature.Although ountries , 31. Nevfamilies , 31, indG. duodenalis in infected children from the three provinces in this study belonged to assemblages A and B. This agrees with the findings of a recent study of G. duodenalis in children in Egypt [G. duodenalis transmission in Egyptian children appears to be mostly anthroponotic. This is also supported by the identification of assemblage A isolates in the study as the sub-assemblage AII, which is preferentially found in humans [The genotypes (assemblages of similar sequence types identified by multilocus molecular characterization) of in Egypt . The assin Egypt , 17 werein Egypt –18. Globin Egypt , G. duodIn this study, a much higher genetic diversity was observed in assemblage B than in assemblage A. Similar observations were made in previous studies . This coC. hominis and common occurrence of G. duodenalis assemblage B and sub-assemblage AII in clinical specimens showcases the important role of anthroponotic transmission in disease epidemiology, although the occurrence of zoonotic infections could not be totally ruled out. Improved sanitation and hygiene and other intervention measures such as better health communication and the provision of clean and safe drinking water should be implemented to reduce the occurrence of cryptosporidiosis and giardiasis and minimize the impact of diarrhea on pediatric health in the country.Giardiasis is apparently common, and cryptosporidiosis remains to be a problem in kindergarten age children in Egypt. The dominance of Additional file 1:Table S1. Specimens from kindergarten-age children in Egypt that were positive for Giardia duodenalis assemblage B at the tpi, gdh and bg loci. (DOCX 16 kb)


AOX adsorption by activated carbon is a chemical process. Hence, the chemical compositions of the bleaching effluent with and without adsorption were analysed by GC-MS. The results revealed that activated carbon exhibits a good AOX removal effect, thereby providing a theoretical basis for monitoring the AOX distribution in the environment.Current research mainly focuses on the reduction of adsorbable organic halogen (AOX) sources, while studies on AOX monitoring and management in the environment are scarce. Organic pollutants in water are mainly fixed by sediments. Thus, in this paper, activated carbon was used to simulate the adsorption of AOX by sediments. AOX volatilization and degradation were also studied to exclude their effect on adsorption. Micromolecule chlorides were more easily volatilized and degraded than chlorobenzene and chlorophenol. The adsorption of activated carbon to AOX in bleaching wastewater was also studied and the optimum conditions for AOX removal were elucidated (particle size, 62 µm; time, 120 min; pH, 2.5; temperature, 40°C; and activated carbon dosage, 1.75 g l A large amount of organic chlorides is produced by hypochlorite bleaching and chlorination reactions during the traditional chlorination-alkali treatment-hypochlorite bleaching (CEH) process. Bleaching pollution based on traditional CEH bleaching is becoming an increasingly serious environmental issue . Thus, lAlthough recent years have seen an increase in research on AOX, studies have mainly focused on AOX formation mechanisms to reduce AOX in the bleaching process. Most studies assume that the residual lignin in the unbleached pulp is the main source of AOX . Hence, The aim of this work is to study the adsorption effect of organic chlorides in bleaching effluents using activated carbon. AOX volatilization and degradation processes were studied to eliminate their effect on AOX adsorption. The effects of active carbon particle size, pH, temperature, dosage and time on the adsorption capacity were also investigated. Finally, the chemical compositions of the bleaching effluent with and without adsorption were analysed by GC-MS. The results present an important guideline for the analysis and treatment of AOX in the environment.2.2.1.−1). Activated carbon was purchased from the Analytik-Jena Instrument Company . Sodium chlorite, hydrochloric acid, sodium hydroxide, sulfuric acid, potassium iodide and sodium thiosulfate were purchased from Sigma-company . All chemicals used in the paper were of analytical grade and used as received.Unbleached bagasse pulp was provided by a pulp mill in Guangxi, China  chlorine dioxide solution was added to the mixture at 65°C (reaction time = 60 min). The mixture was kneaded every 5 min during the reaction and sufficient contact between the pulp and chlorine dioxide solution was ensured. Most of the lignin was removed during bleaching. The pulp was washed to neutral by pure water at the end of the reaction. The basic structural lignin units were chlorinated. Organic chloride is produced during the bleaching process. Finally, the reaction solution was collected . The mixture was thoroughly mixed for 5 min at 100 rpm. The pH of the reaction solution was adjusted to 3.5–4 by the addition of sulfuric acid solution. Next, 120 kg tpollected .2.3.A multi X2500 AOX analyser  was employed to identify the AOX present in the bleaching effluent as follows: the bleaching effluent was passed through an activated carbon column to adsorb the organic chloride. The adsorbed inorganic chloride was then washed with sodium nitrate. The activated carbon column was burned in a combustion furnace and the AOX content was calculated .2.4.In the experiment, 2 l bleaching effluent was loaded in a glass beaker and then purged thoroughly with sodium nitride . Sample solutions were withdrawn at different times during the experiments. The bleaching effluent was collected every 2 days at room temperature to detect the AOX content. It was then extracted with ether three times and subsequently combined with the organic phase. Finally, the AOX content was determined.2.5.About 2 l bleaching effluent was loaded in a glass beaker and purged thoroughly with sodium nitride. Both groups were sealed, one of which was treated without light. The sample solutions were withdrawn at different times during the experiments. The bleaching effluent was collected every 2 days at room temperature. Finally, the AOX content was determined.2.6.The chemical composition of the reaction solution was analysed by GC-MS . The organic chlorides were qualitatively and quantitatively analysed. The solution was concentrated with or without volatilization, degradation and adsorption. The concentrate was extracted by column adsorption and 1 µl of the concentrate was then measured. The detailed operating conditions for GC-MS have been described in previous studies ,30.2.7.−1) was withdrawn and placed in a ground conical flask (100 ml). The amount of activated carbon was controlled and the mixture was sealed and placed in a constant temperature oscillator (amplitude = 118 r min−1) to attain oscillatory adsorption. After 30 min, the sample was centrifuged. Finally, 1 ml supernatant was withdrawn and the total amount of AOXs was calculated.About 50 ml bleaching effluent , indicating that the volatility of AOX is significant. The results also revealed that the volatility of AOX was the fastest during the first 30 days, with the content decreasing from 25.98 mg l−1 to 22.33 mg l−1 from day 1 to day 30, respectively (14.40% decrease). This lower value remained constant throughout the rest of the testing period (day 30 to day 45) indicating that no volatile components were present in the AOX during this period. The bleaching effluent comprised four types of organic chlorides  on the experimental results during the adsorption process could also be excluded. Hence, to investigate the effect of time on AOX photodecomposition, photodegradation experiments were carried out at different light exposure times in the range 5–45 days.−1 to 23.70 mg l−1 (8.78% decrease) after 25 days of photodecomposition. The amount of degradation was stable after 25 days, while the AOX content remained unchanged after 45 days (23.50 mg l−1). These results demonstrate that the effect of photodegradation on AOX is limited. Subsequently, when the photolysis of the AOX components became stable, its components were detected. The afforded results .In the natural environment, pollutants in water are fixed to the sediment. Activated carbon displays the strongest adsorption capacity in sediments . Thus, t−1 to 4.10 mg g−1 (6.49% increase) as the particle size was increased to less than 62 µm. Subsequently, as the particle size was increased further (greater than 62 µm), the AOX content decreased with an increase in particle size until it became stable at sizes greater than 500 µm. This was attributed to more of the microporous structure being exposed when the particle size was small [−1) was achieved at a particle size of 62 µm. In addition, the smaller activated carbon particles were not easily recyclable and exhibited large losses during regeneration. Thus, we concluded that the optimal particle size to achieve maximum AOX removal efficiency was 62 µm.as small , thereby3.4.−1).The study of adsorption time mainly comprises the determination of the equilibrium adsorption time. To investigate the effect of adsorption time on the total amount of AOXs removal, adsorption experiments were carried out in the time range 30–150 min. All other experimental conditions were maintained constant . As the activated surface-active site becomes occupied by AOX, the compounds begin to diffuse from the outer surface into the adsorbent, thereby affecting the effect of the adsorbent. This results in a decrease in the adsorption rate. Thus, after 120 min, the surface-active sites became completely occupied by AOX. At this stage, both the surface and internal adsorption were almost saturated and the adsorption reached equilibrium. We therefore concluded that the optimal adsorption time was 120 min.3.5.2SO4 and NaOH. All other experimental conditions were maintained constant .The adsorption of organics by activated carbon involves a complex reaction process. This reaction not only has a simple physical role in the adsorption process but is also generally affected by electrostatic, chemical and complexation effects. The pH affects the groups present on the surface of the activated carbon and changes the charge of the surface groups, thus affecting the adsorption process. Hence, the adsorption capacity of the activated carbon exhibits different efficiencies under different pH values. The adsorption experiments were therefore carried out at different pH values in the range 2.1–7.5. The pH of the solution was adjusted by H−1) was observed at pH 2.5. However, this value decreased with a further decrease in pH. At pH 2 and 1, the adsorption capacity was 2.95 mg g−1 and 3.16 mg g−1, respectively. In fact, the adsorption effect of the activated carbon on an organic pollutant generally decreases with an increase in the pH so that organic pollutants are not easily adsorbed at pH values greater than 8.0 [than 8.0 . The ion3.6.−1).The reaction temperature is the most basic experimental parameter and affects the efficiency of the activated carbon adsorption process. As an exothermic process, the adsorption process is very sensitive to temperature. Thus, appropriately increasing the temperature facilitates the rapid reaction and adsorption activity. In this study, the adsorption experiments were carried out in the temperature range of 20–50°C. All other experimental conditions were maintained constant . As the temperature was increased further, the adsorption capacity increased slowly until the maximum adsorption capacity (3.6 mg g−1) was reached at 40°C. The adsorption capacity was slightly reduced at 50°C (3.50 mg g−1), indicating that the dynamic equilibrium of the adsorption process was destroyed and the desorption effect was greater than that of the adsorption [sorption . We ther3.7.−1. All other experimental conditions were maintained constant .Adsorption experiments were carried out at different activated carbon dosages in the range 0.25–2.75 g l−1, whereby the adsorption capacity increased from 13.25 mg g−1 to 37.10 mg g−1. These results can be attributed to an increase in the unsaturated adsorption sites, surface area and diffusion length. The gradual stage occurred when the dosage was greater than 1.75 l−1. In this stage, adsorption only increased from 37.10 mg g−1 to 39.75 mg g−1, indicating that equilibrium was approached. This occurred because most of the AOX was adsorbed on the surface of the activated carbon. Thus, the active sites on the surface were occupied and further adsorption was inhibited [−1. At the end of the experiments, the following optimum conditions for the removal of AOX were established: particle size = 62 µm, time = 120 min, pH = 2.5, temperature = 40°C and activated carbon dosage = 1.75 g l−1.nhibited . We ther3.8.G°, ΔH° and ΔS° were calculated from equations (3.1)–(3.3).qe is the adsorption capacity (mg g−1) and Ce is the AOX concentration after adsorption (mg l−1).The thermodynamics of AOX adsorption by activated carbon was studied under different temperatures. The results are presented in G° < 0, ΔH° > 0 and ΔS° > 0 suggest that the adsorption was a spontaneous entropy increasing process of heat absorption. The results revealed that AOX adsorption by activated carbon was a chemical adsorption process.The adsorption thermodynamics parameters Δ3.9.The chemical compositions of the bleaching effluent with and without adsorption are presented in 4.Activated carbon was used to simulate the adsorption of AOX by sediments. The AOX volatilization and degradation processes were studied to exclude their effect on the adsorption process. Micromolecule chlorides were more easily volatilized and degraded than chlorobenzene and chlorophenol. The adsorption of activated carbon to AOX in bleaching wastewater was also studied and the optimum process conditions were elucidated. The chemical compositions of the bleaching effluent with and without adsorption were analysed by GC-MS. The results revealed that activated carbon exhibits good adsorption capacity towards AOX.


Human T-Lymphotropic Virus type 1 (HTLV-1) is a human oncoretrovirus that infects at least 5 to 10 million people worldwide and is associated with severe diseases. Africa appears as the largest HTLV-1 endemic area. However, the risk factors for the acquisition of HTLV-1 remain poorly understood in Central Africa.env gene or LTR region fragments.We conducted an epidemiological survey between 2013 and 2017, in rural areas of 6 provinces of Gabon, in a rainforest environment. Epidemiological data were obtained and blood samples were collected after informed consent. Plasma were screened for HTLV-1 antibodies by ELISA and the positive samples were then tested by Western blot (WB). Genomic DNA derived from buffy-coat was subjected to two semi-nested PCRs amplifying either HTLV-1 env gene and 131 for the LTR region. Based on both serological and molecular results, 179 individuals were considered infected with HTLV-1, leading to an overall prevalence of 8.7%. The distribution of HTLV-1 infection was heterogeneous across the country. Based on multivariable analyses, female gender, increasing age, ethnicity (Pygmy) and multiple hospitalizations (more than 5 times) were found to be independent risk factors for HTLV-1 infection. Furthermore, a non-human primate bite appeared to be marginally associated with a higher risk of HTLV-1 infection.We recruited 2,060 individuals over 15 years old, including 1,205 men and 855 women (mean age: 49 years). Of these, 299 were found to be ELISA HTLV-1/2 seropositive. According to WB criteria, 136 were HTLV-1 (6.6%), 25 HTLV-1/2 (1.2%) and 9 HTLV seroreactive (0.4%). PCR results showed that 146 individuals were positive for at least one PCR: 104 for the Based on state-of-the-art serological and molecular methods, we have demonstrated that rural adult populations in Gabon are highly endemic for HTLV-1. Our results regarding risk factors should lead to public health actions aiming to reduce HTLV-1 transmission. Human T-Lymphotropic Virus type 1 (HTLV-1) infects at least 5 to 10 million people worldwide and is associated with severe diseases. Africa, particularly the sub-Saharan region, is considered as the largest HTLV-1 endemic area. HTLV-1 can be acquired through three main routes: mother-to-child, sexual and through contaminated blood products. In addition, zoonotic transmission from non-human primates still occurs in specific rural African populations. Gabon is considered to be a very high HTLV-1 endemic area. However, risk factors for such a retroviral infection remain poorly known in Central Africa. In this study, using state-of-the-art serological and molecular tests, we aimed to get new insights on risk factors associated with HTLV-1 infection in rural Gabon. We report an overall prevalence of HTLV-1 of 8.7%, demonstrating that HTLV-1 is highly endemic in rural adult Gabonese populations. In the study population, we identified female gender, increasing age, ethnicity (Pygmy) and multiple hospitalizations (more than 5 times) as independent risk factors for HTLV-1 infection. Furthermore, a non-human primate bite appeared to be marginally associated with a higher risk of HTLV-1 infection. Our results regarding the risk factors for such a retroviral infection are important for public health actions aiming to reduce HTLV-1 transmission. Human T-lymphotropic virus type 1 (HTLV-1), the first human retrovirus discovered . HTLV-1 Sub-Saharan Africa is considered as the largest HTLV-1 endemic area accounting for at least half of the infected individuals worldwide (2.5 to 5 millions). However, the situation of HTLV-1 in Africa is not well known. Indeed, the majority of previous studies have been carried out either on very specific populations such as pregnant women, blood donors or hospitalized patient series, or in heterogeneous and relatively small groups of rural or urban inhabitants of a specific town or village or area . All theIn this work, we performed a large epidemiological study among adult inhabitants of rural Gabon. We used state-of-the-art assays for both serological and molecular diagnoses. Our first objective was to provide better knowledge of the prevalence and the geographical distribution of HTLV-1 infection in Gabon. The second was to get new insights into the risk factors for the acquisition of HTLV-1 among adults living in this highly endemic area.Between 2013 and 2017, we conducted epidemiological surveys involving inhabitants of rural areas living mainly in a rainforest environment, in 6 out the 9 provinces of Gabon. A systematic approach for the enrolment of adults (over 15 years old) was carried out in the populations from all reachable villages and settlements, scattered along side roads and tracks across the primary tropical forest. We included all volunteers. A standardized questionnaire was used to collect epidemiological data. Besides demographic information, we focused our questions on the potential risk factors for HTLV-1 acquisition including scarification, hospitalization, transfusion and contacts with wild animals and bush meat during hunting and/or butchering activities . A 5 to 10 ml blood sample was collected on EDTA from all consenting individuals. Plasma and buffy coat were obtained 48 to 72 h after sampling and kept frozen at -80°C.Ethical approval was obtained from the Comité National d’Ethique of Gabon (Permit number PROT 0011/2013/SG/CNE). Prior to field sampling, individual written informed consent was obtained from all participants after detailed information and explanations of the study were provided to the community. Written informed consent for children was obtained from their parents or recognized guardians.Plasma samples were screened for HTLV-1/2 antibodies by ELISA tests , and confirmatory Western blot assays  for all ELISA positive samples. Results were interpreted according to the manufacturer’s instructions. Thus, the samples were classified as HTLV-1 seropositive, HTLV-2 seropositive, both HTLV-1/2 seroreactive, HTLV seroreactive, indeterminate and seronegative.env gene, and a second one to amplify a 450-bp fragment of the LTR-3’ region of HTLV-1. A sample was considered as PCR positive when a band of the expected size was clearly detected on agar gel.High molecular weight DNA was extracted from peripheral blood buffy coats (PB-BC) using the QIAamp blood minikit (Qiagen). DNA samples were determined as amplifiable after a polymerase chain reaction (PCR) positive result, performed on the human β-globin gene. One microgram of each DNA sample was then tested by two different semi-nested PCRs: according to protocols previously described : a firstAn individual was considered as infected with HTLV-1 if the WB profile was either HTLV-1, or HTLV-1/2 or HTLV. Furthermore, an individual with an indeterminate WB profile associated with at least one HTLV-1 positive PCR, was also considered as HTLV-1 infected.t test. HTLV-1 infection prevalence was compared between provinces using the Chi-square test, and between age groups using the Chi-square test for trends. Logistic regression was used to identify factors associated with HTLV-1 infection and to estimate odds ratios (OR) and 95% confidence intervals (95%CI). ORs were presented as crude or age and gender adjusted  and all variables adjusted . Variables retained in the final model were considered statistically significant if p values were < 0.05, and marginally significant if p values were < 0.07. Multiple imputations were performed to replace missing values for the “number of hospitalizations” variable, using the multivariable imputation by chained equations (MICE) method [Age was compared between Pygmy and Bantu ethnic groups using the Student ) method . All anavs 51, p<0.001).We recruited 2,060 individuals (older than 15), including 1,205 men and 855 women , originating from the 6 investigated provinces of Gabon . A largeAmong the 2,060 plasma samples tested by ELISA, 299 were found HTLV-1/2 seropositive. Using WB criteria provided by the manufacturer, 136 were HTLV-1 seropositive (6.6%), 25 HTLV-1/2 (1.2%), 10 HTLV-2 (0.5%), 9 HTLV seroreactive (0.4%) and 85 sero-indeterminate (4.1%). Moreover, 34 were seronegative. Based on strict WB results as defined by the manufacturer’s assay  and including only HTLV-1 and HTLV-1/2 profiles, the overall HTLV-1 seroprevalence was 7.8%  .env gene, 131 for the LTR region), and 89 for both PCRs  the 170 individuals with a WB profile being either HTLV-1, HTLV-1/2 or HTLV, and ii) the 9 individuals with an indeterminate WB profile associated with at least one positive HTLV-1 PCR test . Thus, 1Univariable analysis revealed that women are significantly more likely to be HTLV-1 infected than men , an history of blood transfusion , and an increased number of hospitalization , but not with tattoo nor circumcision. However, when adjusted for age and sex, only individuals with 5 hospitalizations or more were at increased risk of being HTLV-1 infected .Since our study was conducted in primary tropical forest areas and focused on individuals potentially at risk of acquiring HTLV-1 through interspecies transmission, we also obtained information on contacts with NHPs. No association was observed with hunting and butchering activities or keeping NHPs as pets. However, a higher risk was observed among individuals who reported having been bitten by a NHP. Indeed, 8 of 53 individuals (15.1%) were HTLV-1 seropositive , have observed a high level of HTLV-1 infection , 24, 25.In our study, we observed a significant increase in HTLV-1 infection with age, as well as a higher prevalence in women. Such findings are well-known major characteristics of HTLV-1 epidemiology, regardless the endemic level and the studied areas. For instance, this has already been observed in rural populations of Guinea Bissau , 17, as vs 1,797), the prevalence of HTLV-1 is significantly higher in Pygmies. Besides, in our multivariate analysis, being a Pygmy was associated with an increased independent risk of HTLV-1 infection . Such findings were previously observed for HTLV-1 and also for HTLV-2 infection in Bakola’s Pygmies living in the Ocean region, located in the Western part of South Cameroon [Despite the small number of Pygmy individuals included in this study as compared to Bantu . In a previous study, the HTLV-1 age-adjusted prevalence rate was significantly higher in rural areas of Gabon than in urban areas [Concerning the distribution of HTLV-1 prevalence in the different provinces of Gabon, our data indicate a heterogeneous distribution ranging from 5.5% to 14%. Contrary to what was previously suggested, we have not observed a gradient of HTLV-1 prevalence following the North-South axis. Such discrepancy could be related to various factors including the non-homogeneous and therefore non-comparable structure of the populations previously studied . The reasons for the existence of such a risk are not clear. It could be linked to the nosocomial acquisition of this retroviral infection in hospital, either by transfusion of cells infected with HTLV-1, or by contamination through the use of infected syringes or non-sterile utensils. However, transfusion is not associated with HTLV-1 infection in our model. One may suppose that HTLV-1 is not actually transmitted at the hospital. For instance, the virus could be acquired through severe bite, which could secondarily lead to hospitalization. Similarly, a given illness could lead the patient to first visit a traditional healer with risky practices , before heading to more classical hospitalization.We hoped that this study would alert Gabonese public health authorities and promote appropriate measures to prevent HTLV-1 infection throughout the country, at least in rural populations in which we reported high prevalence. Despite the fact that Gabon is both a highly HTLV-1 endemic area and a high development index country, it has not yet introduced routine screening for HTLV-1, especially among blood donors. Importantly, a previous study in Gabon has already demonstrated that transfusion is a major risk factor for HTLV-1 acquisition in children . In addiS1 Checklist(DOC)Click here for additional data file.


However, these signals can then trigger activation of downstream protein cascades that can last from milliseconds to hours. Recent imaging studies provide many insights into the biochemical processes governing signaling events of molecular assemblies at different spatial localizations. Here, we highlight recent findings of signaling dynamics during synaptic plasticity and discuss their roles in long-term structural plasticity of dendritic spines.Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine. Technical advances in monitoring molecular behaviors in single dendritic spines have revealed that each signaling pathway is differently regulated across multiple spatiotemporal domains. The spatial pattern of signaling activity expands from a single spine to the nearby dendritic area, dendritic branch and the nucleus, regulating different cellular events at each spatial scale. Temporally, biochemical events are typically triggered by short Ca The dendritic spine is a small protrusive structure that typically houses a single excitatory postsynapse. The spine is made of a head (~0.01–1 fL) and a narrow neck (~0.1 μm in diameter) that connects the head and dendritic surface. This structure spatially restricts electrical and biochemical access from the spine head to the dendritic shaft . These two forms of actin undergo a cycle called tread-milling: ATP-bound G-actin is added to the fast-growing end (barbed end or plus end) and ADP-bound G-actin is dissociated from the other side (pointed end or minus end) of F-actin Figure . The cycChanges in the actin network are regulated by multiple ABPs Figure . These pSince regulation of actin cytoskeleton is tightly coupled with changes in spine structure, the signaling system connecting synaptic activity and various ABPs plays an important role in spine structural plasticity. Indeed, recent studies using molecular imaging, such as FRET-based fluorescence lifetime microscopy (FLIM) imaging have revealed the spatiotemporal dynamics of key signaling molecules regulating actin cytoskeleton in dendritic spines  in the activated spine , a Ca2+-binding protein and Ca2+ bound CaM (Ca2+/CaM) subsequently activates Ca2+/CaM-dependent kinases and phosphatases such as CaMKII and calcineurin , which makes the kinase activity independent of Ca2+/CaM binding. This Ca2+/CaM-independent activation, which is often referred to as “autonomous” activity, could persist for a long time after Ca2+ decays. Indeed, it has been found that autophosphorylation at Thr286 persists for more than ~1 h after LTP induction  of mRNA is critical for mRNA transport and translational repression  revealed that, in dendrites, β-actin mRNA in RNA granules is sterically masked from the translation machinery as well as FISH probes, and unmasked by neuronal activity  interacting protein 1 . It has been demonstrated that CYFIP1 regulates spine remodeling both through promoting translation initiation and Arp2/3-mediated rapid actin nucleation  pathway, a major pathway that regulates protein synthesis, is also found to regulate dynamics of actin cytoskeleton through Rac1 activation , which upregulates RhoA activity and presumably promotes actin depolymerization  non-coding RNAs, which have important roles for specific translational control at synapses. miRNAs silence translation and induce degradation via making RNA-induced silencing complex (RISC) and binding corresponding sequences in 3’-UTR of mRNAs , schizophrenia and Fragile X syndrome (FXS), are thought to be associated with dysregulation of cytoskeletal and translational signals (Buffington et al., in vitro models such as cultured neurons and brain slices, developments of systems to measure signaling activity in live animals with high spatiotemporal resolution would be necessary to connect biochemical events single dendrite with neuronal circuit plasticity in specific behavioral paradigm.Signal transduction regulating structure and function of dendritic spines are exceedingly complicated, and it will be long way to understand the whole signaling system. Due to the morphological complexity of neurons, the spatiotemporal dynamics of signaling play particularly important roles in neuronal plasticity. While quantitative measurements of more detailed signaling pathways will lead to a better understanding of overall signaling system, it would be critical to create theoretical frameworks that can integrate the spatiotemporal dynamics of many different signaling pathways (Brown et al., Both authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In addition, a statistical method based on the control volume was used to reconcile the effect of loading type, and the predicted data were consistent with the experimental results.High-cycle and very-high-cycle fatigue tests via rotary bending (52.5 Hz), electromagnetic resonance (120 Hz) axial cycling, and ultrasonic (20 kHz) axial cycling were performed for a high-strength steel with three heat treatment conditions, and the effects of loading frequency and loading type on fatigue strength and fatigue life were investigated. The results revealed that the loading frequency effect is caused by the combined response of strain rate increase and induced temperature rise. A parameter  Crack iformance  surroundformance . Due to formance ,17,18,19formance .Several experimental devices have been used for the testing of VHCF, such as rotary bending (RB), servo-hydraulic (SH), electromagnetic resonance (ER), and ultrasonic loading (UL) machines. For the reason that the conventional loading (CL) frequency of RB, SH, and ER machines cannot satisfy efficiency in terms of experimental time in VHCF testing, UL machines have been widely used thanks to their ultra-high loading frequency, e.g., 20 kHz, but the increase in loading frequency will influence the fatigue strength and fatigue life in the VHCF regime, for which quite a number of investigation results ,32,33,34Researchers have proposed explanations to understand the effect of loading frequency. In an early overview  and a reIn addition to the effect of loading frequency, the effect of loading type also exists in fatigue experiments. The common loading types are axial loading (AL), RB, three- or four-point bending, and torsional loading, and several investigations ,41,42,434 s−1, 5 × 10−3 s−1, and 500 s−1) and at high temperatures (100 °C and 200 °C) under 500 s−1 were carried out to investigate the effect of strain rate and temperature on material strength. As a consequence, the combined effect of strain rate and temperature on material strength was used to analyze the effect of loading frequency. In addition, a statistical method based on the control volume was adopted to reconcile the effect of loading type.The aim of this paper is to further investigate the effects of loading frequency and loading type on HCF and VHCF performance for high-strength steels. For this purpose, fatigue tests up to VHCF regime for a high-carbon chromium steel  with three heat treatment conditions were conducted under RB, electromagnetic resonance axial loading (EA), and ultrasonic axial loading with cooling (UA) and without cooling (UA-NC). During EA, UA, and UA-NC tests, the strain rate of the specimen with three heat treatment conditions was readily computed and the temperature on the specimen surface was monitored via a thermocouple system. In addition, monotonic loading tests at room temperature under three strain rates  with the chemical composition (wt %) 1.00 C, 1.52 Cr, 0.31 Mn, 0.21 Si, 0.0086 P, 0.016 S, and Fe balance. The machined specimens were heated at 845 °C for 10 min in a salt-bath furnace, then oil-quenched and tempered in vacuum for 2 h at 150 °C (TT 150), 200 °C (TT 200), or 400 °C (TT 400). The microstructure for TT 150 mainly contains tempered martensite, carbides, and retained austenite, and the microstructure for TT 200 mainly contains tempered martensite and carbides, while the microstructure for TT 400 contains tempered troostite and carbides. The tensile strength under strain rate 10R = −1. All the specimens are of the hourglass type, and the geometry of the specimens is shown in Fatigue tests were conducted with RB, EA, and UA testing machines , and the loading frequencies for the three kinds of testing machines were 52.5 Hz, 120 Hz, and 20 kHz, respectively. All fatigue tests were performed in air, at room temperature, and with a stress ratio of For the purpose of investigating the effect of temperature rise of the specimen caused by ultrasonic frequency, the fatigue tests were performed with compressed air cooling (UA) and without cooling (UA-NC) on the specimen surface. A thermocouple system (made by the authors) was used to monitor the temperature on the minimum cross-sectional surface of EA, UA, and UA-NC specimens. In addition, tests with separated Hopkinson pressure bar were carried out for testing the mechanical property of the three conditions at high strain rate, and a muffle furnace was equipped for testing at high temperature.The fracture surfaces of most failed specimens were examined by using a field-emission type scanning electron microscope .5 and 106 cycles with surface crack initiation mode. One possible reason for this is the very short testing time of 5 s for 105 cycles and 50 s for 106 cycles. Thus, the testing onset point and its small unstable loading period may take up a non-ignorable proportion of the total testing period, which may lead to test data scattering.6 cycles (solid symbols in For specimens of the two high strength conditions (TT 150 and TT 200), the S-N data have a trend of duplex or continuously decreasing pattern. With the increase of fatigue life, fatigue crack initiation turns to occur from the surface of the specimen (hollow symbols in 7 cycles), and the enlargement of the crack origin of 7 cycles). The high magnification of initiation region , and 6 by the UA method). It is seen that the images of both specimens show a clear FiE morphology containing an FGA surrounding an inclusion (with diameters of approximately 20 μm for B1 and 25 μm for C1). The location of the crack origin is rather away from the surface of the specimen compared with the case of the RB method, with the depth from surface being approximately 500 μm for B1 and 1 mm for C1.The S-N data of 6 cycles for UA specimens and 1 × 107 cycles for UA-NC specimens as shown in 7 cycles for UA specimens and from 0 to 2 × 107 cycles for UA-NC specimens. The temperature rise by the UA method was much lower than that by the UA-NC method, suggesting that compressed air cooling effectively reduced the temperature rise of the specimens. The enlargements of the stable stage shown in A thermocouple system was used to monitor the temperature on the minimum cross-sectional surface of EA, UA, and UA-NC specimens. 7  at room temperature (20 °C) and under 500 s−1 at high temperatures (100 °C and 200 °C) were carried out by means of separated Hopkinson pressure bar testing to examine the effect of strain rate and temperature on material strength. The experimental results of −1 for the three material conditions. With regard to fatigue testing under the EA and UA methods, the range of strain rate was calculated as between 2 s−1 and 4 s−1 for the EA specimen and between 300 s−1 and 700 s−1 for the UA specimen. It is obvious that the ultimate stresses of the tested material at 2–4 s−1 and 300–700 s−1 are higher than that at quasi-static condition (10−4 s−1). Therefore, it is reasonable to use the material strength at relevant strain rate and temperature in the evaluation of fatigue strength for EA and UA specimens.Further, monotonic mechanical tests under different strain rates (10−1) and UA (500 s−1) specimens. In order to address the effect of temperature rise by the UA method, we defined a critical temperature Tc . When the temperature of the UA specimen is below Tc, the material strength of the UA specimen is higher than that of the EA specimen, and then the loading frequency effect will occur. When the temperature of the UA specimen is equal to Tc, the material strength of the UA specimen is identical to that of the EA specimen, and then the loading frequency effect will diminish. In addition, due to the large value of temperature rise for the UA-NC specimen, it is likely that its resulting temperature is higher than Tc; thus, the material strength and, therefore, the fatigue strength of the UA-NC specimen will be much less than those of the EA specimen.In Tc, and the material strength and the fatigue strength for the UA specimen are then higher than those for the EA specimen, i.e., the loading frequency effect may prevail. This analysis is consistent with the S-N data under low stress shown in It has been described that the temperature of the UA specimen is less than 70 °C (temperature rise 50 °C plus room temperature 20 °C) under low stress levels for the three heat treatment conditions, which is below the value of T being experimental temperature, rT room temperature, and mT melting temperature of the material. A, B, C, m, and n are material coefficients. The expressions in the second and the third sets of parentheses represent the effect of strain rate and temperature, respectively. Here, we define a parameter η as the ratio of material strength at UL frequency to CL frequency, which is expressed in Equation (2).Above all, for the three material conditions , the effect of loading frequency is caused by the related strain rate under low stress. For a better understanding of the mechanism of the loading frequency effect, the Johnson–Cook formula  of Equatη is larger than unity, the fatigue strength at the UL frequency is higher than that at the CL frequency, which means the existence of a loading frequency effect. When η is equal or close to unity, the fatigue strength at the UA frequency tends to be identical with that at the CL frequency, which means that the effect of loading frequency no longer prevails.When From the testing data, we obtained the Johnson–Cook formulas for the three material conditions of TT 150, TT 200, and TT 400, which are shown in Equations (3)–(5), respectively.η for UA and EA frequencies under low stress (700 MPa) in the VHCF regime. Note that the relevant temperatures of UA specimens for the three material conditions are between 46 °C and 52 °C, and the temperatures of the EA specimen are taken as 20 °C (room temperature) because of the negligible temperature rise. The related strain rates of the UA and EA specimens are 419 s−1 for the UA specimen and 2.5 s−1 for the EA specimen. The calculated values of η according to Equations (3)–(5) are all above unity, indicating the prevalence of the loading frequency effect for the three material conditions under corresponding low stress, which is consistent with the S-N data shown in η for the UA and UA-NC specimens under 584 MPa (the maximum stress in temperature measurement for UA-NC). The related stain rate is 628 s−1, and the values of specimen temperature are between 36 °C and 44 °C for UA specimens and between 127 °C and 146 °C for UA-NC specimens. The ratios of σUA to σUA-NC are all beyond unity, indicating that the fatigue strength of the UA specimen is higher than that of the UA-NC specimen because of the high temperature rise of the UA-NC specimen. The calculated results are consistent with the trend of S-N data shown in In a similar way, As a consequence, it is anticipated that the methodology and the results with regard to the loading frequency effect on the HCF and VHCF performance is applicable to other cases of high-strength steels.6 cycles, which is a result of different loading types: stress gradient feature on the cross section for the RB method against the stress uniform distribution on the cross section for AL, i.e., the EA and UA methods. From Φ = 4 mm, R = 7 mm) was calculated as 5.63 mm3, and that for the EA and UA specimen  was 32.6 mm3. The control volume for EA and UA specimens is almost six times that for the RB specimen. In other words, EA and UA specimens have a higher risky possibility than the RB specimen, which causes the fatigue strength by the EA and UA methods to be inferior to that by the RB method.In a similar way, the size (square root of projection area) of every inclusion as crack origin was measured on fatigue-fractured surfaces and the results are shown in In our previous paper , a statiN) decreases with the increase of applied stress (σ) for the specimens with high strength conditions, which is expressed by Equation (6). Consider that the fatigue life  under a stress level iσ is transformed to an arbitrary given stress Then, the fatigue life k is the shape parameter. The values of λ and k were then obtained from the fitted cumulative distribution of VEA = 32.6 mm3) is about six times as large as that of the RB specimen (VRB = 5.63 mm3), and we can deduce the cumulative distribution function of fatigue life NEA of the EA specimen with n = 6 by Equation (11).If Thus, we were able to get the fatigue life under 700 MPa at the reliabilities of 50%, 90%, 95%, 99%, and 99.9% for the EA specimen. In a similar way, the fatigue life under other stress levels of 750 MPa, 800 MPa, 850 MPa, 900 MPa, 950 MPa, 1000 MPa, and 1050 MPa at the concerned reliabilities for the EA specimen were obtained successively. Finally, the derived P-S-N (probability-stress-life) curves for the EA specimen were readily plotted. VEA = 32.6 mm3) were derived from RB data (VRB = 5.63 mm3) with interior crack initiation mode, which were generally consistent with the experimental data for the EA method. That is to say, the effect of loading type is basically caused by the difference in control volume. This statistical method is a suitable approach to reconcile the data under different loading types with different values of control volume.The derived P-S-N curves together with tested S-N data for TT 150 and TT 200 are shown in It is noticed that the above results were based on the interior crack initiation data for specimens TT 150 and TT 200. The fatigue strength for specimens TT 400 by RB and EA methods c does no(1)For the specimens of the two high strength conditions, the fatigue strength with interior crack initiation mode for the RB method is superior to that for the EA and UA methods because of the small control volume for the former; the fatigue strength for the UA method is slightly higher than that for the EA method in the VHCF regime, suggesting the existence of a loading frequency effect; and the fatigue strength of the UA-NC method is substantially lower than that of the EA and UA methods due to the temperature rise of the specimen for the former.(2)For the specimens in the low strength condition, the fatigue strength for the RB method is almost the same as that for the EA method because fatigue cracking almost initiates from the specimen surface; thus, the loading type effect is diminishing. The fatigue strength for the UA method is higher than that for the UA-NC method, and the fatigue strength for both the UA and UA-NC methods is higher than that for the EA method, showing an evident loading frequency effect.(3)η was proposed to judge whether the loading frequency effect may occur, and the calculated results are in agreement with the experimental data.The combined response of strain rate and the induced temperature rise is the reason for the loading frequency effect. A parameter (4)The statistical method used based on the control volume is suitable for reconciling the effect of loading type. The predicted P-S-N curves of the EA specimen are consistent with the experimental data for the specimens of the two high strength conditions.In this paper, the effects of loading frequency and loading type on fatigue performance for a high-strength steel with three heat treatment conditions were studied. The conclusions are drawn as follows:


RV = 0.810). Partial least squares regression was used to develop a predictive model for crispness from instrumental measurements (R2 = .854). The use of texture analysis and Acoustics provide information of the structures strength and deformation behavior, while X‐ray microCT provides a high resolution and noninvasive method that acquires information on the internal morphology. These instrumental methods collectively demonstrate the relationship between microstructure to sensory. This study investigates how a change in the microstructure of deep‐fried battered and breaded coatings affect crispness perception. These changes were investigated analytically and by using a sensory panel, this is important from a manufacturing perspective in order to understand what the major contributors are to a crisp texture. The key highlights of this study include both instrumental measurements and sensory measurements can be used to measure crispness as both types of testing are correlated. Changes in the size of breadcrumbs affect both instrumental measurements and sensory measurements. A predictive model can be re‐simulated to allow prediction of crispness in deep‐fried battered and breaded coatings.Crusted crispness refers to coatings with a dry and brittle surface contrasting a high‐moisture core; it is desirable for the enjoyment and quality of deep‐fried goods. This study aims to investigate instrumental measurements and sensory measurements of crispness. Deep‐fried breadcrumb coatings of eight sizes were investigated: 4.0 mm, 2.8 mm, 2.0 mm, 1.4 mm, 1.0 mm, 710 μm, 500 μm, and 355 μm. Sensory profiling was carried out to develop a tailored lexicon for deep‐fried battered and breaded shrimp. Principal component analysis highlights that large breadcrumb sizes correlate with crispness, hardness, particle size, surface color, color uniformity, surface irregularity, total porosity, maximum force, area, drop in force, number of sound peaks, and sound pressure level. Agglomerative hierarchical clustering was used to confirm clustering of samples according to breadcrumb size. Multiple factor analysis confirmed overall correlation between sensory measurements and instrumental measurements ( In deep‐fried battered and breaded goods, crispness is a textural parameter that can be used to assess quality and freshness. The perception of crispness is dependent on rheological and mechanical characteristics as well as the sensations during eating  whether a panel is able to visually differentiate between crisp samples, (b) whether a panel is able to identify and describe differences in crispness between samples, (c) investigate any correlations between instrumental and sensory parameters, and (d) develop a predictive model for crispness. By correlating instrumental measurements to sensory data, this will provide useful information for food manufacturers to develop products with a desired level of crispness.22.1Samples of white shrimp were coated in predust flour, liquid batter layer and breadcrumbs prior to deep‐fat frying. Eight breadcrumb coating sizes were investigated and were separated using the following sieve apertures: 4.0 mm, 2.8 mm, 2.0 mm, 1.4 mm, 1.0 mm, 710 μm, 500 μm and 355 μm. All frozen samples were kept at 8°C before use, then deep‐fried for 3 min at 190°C and kept warm under a heat lamp for an additional 5 min prior to sensory evaluation.2.2A panel of eight was recruited externally according to a set criterion . A total of three 3 hr training sessions were held in order to familiarize panelists with the sensory attributes Table , followeAll samples were identified with a random 3‐digit code, then presented so that each panelist received all samples three times in a random order.2.3An analysis of variance (One‐way ANOVA) with post‐hoc Tukey honestly significant difference (HSD) was performed to identify any significant differences between samples. Principal component analysis (PCA) was performed to visualize any relationships among attributes and samples.Multiple factor analysis (MFA) is a factorial method that has been shown to be useful for studying relationships between different sets of variables, different sets of samples and variables to samples  regression was performed to study the regression of attributes in order to predict crispness. All statistical analyses were carried out using XLSTAT statistical software 2018.3 . Model selection function was also incorporated to allow for appropriate variable selection, in order to determine the best model fit. Multicollinearity was confirmed with variance inflation factors and tolerance values, therefore PLS regression was the appropriate method to apply. PLS regression was employed to understand which variables correlated positively or negatively to crispness. It is a recommended analysis if there are a high number of explanatory variables and high correlation between variables Abdi, .2.4Results from a previous study focused on characterizing eight samples instrumentally. The internal structure of the deep‐fried coatings was evaluated to show how the internal morphology changes with breadcrumb size, as well as the physical and mechanical properties . The only significant increase is “crumb coverage” . Increasing crumb coverage can be explained as breadcrumb size decreases, crumbs become more uniform in shape and size, this allows strong adhesion to the batter due to packing ability and therefore, surface coverage and surface uniformity  and “hardness” decreases significantly . Alternatively, “cohesiveness” increases significantly , “denseness” also increases significantly . As stated previously, larger breadcrumbs have higher exposure to frying oil. Therefore, crispness and hardness is expected to be higher as moisture and oil exchange is prolonged. This drying process results in a brittle coating with low moisture. Denseness and cohesiveness have a higher mean score for smaller breadcrumb sizes. This can be explained as increased packing ability allows particles to firmly stick to the batter, this results in less crumbling and cracking.In terms of texture attributes, as breadcrumb size decreases from 4.0 mm to 355 μm, “crispness” decreases significantly , hardness , cohesiveness  and denseness . Surface color , particle size , surface irregularity , crumb coverage , and color uniformity . Figure Figure p‐value 1.00), hardness , cohesiveness , denseness , surface irregularity , and crumb coverage .Sensory cluster of 2.0 and 1.4 mm are not significantly different in terms of crispness , maximum force (r = .882), drop in force (r = .865), sound peaks (r = .926) and sound pressure level (r = .618). This further supports the relationship of instrumental measurements to sensory perception of crispness. The advantage of this predictive model means that mechanical and physical properties can be used to predict a textural property. Therefore, a sensory panel is not required and less input variables are needed for the simulation of the model. This is potentially less time‐consuming and more cost‐effective.Multiple linear regression was previously carried out to test for multicollinearity and to provide validation for using PLS regression. PLS was used with the aim to predict sensory crispness from instrumental parameters (Equation 1). Crispness was selected as the dependent variable as it can be considered to be one of the most important attributes when assessing the quality and freshness of deep‐fried battered and breaded goods Mellema, . AlthougR2 value of .854 indicates high predictive ability of this model (Henseler, Ringle, & Sinkovics, Q2cum value of 0.770, which also measure the goodness of fit and predictive quality. Sensory crispness of deep‐fried battered and breaded shrimps could be predicted by resimulation of this model. As shown in Figure A PLS regression has been previously used to correlate instrumental data and sensory data for meats (Castejón, García‐Segura, Escudero, Herrera, & Cambero, 4In conclusion, the main contributors of crispness in deep‐fried battered and breaded coatings have been investigated in this study. In terms of sensory attributes, PCA showed that crispness was highly correlated with hardness, particle size, surface color, number of sound peaks, color uniformity, and surface uniformity, this was dependant on breadcrumb size.MFA confirmed positive correlations between instrumental and sensory measurements, this was also dependant on breadcrumb size. AHC identified that coatings were clustering into three groups; large, intermediate and small breadcrumb size. These clusters share common sensory and instrumental attributes within their samples. Crispness was found to be one of the most highly correlated variables to instrumental data, this allowed a predictive model to be developed using PLS regression analysis. An instrumental predictive model that allows prediction of crispness will allow a degree of quality control in future products. The use of force‐deformation coupled with acoustic events as well as internal morphology characterization allows for a thorough understanding of how the microstructure relates to texture perception.Conflict of Interest: All authors of this manuscript declare that they do not have any conflict of interest.Ethical Review: This study was approved from the ethics committee at the University of Birmingham.Informed Consent: All participants involved in the sensory study gave written informed consent prior to beginning this study.Author Contributions: Author K.Y.V. constructed the manuscript, collected and analyzed the data. Authors A.N.W, T.B.M., I.T.N. supervised the project and proof‐read the manuscript.


A 58-year-old man presented with general malaise and showed positive results for human T-cell leukemia virus type 1 (HTLV-1) infection. As blood tests revealed abnormal leukocytes and flower cells, smoldering-type adult T-cell leukemia/lymphoma (ATL) was diagnosed. After 7 years, the condition changed to acute-type ATL. Blood tests identified an increase in CD4 from 995 cells/µL to 1,256 cells/µL and monoclonal integration of HTLV-1 provirus into tumor cells. Treatment was started with chemotherapy and allogeneic bone marrow transplantation. During follow-up, he was referred to the ophthalmology department after experiencing sudden visual loss in the right eye.1 In addition, co-infections of the eye in immunocompetent patients are not frequently confirmed using serologic diagnostic methods.2 Multiplex polymerase chain reaction (PCR) and broad-range PCR of a sample of aqueous humor, therefore, ruled out viral , toxoplasma, tuberculosis, syphilis, and bacterial and fungal infections, ruling out opportunistic infection and allowing the diagnosis of intraocular leukemic cell infiltration.3 Elevated lesions on the retina improved after two vitreous injections of 400 μg/0.1 mL of methotrexate and subsided with five sessions of 2-Gy radiotherapy. Corresponding to this combination therapy, retinal lesions gradually resolved within 6 months (Slit-lamp examination revealed cellular infiltration in the anterior chamber and vitreous humor. Fundus examination showed yellowish-white infiltrative foci associated with protrusions in the retina. Optical coherence tomography revealed massive solid infiltrative foci below the retinal pigment epithelium . As diff6 months .4 This infection causes ATL and also visual impairment by ATL-related ocular manifestations.5 As HTLV-1–associated ATL is a neoplasia characterized by massive invasion of leukemic cells into various organs, physicians should keep in mind that intraocular infiltration is the most frequent manifestation observed among HTLV-1–associated ATL patients.1Globally, HTLV-1 infection is now the focus of attention, since the discovery that more than 40% of adults from Aboriginal communities in central Australia are infected with HTLV-1.