A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination.

Current multiple sclerosis (MS) medications are mainly immunomodulatory, having little or no effect on neuroregeneration of damaged central nervous system (CNS) tissue; they are thus primarily effective at the acute stage of disease, but much less so at the chronic stage. An MS therapy that has both immunomodulatory and neuroregenerative effects would be highly beneficial. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that ursolic acid (UA), an antiinflammatory natural triterpenoid, also directly promotes oligodendrocyte maturation and CNS myelin repair. Oral treatment with UA significantly decreased disease severity and CNS inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Importantly, remyelination and neural repair in the CNS were observed even after UA treatment was started on day 60 post immunization when EAE mice had full-blown demyelination and axonal damage. UA treatment also enhanced remyelination in a cuprizone-induced demyelination model in vivo and brain organotypic slice cultures ex vivo and promoted oligodendrocyte maturation in vitro, indicating a direct myelinating capacity. Mechanistically, UA induced promyelinating neurotrophic factor CNTF in astrocytes by peroxisome proliferator-activated receptor γ(PPARγ)/CREB signaling, as well as by up-regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation. Together, our findings demonstrate that UA has significant potential as an oral antiinflammatory and neural repair agent for MS, especially at the chronic-progressive stage.

Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone.

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.

Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice.

The human body has a remarkable ability to regulate inflammation, a biophysical response triggered by virus infection and tissue damage. Sirt6 is critical for metabolism and lifespan; however, its role in inflammation is unknown. Here we show that Sirt6-null (Sirt6(-/-)) mice developed chronic liver inflammation starting at ∼2 months of age, and all animals were affected by 7-8 months of age. Deletion of Sirt6 in T cells or myeloid-derived cells was sufficient to induce liver inflammation and fibrosis, albeit to a lesser degree than that in the global Sirt6(-/-) mice, suggesting that Sirt6 deficiency in the immune cells is the cause. Consistently, macrophages derived from the bone marrow of Sirt6(-/-) mice showed increased MCP-1, IL-6, and TNFα expression levels and were hypersensitive to LPS stimulation. Mechanistically, SIRT6 interacts with c-JUN and deacetylates histone H3 lysine 9 (H3K9) at the promoter of proinflammatory genes whose expression involves the c-JUN signaling pathway. Sirt6-deficient macrophages displayed hyperacetylation of H3K9 and increased occupancy of c-JUN in the promoter of these genes, leading to their elevated expression. These data suggest that Sirt6 plays an anti-inflammatory role in mice by inhibiting c-JUN-dependent expression of proinflammatory genes.

Molecular signatures for the class Coriobacteriia and its different clades; proposal for division of the class Coriobacteriia into the emended order Coriobacteriales, containing the emended family Coriobacteriaceae and Atopobiaceae fam. nov., and Eggerthellales ord. nov., containing the family Eggerthellaceae fam. nov.

The species of the class Coriobacteriia are currently distinguished from other bacteria primarily on the basis of their branching in the 16S rRNA gene trees. No reliable molecular marker is known that distinguishes the bacteria of this class from other organisms. We report here the results of detailed phylogenetic and comparative analyses on 22 sequenced genomes from members of the class Coriobacteriia. Detailed comparative analyses on protein sequences from these genomes, reported here, have identified 66 conserved signature inserts or deletions (i.e. indels) (CSIs) in widely distributed proteins that are specific for a number of different clades of the class Coriobacteriia at multiple phylogenetic levels, which are also supported by phylogenetic analyses. A set of 24 CSIs in different proteins are specific for all sequenced members of the class Coriobacteriia, providing novel molecular markers distinguishing and delimiting this class. One additional CSI is uniquely present in all members of the class Coriobacteriia and the phylum Actinobacteria supporting their placement within this bacterial phylum. A set of 16 CSIs in divergent proteins are uniquely found in the genomes of all species for which sequences are available from the glucose-fermenting genera Coriobacterium, Collinsella, Atopobium and Olsenella, but they are not present in any other bacteria. The species from these genera also form a strongly supported clade (Clade I) in the phylogenetic trees based upon concatenated protein sequences and the 16S rRNA. An additional 10 CSIs in different proteins are specifically present in all members of the asaccharolytic genera Eggerthella, Cryptobacterium, Slackia and Gordonibacter for which sequence data is available. A clade consisting of these genera (Clade II) is also supported by our phylogenetic analyses. Within Clade I, two smaller clades, one consisting of the genera Coriobacterium and Collinsella and the other containing the genera Atopobium and Olsenella, are independently supported by multiple CSIs (eight and seven respectively) and our phylogenetic analyses. Based upon the results of phylogenetic studies and the identified molecular markers, which clearly distinguish and demarcate the above indicated clades of the class Coriobacteriia at different phylogenetic depths, we propose division of the class Coriobacteriia into two orders (viz. Coriobacteriales and Eggerthellales ord. nov.) and three families (viz. Coriobacteriaceae, Atopobiaceae fam. nov. and Eggerthellaceae fam. nov.). Additionally, descriptions of the class Coriobacteriia, the order Coriobacteriales and the family Coriobacteriaceea are also emended.

High-quality genomes reveal significant genetic divergence and cryptic speciation in the model organism Folsomia candida (collembola).

The collembolan Folsomia candida Willem, 1902, is widely distributed throughout the world and has been frequently used as a test organism in soil ecology and ecotoxicology studies. However, it is questioned as an ideal "standard" because of differences in reproductive modes and cryptic genetic diversity between strains from various geographical origins. In this study, we obtained two high-quality chromosome-level genomes of F. candida, for a parthenogenetic strain (named FCDK, 219.08 Mb, 25,139 protein-coding genes) and a sexual strain (named FCSH, 153.09 Mb, 21,609 protein-coding genes), reannotated the genome of the parthenogenetic strain reported by Faddeeva-Vakhrusheva et al. in 2017 (named FCBL, 221.7 Mb, 25,980 protein-coding genes) and conducted comparative genomic analyses of the three strains. High genome similarities between FCDK and FCBL based on synteny, genome architecture, mitochondrial and nuclear gene sequences suggest that they are conspecific. The seven chromosomes of FCDK are each 25%-54% larger than the corresponding chromosomes of FCSH, showing obvious repetitive element expansions and large-scale inversions and translocations but no whole-genome duplication. The strain-specific genes, expanded gene families and genes in nonsyntenic chromosomal regions identified in FCDK are highly related to the broader environmental adaptation of parthenogenetic strains. In addition, FCDK has fewer strain-specific microRNAs than FCSH, and their mitochondrial and nuclear genes have diverged greatly. In conclusion, FCDK/FCBL and FCSH have accumulated independent genetic changes and evolved into distinct species after 10 million years ago. Our work provides important genomic resources for studying the mechanisms of rapidly cryptic speciation and soil arthropod adaptation to soil ecosystems.

A resting-state electroencephalographic microstates study in depressed adolescents with non-suicidal self-injury.

Neuroimaging studies have revealed abnormal brain activities in depressed teenagers who engage in non-suicidal self-injury (NSSI). We used resting-state electroencephalography (EEG) microstate analysis, which indicates the brief overlap of brain network activation for exploring the characteristics of large-scale cortical activities in depressed adolescents engaged with NSSI to clarify the underlying temporal mechanism. A modified k-means cluster algorithm was used to segment 64-channel resting-state EEG data into microstates. Data from 27 healthy adolescents, 37 adolescents with major depressive disorder (MDD), and 53 adolescents with both MDD and NSSI were examined in this study. The resting-state microstate parameters were compared among groups using the one-way ANOVA and Spearman correlation. Then the associations between significantly different microstate parameters and the depressive severity and self-harming data in the patient groups were further analyzed. The MDD group had higher contribution (p < 0.01), occurrence (p < 0.01) of microstate A, and higher microstate E→A transition (p < 0.05) than the HC and the NSSI group. The MDD group showed a distinctly longer duration (p < 0.05) of microstate A and microstate A→C transition than the HC. The transition probability from B to C was increased in the NSSI group compared to the HC. In the MDD group, the HAMD correlated with the duration of microstate A (Spearman's rho = 0.34, p = 0.044), as the PHQ-9 correlated with its occurrence (Spearman's rho = 0.37, p = 0.028). This research revealed that whereas depressive adolescents with NSSI and MDD displayed similar patterns with healthy controls in EEG microstate, the MDD group did not. Additionally, the non-random transition from microstate E→A may protect against recent self-harm in adolescents with MDD.

[Adjunctive therapy of hypopharyngeal carcinoma by Qingliu Lianghou Recipe].

OBJECTIVE: To study the adjunctive roles of Qingliu Lianghou Recipe (QLR) in treatment of hypopharyngeal carcinoma. METHODS: A total of 156 patients with hypopharyngeal squamous cell carcinoma were recruited, including 21 cases of stage I, 34 in stage II, 55 in stage III, and 46 in stage IV. Of them, 31 patients (Group A) were managed with operation and post-operative radiotherapy, 40 patients (Group B) with operation, post-operative radiotherapy, and QLR, 45 patients (Group C) were managed with concomitant chemoradiotherapy, 40 patients (Group D)with concomitant chemoradiation and QLR. QLR was given for 12 weeks. The radio- and chemotoxic reactions, quality of life (KPS score), and long-term efficacy (the recurrence time and the survival time) were observed. RESULTS: The toxicity levels were significantly lower in Group B than in Group A, manifested as radioactive dermatitis, mucositis, dysphagia, changes in body weight, and lymphatic edema (P < 0.05, P < 0.01). The toxicity levels were significantly lower in Group D than in Group C, manifested as radioactive dermatitis, mucositis, dysphagia, marrow depression, changes in body weight, and gastrointestinal reactions (P < 0.05, P < 0.01). After treatment the KPS scores of all patients obviously decreased (P < 0.05, P < 0.01). But the KPS scores were significantly higher in Group B than in Group A (P < 0.05), and they were significantly higher in Group D than in Group C (P < 0.05). The 3-year recurrence rate of patients in Group A was 41.94%, 20.00% in Group B, 60.00% in Group C, and 37.50% in Group D (P < 0.05). The 5-year survival rate of patients in Group A was 38.71%, 62.50% in Group B, 22.22% in Group C, and 42.50% in Group D (P < 0.05). CONCLUSIONS: QLR could effectively prevent and reduce the toxicity response caused by operation, radiotherapy and chemotherapy. The combination therapy of integrative medicine could postpone the recurrence and prolong the lifespan of patients. Therefore, we must not neglect the adjunctive therapy of QLR in treating hypopharyngeal carcinoma.

Cold Roll Forming Process Design for Complex Stainless-Steel Section Based on COPRA and Orthogonal Experiment.

Cold roll forming can fabricate products with complex profiles, and its parameter optimization can achieve high quality and improved precision of products. In this paper, taking the side shield as a typical product, the cold roll forming of a complex section of stainless steel SUS301L-ST is analyzed, establishing a 3D finite element model by using the professional roll forming software COPRA. We propose a floating roll device for complex sections with asymmetry and large depth. We use an orthogonal experiment to obtain the inter-distance between rolls, friction coefficients, the diameter increments, and line velocities to investigate the effects on the maximum longitudinal strain of the edge. Results show that the diameter increment has the greatest influence on the maximum strain, and its increases can reduce the strain. The inter-distance value needs a suitable range. A small value is not conducive to the release of elastic deformation, while a large value will cause unexpected displacement and increase the cost. The friction coefficient increases; although it helps to reduce the strain, it will cause scratches and other defects on the stainless steel. The increase in velocity increases the strain. We derive the optimal parameters for the complex section, providing a theoretical basis for practical production.

Altered Neural Reactivity in Adolescents With Nonsuicidal Self-Injury During Exposure to Self-Injury Related Cues: Electrophysiological Evidence From a Two-Choice Oddball Paradigm.

Background: Nonsuicidal self-injury (NSSI) may be a type of addiction, that is characterized by cue reactivity. We aimed to explore the behavioral performance and neural reactivity during exposure to self-injury cues in adolescents with NSSI and major depressive disorder (MDD). Methods: Eighteen MDD patients, 18 MDD patients with NSSI, and 19 healthy controls (HC) were recruited to perform a two-choice oddball paradigm. All subjects were 12-18 years old. Neutral cues and self-injury related cues separately served as deviant stimuli. Difference waves in N2 and P3 (N2d and P3d) were derived from deviant waves minus standard waves. Accuracy cost and reaction time (RT) cost were used as behavioral indexes, while the N2d and P3d were used as electrophysiological indexes; the N2d reflects early conflict detection, and the P3d reflects the process of response inhibition. Results: No significant main effects of group or cue or an effect of their interaction were observed on accuracy cost and P3d latency. For RT cost, N2d amplitude, and N2d latency, there was a significant main effect of cue. For P3d amplitude, there was a significant main effect of cue and a significant group × cue interaction. In the NSSI group, the P3d amplitude with self-injury cues was significantly larger than that with neutral cues. However, there was no such effect in the MDD and HC groups. Conclusions: Adolescents with NSSI showed altered neural reactivity during exposure to self-injury cue. Further studies with larger sample sizes are needed to confirm our results.

The mitochondrial genome of Sinentomon erythranum (Arthropoda: Hexapoda: Protura): an example of highly divergent evolution.

BACKGROUND: The phylogenetic position of the Protura, traditionally considered the most basal hexapod group, is disputed because it has many unique morphological characters compared with other hexapods. Although mitochondrial genome information has been used extensively in phylogenetic studies, such information is not available for the Protura. This has impeded phylogenetic studies on this taxon, as well as the evolution of the arthropod mitochondrial genome. RESULTS: In this study, the mitochondrial genome of Sinentomon erythranum was sequenced, as the first proturan species to be reported. The genome contains a number of special features that differ from those of other hexapods and arthropods. As a very small arthropod mitochondrial genome, its 14,491 nucleotides encode 37 typical mitochondrial genes. Compared with other metazoan mtDNA, it has the most biased nucleotide composition with T = 52.4%, an extreme and reversed AT-skew of -0.351 and a GC-skew of 0.350. Two tandemly repeated regions occur in the A+T-rich region, and both could form stable stem-loop structures. Eighteen of the 22 tRNAs are greatly reduced in size with truncated secondary structures. The gene order is novel among available arthropod mitochondrial genomes. Rearrangements have involved in not only small tRNA genes, but also PCGs (protein-coding genes) and ribosome RNA genes. A large block of genes has experienced inversion and another nearby block has been reshuffled, which can be explained by the tandem duplication and random loss model. The most remarkable finding is that trnL2(UUR) is not located between cox1 and cox2 as observed in most hexapod and crustacean groups, but is between rrnL and nad1 as in the ancestral arthropod ground pattern. The "cox1-cox2" pattern was further confirmed in three more representative proturan species. The phylogenetic analyses based on the amino acid sequences of 13 mitochondrial PCGs suggest S. erythranum failed to group with other hexapod groups. CONCLUSIONS: The mitochondrial genome of S. erythranum shows many different features from other hexapod and arthropod mitochondrial genomes. It underwent highly divergent evolution. The "cox1-cox2" pattern probably represents the ancestral state for all proturan mitogenomes, and suggests a long evolutionary history for the Protura.

The mitochondrial genome of a minute springtail species Megalothorax incertus (Collembola: Neelipleona: Neelidae).

In this study, the complete mitochondrial genome for the Wolbachia infected parthenogenetic collembola Megalothorax incertus Börner, 1903 was determined. It represents the first report of a complete mitochondrial genome from Neelipleona, one of the four orders of Collembola. The circularized 14,994 bp mitochondrial genome sequence consists of canonical 37 mito-genes, including 13 protein-coding genes (PCGs), 22 tRNA genes, and two rRNA genes. The base composition of the majority strand (same direction as most of the mitochondrial genes) is 32.0% for A, 24.1% for C, 11.9% for G, and 32.1% for T. The phylogenetic trees inferred from 13 PCGs using the Maximum-likelihood (ML) and Bayesian inference (BI) methods suggested that Neelidae is basal to the remaining springtails. This mitochondrial genome provides new insights to decipher the phylogeny of Collembola.

A multi-generational risk assessment of Cry1F on the non-target soil organism Folsomia candida (Collembola) based on whole transcriptome profiling.

The Bacillus thuringiensis toxin Cry1F has been used to develop insect-resistant genetically engineered crops. There has been great interest in evaluating its potential risk to non-target organisms (NTOs). However, the majority of previous risk assessments only examined one generation of NTOs using several physiological indicators, which cannot comprehensively detect some potential sub-lethal effects at the molecular level. In this study, we conducted a laboratory-based, multi-generational risk assessment of Cry1F for the collembolan Folsomia candida, an important representative of soil arthropods in terms of survival, reproduction, and differentially expressed genes (DEGs) identified from whole transcriptome profiles. Our results demonstrated that Cry1F was continuously ingested by collembolans over three consecutive generations, but it did not affect the survival or reproduction of F. candida. There were no significant differences in the global gene expression between F. candida-fed diets with and without Cry1F, and no consistent co-expressed DEGs over three generations. In addition, Cry1F did not obviously alter the expression profiles of seven sensitive biological markers. Our composite data indicates that Cry1F had no long-term harmful effects on collembolan F. candida.

Going Deeper into High and Low Phylogenetic Relationships of Protura.

Proturans are small, wingless, soil-dwelling arthropods, generally associated with the early diversification of Hexapoda. Their bizarre morphology, together with conflicting results of molecular studies, has nevertheless made their classification ambiguous. Furthermore, their limited dispersal capability (due to the primarily absence of wings) and their euedaphic lifestyle have greatly complicated species-level identification. Mitochondrial and nuclear markers have been applied herein to investigate and summarize proturan systematics at different hierarchical levels. Two new mitochondrial genomes are described and included in a phylum-level phylogenetic analysis, but the position of Protura could not be resolved with confidence due to an accelerated rate of substitution and extensive gene rearrangements. Mitochondrial and nuclear loci were also applied in order to revise the intra-class systematics, recovering three proturan orders and most of the families/subfamilies included as monophyletic, with the exception of the subfamily Acerentominae. At the species level, most morphologically described species were confirmed using molecular markers, with some exceptions, and the advantages of including nuclear, as well as mitochondrial, markers and morphology are discussed. At all levels, an enlarged taxon sampling and the integration of data from different sources may be of significant help in solving open questions that still persist on the evolutionary history of Protura.

Low FT3 is a valuable predictor of severe acute pancreatitis in the emergency department.

OBJECTIVE: To investigate the relationship between serum levels of thyroid hormones and disease severity at the early stage of acute pancreatitis (AP). METHODS: Cohort data from 172 patients with AP attending the Emergency Department of our hospital from 2012 to 2017 were retrospectively reviewed and analyzed. Patients were categorized into mild (MAP), moderately severe (MSAP) and severe AP (SAP) groups based on the disease severity. The MSAP and SAP groups were combined into a non-MAP group for analysis. The predictive values of C-reactive protein (CRP) levels, Ranson score, APACHE II score and serum thyroid hormone levels were analyzed. RESULTS: In total, 76 (44.2%), 85 (49.4%) and 11 (6.4%) patients were included in the MAP, MSAP and SAP groups, respectively. The free triiodothyronine (FT3) levels were significantly lower in the combined non-MAP group than in the MAP group. The tetraiodothyronine (T4) levels were significantly lower in the SAP group than in the MAP and MSAP groups (P = 0.002). Logistic regression analysis revealed that a low FT3 level was an independent risk factor for the incidence of non-MAP (P = 0.004). The area under the receiver operating characteristic curve and sensitivity of FT3 were 0.729 and 88.2%, respectively, which were higher than those of CRP, Ranson and APACHE II scores. CONCLUSION: Monitoring FT3 levels in the early stage of AP is helpful for evaluating disease severity and predicting the incidence of non-MAP, making it a useful tool for guiding AP treatment.

Revisiting the phylogeny of Wolbachia in Collembola.

The endosymbiont Wolbachia has been detected in a few parthenogenetic collembolans sampled in Europe and America, including three species of Poduromorpha, two species of Entomobryomorpha, and two species of Neelipleona. Based on 16S rRNA and ftsZ gene sequences, most of the Wolbachia infecting parthenogenetic collembolans were characterized as members of supergroup E and showed concordant phylogeny with their hosts. However, the two neelipleonan symbionts form another unique group, indicating that Wolbachia has infected parthenogenetic collembolans multiple times. In this study, five parthenogenetic collembolan species were identified as hosts of Wolbachia, and four new Wolbachia strains were reported for four collembolan species sampled in China, respectively, including a neelipleonan strain from Megalothorax incertus (wMinc). Our results demonstrated that the Wolbachia multilocus sequence typing (MLST) system is superior to the 16S rRNA + ftsZ approach for phylogenetic analyses of collembolan Wolbachia. The MLST system assigned these Wolbachia of parthenogenetic collembolans to supergroup E as a unique clade, which included wMinc, supporting the monophyletic origin of Wolbachia in parthenogenetic collembolan species. Moreover, our data suggested supergroup E as one of the most divergent lineages in Wolbachia and revealed the discrepancy between the phylogenies of Wolbachia from parthenogenetic collembolans and their hosts, which may result from the high level of genetic divergence between collembolan Wolbachia, in association with the geographic differentiation of their hosts, or the possible horizontal transmission of Wolbachia between different collembolan species.

Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants.

OBJECTIVE: To investigate the clinical characteristics of patients with hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to hypertriglyceridemia in such patients. METHODS: Clinical data from 329 patients with acute pancreatitis (AP) were analyzed. The patients were divided into the HTGAP group, with fasting serum triglyceride (TG) levels ≥500 mg/dL (5.65 mmol/L), and the non-HTGAP (NHTGAP) group. Targeted next-generation sequencing was applied to 11 HTGAP patients to identify the genetic mutations associated with hypertriglyceridemia, including apolipoprotein A-V (APOA5), APOC2, APOC3 and APOE, BLK, LPL, GPIHBP1 and LMF1. RESULTS: Patients in the HTGAP group, compared with those in the NHTGAP group, had a higher mortality rate (7.5% vs 0.7%, P = 0.001), more commonly seen severe AP (17.5% vs 5.2%, P = 0.004) as well as a higher recurrence rate (32.4% vs 19.9%, P = 0.070). DNA sequencing showed that two patients carried the same compound of p.G185C and p.V153M heterozygous mutations located in the APOA5 gene. Two patients carried a homozygous variation of p.C14F, in the GPIHBP1 gene. One patient had a homozygous variation of p.R176C in the APOE gene. And a rare heterozygous LMF1 gene mutation of p.P562R was detected in two patients. CONCLUSIONS: HTGAP was significantly severe than NHTGAP, with a high recurrence rate. Genetic information may be useful in the clinical setting for the investigation of the pathogenesis of HTGAP and its interventions.

Importance of ticks and their chemical and immunological control in livestock.

The medical and economic importance of ticks has long been recognized due to their ability to transmit diseases to humans and animals. Ticks cause great economic losses to livestock, and adversely affect livestock hosts in several ways. Loss of blood is a direct effect of ticks acting as potential vector for haemo-protozoa and helminth parasites. Blood sucking by large numbers of ticks causes reduction in live weight and anemia among domestic animals, while their bites also reduce the quality of hides. However, major losses caused by ticks are due to their ability to transmit protozoan, rickettsial and viral diseases of livestock, which are of great economic importance world-wide. There are quite a few methods for controlling ticks, but every method has certain shortcomings. The present review is focused on ticks importance and their control.

Comparison of three scoring systems in predicting clinical outcomes in patients with acute upper gastrointestinal bleeding: a prospective observational study.

OBJECTIVE: To compare the performances of the Glasgow-Blatchford score (GBS), modified GBS (mGBS) and AIMS65 in predicting clinical outcomes in patients with acute upper gastrointestinal bleeding (AUGIB). METHODS: This study enrolled 320 consecutive patients with AUGIB. Patients at high and low risks of developing adverse clinical outcomes (rebleeding, the need of clinical intervention and death) were categorized according to the GBS, mGBS and AIMS65 scoring systems. The outcome of the patients were the occurrences of adverse clinical outcomes. The areas under the receiver operating characteristics curve (AUROC) of three scoring systems were compared. RESULTS: Irrespective of the systems used, the high-risk groups showed higher rates of rebleeding, intervention and death compared with the low-risk groups (P < 0.05). For the prediction of rebleeding, AIMS65 (AUROC 0.735, 95% CI 0.667-0.802) performed significantly better than GBS (AUROC 0.672, 95% CI 0.597-0.747; P < 0.01) and mGBS (AUROC 0.677, 95% CI 0.602-0.753; P < 0.01). For the prediction of interventions, there was no significant difference among the three systems (GBS: AUROC 0.769, 95% CI 0.668-0.870; mGBS: AUROC 0.745, 95% CI 0.643-0.847; AIMS65: AUROC 0.746, 95% CI 0.640-0.851). For the prediction of in-hospital mortality, there was no significant difference among the three systems (GBS: AUROC 0.796, 95% CI 0.694-0.898; mGBS: AUROC 0.803, 95% CI 0.703-0.904; AIMS65: AUROC 0.786, 95% CI 0.670-0.903). CONCLUSIONS: The three scoring systems are reliable and accurate in predicting the rates of rebleeding, surgery and mortality in AUGIB. However, AIMS65 outperforms GBS and mGBS in predicting rebleeding.

Mapping the Distribution of Anthrax in Mainland China, 2005-2013.

BACKGROUND: Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30-49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0-2 months. A boosted regression trees (BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level. CONCLUSIONS/SIGNIFICANCE: Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections.

PD-1 blockade attenuates immunosuppressive myeloid cells due to inhibition of CD47/SIRPα axis in HPV negative head and neck squamous cell carcinoma.

Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) play key roles in the tumor immune suppressive network and tumor progression. However, precise roles of programmed death-1 (PD-1) in immunological functions of MDSCs and TAMs in head and neck squamous cell carcinoma (HNSCC) have not been clearly elucidated. In the present study, we show that PD-1 and PD-L1 levels were significantly higher in human HNSCC specimen than in normal oral mucosa. MDSCs and TAMs were characterized in mice and human HNSCC specimen, correlated well with PD-1 and PD-L1 expression. αPD-1 treatment was well tolerated and significantly reduced tumor growth in the HNSCC mouse model along with significant reduction in MDSCs and TAMs in immune organs and tumors. Molecular analysis suggests a reduction in the CD47/SIRPα pathway by PD-1 blockade, which regulates MDSCs, TAMs, dendritic cell as well as effector T cells. Hence, these data identify that PD-1/PD-L1 axis is significantly increased in human and mouse HNSCC. Adoptive αPD-1 immunotherapy may provide a novel therapeutic approach to modulate the micro- and macro-environment in HNSCC.