Human prion diseases are a group of transmissible, progressive, and invariably fatal neurodegenerative disorders, which include Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Human prion diseases affect approximately 1–2 persons per million worldwide annually, occurring in sporadic, inherited, and acquired forms. These diseases have attracted both scientific and public attention not only because of their mysterious pathogen, but also due to their considerable threat to public health since the emergence of the variant CJD.There are still no specific therapeutic and prophylactic interventions available for prion diseases, thus active surveillance of human prion diseases is critical for disease control and prevention. Since 1993, CJD surveillance systems have been established in many countries and regions, and several long-term multinational cooperative projects have been conducted.In this paper, the epidemiological characteristics of various human prion diseases and the active surveillance systems pertaining to them in different countries and regions are summarized and reviewed.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0143-8) contains supplementary material, which is available to authorized users.

This study focused on producing flash flood hazard susceptibility maps (FFHSM) using frequency ratio (FR) and statistical index (SI) models in the Xiqu Gully (XQG) of Beijing, China. First, a total of 85 flash flood hazard locations (n = 85) were surveyed in the field and plotted using geographic information system (GIS) software. Based on the flash flood hazard locations, a flood hazard inventory map was built. Seventy percent (n = 60) of the flooding hazard locations were randomly selected for building the models. The remaining 30% (n = 25) of the flooded hazard locations were used for validation. Considering that the XQG used to be a coal mining area, coalmine caves and subsidence caused by coal mining exist in this catchment, as well as many ground fissures. Thus, this study took the subsidence risk level into consideration for FFHSM. The ten conditioning parameters were elevation, slope, curvature, land use, geology, soil texture, subsidence risk area, stream power index (SPI), topographic wetness index (TWI), and short-term heavy rain. This study also tested different classification schemes for the values for each conditional parameter and checked their impacts on the results. The accuracy of the FFHSM was validated using area under the curve (AUC) analysis. Classification accuracies were 86.61%, 83.35%, and 78.52% using frequency ratio (FR)-natural breaks, statistical index (SI)-natural breaks and FR-manual classification schemes, respectively. Associated prediction accuracies were 83.69%, 81.22%, and 74.23%, respectively. It was found that FR modeling using a natural breaks classification method was more appropriate for generating FFHSM for the Xiqu Gully.

This study focused on landslide susceptibility analysis mapping of the Xulong hydropower station reservoir, which is located in the upstream of Jinsha River, a rapidly uplifting region of the Tibetan Plateau region. Nine factors were employed as landslide conditioning factors in landslide susceptibility mapping. These factors included the slope angle, slope aspect, curvature, geology, distance-to-fault, distance-to-river, vegetation, bedrock uplift and annual precipitation. The rapid bedrock uplift factor was represented by the slope angle. The eight factors were processed with the information content model. Since this area has a significant vertical distribution law of precipitation, the annual precipitation factor was analyzed separately. The analytic hierarchy process weighting method was used to calculate the weights of nine factors. Thus, this study proposed a component approach to combine the normalized eight-factor results with the normalized annual precipitation distribution results. Subsequently, the results were plotted in geographic information system (GIS) and a landslide susceptibility map was produced. The evaluation accuracy analysis method was used as a validation approach. The landslide susceptibility classes were divided into four classes, including low, moderate, high and very high. The results show that the four susceptibility class ratios are 12.9%, 35.06%, 34.11%and 17.92% of the study area, respectively. The red belt in the high elevation area represents the very high susceptibility zones, which followed the vertical distribution law of precipitation. The prediction accuracy was 85.74%, which meant that the susceptibility map was confirmed to be reliable and reasonable. This susceptibility map may contribute to averting the landslide risk in the future construction of the Xulong hydropower station.

In view of the effect of water on the physical and mechanical parameters of natural gypsum rock, in this study, gypsum rock in the goaf of a gypsum mine was selected as the research object, and gypsum rock samples were prepared with different immersion times. In addition, uniaxially tests were performed separately on the gypsum rock samples. Compression and scanning electron microscopy experiments were carried out to analyze the effects of immersion time on the uniaxial compressive strength, elastic modulus, Poisson's ratio, and microstructure of gypsum. The results show that the uniaxial compressive strength and elastic modulus of gypsum are inversely proportional to the water content. However, the Poisson's ratio is direly proportional to the water content, and the failure mode is destroyed by the brittle fracture of a single crack and is transformed into the shear ductile failure of the Y-shaped crack. Microscopically, with increasing immersion time, the bonds in the crystal of the microporous cracks and microcrack tips are weakened by hydrolysis, and the macroscopic structure is complicated by the internal structure of gypsum, and the end of the crack is expanded by the compressive action of water. Based on the damage mechanics, the evolution equation of gypsum soaking softening damage based on time factor was derived. The relationship between the brittleness coefficient and softening damage variable is revealed, providing a theoretical basis for the determination of the softening degree of gypsum in the goaf. INDEX TERMS Gypsum rock, water immersion, softening damage, brittleness coefficient.

BACKGROUND Tonsillectomy is the most common procedure for treatment of pediatric recurrent acute tonsillitis and tonsillar enlargement that contributes to obstructive sleep apnea hypopnea syndrome. Postoperative hemorrhage of tonsillectomy is a life-threatening complication. AIM To identify the risk factors that may contribute to primary and secondary post-operative hemorrhage in pediatric tonsillectomy. METHODS The clinical data from 5015 children, 3443 males and 1572 females, aged 1.92-17.08 years, with recurrent tonsillitis and/or tonsil hypertrophy who underwent tonsillectomy in our hospital from January 2009 to December 2018 were retrospectively collected. The variables including sex, age, time of onset, diagnosis, method of tonsillectomy, experience of surgeon, time when the surgery started and monthly average air temperature were abstracted. The patients with postoperative hemorrhage were classified into two groups, the primary bleeding group and the secondary bleeding group, and their characteristics were compared with those of the nonbleeding group separately. Statistical analysis was performed by chi-square test with SPSS 20. RESULTS Ninety-two patients had post-tonsillectomy hemorrhage, and the incidence rate of post-tonsillectomy hemorrhage was 1.83%. The mean age was 5.75 years. Cases of primary hemorrhage accounted for approximately 33.70% (31/92), and cases of secondary hemorrhage occurred in 66.30% (61/92). The rate of reoperation for bleeding was 0.92%, and the rate of rehospitalization for bleeding was 0.88% in all patients. Multiple hemostasis surgery was performed in 6.52% (3/46) of patients. The method of tonsillectomy (coblation tonsillectomy) and experience of the surgeon (junior surgeon with less than 5 years of experience) were significantly associated with primary hemorrhage ( χ 2 = 5.830, P = 0.016, χ 2 = 6.621, P = 0.010, respectively). Age (over 6 years old) and time of onset (more than a 1-year history) were significantly associated with secondary hemorrhage ( χ 2 = 15.242, P = 0.000, χ 2 =4.293, P = 0.038, respectively). There was no significant difference in sex, diagnosis, time when the surgery started or monthly average air temperature. There was a significant difference in the intervention measures between the primary bleeding group and the secondary bleeding group ( χ 2 = 10.947, P = 0.001). The lower pole and middle portion were the common bleeding sites, followed by the upper pole and palatoglossal arch. CONCLUSION The incidence rate of post-tonsillectomy hemorrhage is low. Coblation tonsillectomy and less tha...

As an integral part of the innate immunity, the complement system has been reported to involve in the pathogenesis of prion diseases (PrD). However, the states of expression and activity of complement proteins in experimental models of scrapie infection are still not fully understood. Herein, the state of complement activation, the presence, and distribution as well as localization of C3 and membrane attack complex (MAC) in the brains of several scrapie-infected rodents were comparatively assessed through various methodologies. Our data illustrated a significant increase in the total complement activity (CH50, U/ml) in several scrapie-infected rodent brains at the terminal stage and a time-dependent upregulation of C1q in 263K-infected hamsters during the incubation period, intimating the sustained and progressive activation of the classical pathway during PrD progression. Confocal microscopy revealed robust activation of C3 and its localization to various central nervous system (CNS) cells with differential morphology in the brain tissues of both 263K-infected hamsters and 139A-infected C57BL/6 mice at disease end stages. Dynamic analyses of MAC in the brains of 263K-infected hamsters and 139A-infected C57BL/6 mice demonstrated remarkably time-dependent deposition during the incubation period, which may highlight a persistently activated terminal complement components. Moreover, immunofluorescent assays (IFAs) showed that MAC-specific signals appeared to overlap with morphologically abnormal neurons rather than proliferative astrocytes or activated microglia throughout the CNS of both 263K-infected hamsters and 139A-infected C57BL/6 mice. Overall, these results indicate that the activation of the complement system and the subsequent localization of the complement components to neurons may be a hallmark during prion infection, which ultimately contribute to the neurodegeneration in PrD.

The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed. Significant decreases of brain Drp1 were observed in scrapie-infected rodents at terminal stage by Western blots and immunohistochemical assays, while the levels of Opa1 also showed declined tendency in the brains of scrapie-infected rodents. Immunofluorescent assays illustrated well localization of Drp1 or Opa1 within NeuN-positive cells. Moreover, the S-nitrosylated forms of Drp1significantly increased in the brain tissues of 139A- and ME7-infected mice at terminal stage. Dynamic analysis of Drp1 and SNO-Dpr1 in the brains collected at different time points within the incubation period of 139A-infected mice demonstrated that the whole Drp1 decreased at all tested samples, whereas the SNO-Drp1 remarkably increased in the sample of 90-day post-infection (dpi), reached to the peak in that of 120 dpi and dropped down but still maintained at higher level at the end of disease. The levels of apoptotic factors cleaved caspase 9, caspase 3, and Bax were also markedly increased in the brain tissues of the mice infected with agents 139A and ME7. Our data indicate a disorder of mitochondria dynamics in the brains of prion infection, largely depending on the abnormal alteration of brain Drp1.

Background: Recently, mesenchymal stem cells (MSCs) have been shown to have immunomodulatory properties which hold promise for their clinical use to treat inflammatory conditions. Relative to bone marrow-derived MSCs (BMSCs), which are typically isolated from the iliac crest, we have recently demonstrated that MSCs can be predictably isolated from the alveolar bone (aBMSCs) by less invasive means. As such, the aim of this study was to characterize the immunomodulatory properties of aBMSCs relative to BMSCs. Methods: aBMSCs isolated from the human alveolar bone and BMSCs isolated from the human bone marrow of the iliac crest were cultured in the same conditions. Cytokine arrays and enzyme-linked immunosorbent assays (ELISA) of a conditioned medium were used to evaluate differences in the secretion of cytokines. In different functional assays, aBMSCs and BMSCs were cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cells (PBMCs) to evaluate their effects on important immune cell functions including proliferation, differentiation, and activation. Results: The protein arrays identified interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 to be the major cytokines secreted by aBMSCs and BMSCs. ELISA determined that aBMSCs secreted 268.64 ± 46.96 pg/mL of IL-6 and 196.14 ± 97.31 pg/mL of MCP-1 per microgram of DNA, while BMSCs secreted 774.86 ± 414.29 pg/mL of IL-6 and 856.37 ± 433.03 pg/mL of MCP-1 per microgram of DNA. The results of the coculture studies showed that aBMSCs exhibited immunosuppressive effects on monocyte activation and T cell activation and proliferation similar to BMSCs. Both aBMSCs and BMSCs drove macrophages into an anti-inflammatory phenotype with increased phagocytic ability. Taken together, these data suggest that aBMSCs have potent immunomodulatory properties comparable to those of BMSCs. Conclusions:The findings of this study have important implications for the development of immunomodulatory stem cell therapies aimed to treat inflammatory conditions using aBMSCs, a more feasible tissue source of MSCs.