Towards Robust and Accurate Image Registration by Incorporating Anatomical and Appearance Priors

Ph.DDOCTOR OF PHILOSOPH

Necrosis is the dominant cell death pathway in uropathogenic Escherichia coli elicited epididymo-orchitis and is responsible for damage of rat testis

Male infertility is a frequent medical condition, compromising approximately one in twenty men, with infections of the reproductive tract constituting a major etiological factor. Bacterial epididymo-orchitis results in acute inflammation most often caused by ascending canalicular infections from the urethra via the continuous male excurrent ductal system. Uropathogenic Escherichia coli (UPEC) represent a relevant pathogen in urogenital tract infections. To explore how bacteria can cause damage and cell loss and thus impair fertility, an in vivo epididymo-orchitis model was employed in rats by injecting UPEC strain CFT073 into the vas deference in close proximity to the epididymis. Seven days post infection bacteria were found predominantly in the testicular interstitial space. UPEC infection resulted in severe impairment of spermatogenesis by germ cell loss, damage of testicular somatic cells, a decrease in sperm numbers and a significant increase in TUNEL (+) cells. Activation of caspase-8 (extrinsic apoptotic pathway), caspase-3/−6 (intrinsic apoptotic pathway), caspase-1 (pyroptosis pathway) and the presence of 180 bp DNA fragments, all of which serve as indicators of the classical apoptotic pathway, were not observed in infected testis. Notably, electron microscopical examination revealed degenerative features of Sertoli cells (SC) in UPEC infected testis. Furthermore, the passive release of high mobility group protein B1 (HMGB1), as an indication of necrosis, was observed in vivo in infected testis. Thus, necrosis appears to be the dominant cell death pathway in UPEC infected testis. Substantial necrotic changes seen in Sertoli cells will contribute to impaired spermatogenesis by loss of function in supporting the dependent germ cells

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated) and TM (IL-1β, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells

Influencing factors for the length of hospital stay in patients with drug-induced liver injury

ObjectiveTo investigate the influencing factors for the length of hospital stay in patients with drug-induced liver injury (DILI), and to guide clinical practice, reduce the pressure of hospitalization, and reduce the patients′ economic burden. MethodsThe clinical data of the patients with DILI who were hospitalized in Qingdao Municipal Hospital from January 2012 to December 2014 were collected, including age, sex, primary disease, medication history, routine blood test, liver function parameters, DILI type, medication, and prognosis. The Spearman rank correlation, Wilcoxon rank sum test, and Kruskal-Wallis H rank sum test were used to analyze the influencing factors for the length of hospital stay. A multivariate linear regression analysis was performed for the factors with statistical significance determined by the univariate analysis. ResultsThe clinical data of 191 patients with DILI were collected. Among these patients, there were 114 male and 77 female patients aged 11-84 years (mean 50.83±2.72 years), and the mean hospital stay was 14 days (range 4-41 days). Patient′s age, the highest levels of alanine aminotransferase (ALT)/alkaline phosphatase (ALP)/total bilirubin (TBil), and the lowest level of prothrombin activity (PTA) were positively correlated with the length of hospital stay (rs=0.388, 0.247, 0.172, 0.487, and 0.120, all P＜0.05). The presence or absence of the histories of underlying liver disease, hypertension, malignant tumors, tuberculosis, and hyperthyroidism, use of different suspected drugs, therapies for DILI, and DILI types were the influencing factors for the length of hospital stay in patients with DILI (all P＜0.05). The multivariate linear regression analysis showed that age, the histories of underlying liver disease and malignant tumors, traditional Chinese medicine, antipyretic and analgesic drugs, the highest levels of ALT/ALP/TBil, the lowest level of PTA, therapies for DILI, and DILI types were independent risk factors for the length of hospital stay in patients with DILI (all P＜0.05). ConclusionAge, the histories of underlying liver disease and malignant tumors, traditional Chinese medicine, antipyretic and analgesic drugs, the highest levels of ALT/ALP/TBil, the lowest level of PTA, therapies for DILI, and DILI types are influencing factors for the length of hospital stay in patients with DILI. Regulation of the influencing factors for the length of hospital stay during clinical diagnosis and treatment can reduce hospital costs and plays an important role in reducing healthcare burden

Correlation-constrained and sparsity-controlled vector autoregressive model for spatio-temporal wind power forecasting

The ever-increasing number of wind farms has brought both challenges and opportunities in the development of wind power forecasting techniques to take advantage of interdependencies between tens or hundreds of spatially distributed wind farms, e.g., over a region. In this paper, a sparsity-controlled vector autoregressive (SC-VAR) model is introduced to obtain sparse model structures in a spatio-temporal wind power forecasting framework by reformulating the original VAR model into a constrained mixed integer nonlinear programming (MINLP) problem. It allows controlling the sparsity of the coefficient matrices in direct manner. However this original SC-VAR is difficult to implement due to its complicated constraints and the lack of guidelines for setting its parameters. To reduce the complexity of this MINLP and to make it possible to incorporate prior expert knowledge to benefit model building and forecasting, the original SC-VAR is modified and a correlation-constrained SC-VAR (CCSC-VAR) is proposed based on spatial correlation information about wind farms. Our approach is evaluated based on a case study of very-short-term forecasting for 25 wind farms in Denmark. Comparison is performed with a set of traditional local methods and spatio-temporal methods. The results obtained show the proposed CCSC-VAR has better overall performance than both the original SC-VAR and other benchmark methods, taking into account all evaluation indicators, including sparsity-control ability, sparsity, accuracy, and efficiency