Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

How can patient registries facilitate guideline-based healthcare? A retrospective analysis of the CEDATA-GPGE registry for pediatric inflammatory bowel disease.

BACKGROUND: Early diagnosis is mandatory for the medical care of children and adolescents with pediatric-onset inflammatory bowel disease (PIBD). International guidelines ('Porto criteria') of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend medical diagnostic procedures in PIBD. Since 2004, German and Austrian pediatric gastroenterologists document diagnostic and treatment data in the patient registry CEDATA-GPGE on a voluntary basis. The aim of this retrospective study was to analyze whether the registry CEDATA-GPGE reflects the Porto criteria and to what extent diagnostic measures of PIBD according to the Porto criteria are documented. METHODS: Data of CEDATA-GPGE were analyzed for the period January 2014 to December 2018. Variables representing the Porto criteria for initial diagnostic were identified and categorized. The average of the number of measures documented in each category was calculated for the diagnoses CD, UC, and IBD-U. Differences between the diagnoses were tested by Chi-square test. Data on possible differences between data documented in the registry and diagnostic procedures that were actually performed were obtained via a sample survey. RESULTS: There were 547 patients included in the analysis. The median age of patients with incident CD (n = 289) was 13.6 years (IQR: 11.2-15.2), of patients with UC (n = 212) 13.1 years (IQR: 10.4-14.8) and of patients with IBD-U (n = 46) 12.2 years (IQR: 8.6-14.7). The variables identified in the registry fully reflect the recommendations by the Porto criteria. Only the disease activity indices PUCAI and PCDAI were not directly provided by participants but calculated from obtained data. The category 'Case history' were documented for the largest part (78.0%), the category 'Imaging of the small bowel' were documented least frequently (39.1%). In patients with CD, the categories 'Imaging of the small bowel' (χ2 = 20.7, Cramer-V = 0.2, p < 0.001) and 'Puberty stage' (χ2 = 9.8, Cramer-V = 0.1, p < 0.05) were documented more often than in patients with UC and IBD-U. CONCLUSION: The registry fully reproduces the guideline's recommendations for the initial diagnosis of PIBD. The proportion of documented diagnostic examinations varied within the diagnostic categories and between the diagnoses. Despite technological innovations, time and personnel capacities at participating centers and study center are necessary to ensure reliable data entry and to enable researchers to derive important insights into guideline-based care.

The effects of green tea on acne vulgaris: A systematic review and meta-analysis of randomized clinical trials.

Green tea extract (GTE) has been studied for the treatment of acne based on its anti-inflammatory/antioxidant properties. This systematic review and meta-analysis aimed to examine the effects of GTE on acne. Electronic databases, including PubMed, Embase, and the Cochrane Library were systematically searched up to August 2019. The effect size of acne lesion counts is presented as mean differences and 95% confidence intervals (CIs). Five randomized-controlled studies were included in the meta-analysis (N; experimental = 125, control = 122). GTE significantly reduced the number of inflammatory lesions (-9.38; 95% CI: -14.13 to -4.63). In subgroup analysis, topical GTE application significantly reduced the inflammatory lesion counts (-11.39; 95% CI: -15.91 to -6.86) whereas oral GTE intake showed minimal effect (-1.40; 95% CI: -2.50 to -0.30). Although GTE did not significantly reduce the number of non-inflammatory lesions (-21.65; 95% CI: -47.52 to 4.22), when stratified by the route of admission, non-inflammatory acne lesions were significantly reduced by topical GTE application (-32.44; 95% CI: -39.27 to -25.62) but not with oral GTE administration (0.20; 95% CI: 0.00 to 0.40). This systematic review and meta-analysis suggest that topical GTE application is beneficial for the treatment of acne without causing significant adverse events while oral GTE intake has limited effects. Further high-quality clinical trials are warranted.

Exosomes derived from human dermal papilla cells promote hair growth in cultured human hair follicles and augment the hair-inductive capacity of cultured dermal papilla spheres.

Dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Owing to the established roles of exosomes (Exos) in the regulation of cell functions, we investigated whether DP-derived Exos, especially those from three-dimensional (3D)-cultured DP cells, affect hair growth, cycling and regeneration. Exos derived from 3D DP (3D DP-Exos) promoted the proliferation of DP cells and outer root sheath (ORS) cells and increased the expression of growth factors (IGF-1, KGF and HGF) in DP cells. 3D DP-Exo treatment also increased hair shaft elongation in cultured human hair follicles. In addition, local injections of 3D DP-Exos induced anagen from telogen and also prolonged anagen in mice. Moreover, Exo treatment in human DP spheres augmented hair follicle neogenesis when the DP spheres were implanted with mouse epidermal cells. Similar results were obtained using Exos derived from 2D-cultured DP cells (2D DP-Exo). Collectively, our data strongly suggest that Exos derived from DP cells promote hair growth and hair regeneration by regulating the activity of follicular dermal and epidermal cells; accordingly, these findings have implications for the development of therapeutic strategies for hair loss.

RRAM-based synapse devices for neuromorphic systems.

Hardware artificial neural network (ANN) systems with high density synapse array devices can perform massive parallel computing for pattern recognition with low power consumption. To implement a neuromorphic system with on-chip training capability, we need to develop an ideal synapse device with various device requirements, such as scalability, MLC characteristics, low power operation, data retention, and symmetric/linear conductance changes under potentiation/depression modes. Although various devices have been proposed for synapse applications, they have limitations for application in neuromorphic systems. In this paper, we will cover various RRAM synapse devices, such as filamentary switching RRAM (HfOx, TaOx, Cu-CBRAM) and analog RRAM devices, based on interface resistive switching (Pr0.7Ca0.3MnOx and TiOx) and ferroelectric polarization (HfZrOx). By optimizing potentiation/depression conditions, we could improve the conductance linearity and MLC characteristics of filamentary synapse devices. Interface RRAM has better MLC characteristics with limited retention and conductance linearity. By controlling the reactivity of metal electrodes and the oxygen concentration in oxides, we can modulate the synapse characteristics. Metal-Ferroelectric-Insulator-Semiconductor (MFIS) FET devices exhibit good retention characteristics and analog memory characteristics due to polarization. Based on various synapse device characteristics, we have estimated the pattern recognition accuracy of MNIST handwritten digits and CIFAR-10 datasets. We have confirmed that synapse device characteristics directly affect the pattern recognition accuracy of ANNs. In order to simultaneously satisfy all the requirements of synapse devices, it is necessary to develop new technology capable of controlling the movement of oxygen vacancies and metal ions at the atomic scale. Considering the limited synapse characteristics of current 2-terminal RRAM devices, hardware ANNs capable of only off-chip training can be constructed by optimizing the current RRAM devices by limiting the bit number. A 3-terminal synapse device or a device based on a new operation principle should be developed as an alternative for on-chip training applications.

Activin A-induced signalling controls hair follicle neogenesis.

Acquisition of potent human dermal papilla (DP) cells that can induce hair follicle neogenesis is an overarching concern, and various approaches have been tried. In an attempt to solve the problem, we previously introduced the three-dimensional (3D) culture of human DP cells and observed de novo formation of hair follicles when conducting a patch hair reconstitution assay using 3D cultured DP spheres with mouse epidermal cells. In this study, we have subsequently focused our attention on activin A, one of the notably upregulated proteins in DP spheres compared with 2D cultured DP cells. We then adopted a small interfering RNA-mediated gene knock-down approach and hair reconstitution assay to investigate the role of activin A. We observed that human DP spheres with activin A knock-down are severely impaired in hair follicle neogenesis when combined with mouse epidermal cells. In addition, activin receptor 2B (ActvR2B) knock-down mouse epidermal cells showed severe impairment of hair follicle neogenesis when combined with human DP spheres. Moreover, recombinant activin A treatment of mouse epidermal cells increased the expression of downstream genes of the activin pathway. Taken together, our data strongly suggest that activin A-induced signalling plays a critical role in hair follicle neogenesis, which has not been previously reported.

Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats.

Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30 min of low-level electrical stimulation (4 µA at 5 Hz; n = 10) or sham stimulation (Sham group; n = 15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30 min, and retinal tissue harvested at 1 h and 24 h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1 h, but not 24 h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.

Associations between osteoporosis and coronary artery disease in postmenopausal women.

OBJECTIVE: Coronary artery disease (CAD) and osteoporosis are major causes of mortality and morbidity in postmenopausal women. We aimed to investigate the association between osteoporosis and CAD in asymptomatic postmenopausal women at a single center. METHODS: This study included 863 postmenopausal women without histories of cardiovascular diseases who visited the Health Promotion Center from June 1, 2004 to May 31, 2015. All subjects were screened for bone mineral density (BMD) by dual-energy X-ray absorptiometry and for the degree of CAD by multidetector computed tomography. RESULTS: Low BMD including osteopenia and osteoporosis was found to be significantly associated with old age, low body mass index, and a higher prevalence of diabetes mellitus. The incidences of CAD including a high coronary artery calcium score (≥100), obstructive coronary artery disease, and multivessel disease were significantly higher in subjects with low BMD. After adjusting for age and cardiovascular risk factors, osteoporosis was associated with a high coronary artery calcium score (p = 0.015) and with obstructive coronary artery disease (p = 0.002). There was a trend toward significance with multivessel disease (p = 0.052). CONCLUSIONS: High coronary artery calcium score and obstructive coronary artery disease, as revealed by multidetector computed tomography, were associated with osteoporosis in asymptomatic postmenopausal women, independent of cardiovascular risk factors and age.

Tauroursodeoxycholic Acid Protects Retinal Function and Structure in rd1 Mice.

We explored the potential protective effects of tauroursodeoxycholic acid (TUDCA) on cone photoreceptor survival in a model of rapid retinal degeneration, the ß-Pde6 (rd1) (rd1) mouse model. We injected two strains of rd1 mice (B6.C3-Pde6b (rd1) Hps4(le)/J and C57BL/6J-Pde6b (rd1-2)/J mice) daily from postnatal day (P) 6 to P21 with TUDCA or vehicle. At P21, retinal function was evaluated with light-adapted electroretinography (ERG) and retinal structure was observed with plastic or frozen sections. TUDCA treatment partially preserved function and structure in B6.C3-Pde6b (rd1) Hps4(le)/J mice but only partially preserved structure in C57BL/6J-Pde6b (rd1-2)/J mice. Our results suggest a possible intervention for patients undergoing rapid retinal degeneration.

Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal Degeneration and Evoke Similar Gene Expression Patterns.

To compare patterns of gene expression following preconditioning cyclic light rearing versus preconditioning aerobic exercise. BALB/C mice were preconditioned either by rearing in 800 lx 12:12 h cyclic light for 8 days or by running on treadmills for 9 days, exposed to toxic levels of light to cause light-induced retinal degeneration (LIRD), then sacrificed and retinal tissue harvested. Subsets of mice were maintained for an additional 2 weeks and for assessment of retinal function by electroretinogram (ERG). Both preconditioning protocols partially but significantly preserved retinal function and morphology and induced similar leukemia inhibitory factor (LIF) gene expression pattern. The data demonstrate that exercise preconditioning and cyclic light preconditioning protect photoreceptors against LIRD and evoke a similar pattern of retinal LIF gene expression. It may be that similar stress response pathways mediate the protection provided by the two preconditioning modalities.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma for differential diagnosis from benign papillary urothelial lesions: logistic regression analysis in SurePath(™) liquid-based voided urine cytology.

OBJECTIVE: The diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology specimens is challenging because of its subtle, minimally atypical findings. Furthermore, as SurePath(™) liquid-based cytology (LBC) is becoming a widely used method in urine cytology, the inevitable cytomorphological alterations resulting from this technique call for new morphological diagnostic criteria in LGPUC. METHODS: Logistic regression analysis was carried out on SurePath slides from surgically proven voided urine specimens. The study was designed to include a test set (n = 141) and a validation set (n = 61), and evaluated significant discriminative parameters between LGPUC and benign papillary urothelial neoplasm (BPUN). RESULTS: Of the seven cytological findings that were found to have statistical significance in univariate analysis, five were found to be independent variables: loss of polarity of papillaroid clusters, irregular contours, absence of columnar cells, hobnail features and hyperchromasia. These independent variables had an area under the curve (AUC) of 0.781. CONCLUSIONS: The distinctive cytological criteria identified above may prove to be helpful in cases in which other conventional criteria for LGPUC are insufficient for diagnosis.

Aerobic exercise protects retinal function and structure from light-induced retinal degeneration.

Aerobic exercise is a common intervention for rehabilitation of motor, and more recently, cognitive function (Intlekofer and Cotman, 2013; Wood et al., 2012). While the underlying mechanisms are complex, BDNF may mediate much of the beneficial effects of exercise to these neurons (Ploughman et al., 2007; Griffin et al., 2011; Real et al., 2013). We studied the effects of aerobic exercise on retinal neurons undergoing degeneration. We exercised wild-type BALB/c mice on a treadmill (10 m/min for 1 h) for 5 d/week or placed control mice on static treadmills. After 2 weeks of exercise, mice were exposed to either toxic bright light (10,000 lux) for 4 h to induce photoreceptor degeneration or maintenance dim light (25 lux). Bright light caused 75% loss of both retinal function and photoreceptor numbers. However, exercised mice exposed to bright light had 2 times greater retinal function and photoreceptor nuclei than inactive mice exposed to bright light. In addition, exercise increased retinal BDNF protein levels by 20% compared with inactive mice. Systemic injections of a BDNF tropomyosin-receptor-kinase (TrkB) receptor antagonist reduced retinal function and photoreceptor nuclei counts in exercised mice to inactive levels, effectively blocking the protective effects seen with aerobic exercise. The data suggest that aerobic exercise is neuroprotective for retinal degeneration and that this effect is mediated by BDNF signaling.

Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes.

Dopamine (DA) functions as an essential neuromodulator in the brain and retina such that disruptions in the dopaminergic system are associated with common neurologic disorders such as Parkinson's disease. Although a reduction in DA content has been observed in diabetes, its effects in the development of diabetes-induced neuropathy remains unknown. Because the retina is rich in DA and has a well known diabetes-induced pathology (diabetic retinopathy or DR), this study was designed to examine the role of retinal DA deficiency in early visual defects in DR. Using rodent models of type 1 diabetes mellitus, we investigated whether diabetes caused a reduction in retinal DA content in both rats and mice and determined whether restoring DA levels or activating specific DA receptor pathways could improve visual function (evaluated with optokinetic tracking response) of diabetic mice, potentially via improvement of retinal function (assessed with electroretinography). We found that diabetes significantly reduced DA levels by 4 weeks in rats and by 5 weeks in mice, coincident with the initial detection of visual deficits. Treatment with l-DOPA, a DA precursor, improved overall retinal and visual functions in diabetic mice and acute treatment with DA D1 or D4 receptor agonists improved spatial frequency threshold or contrast sensitivity, respectively. Together, our results indicate that retinal DA deficiency is an underlying mechanism for early, diabetes-induced visual dysfunction and suggest that therapies targeting the retinal dopaminergic system may be beneficial in early-stage DR.

Secondary cutaneous lymphoma: comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage.

BACKGROUND: The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. OBJECTIVES: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. MATERIALS AND METHODS: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. RESULTS: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. CONCLUSIONS: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Prostate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction.

BACKGROUND: Androgen ablation is the first-line therapy for patients with metastatic prostate cancer (CaP). However, castration resistance will eventually emerge. In the present study, we have investigated the role of bone morphogenetic protein-6 (BMP-6) in the development of castration-resistant prostate cancer (CRPC) in the context of bone metastases. METHODS: We initially investigated the clinical course of 158 men with advanced CaP who were treated with primary androgen deprivation therapy. To elucidate the underlying mechanism of CRPC in the context of bone metastases, we examined the impact of bone stromal cells on CaP in the absence of androgens using a co-culture model. RESULTS: In the 158 patients, we found that the median time to prostate-specific antigen progression was significantly shorter when bone metastases were present (14 months (95% CI, 10.2-17.8 months) vs 57 months (95% CI, 19.4-94.6 months)). These results suggest that bone-tumour interactions may accelerate castration resistance. Consistent with this hypothesis, in vitro co-cultures demonstrated that CaP cells proliferated under an androgen-depleted condition when incubated with bone stromal cells. Mechanistically, gene expression analysis using quantitative polymerase chain reaction arrays showed a dramatic induction of BMP-6 by CaP cell lines in the presence of bone stromal cells. Further studies revealed that WNT5A derived from bone stromal cells induced the expression of BMP-6 by CaP cells; BMP-6 in turn stimulated cellular proliferation of CaP cells in an androgen-deprived media via a physical interaction between Smad5 and ß-catenin. Intracellularly, WNT5A increased BMP-6 expression via protein kinase C/NF-κB pathway in CaP cell lines. CONCLUSIONS: These observations suggest that bone-CaP interaction leads to castration resistance via WNT5A/BMP-6 loop.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

BACKGROUND: Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. OBJECTIVES: To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. METHODS: Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. RESULTS: There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. CONCLUSIONS: The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites.

Comparison of skin elasticity test results from the Ballistometer(®) and Cutometer(®).

BACKGROUND: Long-term exposure to sunlight changes skin features like amount of facial wrinkling and skin elasticity, which is useful in estimating skin health and age-related changes. Skin elasticity is evaluated by quantitative methods such as the noninvasive suction device Cutometer(®) , which is widely used to evaluate regional body-elasticity differences and correlate these findings with the results of other instrumental data. Few field studies have been done with the Ballistometer(®) device, another noninvasive method for measuring skin elasticity. METHOD: In this study, we measured the skin elasticity of each subject's forehead, cheek, and volar forearm using two devices with different means of obtaining quantitative measurements - Ballistometer(®) (Diastron Ltd.) and Cutometer(®) (CK electronics). RESULTS: The results from testing with the Ballistometer(®) and Cutometer(®) devices showed that the degree of skin elasticity of the volar forearm is greater than those found on the cheek and forehead. The parameters measured by the Ballistometer(®) showed high correlation patterns. On the cheek skin, the correlation coefficient between Ballisto-parameters and R parameters (R0, R3, R8) was higher than other skin sites. CONCLUSION: Taken together, R parameters measured by the Cutometer(®) device have been widely distributed in the evaluation of skin elasticity in research and cosmetics. Although the methodologies are different, the Ballistometer(®) device is also a useful tool to evaluate skin elasticity.

Paediatric cutaneous lymphoma in Korea: a retrospective study at a single institution.

BACKGROUND: The clinical features and incidences of cutaneous lymphoma (CL) differ by ethnicity and age. However, there is to our knowledge no study to show characteristics and distribution of paediatric CL in Asian population. OBJECTIVE: The aim of this study was to investigate distinctive clinicopathological features of CL in paediatric population, particularly in Korea. METHODS: We conducted a clinicopathological review of 41 paediatric cases with CL, diagnosed at Asan Medical Center from January 1990 to December 2012. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from paediatric patients with CL were analyzed. In addition, the results in this present paediatric group were compared with previously reported studies in the Korean all-ages group and Western paediatric group. RESULTS: Lymphomatoid papulosis was more common in the present paediatric group than in the all-ages group (34.5% vs. 9.4%) and Western paediatric group (34.5% vs. 17.7%). Mycosis fungoides, the most common cutaneous lymphoma in the all-ages group and Western paediatric group, is the second most common subtype in this study. Three of nine paediatric mycosis fungoides patients (33%) have the follicular variant. Compared with all-ages group, B-lmphoblastic lymphoma was relatively higher incidence (10.3% vs. 1%) and NK-/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma was relatively in lower proportions in the paediatric group. CONCLUSION: The clinical features and distribution of paediatric CL in our study suggest that CL of Asian childhood is quite different from that of adulthood and Western childhood.

Citrobacter rodentium possesses a functional type II secretion system necessary for successful host infection.

Infectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.

External validation of an online nomogram in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma.

BACKGROUND: The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort. METHODS: The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan-Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis. RESULTS: The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan-Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis. CONCLUSION: The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.