Dunnbutt4320

Buruli ulcer (BU) is a neglected tropical disease caused by subcutaneous infection with Mycobacterium ulcerans and its exotoxin mycolactone. BU displays coagulative necrosis and widespread fibrin deposition in affected skin tissues. Despite this, the role of the vasculature in BU pathogenesis remains almost completely unexplored. We hypothesise that fibrin-driven ischemia can be an 'indirect' route to mycolactone-dependent tissue necrosis by a mechanism involving vascular dysfunction. Here, we tracked >900 vessels within contiguous tissue sections from eight BU patient biopsies. Our aim was to evaluate their vascular and coagulation biomarker phenotype and explore potential links to fibrin deposition. We also integrated this with our understanding of mycolactone's mechanism of action at Sec61 and its impact on proteins involved in maintaining normal vascular function. Our findings showed that endothelial cell dysfunction is common in skin tissue adjacent to necrotic regions. There was little evidence of primares and plasma proteins into skin tissue, ultimately leading to local coagulopathy and tissue ischemia.Information sharing via social networking systems (SNS) is a common practice among academics, as well as others, that brings substantial benefits. At the same time, privacy concerns are widespread among SNS users, which may tend to inhibit their maximising the benefit from using the systems. This paper investigates the proposition that SNS user attitudes and behaviour are affected by privacy concerns, and that the effects are subject to significant cultural factors. A broad assessment of the literature provides the context for the study. Working in the context of Saudi Arabia, we apply a mixed-methods approach beginning with in-depth interviews, exposing in detail a range of views and concerns about privacy and SNS use, also allowing us to identify three key factors that bear on SNS usage and users' concerns. Analysis of these factors in the light of the "theory of reasoned action" derives a structural model predicting several hypotheses relating the factors and users' attitudes and behaviour. We assess the model through development of a questionnaire, administered to a large pool of academic participants, that allows us to examine how the model responds in general, and via multigroup partial least squares analyses, differentially to gender and to culturally distinct (Arab vs. non-Arab) constituents of the participant group. Results show good support for the hypotheses and clear gender and culture effects. Picking up issues from the interviews, discussion focuses on users' views about SNS providers' privacy policies and their inadequacy regarding culturally specific ethical concerns. We argue that these views may reflect different regulatory environments in combination with other cultural factors.The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. check details We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.Many pathogens and parasites have evolved to overwhelm and suppress their host's immune system. Nevertheless, the interactive effects of these agents on colony productivity and wintering success have been relatively unexplored, particularly in large-scale phenomic studies. As a defense mechanism, honey bees have evolved remarkable social behaviors to defend against pathogen and parasite challenges, which reduce the impact of disease and improve colony health. To investigate the complex role of pathogens, parasites and social immunity behaviors in relation to colony productivity and outcomes, we extensively studied colonies at several locations across Canada for two years. In 2016 and 2017, colonies founded with 1-year-old queens of diverse genetic origin were evaluated, which represented a generalized subset of the Canadian bee population. During each experimental year (May through April), we collected phenotypic data and sampled colonies for pathogen analysis in a standardized manner. Measures included colonony size and weight in both fall and spring periods. Finally, this study also provides information about the incidence and abundance of pathogens, colony phenotypes, and further disentangles their inter-correlation, so as to better understand drivers of honey bee colony health and productivity.[This corrects the article DOI 10.1371/journal.pone.0253755.].We aimed to investigate and compare activities of daily living (ADL), instrumental ADL (IADL), poor self-rated health and the health behaviours among immigrants and the native population in Norway. We present results from analysis of two Norwegian surveys, (Living Conditions Survey on Health from 2015, Living Conditions Survey among Immigrants 2016). Using logistic regression models, odds ratios were estimated for functional ability, self-reported health, and health behavior among immigrants, with Norwegian born being the reference category. The first model was controlled for age and gender and the second model was additionally adjusted for educational level. Our analysis included 5343 participants, 2853 men (913 immigrants), and 2481 women (603 immigrants), aged 45-79 years. The age-group 45-66 years includes n = 4187 (immigrants n = 1431, men n = 856; women n = 575) and 67-79 years n = 1147 (immigrants n = 85, men n = 57; women n = 28). The percentage of Norwegians having ≥ 14 years of education was 86%, as compared to 56% among immigrants. The percentage of immigrants with no education at all was 11%. The employment rate among the Norwegian eldest age group was nearly double (14%) as compared to the immigrant group. Adjusted for age, gender and education, immigrants had higher odds than Norwegian of ADL and IADL, chronic diseases and overweight. There were no differences between immigrants and Norwegians in prevalence of poor self-reported health and smoking. Overall elderly immigrants are worse-off than Norwegians in parameters of health and functioning. Knowledge about health and functioning of elderly immigrants can provide a basis for evidence-based policies and interventions to ensure the best possible health for a growing number of elderly immigrants. Furthermore, for a better surveillance, planning of programs, making policies, decisions and improved assessment and implementation, ADL and IADLs limitations should be included as a variable in public health studies.Anomaly detection in network traffic is becoming a challenging task due to the complexity of large-scale networks and the proliferation of various social network applications. In the actual industrial environment, only recently obtained unlabelled data can be used as the training set. The accuracy of the abnormal ratio in the training set as prior knowledge has a great influence on the performance of the commonly used unsupervised algorithms. In this study, an anomaly detection algorithm based on X-means and iForest is proposed, named X-iForest, which clusters the standard Euclidean distance between the abnormal points and the normal cluster centre to achieve secondary filtering by using X-means. We compared X-iForest with seven mainstream unsupervised algorithms in terms of the AUC and anomaly detection rates. A large number of experiments showed that X-iForest has notable advantages over other algorithms and can be well applied to anomaly detection of large-scale network traffic data.

The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus-pituitary-gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism.

This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change.

Overall, the patients' T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use.

Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.

Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio less then 200), providing practitioners with guidance on the use of clomiphene in this demographic.The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-lasting protective antibodies and a cellular immune response in mice after three immunizations. Unfortunately, compared with the mice in RBF group, mice in RBF/Adju-Phos generated a serious Th2 humoral immune response that elicited Th2-mediated lung pathology. From the IL-4+IFNγ+ ratio, there was also a robust Th2 cellullar immunologic response in the RBF/Adju-Phos group. This study demonstrates that it may not be enough for RBF to increase the titer of neutralizing antibodies. A balanced immune response must be induced for hRSV vaccine safety.Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the data-driven approach to assess the QT prolongation risk of all the frequently used drugs in a tertiary teaching hospital using both standard 12-lead ECGs and intensive care unit (ICU) continuous ECGs. We used the standard 12-lead ECG results (n = 1,040,752) measured in the hospital during 1994-2019 and the continuous ECG results (n = 4,835) extracted from the ICU's patient-monitoring devices during 2016-2019. Based on the drug prescription frequency, 167 drugs were analyzed using 12-lead ECG data under the case-control study design and 60 using continuous ECG data under the retrospective cohort study design. Whereas the case-control study yielded the odds ratio, the cohort study generated the hazard ratio for each candidate drug. Further, we observed the possibility of inducing QT prolongation in 38 drugs in the 12-lead ECG analysis and 7 drugs in the continuous ECG analysis.