Effect of sugars on Chlamydia trachomatis infectivity

Background. Previous works suggest that sugars can have a beneficial effect on C. trachomatis (CT) survival and virulence. In this study, we investigated the effect of different sugars on CT infectivity, elucidating some of the molecular mechanisms behind CT-sugar interaction. Methods. CT infectivity was investigated on HeLa cells after 2 hour-incubation of elementary bodies (EBs) with glucose, sucrose, or mannitol solutions (0.5, 2.5, 5.0 mM). The effect of sugars on EB membrane fluidity was investigated by fluorescence anisotropy measurement, whereas the changes in lipopolysaccharide (LPS) exposure were examined by cytofluorimetric analysis. By means of a Western blot, we explored the phosphorylation state of Focal Adhesion Kinase (FAK) in HeLa cells infected with EBs pre-incubated with sugars. Results. All sugar solutions significantly increased CT infectivity on epithelial cells, acting directly on the EB structure. Sugars induced a significant increase of EB membrane fluidity, leading to changes in LPS membrane exposure. Especially after incubation with sucrose and mannitol, EBs led to a higher FAK phosphorylation, enhancing the activation of anti-apoptotic and proliferative signals in the host cells. Conclusions. Sugars can increase CT infectivity and virulence, by modulating the expression/exposure of chlamydial membrane ligands. Further in-depth studies are needed to better understand the molecular mechanisms involved

Singularity and consciousness: A neuropsychological contribution

none6siIn common sense experience based on introspection, consciousness is singular. There is only one ‘me’ and that is the one that is conscious. This means that ‘singularity’ is a defining aspect of ‘consciousness’. However, the three main theories of consciousness, Integrated Information, Global Workspace and Recurrent Processing theory, are generally not very clear on this issue. These theories have traditionally relied heavily on neuropsychological observations and have interpreted various disorders, such as anosognosia, neglect and split-brain as impairments in conscious awareness without any reference to ‘the singularity’. In this review, we will re-examine the theoretical implications of these impairments in conscious awareness and propose a new way how to conceptualize consciousness of singularity. We will argue that the subjective feeling of singularity can coexist with several disunified conscious experiences. Singularity awareness may only come into existence due to environmental response constraints. That is, perceptual, language, memory, attentional and motor processes may largely proceed unintegrated in parallel, whereas a sense of unity only arises when organisms need to respond coherently constrained by the affordances of the environment. Next, we examine from this perspective psychiatric disorders and psycho-active drugs. Finally, we present a first attempt to test this hypothesis with a resting state imaging experiment in a split-brain patient. The results suggest that there is substantial coherence of activation across the two hemispheres. These data show that a complete lesioning of the corpus callosum does not, in general, alter the resting state networks of the brain. Thus, we propose that we have separate systems in the brain that generate distributed conscious. The sense of singularity, the experience of a ‘Me-ness’, emerges in the interaction between the world This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. and response-planning systems, and this leads to coherent activation in the different functional networks across the cortex.openHaan, Edward H. F.; Scholte, Huibert Steven; Pinto, Yair; Foschi, Nicoletta; Polonara, Gabriele; Fabri, MaraHaan, Edward H. F.; Scholte, Huibert Steven; Pinto, Yair; Foschi, Nicoletta; Polonara, Gabriele; Fabri, Mar

Individualized Prediction of Drug Resistance in People with Post-Stroke Epilepsy: A Retrospective Study

Background: The study aimed to develop a model and build a nomogram to predict the probability of drug resistance in people with post-stroke epilepsy (PSE). Methods: Subjects with epilepsy secondary to ischemic stroke or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of drug-resistant epilepsy defined according to International League Against Epilepsy criteria. Results: One hundred and sixty-four subjects with PSE were included and 32 (19.5%) were found to be drug-resistant. Five variables were identified as independent predictors of drug resistance and were included in the nomogram: age at stroke onset (odds ratio (OR): 0.941, 95% confidence interval (CI) 0.907–0.977), intracerebral hemorrhage (OR: 6.292, 95% CI 1.957–20.233), severe stroke (OR: 4.727, 95% CI 1.573–14.203), latency of PSE (>12 months, reference; 7–12 months, OR: 4.509, 95% CI 1.335–15.228; 0–6 months, OR: 99.099, 95% CI 14.873–660.272), and status epilepticus at epilepsy onset (OR: 14.127, 95% CI 2.540–78.564). The area under the receiver operating characteristic curve of the nomogram was 0.893 (95% CI: 0.832–0.956). Conclusions: Great variability exists in the risk of drug resistance in people with PSE. A nomogram based on a set of readily available clinical variables may represent a practical tool for an individualized prediction of drug-resistant PSE

Quality of care indicators for head and neck cancers : the experience of the European project RARECAREnet

Background: Monitoring and improving quality of cancer care has become pivotal today. This is especially relevant for head and neck cancers since the disease is complex, it needs multi therapy, patients tend to be older, they tend to have comorbidities and limited social support. However, information on quality of care for head and neck cancers is scarce. In the context of the project "Information Network on Rare Cancers" we aimed to identify indicators of quality of care specific for the head and neck cancers management and to measure the quality of care for head and neck cancers in different EU Member States. Methods: We defined indicators of quality of care for head and neck cancers based on a multidisciplinary and expert-based consensus process at a European level. To test the proposed indicators, we performed an observational population-based retrospective study in four countries (Ireland, Italy, Netherlands, and Slovenia) in the years 2009-2011. Results: The main quality indicators identified are: availability of formalized multidisciplinary team, participation in clinical and translational research; timeliness of care, high quality of surgery and radiotherapy, and of pathological reporting. For head and neck cancers, the quality of care did not reach the optimal standards in most of the countries analyzed. A high proportion of patients was diagnosed at an advanced disease stage, showed delays in starting treatment (especially for radiotherapy), and there was only a very limited use of multi therapy. Conclusions: According to the achieved consensus, indicators of quality of care for head and neck cancers have to cover the patient journey (i.e., diagnosis and treatment). Our results, showed suboptimal quality of care across countries and call for solutions for ensuring good quality of care for head and neck cancer patients in all EU countries. One possible option might be to refer head and neck cancer patients to specialized centers or to networks including specialized centers

Nonexistence of extremals for the adjoint restriction inequality on the hyperboloid

We study the problem of existence of extremizers for the $L^2$ to $L^p$ adjoint Fourier restriction inequalities on the hyperboloid in dimensions 3 and 4, in which cases $p$ is an even integer. We will use the method developed by Foschi to show that extremizers do not exist.Comment: 32 pages. Correction for Theorem 1.2 and Proposition 7.5 and addition of Remark 1.

PATIENT VOICES, a project for the integration of the systematic assessment of patient reported outcomes and experiences within a comprehensive cancer center: a protocol for a mixed method feasibility study

BACKGROUND: Listening to "patient voices" in terms of symptoms, emotional status and experiences with care, is crucial for patient empowerment in clinical practice. Despite convincing evidence that routine patient reported outcomes and experience measurements (PRMs) with rapid feed-back to oncologists can improve symptom control, patient well-being and cost effectiveness, PRMs are not commonly used in cancer care, due to barriers at various level. Part of these barriers may be overcome through electronic PRMs collection (ePRMs) integrated with the electronic medical record (EMR). The PATIENT VOICES initiative is aimed at achieving a stepwise integration of ePRMs assessment into routine cancer care. The feasibility project presented here is aimed at assessing the knowledge, use and attitudes toward PRMs in a comprehensive cancer centre; developing and assessing feasibility of a flexible system for ePRM assessment; identifying barriers to and developing strategies for implementation and integration of ePRMs clinical practice. METHODS: The project has been organized into four phases: a) pre-development; b) software development and piloting; c) feasibility assessment; d) post-development. A convergent mixed method design, based on concurrent quantitative and qualitative data collection will be applied. A web-survey on health care providers (HCPs), qualitative studies on patients and HCPs (semi-structured interviews and focus groups) as well as longitudinal and cross-sectional quantitative studies will be carried out. The quantitative studies will enroll 600 patients: 200 attending out-patient clinics (physical symptom assessement), 200 attending inpatient wards (psychological distress assessment) and 200 patients followed by multidisciplinary teams (patient experience with care assessment). The Edmonton symptom assessment scale, the Distress Thermometer, and a tool adapted from existing patient reported experience with cancer care questionnaires, will be used in quantitative studies. A multi-disciplinary stakeholder team including researchers, clinicians, health informatics professionals, health system administrators and patients will be involved in the development of potentially effective implementation strategies in the post development phase. DISCUSSION: The documentation of potential advantages and implementation barriers achieved within this feasibility project, will serve as a starting point for future and more focused interventions aimed at achieving effective ePRMs routine assessment in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03968718 ) May 30th, 2019

Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced hcc patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group

Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (-0.30, p=0.0008) in the responder group (-0.58, p=0.003) than in those with progressive disease (-0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatmen