The role of reactive oxygen species in oxidative-induced neoplastic transformation

The generation of reactive oxygen species (ROS) is a normal occurrence in the life of a cell. ROS are derived from both exogenous and endogenous sources and take part in a plethora of normal physiological mechanisms from host immunity to cell cycle regulation. However, ROS also exhibit a deleterious, disruptive character that means they must now be taken seriously as a genuine carcinogenic agent able to alter a variety of pathways leading to the initiation of cancer. The two-sidedness of ROS means that the relationship between ROS and the onset and progression of cancer is hard to determine. ROS and reactive nitrogen species (RNS) are able to initiate cancer through the damage of DNA leading to the genetic instability that drives the early stages of cancer. Simultaneously, they can activate a number of signalling cascades and transcription factors that facilitate uncontrolled cell growth. The production of ROS in neoplastic cells can lead to the production of new blood vessels that provide the machinery for subsequent metastasis and tumour invasion. It is important that the role of ROS in these pathways are fully elucidated in order to provide potential therapies measures

The relationship between chiropractor required and current level of business knowledge

Background: Chiropractors frequently practice within health care systems requiring the business acumen of an entrepreneur. However, some chiropractors do not know the relationship between the level of business knowledge required for practice success and their current level of business knowledge. The purpose of this quantitative study was to examine the relationship between chiropractors’ perceived level of business knowledge required and their perceived level of current business knowledge. Methods: Two hundred and seventy-four participants completed an online survey (Health Care Training and Education Needs Survey) which included eight key business items. Participants rated the level of perceived business knowledge required (Part I) and their current perceived level of knowledge (Part II) for the same eight items. Data was collected from November 27, 2013 to December 18, 2013. Data were analyzed using Spearman’s ranked correlation to determine the statistically significant relationships for the perceived level of knowledge required and the perceived current level of knowledge for each of the paired eight items from Parts I and II of the survey. Wilcoxon Signed Ranks Tests were performed to determine the statistical difference between the paired items. Results: The results of Spearman’s correlation testing indicated a statistically significant (p < 0.01) positive correlation for the perceived level of knowledge required and perceived current level of knowledge for six variables: (a) organizational behavior, (b) strategic management, (c) marketing, (d) legal and ethical, (e) managerial decisions, and (f) operations. Wilcoxon Signed Ranks testing indicated a significant difference for three paired items: strategic management; marketing and; legal and ethical. The results suggest that relationships exist for the majority of business items (6 of 8) however a statistically difference was demonstrated in only three of the paired business items. Conclusion: The implications of this study for social change include the potential to improve chiropractors’ business knowledge and skills, enable practice success, enhance health services delivery and positively influence the profession as a viable career.https://doi.org/10.1186/s12998-017-0134-

A Methodological Framework for the Evaluation of Syndromic Surveillance Systems: A Case Study of England

Background: Syndromic surveillance complements traditional public health surveillance by collecting and analysing health indicators in near real time. The rationale of syndromic surveillance is that it may detect health threats faster than traditional surveillance systems permitting more timely, and hence potentially more effective public health action. The effectiveness of syndromic surveillance largely relies on the methods used to detect aberrations. Very few studies have evaluated the performance of syndromic surveillance systems and consequently little is known about the types of events that such systems can and cannot detect. Methods: We introduce a framework for the evaluation of syndromic surveillance systems that can be used in any setting based upon the use of simulated scenarios. For a range of scenarios this allows the time and probability of to be determined and uncertainty is fully incorporated. In addition, we demonstrate how such a framework can model the benefits of increases in the number of centres reporting syndromic data and also determine the minimum size of outbreaks that can or cannot be detected. Here, we demonstrate its utility using simulations of national influenza outbreaks and localised outbreaks of cryptosporidiosis. Results: Influenza outbreaks are consistently detected with larger outbreaks being detected in a more timely manner. Small cryptosporidiosis outbreaks (<1000 symptomatic individuals) are unlikely to be detected. We also demonstrate the advantages of having multiple syndromic data streams (e.g. emergency attendance data, telephone helpline data, general practice consultation data) as different streams are able to detect different types outbreaks with different efficacy (e.g. emergency attendance data are useful for the detection of pandemic influenza but not for outbreaks of cryptosporidiosis). We also highlight that for any one disease, the utility of data streams may vary geographically, and that the detection ability of syndromic surveillance varies seasonally (e.g. an influenza outbreak starting in July is detected sooner than one starting later in the year). We argue that our framework constitutes a useful tool for public health emergency preparedness in multiple settings. Conclusions: The proposed framework allows the exhaustive evaluation of any syndromic surveillance system and constitutes a useful tool for emergency preparedness and response

Adhesion Molecules Associated with Female Genital Tract Infection

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la DonaEfforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes

Control Twisting con Adaptación Basada en Cruce por Cero para un Sistema de Columna de Agua Oscilante con Generador Sincrónico

Este trabajo presenta el control de un dispositivo de columna de agua oscilante, que incluye un generador sincrónico de imán permanente, para la extracción óptima de potencia. Se diseñan dos controladores de modo deslizante de segundo orden adaptables, que funcionan de manera robusta en modo deslizante real y muestran una notable mejora en la reducción del chattering cuando se los compara con el mismo esquema con ganancias fijas, al ser probados sobre el modelo completo del sistema

Control para maxima extracción de energía undimotriz por Modos Deslizantes de Segundo Orden real con Ganancias Adaptivas

La optimización del aprovechamiento de la energıa de las olas se está desarrollando fuertemente de manera internacional y Argentina tiene gran potencial de este recurso. Entre todos los dispositivos capaces de transformar la energıa undimotriz, los sistemas de Columna de Agua Oscilante han sido los más estudiados y maximizar la extracción de potencia de la ola es el objetivo primordial de los últimos anos. Este trabajo avanza sobre una propuesta inicial de controladores de Modo Deslizante de Segundo Orden, considerando condiciones realistas de funcionamiento para el sistema y una configuración de ganancias adaptivas que reduce el chattering. Los resultados muestran notablemente la mejora esperada, a partir de reducir el esfuerzo de control, manteniendo la robustez ante incertidumbre en los parámetros, dinámica no modelada y perturbaciones

Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments

Apoptotic cell clearance (efferocytosis), a process essential for organismal homeostasis, is performed by phagocytes that inhabit harsh tissue environments, including physiologic hypoxia. Here, we find macrophages, the predominant tissue-resident phagocyte, display enhanced efferocytosis under chronic hypoxia, characterized by increased internalization and accelerated degradation of apoptotic cells. Analysis of transcriptional and translational programs revealed that macrophages under chronic hypoxia induce two distinct states. The first, ‘primed’, state consists of concomitant induction of transcriptional and translational programs broadly associated with metabolism in naïve macrophages that persist during efferocytosis. The second, ‘poised’, state consists of transcription, but not translation, of phagocyte function programs in naïve macrophages that are subsequently translated during efferocytosis. We discovered that one such primed state consists of the efficient flux of glucose into a noncanonical pentose phosphate pathway (PPP) loop, whereby PPP-derived intermediates cycle back through the PPP to enhance production of NADPH. Mechanistically, we found that PPP activity directly supports enhanced efferocytosis activity under chronic hypoxia while simultaneously maintaining redox homeostasis. Thus, macrophages adapt to chronic hypoxia by adopting states that both support cell fitness and ensure ability to rapidly and safely perform essential homeostatic functions

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events