Nanomagnetic Modulation of Tumor Redox State

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe₃O₄ nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day^–1 (compared to 0.58 ± 0.02 day^–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.     

Obese rats with deficient leptin signaling exhibit heightened sensitivity to olfactory food cues

The Zucker rat is used as a model of genetic obesity, and while Zucker rats have been well studied for their reduced sensitivity to leptin signaling and subsequent weight gain, little work has examined their responses to environmental signals that are associated with “hedonic” feeding. This study evaluated the effects of a high‐fat food olfactory cue (bacon) in stimulating nose‐poke food‐seeking behavior on first exposure (novel) and after a period of access for consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of age, and under ad‐lib fed (unrestricted; U) or chronically food‐restricted (70% of ad‐lib; R) conditions. Baseline nose‐poke levels were comparable amongst all groups. At 4 months of age, only ObU rats displayed increased behavioral activation to familiar food cues. Twelve‐month‐old Ob rats, regardless of diet, exhibited substantially greater food‐seeking behavior when exposed to both the novel and familiar olfactory cues. A strong positive correlation between body weight and nose‐poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Similarly, there were strong positive correlations between food intake and poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12–month‐old rats only. Although it is possible that differences in olfactory sensitivity contribute to these behavioral effects, our findings support the interactions between food intake, obesity, and food‐seeking behavior and are consistent with leptin inhibiting the brain's reactivity to food cues and suggest that the enhanced sensitivity to the food cues with leptin deficiency is likely to contribute to overeating and weight gain. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

Assessment of the cerebral cortex during motor task behaviours in adults: a systematic review of functional near infrared spectroscopy (fNIRS) studies

Functional near infrared spectroscopy (fNIRS) is an emerging tool for non-invasively monitoring the haemodynamic response to brain activation. The technique has been widely adopted to investigate cortical responses during motor tasks in health and disease. This systematic review provides a critical analysis of the research findings in the hope of summating relevant information, identifying consistent outcomes acquired using different spectrometers, clarifying data inconsistencies, and learning from the common challenges across disciplines. The spatiotemporal characteristics, reliability, repeatability and modulation of typical cortical response evoked by motor stimulation are all evaluated in detail. The review assesses the contribution of the technique to advancing our understanding of motor skill learning and control in the context of tasks of everyday living, athletic performance, and recovery from neurological illness. Finally, the limitations of current fNIRS technologies are examined and a series of recommendations for future studies are provided based upon the reviewed literature.     

Developments in surgical revascularization to achieve improved morbidity and mortality

Coronary artery bypass graft surgery remains the main treatment modality for multivessel coronary artery disease and has consistently been demonstrated to have significantly lower rates of major adverse cardiac and cerebrovascular events in comparison to percutaneous coronary intervention. In this article we will explore the advances over time and the recent refinements in the techniques of surgical revascularization and how these contribute to the superior outcome profile associated with coronary artery bypass graft surgery. These include the current outcome status of coronary artery bypass grafting; the major landmark trials, registries and meta-analyses comparing coronary artery bypass grafting and percutaneous coronary intervention; the developments in coronary artery disease lesion classification; the techniques for the physiological assessment of coronary artery lesions; bypass grafting using arterial conduits; the role of off-pump coronary artery surgery; the outcomes of reoperative surgery; hybrid techniques for coronary revascularization; minimally invasive coronary artery surgery and finally robotic surgery.     

The effect of prehospital time related variables on mortality following severe thoracic trauma

ObjectivesThe aims of this study is firstly to analyse the impact of prehospital time related variables on mortality, in a specific subset of HEMS patients and secondly to demonstrate any interactions between time related variables and factors taking place in the prehospital setting.MethodsRetrospective analysis of 688 consecutive London HEMS transfers with severe thoracic trauma and mean injury severity score (ISS) of 35, during a 9-year period (1994–2002). We have analysed the effect of the following time related variables on mortality: activation time, arrival on scene time (AoS), stay on scene time (SoS), total time (ToT), rush-hour time (RhT) and leisure-hour time (LhT). We have also investigated the interaction of the above mentioned variables with observations and interventions taken place on scene and at accident and emergency department (A&;E) following adjustment for type and severity of injury. For statistical analysis the time variables were grouped into quintiles.ResultsSix hundred eighty eight victims (510 males) with mean age of 38.5 ± 17.5 had total survival rate of 59.6%. The mean AoS and SoS were 11.6 ± 5.8 min and 36.6 ± 16.8 min, respectively. ToT > 65 min, as in quintiles III, IV and V with mean ToT of 65.3 min, 74.9 min and 102.7 min respectively, had an influence on mortality with calculated adjusted OR of 1.37 (95%CI = 0.47–3.94), 3.36 (95%CI = 1.22–9.23) and 1.43 (95%CI = 0.52–3.92) respectively with concomitant adjustment for type of injury, severity of injury, age, physiological variables on scene and on scene emergency thoracotomy (ET). ET on scene was an independent predictor for mortality (OR 3.94, 95%CI = 1.03–15.06). SoS of more than 34 min can lead to harmful changes on patients’ pathophysiological status. ISS has no significant effect on AoS or SoS. RhT and LhT have no significant effect on mortality and they did not influence the AoS and SoS.ConclusionThis study suggests that time related variables have a complex and heterogeneous effect on mortality. Thoracic trauma victims usually have high ISS, in such population, ToT <65 min may be associated with lower possibility of death. Neither AoS nor SoS was influenced by time of incident or severity of injury.     

Metabolic surgery and obstructive sleep apnoea: the protective effects of bariatric procedures

The global epidemic of obesity and the worldwide prevalence of obstructive sleep apnoea (OSA) are both increasing. Epidemiological studies reveal an association between obesity, weight gain and OSA. Metabolic or bariatric operations provide sustained weight loss and resolve or improve the symptoms of OSA in the majority of morbidly obese individuals. These operations also modulate the metabolic profile to improve glycaemic control, to decrease cardiovascular risk and obesity-related mortality. The beneficial effects of metabolic operations on OSA include mechanical weight-dependent and metabolic weight-independent effects that are achieved through the BRAVE effects: (Bile flow alteration; Reduction of gastric size; Anatomical gut rearrangement and altered flow of nutrients; Vagal manipulation; and Enteric gut hormone modulation). These result in an improvement in insulin resistance, adipokines, cytokines and systemic inflammation. A literature analysis was performed with statistical pooling of available surgical and medical studies to determine whether the weighted mean decrease in body mass index and sleep apnoea severity (measured by the apnoea-hypopnoea index) are larger in metabolic surgical studies than in non-surgical weight loss studies (diet, exercise and medication). However, heterogeneity across available trials, poor follow-up measures and a deficiency in comparative studies between surgical and non-surgical therapy precludes definitive statements regarding the relative benefits of surgical therapy. Further research is required to quantify robustly the effects and mechanisms of sleep apnoea resolution by metabolic surgery, which may reveal novel non-surgical treatments or enhanced surgical strategies in the management of this multisystem sleep disorder.     

Equity in public health standards: a qualitative document analysis of policies from two Canadian provinces

ABSTRACT: INTRODUCTION: Promoting health equity is a key goal of many public health systems. However, little isknown about how equity is conceptualized in such systems, particularly as standards ofpractice are established. As part of a larger study examining the renewal of public health intwo Canadian provinces, Ontario and British Columbia (BC), we undertook an analysis ofrelevant public health documents related to equity. The aim of this paper is to discuss howequity is considered within documents that outline standards for public health. METHODS: A research team consisting of policymakers and academics identified key documents relatedto the public health renewal process in each province. The documents were analyzed usingconstant comparative analysis to identify key themes related to the conceptualization andintegration of health equity as part of public health renewal in Ontario and BC. Documentswere coded inductively with higher levels of abstraction achieved through multiple readings.Sets of questions were developed to guide the analysis throughout the process. RESULTS: In both sets of provincial documents health inequities were defined in a similar fashion, as theconsequence of unfair or unjust structural conditions. Reducing health inequities was anexplicit goal of the public health renewal process. In Ontario, addressing "prioritypopulations" was used as a proxy term for health equity and the focus was on existingprograms. In BC, the incorporation of an equity lens enhanced the identification of healthinequities, with a particular emphasis on the social determinants of health. In both, prioritywas given to reducing barriers to public health services and to forming partnerships withother sectors to reduce health inequities. Limits to the accountability of public health toreduce health inequities were identified in both provinces. CONCLUSION: This study contributes to understanding how health equity is conceptualized and incorporatedinto standards for local public health. As reflected in their policies, both provinces haveembraced the importance of reducing health inequities. Both conceptualized this as rooted instructural injustices and the social determinants of health. Differences in theconceptualization of health equity likely reflect contextual influences on the public healthrenewal processes in each jurisdiction.     

Sternal tuberculosis after coronary artery bypass graft surgery.

We report a case of sternal tuberculosis following sternotomy, which was performed during coronary artery bypass graft surgery. Although pre-operative evaluation revealed signs of asymptomatic tuberculosis of the lung, isoniazid chemoprophylaxis was not instituted, and the patient developed active tuberculosis in both the lung and sternum 5 y later.     

Monoclonal antibody HMB-45 in diagnosis of intra-ocular melanoma]

69 eyes, which had to be enucleated because of an uveal melanoma, were investigated immunohistologically. HMB-45-antigen, which is supposed to be highly specific for melanocytic tumours, was found in 68 cases (sensitivity 99%) with a monoclonal antibody. S 100-antigen was positive in 63 cases (sensitivity 91%) using a polyclonal antibody. The addition of HMB-45-immunohistochemistry to routine histological diagnostic procedures is valuable, when a non-melanocytic uveal tumour cannot be ruled out or when the degree of melanoma-invasion has to be determined with greater accuracy. At the site of melanoma-invasion changes of cellular reactivity seem to occur, as 11 of the 69 studied tumours (16%) showed an increased HMB-45-expression in this area. HMB-45-antigen was detectable even in paraffin embedded material obtained from eyes enucleated 30 years ago.