Liver Parenchyma Perforation following Endoscopic Retrograde Cholangiopancreatography

Although endoscopic retrograde cholangiopancreatography (ERCP) is an effective modality for the diagnosis and treatment of biliary and pancreatic diseases, it is still related with several severe complications. We report on the case of a female patient who developed liver parenchyma perforation following ERCP. She underwent ERCP with sphincterotomy and extraction of a common bile duct stone. Shortly after ERCP, abdominal distension was identified. Abdominal computed tomography revealed intraabdominal air leakage and leakage of contrast dye penetrating the liver parenchyma into the space around the spleen. Since periampullary perforation related to sphincterotomy could not be denied, she was referred for immediate surgery. Obvious perforation could not be found at surgery. Cholecystectomy, insertion of a T tube into the common bile duct, placement of a duodenostomy tube and drainage of the retroperitoneum were performed. She did well postoperatively and was discharged home on postoperative day 28. In conclusion, as it is well recognized that perforation is one of the most serious complication related to ERCP, liver parenchyma perforation should be suspected as a cause

Treatment of distal humeral fractures using conventional implants. Biomechanical evaluation of a new implant configuration

<p>Abstract</p> <p>Background</p> <p>In the face of costly fixation hardware with varying performance for treatment of distal humeral fractures, a novel technique (U-Frame) is proposed using conventional implants in a 180° plate arrangement. In this in-vitro study the biomechanical stability of this method was compared with the established technique which utilizes angular stable locking compression plates (LCP) in a 90° configuration.</p> <p>Methods</p> <p>An unstable distal 3-part fracture (AO 13-C2.3) was created in eight pairs of human cadaveric humeri. All bone pairs were operated with either the "Frame" technique, where two parallel plates are distally interconnected, or with the LCP technique. The specimens were cyclically loaded in simulated flexion and extension of the arm until failure of the construct occurred. Motion of all fragments was tracked by means of optical motion capturing. Construct stiffness and cycles to failure were identified for all specimens.</p> <p>Results</p> <p>Compared to the LCP constructs, the "Frame" technique revealed significant higher construct stiffness in extension of the arm (P = 0.01). The stiffness in flexion was not significantly different (P = 0.16). Number of cycles to failure was found significantly larger for the "Frame" technique (P = 0.01).</p> <p>Conclusions</p> <p>In an in-vitro context the proposed method offers enhanced biomechanical stability and at the same time significantly reduces implant costs.</p

Physical health behaviours and health locus of control in people with schizophrenia-spectrum disorder and bipolar disorder: a cross-sectional comparative study with people with non-psychotic mental illness

<p>Abstract</p> <p>Background</p> <p>People with mental illness experience high levels of morbidity and mortality from physical disease compared to the general population. Our primary aim was to compare how people with severe mental illness (SMI; i.e. schizophrenia-spectrum disorders and bipolar disorder) and non-psychotic mental illness perceive their: (i) global physical health, (ii) barriers to improving physical health, (iii) physical health with respect to important aspects of life and (iv) motivation to change modifiable high-risk behaviours associated with coronary heart disease. A secondary aim was to determine health locus of control in these two groups of participants.</p> <p>Methods</p> <p>People with SMI and non-psychotic mental illness were recruited from an out-patient adult mental health service in London. Cross-sectional comparison between the two groups was conducted by means of a self-completed questionnaire.</p> <p>Results</p> <p>A total of 146 people participated in the study, 52 with SMI and 94 with non-psychotic mental illness. There was no statistical difference between the two groups with respect to the perception of global physical health. However, physical health was considered to be a less important priority in life by people with SMI (OR 0.5, 95% CI 0.2-0.9, <it>p </it>= 0.029). There was no difference between the two groups in their desire to change high risk behaviours. People with SMI are more likely to have a health locus of control determined by powerful others (<it>p </it>< 0.001) and chance (<it>p </it>= 0.006).</p> <p>Conclusions</p> <p>People with SMI appear to give less priority to their physical health needs. Health promotion for people with SMI should aim to raise awareness of modifiable high-risk lifestyle factors. Findings related to locus of control may provide a theoretical focus for clinical intervention in order to promote a much needed behavioural change in this marginalised group of people.</p

Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin

Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed

Effect of a web-based chronic disease management system on asthma control and health-related quality of life: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Asthma is a prevalent and costly disease resulting in reduced quality of life for a large proportion of individuals. Effective patient self-management is critical for improving health outcomes. However, key aspects of self-management such as self-monitoring of behaviours and symptoms, coupled with regular feedback from the health care team, are rarely addressed or integrated into ongoing care. Health information technology (HIT) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team, and access to their health information, presented in personalized ways that can alert them when there is a need for action. The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system, My Asthma Portal (MAP), linked to a case-management system on asthma control, and asthma health-related quality of life.</p> <p>Methods</p> <p>The trial is a parallel multi-centered 2-arm pilot randomized controlled trial. Participants are randomly assigned to one of two conditions: a) MAP and usual care; or b) usual care alone. Individuals will be included if they are between 18 and 70, have a confirmed asthma diagnosis, and their asthma is classified as not well controlled by their physician. Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug database, and asthma quality of life using the Mini Asthma Related Quality of Life Questionnaire. Power calculations indicated a needed total sample size of 80 subjects. Data are collected at baseline, 3, 6, and 9 months post randomization. Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010.</p> <p>Discussion</p> <p>Self-management support from the care team is critical for improving chronic disease outcomes. Given the high volume of patients and time constraints during clinical visits, primary care physicians have limited time to teach and reinforce use of proven self-management strategies. HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN34326236">ISRCTN34326236</a>.</p

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Sources, Distribution, and Fate of Microscopic Plastics in Marine Environments

Microplastics are pieces of plastic debris <5 mm in diameter. They enter the environment from a variety of sources including the direct input of small pieces such as exfoliating beads used in cosmetics and as a consequence of the fragmentation of larger items of debris. A range of common polymers, including polyethylene, polypropylene, polystyrene, and polyvinyl chloride, are present in the environment as microplastic particles. Microplastics are widely distributed in marine and freshwater habitats. They have been reported on shorelines from the poles to the equator; they are present at the sea surface and have accumulated in ocean systems far from land. Microplastics are also present in substantial quantities on the seabed. A wide range of organisms including birds, fish, and invertebrates are known to ingest microplastics and for some species it is clear that a substantial proportion of the population have microplastic in their digestive tract. The extent to which this might have harmful effects is not clear; however, the widespread encounter rate indicates that substantial quantities of microplastic may be distributed within living organisms themselves as well as in the habitats in which they live. Our understanding about the long-term fate of microplastics is relatively limited. Some habitats such as the deep sea may be an ultimate sink for the accumulation of plastic debris at sea; indeed, some recent evidence indicates quantities in the deep sea can be greater than at the sea surface. It has also been suggested that microplastics might be susceptible to biodegradation by microorganisms; however, this is yet to be established and the prevailing view is that even if emissions of debris to the environment are substantially reduced, the abundance of microplastics will increase over the next few decades. However, it is also clear that the benefits which plastics bring to society can be realized without the need for emissions of end-of-life plastics to the ocean. To some extent the accumulation of microplastic debris in the environment is a symptom of an outdated business model. There are solutions at hand and many synergistic benefits can be achieved in terms of both waste reduction and sustainable use of resources by moving toward a circular economy