No evidence for collateral effects of electromagnetic fields used to increase dissolved oxygen levels on the behavior and physiology of freshwater fishes.

Hypoxia in surface waters driven by warming climate and other anthropogenic stressors is a major conservation concern, and technological solutions for water quality remediation are sorely needed. One potential solution involves the use of low-intensity electromagnetic fields (EMFs) to increase dissolved oxygen levels, but potential collateral effects of the EMFs on aquatic animals have not been formally evaluated. We examined the effects of EMF exposure on wild-caught, captive sunfish (Lepomis spp.) over 8-day and 3-day exposures, with and without aeration in mesocosms and stock tanks (respectively). We also quantified ambient fish abundance in close proximity to EMF devices deployed in Opinicon Lake (ON). We found no significant differences in a suite of blood-based stress physiology biomarkers, behaviors, and putative aerobic capacities between EMF and control conditions over 8 days. Aerated mesocosms equipped with activated EMFs consistently had higher oxygen levels in the water than aerated controls. There were no differences in mortality during 3-day oxygen depletion trials under EMF or control conditions, and we detected no differences in fish abundance when the devices were activated in the lake. Our findings suggest that deploying EMF devices in field settings is not likely to exert negative effects on exposed fish populations. PRACTITIONER POINTS: Low-cost, low-energy technological solutions to remediate aquatic hypoxia are sorely needed Electromagnetic fields (EMFs) can increase oxygen flux across air/water interfaces and increase dissolved oxygen levels We found no evidence of negative effects of EMFs on fish physiology or behavior and our results support their use in alleviating hypoxic conditions.

Advances in the development of gene therapy, noncoding RNA, and exosome-based treatments for tendinopathy.

Tendinopathy is a common musculoskeletal disorder characterized by chronic low-grade inflammation and tissue degeneration. Tendons have poor innate healing ability and there is currently no cure for tendinopathy. Studies elucidating mechanisms underlying the pathogenesis of tendinopathy and mechanisms mediating the genesis of tendons during development have provided novel targets and strategies to enhance tendon healing and repair. This review summarizes the current understanding and treatments for tendinopathy. The review also highlights recent advances in gene therapy, the potential of noncoding RNAs, such as microRNAs, and exosomes, which are nanometer-sized extracellular vesicles secreted from cells, for the treatment of tendinopathy.

Electroconvulsive therapy, personal protective equipment and aerosol generating procedures: a review to guide practice during Coronavirus Disease 2019 (COVID-19) pandemic.

OBJECTIVE: To review the literature on the definition of aerosol-generating procedures (AGPs), identify high-risk AGPs, guidelines to use personal protective equipment (PPE) and review evidence to see if electroconvulsive therapy (ECT) is a high-risk AGP requiring the use of PPE. METHODS: Existing guidelines and research data were reviewed to answer the questions. RESULTS: There is consensus about the type of anaesthesia used during ECT, what constitutes AGPs and what PPE should be used. It was not clear if ECT was an AGP, but we argue that it is one based on evidence. CONCLUSION: We conclude that ECT is an AGP and that it requires the appropriate use of PPE after taking in to account local supply and demand.

Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers.

Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30-35 and 190-240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers. In summary, we developed an aerosol system that can produce clinically relevant chronic intermittent nicotine exposure in unanesthetized, unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for understanding the health effects of chronic intermittent nicotine exposure such as with tobacco cigarettes and electronic cigarettes for studies of behavior, pharmacology and toxicology, nicotine addiction, tobacco-related diseases, and teratogenicity, and for the discovery of therapeutics. NEW & NOTEWORTHY We developed a lung alveolar region-targeted aerosol method and a system that provides chronic intermittent nicotine exposure in freely moving rodents. The method produces in rodents clinically relevant nicotine exposure with the route and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health impacts of chronic nicotine exposures such as with tobacco cigarettes and electronic cigarettes, for studying nicotine pharmacology, toxicology, addiction, and tobacco-related diseases, and for the discovery of therapeutics.

Understanding outcomes and toxicological aspects of second generation metal-on-metal hip implants: a state-of-the-art review.

Hip implants have improved the mobility and quality of life in millions of individuals. This review presents the evolution of scientific knowledge regarding the history and understanding of systemic and local metal toxicological concerns of hip implants designs utilizing metal-on-metal (MoM) bearing surfaces used in hip resurfacing arthroplasty (HRA) and total hip arthroplasty (THA). This analysis addresses: (1) the history of the development of MoM hip implants; (2) the clinical and toxicological rationale for introducing second-generation MoM implants in the early 2000s as an alternative to metal-on-polyethylene bearings; (3) the subsequent history regarding success and failure of second-generation MoM devices; (4) a detailed review of the history of MoM toxicology, including carcinogenic potential, metal blood levels, hypersensitivity, and release of wear particles; and (5) a review of local tissue effects and MoM patient management. We have included an analysis of MoM THA and HRA survivorship trends aggregated from over 200 studies. By around 2008, HRA continued to be a challenging procedure with variable success rates, and concurrently, some THA devices began to experience higher than expected revision rates based on annual registry reports. The unexpected THA outcomes and continued challenges with HRA devices prompted many surgeons to question the role of toxicological effects in device performance. Regarding hypersensitivity, while conversion to metal sensitized status in some MoM patients occurs based on the skin patch or lymphocyte transformation testing, there is no evidence of a causal relationship between positive test results and device failure. The weight of evidence indicates that nanoparticles released from MoM implants are cleared from the local synovial space under normal wear conditions. The available data indicate that there are no discernible increases in local or systemic tumors following CoCr alloy implantation. Systemic health effects are rarely reported in MoM implant patients and are unlikely when blood concentrations are below 300 µg/L except when patients have specific risk factors. Over time, patient management evolved to include assays aimed at predicting implant function (blood monitoring) and soft tissue reactions (MRI and ultrasound imaging). Validation of these biomarkers as a diagnostic tool for implant function, patient pain, and, ultimately, implant survival, remains lacking. After the introduction of these biomarkers, differences in implant revision decisions emerged based on imaging abnormalities, increased serum metal ion levels, and overall clinical presentation. Discrepancies in patient management algorithms and the lack of consensus in local biological effects terminology have contributed to variability in reporting incidence, etiology, and dose effects on local tissue responses in MoM implants. This variability has contributed to a debate regarding the benefit or risk of revising asymptomatic patients. Therefore, while toxicological assessments of normal functioning MoM implants indicate that MoM implants are relatively safe because of low wear and clearance of metal, more analysis of revision data is needed in order to best inform patient management decisions, particularly for asymptomatic patients, as well as patients with minor symptoms under consideration for conservative pain management treatments.

Cryostored autologous skull bone for cranioplasty? A study on cranial bone flaps' viability and microbial contamination after deep-frozen storage at -80°C.

Craniectomy is a life-saving procedure. Subsequent cranioplasty with autologous skull bone has a bone resorption rate from 4% to 22.8% and an infection rate from 3.3% to 26%. There are concerns with their viability and the potential microbial contamination as they were explanted for a long period of time. Eighteen cranial bone flaps stored at Prince of Wales Hospital Skull Bone Bank during the period from June 2011 to March 2016 were identified. Ethics approval was obtained. Bone chips and deep bone swabs were collected for osteoblast culture and microbial culture. Skull Bone Bank was kept at -80°C under strict aseptic technique during the study period. The storage period ranged from 4months to 55months. For the osteoblast culture, all eighteen bone flaps had no viable osteoblast growth. For the bacterial culture, five had positive bacteria growth (27.8%). Three were Pasteurella multocida and two were Methicillin-resistant Staphylococcus aureus. The mean duration of storage of the infected bone flap was 32.9months (±15.1months) versus 19.9months (±17.9months) of those bone flaps with no bacterial growth (p=0.1716). The mean size of the infected versus non-infected bone flaps was 117.7cm2 (±44.96cm2) versus 76.8cm2 (±50.24cm2) respectively (p=0.1318). Although in this study statistical significance was not reached, it was postulated that infected bone flaps tended to be larger in size and had a longer duration of storage. In conclusion, cryostored skull bone flaps beyond four months showed no viable osteoblasts. Bacterial contamination rate of bone flaps was 27.8% in this study.

Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure.

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg-1·day-1) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients.NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms.

Use of subdural drain for chronic subdural haematoma? A 4-year multi-centre observational study of 302 cases.

Chronic subdural haematoma (CSDH) is a common neurosurgical condition and is more prevalent in the ageing population. Studies have suggested that placement of subdural drains after burr-hole drainage was associated with lower recurrence rates. However, a considerable proportion of surgeons remained unconvinced of the effectiveness of drain placement and concerns exist with the potential complications this additional manoeuvre entails such as infection or bleeding. The aim of the present study is to evaluate the impact of subdural drain on CSDH recurrence and its safety. This is a multicentre observational study. Data of consecutive patients with burr-hole drainage performed for CSDH in three hospitals in Hong Kong during a four-year period from January 2008 to December 2011 were prospectively collected and retrospectively analysed. The primary outcome was symptomatic recurrence requiring re-operation. Secondary outcomes included the modified Rankin scales (mRS), morbidity and mortality at six months. A total of 302 patients were identified. The recurrence rate was 8.72% (13/149) with drain placement versus 16.3% (25/153) with no drain (Odds Ratio=0.489, 95%CI 0.240-0.998; p=0.0463). Local wound infection, subdural empyema, acute subdural haematoma and other complications had no significant difference. Six-month mRS, 30-day mortality and six-month mortality were comparable in both groups. In conclusion, the use of subdural drain significantly reduced recurrence with no significant increase in complications.

The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study.

Chronic subdural haematoma (CSDH) is a common neurosurgical condition. Burr-hole for drainage is an effective treatment. However, recurrence can be up to 8-33% and is associated with morbidities and mortalities. The underlying pathogenesis was postulated to be localised inflammation and pathological aberrant vessels formation. Atorvastatin, an HMG-CoA reductase inhibitor, is a type of lipid-lowering medication. In animal studies and a preliminary clinical trial, Atorvastatin was shown to be effective in the treatment of CSDH. It was found to inhibit inflammation and promote vascular maturation at the neomembrane of CSDH. Our study aimed to investigate the efficacy of Atorvastatin in CSDH. During the study period from January to December 2014, Atorvastatin was used in 12 CSDH patients with Glasgow Coma Scale (GCS) 13-15 or Markwalder's Grading Scale (MGS) Grade 0-2. They were retrospectively compared with GCS- and MGS-matched controls who had not used statin. Improvement with haematoma resolution at 3 months was 75% (9/12) for the Atorvastatin group, versus 42% (5/12) for the Control group (p = 0.0977). The risk of deterioration requiring burr-hole drainage was 16.7% (2/12) in the Atorvastatin group, versus 58.3% (7/12) in the Control group (p = 0.0447). The Odds Ratio (OR) of deterioration requiring burr-hole drainage with Atorvastatin was 0.143 (95%CI: 0.021-0.958), which favours the use of Atorvastatin in CSDH (p = 0.0451). The Number needed to treat (NNT) was 2.4 (p = 0.0447; 95%CI: 1.31-14.93). In conclusion, this retrospective cohort comparison study has shown that CSDH with Atorvastatin had a lower rate of deterioration and burr-hole drainage.

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high-fat diet.

Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.

Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response.

AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism.

AIMS: AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown to inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK ß1/ß2 subunits (AMPKß1ß2-deficient mice, ß1ß2M-KO) have been generated and possess <10% of normal AMPK activity in muscle. However, how/if dramatic AMPK deficiency alters cardiac metabolism, function, or morphology has not been investigated. Therefore, the aim of this study was to determine whether a significant loss of AMPK activity alters cardiac function, metabolism, and hypertrophy, and whether this may play a role in the pathogenesis of heart failure. METHODS AND RESULTS: ß1ß2M-KO mice exhibit an approximate 25% reduction in systolic and diastolic function compared with wild-type (WT) littermates. Despite the well-documented role of AMPK in controlling myocardial energy metabolism, there was no difference in basal glucose and fatty acid oxidation rates between ß1ß2M-KO and WT mice. However, there was reduced AMPK-mediated phosphorylation of troponin I in ß1ß2M-KO and reduced ventricular cell shortening in the presence of low Ca(2+), which may explain the impaired cardiac function in these mice. Interestingly, ß1ß2M-KO mice did not display any signs of compensatory cardiac hypertrophy, which could be attributed to impaired activation of p38 MAPK. CONCLUSIONS: ß1ß2M-KO mice display evidence of dilated cardiomyopathy. This is the first mouse model of AMPK deficiency that demonstrates cardiac dysfunction in the absence of pathological stress and provides insights into the role of AMPK in regulating myocardial function, metabolism, hypertrophy, and the progression to heart failure.

Resveratrol treatment of mice with pressure-overload-induced heart failure improves diastolic function and cardiac energy metabolism.

BACKGROUND: Although resveratrol has multiple beneficial cardiovascular effects, whether resveratrol can be used for the treatment and management of heart failure (HF) remains unclear. In the current study, we determined whether resveratrol treatment of mice with established HF could lessen the detrimental phenotype associated with pressure-overload-induced HF and identified physiological and molecular mechanisms contributing to this. METHODS AND RESULTS: C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks post surgery, a cohort of mice with established HF (% ejection fraction <45) was administered resveratrol (≈320 mg/kg per day). Despite a lack of improvement in ejection fraction, resveratrol treatment significantly increased median survival of mice with HF, lessened cardiac fibrosis, reduced gene expression of several disease markers for hypertrophy and extracellular matrix remodeling that were upregulated in HF, promoted beneficial remodeling, and improved diastolic function. Resveratrol treatment of mice with established HF also restored the levels of mitochondrial oxidative phosphorylation complexes, restored cardiac AMP-activated protein kinase activation, and improved myocardial insulin sensitivity to promote glucose metabolism and significantly improved myocardial energetic status. Finally, noncardiac symptoms of HF, such as peripheral insulin sensitivity, vascular function, and physical activity, were improved with resveratrol treatment. CONCLUSIONS: Resveratrol treatment of mice with established HF lessens the severity of the HF phenotype by lessening cardiac fibrosis, improving molecular and structural remodeling of the heart, and enhancing diastolic function, vascular function, and energy metabolism.

Quantitative gait analysis of long-term locomotion deficits in classical unilateral striatal intracerebral hemorrhage rat model.

Gait analysis is a systematic collection of quantitative information on bodily movements during locomotion. Gait analysis has been employed clinically in stroke patients for their rehabilitation planning. In animal studies, gait analysis has been employed for the assessment of their locomotive disturbances in ischemic stroke, spinal cord injury and Parkinson's disease. The aims of the work reported here were to identify the gait parameters, collected from the computer-generated CatWalk System, that change after unilateral intracerebral hemorrhage (ICH) in the acute stage and long term up to 56 days post-ICH. The results showed that with the collagenase-induced unilateral striatal lesion, the rats displayed a significant contralateral decrease in print and maximum contact area and paw intensity, a diagonal increase in the stance duration of the left front and right hind paws, a significant decrease in the stride length of all four limbs, and foot pattern instability as reflected by the base of support, support on styles, and cadence. These deficits, including those in print area, stance and pressure, were demonstrated throughout the long-term period following ICH. The correlations between the gait parameters, lesion volume and asymmetrical forelimb use were also reported in this paper. This work has provided a systematic description on gait parameters in the classical striatal ICH model, which might become an essential assessment tool in future studies of pathophysiology and the development of novel treatments for experimental unilateral intracerebral hemorrhage with gait deficits.

Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery.

Although pre-clinical evidence has suggested that partial inhibition of myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose oxidation for ATP production can prevent ischemia/reperfusion injury, controversy about this approach persists. For example, mice with germline deletion of the FA transporter CD36, exhibited either impaired or unchanged post-ischemic functional recovery despite a 40-60% reduction in FAO rates. Because there are limitations to cardiac studies utilizing whole body CD36 knockout (totalCD36KO) mice, we have now generated an inducible and cardiomyocyte-specific CD36 KO (icCD36KO) mouse to better address the role of cardiomyocyte CD36 and its regulation of FAO and post-ischemic functional recovery. Four to six weeks following CD36 ablation, hearts from icCD36KO mice had significantly decreased FA uptake compared to controls, which was paralleled by significant reductions in intramyocardial triacylglycerol content. Analysis of cardiac energy metabolism using ex vivo working heart perfusions showed that reduced FAO rates were compensated by enhanced glucose oxidation in the hearts from icCD36KO mice. In contrast to the totalCD36KO mice, hearts from icCD36KO mice exhibited significantly improved functional recovery following ischemia/reperfusion (18min of global no-flow ischemia followed by 40min of aerobic reperfusion). This improved recovery was associated with lower calculated proton production prior to and following ischemia compared to controls. Moreover, the amount of ATP generated relative to cardiac work was significantly lower in the hearts from icCD36KO mice compared to controls, indicating significantly increased cardiac efficiency in the hearts from icCD36KO mice. These data provide genetic evidence that reduced FAO as a result of diminished CD36-mediated FA uptake improves post-ischemic cardiac efficiency and functional recovery. As such, targeting cardiomyocyte FA uptake and FAO via inhibition of CD36 in the adult myocardium may provide therapeutic benefit during ischemia-reperfusion.

Disturbed protein-protein interaction networks in metastatic melanoma are associated with worse prognosis and increased functional mutation burden.

For disseminated melanoma, new prognostic biomarkers and therapeutic targets are urgently needed. The organization of protein-protein interaction networks was assessed via the transcriptomes of four independent studies of metastatic melanoma and related to clinical outcome and MAP-kinase pathway mutations (BRAF/NRAS). We also examined patient outcome-related differences in a predicted network of microRNAs and their targets. The 32 hub genes with the most reproducible survival-related disturbances in co-expression with their protein partner genes included oncogenes and tumor suppressors, previously known correlates of prognosis, and other proteins not previously associated with melanoma outcome. Notably, this network-based gene set could classify patients according to clinical outcomes with 67-80% accuracy among cohorts. Reproducibly disturbed networks were also more likely to have a higher functional mutation burden than would be expected by chance. The disturbed regions of networks are therefore markers of clinically relevant, selectable tumor evolution in melanoma which may carry driver mutations.

Visualization of the interactome: what are we looking at?

Network visualization of the interactome has been become routine in systems biology research. Not only does it serve as an illustration on the cellular organization of protein-protein interactions, it also serves as a biological context for gaining insights from high-throughput data. However, the challenges to produce an effective visualization have been great owing to the fact that the scale, biological context and dynamics of any given interactome are too large and complex to be captured by a single visualization. Visualization design therefore requires a pragmatic trade-off between capturing biological concept and being comprehensible. In this review, we focus on the biological interpretation of different network visualizations. We will draw on examples predominantly from our experiences but elaborate them in the context of the broader field. A rich variety of networks will be introduced including interactomes and the complexome in 2D, interactomes in 2.5D and 3D and dynamic networks.

Classification of cancer patients using pathway analysis and network clustering.

Molecular expression patterns have often been used for patient classification in oncology in an effort to improve prognostic prediction and treatment compatibility. This effort is, however, hampered by the highly heterogeneous data often seen in the molecular analysis of cancer. The lack of overall similarity between expression profiles makes it difficult to partition data using conventional data mining tools. In this chapter, the authors introduce a bioinformatics protocol that uses REACTOME pathways and patient-protein network structure (also called topology) as the basis for patient classification.

Particle release from respirators, part I: determination of the effect of particle size, drop height, and load.

In late 2001, some U.S. Postal Service workers and a few members of Congress were exposed to anthrax spores. This led to an increased effort to develop employable methods to protect workers from exposure to anthrax. Some investigations focused on selection and use of respirators to protect workers against airborne anthrax. The present study evaluated the potential for several types of half-mask respirators to release deposited particles. Four brands of the most commonly used filtering facepiece respirators (hereafter termed masks) were loaded with 0.59-µm, 1.0-µm, and 1.9-µm polystyrene latex (PSL) microspheres (nominally 0.6, 1.0, and 2.0 µm) and then dropped onto a rigid surface. The load conditions were 10, 20, or 40 million particles, and drop heights were 0.15, 0.76, and 1.37 m. For the average conditions of 0.76 m, 1.15 µm size and 22 million particles loaded, the average particle release was 0.604 particles per 10,000 (95% CI: .552, .662) particles loaded for all of the filtering facepieces tested. The averaging of conditions is a useful tool to provide generalized information and is also useful when making risk estimates. For most filtering facepiece respirators, particle release tended to increase with drop height and particle size, and there appeared to be a slight inverse relationship with particle load. Two brands of reusable elastomeric half-mask respirators with P100 high-efficiency particulate air (HEPA) filter cartridges were also evaluated. Results of these tests were inconclusive. Part II in this issue addresses the release of particles when simulating removal of a filtering facepiece from a wearer's head.

Particle release from respirators, part II: determination of the effect of tension applied in simulation of removal.

This study evaluated the potential for disposable filtering facepiece respirators (hereafter termed masks) contaminated with 1-µ m particles to release particles as a result of lateral tension applied to the mask. The lateral tension was designed to simulate the removal of a contaminated mask from a user's head. Four brands of filtering facepieces were loaded with approximately 20 million 1.0-µ m polystyrene latex (PSL) microspheres. The respirators were then placed in a test chamber and subjected to lateral tension between 17.8-26.7 N (4-6 lbs) for 1 to 2 sec. The findings suggest that neither mask type nor loading condition affects particle release. This supports our hypothesis that when filtering facepiece respirators are properly removed from the head they will not release a significant number of particles.