The Known and Unknown: Investigating the Carcinogenic Potential of Plastic Additives.

Microplastics are routinely ingested and inhaled by humans and other organisms. Despite the frequency of plastic exposure, little is known about its health consequences. Of particular concern are plastic additives─chemical compounds that are intentionally or unintentionally added to plastics to improve functionality or as residual components of plastic production. Additives are often loosely bound to the plastic polymer and may be released during plastic exposures. To better understand the health effects of plastic additives, we performed a comprehensive literature search to compile a list of 2,712 known plastic additives. Then, we performed an integrated toxicogenomic analysis of these additives, utilizing cancer classifications and carcinogenic expression pathways as a primary focus. Screening these substances across two chemical databases revealed two key observations: (1) over 150 plastic additives have known carcinogenicity and (2) the majority (∼90%) of plastic additives lack data on carcinogenic end points. Analyses of additive usage patterns pinpointed specific polymers, functions, and products in which carcinogenic additives reside. Based on published chemical-gene interactions, both carcinogenic additives and additives with unknown carcinogenicity impacted similar biological pathways. The predominant pathways involved DNA damage, apoptosis, the immune response, viral diseases, and cancer. This study underscores the urgent need for a systematic and comprehensive carcinogenicity assessment of plastic additives and regulatory responses to mitigate the potential health risks of plastic exposure.

An audit to assess the impact of prescribing a monofilament fibre debridement pad for patients with unhealed wounds after six months.

A monofilament fibre debridement pad has been found to be a rapid and effective mechanical method of removing dry skin, biofilm and debris from acute and chronic wounds with minimal patient discomfort. Evidence of its impact on prescribing and wound healing, however, has been more limited. The aim of this audit was to show evidence of the monofilament fibre debridement pad's impact on wound treatment costs through an analysis of NHS wound-care prescribing data in England. A dataset for 486 uniquely identified patients who had been newly prescribed the monofilament fibre debridement pad was obtained from the NHS Business Services Authority. All data were anonymised. Costs were identified for the six months before and six months after the month of first prescription of the monofilament fibre debridement pad. The total cost of wound-care prescribing fell by 14% or £101,723 in the six months after the intervention compared with the six months before. The average monthly expenditure per patient fell from £244 before the intervention to £209 (n=486) after. These results indicate that use of the monofilament fibre debridement pad could reduce prescribing costs and the use of antimicrobial and negative pressure therapies. Further research is warranted to investigate the clinical role of the monofilament fibre debridement pad in wound healing.

Exercise prescription improves exercise tolerance in young children with CHD: a randomised clinical trial.

OBJECTIVE: The main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention. METHODS: Patients aged 5-10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline. RESULTS: One hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels. CONCLUSION: Overall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes.

Cardiac strangulation after epicardial pacing: the importance of non-specific symptoms and a low index of suspicion.

Cardiac strangulation is a rare and potentially deadly complication of epicardial pacemaker implantation. A young boy presenting with chest pain and tiredness almost 7 years after pacemaker implantation was found to have cardiac strangulation. Literature review revealed 22 cases reported to date with a worrying rise in the number of reports over the past 3 years. Strangulation is associated with implantation of leads at a young age and appears to be related to somatic growth. Serial assessment with chest X-ray and echocardiogram is recommended, at least until full adult growth is attained with further coronary artery imaging reserved for symptoms or suspicious echocardiographic findings. If cardiac strangulation is diagnosed prompt replacement of the offending system is needed.

P076 The Role of Dual Biologic Therapy in Inflammatory Bowel Disease.

BACKGROUND: As the prevalence of complex inflammatory bowel disease and extraintestinal manifestations continue to rise, more patients are requiring complex treatment regimens. In some cases, patients may require more than one biologic agent to target different areas in the inflammatory cascade. Although a body of data is emerging, there is currently no consensus on patient and agent selection for dual therapy or adverse outcomes of therapy. METHODS: A retrospective chart review of all patients receiving dual biologic therapy for IBD at a single tertiary care center was conducted. This was exempted by the IRB. Data regarding the patient and disease course, indication for dual biologic use, other concurrent therapies, infections and any adverse events was collected from the EMR. RESULTS: Ten patients (9 Crohn's Disease, 1 Ulcerative Colitis) were identified as receiving dual biologic therapy. The most common combination therapy was ustekinumab with vedolizumab (5) or an anti-TNF (4); one patient was receiving adalimumab with vedolizumab. Nine patients were also on an immunomodulator (6 methotrexate, 2 6-mercaptopurine, 1 azathioprine) and three required steroids in addition to dual biologic therapy. The majority (8) of the patients were started on dual biologic therapy due to refractory GI symptoms, the others were due to extraintestinal manifestations (EIMs) with psoriatic arthritis and ankylosing spondylitis. Nine patients had significant symptomatic improvement on dual biologic regimen and all six patients with follow-up endoscopy demonstrated improvement. Two patients developed infectious diarrhea (C.difficile and e. coli), no other significant infections were noted. No patients were found to have malignancy or any other adverse effects of treatment during the reviewed period. CONCLUSION: Dual biologic therapy can be used with improvement in symptomatic and endoscopic findings of IBD. The combination use of two biologic agents does not appear to have additional infectious risk compared to single agent and no other adverse events were described. Longer follow-up and larger patient populations are needed to verify the combination of biologic mechanisms for therapy of refractory IBD and EIMs.

Nonalcoholic Fatty Liver Disease Among Individuals with HIV Mono-infection: A Growing Concern?

PURPOSE OF REVIEW: Liver disease is a leading cause of non-AIDS-related death in the HIV population since the introduction of highly active antiretroviral treatment (HAART). Recent studies suggest that patients with HIV are at high risk for nonalcoholic fatty liver disease (NAFLD) and progressive liver fibrosis. Evidence for the prevalence, risk factors, and diagnostic methodologies of NAFLD in patients with HIV mono-infection is summarized here. RECENT FINDINGS: Although limited, published studies suggest that the prevalence of NAFLD is higher (30-50%) and progresses at an increased rate in patients with HIV compared to the general population. Identifying those at risk for significant liver fibrosis is critical, preferably with non-invasive screening tests. While there is a paucity of evidence in this population, transient elastography (TE) appears to provide a sensitive, non-invasive screening modality. Identifying NAFLD early will allow for dietary and lifestyle interventions, as well as future drug therapies to decrease the risk of progressive liver fibrosis and cirrhosis in the high-risk HIV population. Clinicians should be aware of this risk and consider using TE for NAFLD diagnosis and surveillance.

'Draw your pelvis' test for assessing pelvic schema in people with Parkinson's disease: a validity and reliability study.

Aim: Body schema (i.e., the mental representation of the body and its parts) is important for cognitive and motor functions, with the pelvis constituting a core element in such schema. Although people with Parkinson's disease exhibit misperceptions and deficits in body schema, there are currently no published tools available for assessing pelvic schema in this population. This study aimed to develop and establish feasibility, reliability, and validity of a novel drawing test - 'Draw Your Pelvis' - for assessing pelvic schema in people with Parkinson's disease. Materials and methods: Twenty people with idiopathic Parkinson's disease (Hoehn &Yahr stages I-III; M age: 65.75 ± 10.13) volunteered and were asked to manually draw a picture of their pelvis. Drawings were assessed and scored by 13 blinded raters over two sessions. Intra- and inter-rater reliability and content and criterion validity were investigated. Results: The 'Draw Your Pelvis' test is shown to be feasible and quick to administer, with excellent inter-rater reliability for consistency (0.954-0.968) and absolute agreement (0.946-0.961). It also demonstrates good-excellent (0.614-0.950) intra-rater reliability, and is content valid. Conclusions: The 'Draw Your Pelvis' test holds potential for clinicians and researchers in assessing pelvic schema and its deficits in people with Parkinson's disease. In addition, this test could be used for investigating the effect of therapeutic interventions on body schema in this population. Future studies should explore this test in additional populations.

Psychometric properties of clock and pelvic drawings in Parkinson's disease: A validity and cross-sectional study.

OBJECTIVES: Parkinson's disease (PD) is characterized by visuospatial and body schema deficits. People with PD often exhibit hypometric movements and graphic hypometria (i.e., small drawing dimensions). The goal of the current study was to explore graphic-metric representation in people with PD by assessing pelvic and clock drawing dimensions (i.e., height and width) and by investigating associations between pelvic drawing dimensions and participant characteristics. METHODS: Twenty people (16 males, 4 females; M age: 65.75 ± 10.13 years) with idiopathic PD (Hoehn &Yahr Stages I-III) volunteered to participate in this study. Draw Your Pelvis and Clock Drawing tests were used for assessing drawing dimensions, which were then correlated with PD severity, stage and duration, cognitive level, side of symptoms onset, and pelvic schema score. Bivariate and multiple linear regression analyses were also used. RESULTS: Excellent (.844-.999) interrater reliability was shown for measuring pelvic and clock drawing dimensions. Pelvic drawing dimensions did not significantly (P > .05) differ in magnitude, whereas clock drawing height was significantly (p < .01) greater than width, both suggesting graphic dysmetria (i.e., distorted graphic dimensions). Pelvic drawing width was negatively associated with PD severity and stage, was positively associated with pelvic schema score, and predicted all three parameters. CONCLUSION: Measuring pelvic drawing dimensions, and specifically pelvic drawing width, holds potential as an adjunct diagnostic measure in PD assessments and for detecting pelvic schema deficits or misperceptions. This test can be used by physical therapists in the clinic for assessing disease severity, stage, and pelvic schema in people with PD. The knowledge gained from this study contributes to a greater understanding of graphic-metric representation and associated deficits in people with PD. Future studies should explore the relationship between pelvic drawing dimensions and pelvic mentally imaged estimates, and their role in motor planning, control, and execution in people with PD.

Contemporary imaging following atrial redirection surgery for transposition of the great arteries.

CLINICAL INTRODUCTION: A young man attended the adult congenital heart disease clinic for routine follow-up. He had a diagnosis of transposition of the great arteries (TGA) and underwent a Senning procedure at 10 months of age. He had remained well over the intervening years, was fully saturated, with a normal exercise tolerance, no cardiovascular symptoms and no history of arrhythmia or symptoms suggesting thromboembolic events. Transthoracic echocardiogram is shown in figure 1A and cardiac MRI image in figure 1B. QUESTION: Which of the following is the most likely diagnosis? Intact atrial pathwaysSecundum atrial septal defectBaffle leakPrimum atrial septal defectBaffle obstruction.

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3ß4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with dextromethorphan and pyrilamine as well as lorcaserin. These findings suggest that combination therapy may be more effective smoking cessation treatments than monotherapy.

Modulation of vascular cell function by bim expression.

Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

Postoperative pulmonary calcification in a child with truncus arteriosus.

Pulmonary calcification is uncommon in children. It is rarely described following cardiac surgery. Here, the authors describe the case of an infant who developed extensive pulmonary calcification following the repair of truncus arteriosus.

Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes.

Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

BIM deficiency differentially impacts the function of kidney endothelial and epithelial cells through modulation of their local microenvironment.

The extracellular matrix (ECM) acts as a scaffold for kidney cellular organization. Local secretion of the ECM allows kidney cells to readily adapt to changes occurring within the kidney. In addition to providing structural support for cells, the ECM also modulates cell survival, migration, proliferation, and differentiation. Although aberrant regulation of ECM proteins can play a causative role in many diseases, it is not known whether ECM production, cell adhesion, and migration are regulated in a similar manner in kidney epithelial and endothelial cells. Here, we demonstrate that lack of BIM expression differentially impacts kidney endothelial and epithelial cell ECM production, migration, and adhesion, further emphasizing the specialized role of these cell types in kidney function. Bim -/- kidney epithelial cells demonstrated decreased migration, increased adhesion, and sustained expression of osteopontin and thrombospondin-1 (TSP1). In contrast, bim -/- kidney endothelial cells demonstrated increased cell migration, and decreased expression of osteopontin and TSP1. We also observed a fivefold increase in VEGF expression in bim -/- kidney endothelial cells consistent with their increased migration and capillary morphogenesis. These cells also had decreased endothelial nitric oxide synthase activity and nitric oxide bioavailability. Thus kidney endothelial and epithelial cells make unique contributions to the regulation of their ECM composition, with specific impact on adhesive and migratory properties that are essential for their proper function.

An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm.

On May 2, 2009 the Canadian Food Inspection Agency notified the World Organization for Animal Health that an emerging novel influenza A virus (pandemic H1N1 2009) had been confirmed on a swine farm in Alberta. Over a 4-week period pigs in this farrow-to-finish operation were clinically affected by respiratory disease consistent with an influenza A virus infection and the presence of active viral infection was confirmed in all production areas by real-time polymerase chain reaction (RT-PCR). Despite clinical recovery of animals, there was reluctance by purchasers to receive animals from this operation due to concerns about the effect on both domestic and international markets. The owner decided to depopulate the entire herd due to impending welfare issues associated with overcrowding and economic concerns resulting from the inability to market these animals. Carcasses were rendered or composted and did not enter the human food or animal feed chain. The source of virus in this herd was determined to be an infected human. Zoonotic transmission to 2 individuals responding to the outbreak was suspected and recommendations to prevent occupational exposure are discussed.

Under the radar: smokeless tobacco advertising in magazines with substantial youth readership.

OBJECTIVES: In light of the Smokeless Tobacco Master Settlement Agreement (STMSA) and the fact that smokeless tobacco advertising has received little attention, we examined industry data to assess smokeless tobacco advertising in popular magazines. Of particular interest was the level of advertising in magazines with high youth readership and the amount of reach and frequency that was generated among readers aged 12 to 17 years. METHODS: We used readership data from Mediamark Research Inc, advertising expenditure data from TNS Media Intelligence, and Adplus, a media planning program from Telmar to document the composition of adult and youth readership of magazines in which smokeless tobacco products were advertised, industry expenditures on advertising, and adolescents' exposure to smokeless tobacco advertising. RESULTS: The STMSA appears to have had a limited effect on the advertising of smokeless tobacco products to youth; both before and after the agreement, smokeless tobacco companies advertised in magazines with high adolescent readership. CONCLUSIONS: Popular magazines with smokeless tobacco advertising reach a large number of adolescents through a combination of both youth-oriented and adult magazines. These exposure levels have generally increased since the STMSA.

Understanding the role of cigarette promotion and youth smoking in a changing marketing environment.

In 2001, $11.21 billion was spent on domestic cigarette advertising and promotion, an increase of 16.9% over 2000. This article explains how cigarette industry efforts stimulate demand and encourage smoking within the context of recent changes, including the 1998 Master Settlement Agreement (MSA) and resulting litigation, and variations in tobacco marketing policies. Communication concepts are combined with adolescent development concepts to explain how youth are impacted. Industry documents and current syndicated research data are used to reveal and explain key concepts.