Polyaromatic hydrocarbons in pollution: a heart-breaking matter

Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution‐based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho‐physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.publishedVersio

Enhancing self-regulation as a strategy for obesity prevention in Head Start preschoolers: the growing healthy study

Abstract Background Nearly one in five 4-year-old children in the United States are obese, with low-income children almost twice as likely to be obese as their middle/upper-income peers. Few obesity prevention programs for low-income preschoolers and their parents have been rigorously tested, and effects are modest. We are testing a novel obesity prevention program for low-income preschoolers built on the premise that children who are better able to self-regulate in the face of psychosocial stressors may be less likely to eat impulsively in response to stress. Enhancing behavioral self-regulation skills in low-income children may be a unique and important intervention approach to prevent childhood obesity. Methods/design The Growing Healthy study is a randomized controlled trial evaluating two obesity prevention interventions in 600 low-income preschoolers attending Head Start, a federally-funded preschool program for low-income children. Interventions are delivered by community-based, nutrition-education staff partnering with Head Start. The first intervention (n = 200), Preschool Obesity Prevention Series (POPS), addresses evidence-based obesity prevention behaviors for preschool-aged children and their parents. The second intervention (n = 200) comprises POPS in combination with the Incredible Years Series (IYS), an evidence-based approach to improving self-regulation among preschool-aged children. The comparison condition (n = 200) is Usual Head Start Exposure. We hypothesize that POPS will yield positive effects compared to Usual Head Start, and that the combined intervention (POPS + IYS) addressing behaviors well-known to be associated with obesity risk, as well as self-regulatory capacity, will be most effective in preventing excessive increases in child adiposity indices (body mass index, skinfold thickness). We will evaluate additional child outcomes using parent and teacher reports and direct assessments of food-related self-regulation. We will also gather process data on intervention implementation, including fidelity, attendance, engagement, and satisfaction. Discussion The Growing Healthy study will shed light on associations between self-regulation skills and obesity risk in low-income preschoolers. If the project is effective in preventing obesity, results can also provide critical insights into how best to deliver obesity prevention programming to parents and children in a community-based setting like Head Start in order to promote better health among at-risk children. Trial registration number Clinicaltrials.gov Identifier: NCT01398358http://deepblue.lib.umich.edu/bitstream/2027.42/112539/1/12889_2012_Article_4758.pd

Telehealth and Mobile Health Applied To IntegratedBehavioral Care: OpportunitiesFor Progress In New Hampshire

This paper is an accompanying document to a webinar delivered on May 16, 2017, for the New Hampshire Citizens Health Initiative (Initiative). As integrated behavioral health efforts in New Hampshire gain traction, clinicians, administrators, payers, and policy makers are looking for additional efficiencies in delivering high quality healthcare. Telehealth and mobile health (mHealth) have the opportunity to help achieve this while delivering a robust, empowered patient experience. The promise of video-based technology was first made in 1964 as Bell Telephone shared its Picturephone® with the world. This was the first device with audio and video delivered in an integrated technology platform. Fast-forward to today with Skype, FaceTime, and webinar tools being ubiquitous in our personal and business lives, but often slow to be adopted in the delivery of medicine. Combining technology-savvy consumers with New Hampshire’s high rate of electronic health record (EHR) technology adoption, a fairly robust telecommunications infrastructure, and a predominately rural setting, there is strong foundation for telehealth and mHealth expansion in New Hampshire’s integrated health continuum

Integrating Behavioral Health & Primary Care in New Hampshire: A Path Forward to Sustainable Practice & Payment Transformation

New Hampshire residents face challenges with behavioral and physical health conditions and the interplay between them. National studies show the costs and the burden of illness from behavioral health conditions and co-occurring chronic health conditions that are not adequately treated in either primary care or behavioral health settings. Bringing primary health and behavioral health care together in integrated care settings can improve outcomes for both behavioral and physical health conditions. Primary care integrated behavioral health works in conjunction with specialty behavioral health providers, expanding capacity, improving access, and jointly managing the care of patients with higher levels of acuity In its work to improve the health of NH residents and create effective and cost-effective systems of care, the NH Citizens Health Initiative (Initiative) created the NH Behavioral Health Integration Learning Collaborative (BHI Learning Collaborative) in November of 2015, as a project of its Accountable Care Learning Network (NHACLN). Bringing together more than 60 organizations, including providers of all types and sizes, all of the state’s community mental health centers, all of the major private and public insurers, and government and other stakeholders, the BHI Learning Collaborative built on earlier work of a NHACLN Workgroup focused on improving care for depression and co-occurring chronic illness. The BHI Learning Collaborative design is based on the core NHACLN philosophy of “shared data and shared learning” and the importance of transparency and open conversation across all stakeholder groups. The first year of the BHI Learning Collaborative programming included shared learning on evidence-based practice for integrated behavioral health in primary care, shared data from the NH Comprehensive Healthcare Information System (NHCHIS), and work to develop sustainable payment models to replace inadequate Fee-for-Service (FFS) revenues. Provider members joined either a Project Implementation Track working on quality improvement projects to improve their levels of integration or a Listen and Learn Track for those just learning about Behavioral Health Integration (BHI). Providers in the Project Implementation Track completed a self-assessment of levels of BHI in their practice settings and committed to submit EHR-based clinical process and outcomes data to track performance on specified measures. All providers received access to unblinded NHACLN Primary Care and Behavioral Health attributed claims data from the NHCHIS for provider organizations in the NH BHI Learning Collaborative. Following up on prior work focused on developing a sustainable model for integrating care for depression and co-occurring chronic illness in primary care settings, the BHI Learning Collaborative engaged consulting experts and participants in understanding challenges in Health Information Technology and Exchange (HIT/HIE), privacy and confidentiality, and workforce adequacy. The BHI Learning Collaborative identified a sustainable payment model for integrated care of depression in primary care. In the process of vetting the payment model, the BHI Learning Collaborative also identified and explored challenges in payment for Substance Use Disorder Screening, Brief Intervention and Referral to Treatment (SBIRT). New Hampshire’s residents will benefit from a health care system where primary care and behavioral health are integrated to support the care of the whole person. New Hampshire’s current opiate epidemic accentuates the need for better screening for behavioral health issues, prevention, and treatment referral integrated into primary care. New Hampshire providers and payers are poised to move towards greater integration of behavioral health and primary care and the Initiative looks forward to continuing to support progress in supporting a path to sustainable integrated behavioral and primary care

Cross- lagged associations between behaviour problems and obesity in head start preschoolers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155893/1/ijpo12627_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155893/2/ijpo12627.pd

Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers

BACKGROUND: We sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM). MATERIALS AND METHODS: With the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers. RESULTS: The mean and median intra-observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or inter-observer error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm. CONCLUSION: We have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging

Reflections on the Cost of Low-Cost Whole Genome Sequencing: Framing the Health Policy Debate

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy

Loss of DAP12 and FcRγ drives exaggerated IL-12 production and CD8(+) T cell response by CCR2(+) Mo-DCs

Dap12 and FcRγ, the two transmembrane ITAM-containing signaling adaptors expressed in dendritic cells (DC), are implicated in the regulation of DC function. Several activating and adhesion receptors including integrins require these chains for their function in triggering downstream signaling and effector pathways, however the exact role(s) for Dap12 and FcRγ remains elusive as their loss can lead to both attenuating and enhancing effects. Here, we report that mice congenitally lacking both Dap12 and FcRγ chains (DF) show a massively enhanced effector CD8(+) T cell response to protein antigen immunization or West Nile Virus (WNV) infection. Thus, immunization of DF mice with MHCI-restricted OVA peptide leads to accumulation of IL-12-producing monocyte-derived dendritic cells (Mo-DC) in draining lymph nodes, followed by vastly enhanced generation of antigen-specific IFNγ-producing CD8(+) T cells. Moreover, DF mice show increased viral clearance in the WNV infection model. Depletion of CCR2+ monocytes/macrophages in vivo by administration anti-CCR2 antibodies or clodronate liposomes completely prevents the exaggerated CD8+ T cell response in DF mice. Mechanistically, we show that the loss of Dap12 and FcRγ-mediated signals in Mo-DC leads to a disruption of GM-CSF receptor-induced STAT5 activation resulting in upregulation of expression of IRF8, a transcription factor. Consequently, Dap12- and FcRγ-deficiency exacerbates GM-CSF-driven monocyte differentiation and production of inflammatory Mo-DC. Our data suggest a novel cross-talk between DC-ITAM and GM-CSF signaling pathways, which controls Mo-DC differentiation, IL-12 production, and CD8(+) T cell responses

Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided High Dose Rate brachytherapy boost

PURPOSE: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. RESULTS: Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. CONCLUSION: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive

Effect of the Glycemic Index of Carbohydrates on Acne vulgaris

Acne vulgaris may be improved by dietary factors that increase insulin sensitivity. We hypothesized that a low-glycemic index diet would improve facial acne severity and insulin sensitivity. Fifty-eight adolescent males (mean age ± standard deviation 16.5 ± 1.0 y and body mass index 23.1 ± 3.5 kg/m2) were alternately allocated to high or low glycemic index diets. Severity of inflammatory lesions on the face, insulin sensitivity (homeostasis modeling assessment of insulin resistance), androgens and insulin-like growth factor-1 and its binding proteins were assessed at baseline and at eight weeks, a period corresponding to the school term. Forty-three subjects (n = 23 low glycemic index and n = 20 high glycemic index) completed the study. Diets differed significantly in glycemic index (mean ± standard error of the mean, low glycemic index 51 ± 1 vs. high glycemic index 61 ± 2, p = 0.0002), but not in macronutrient distribution or fiber content. Facial acne improved on both diets (low glycemic index −26 ± 6%, p = 0.0004 and high glycemic index −16 ± 7%, p = 0.01), but differences between diets did not reach significance. Change in insulin sensitivity was not different between diets (low glycemic index 0.2 ± 0.1 and high glycemic index 0.1 ± 0.1, p = 0.60) and did not correlate with change in acne severity (Pearson correlation r = −0.196, p = 0.244). Longer time frames, greater reductions in glycemic load or/and weight loss may be necessary to detect improvements in acne among adolescent boys