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Regulatory and Exhausted T Cell Responses to AAV Capsid

Wed, 06/07/2017 - 12:13pm

Recombinant adeno-associated viruses (AAVs) are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting hemophilia B patients 10 years ago, immune responses to the AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells, which have correlated with a decline in AAV-transduced tissue in some patients. Importantly, clinical trials have also shown that this reactivation can be quelled by administering time-course taper of glucocorticoid steroids before or after dosing. More recently, two clinical studies have shown that AAV gene transfer is not only able to induce a deleterious immune response, but also can result in the initiation of a tolerance to the AAV capsid mediated by regulatory T cells and exhausted T cells. This article reviews clinical trials describing immune responses to AAV, as well as the mechanisms responsible for immune tolerance in chronic infections and how it could apply to AAV-based gene transfer. A better understanding of both cytotoxic and tolerogenic immune responses to recombinant AAV will lead to safer gene transfer protocols in patients.

Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic Burkitt Lymphoma

Wed, 06/07/2017 - 12:12pm

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation.

Effect of AHA dietary counselling on added sugar intake among participants with metabolic syndrome

Wed, 06/07/2017 - 12:12pm

BACKGROUND: High added sugar consumption has been associated with the development of metabolic syndrome (MetS). The American Heart Association (AHA) diet is designed to prevent and treat MetS; however, it remains unclear whether the AHA diet is effective on decreasing added sugar consumption. The aim of our study was to evaluate the effect of the AHA dietary counselling on added sugar consumption among participants with MetS.

METHODS: The AHA dietary counselling was conducted among 119 participants with MetS from June 2009 to January 2014 (ClinicalTrials.gov: NCT00911885). Unannounced 24-hour recalls were collected at baseline, 3, 6 and 12 months. Added sugar consumption patterns over time were examined using linear mixed models.

RESULTS: After 1-year dietary counselling, intake of added sugars decreased by 23.8 g/day (95% CI 15.1, 32.4 g/day); intake of nonalcoholic beverages dropped from the leading contributor of added sugar intake to number 7 (from 11.9 to 4.4%); the Alternative Healthy Eating Index (AHEI) score increased by 5.4 (95% CI 2.9, 8.0); however, added sugar intake for 48% participants still exceeded the recommendation. Added sugar intake per meal among different meal type was similar (24.2-25.8%) at baseline. After the 1-year dietary counselling, breakfast became the major resource of added sugar intake (33.3%); the proportion of added sugar intake from snacks decreased from 25.8% (CI 23.1, 28.5%) to 20.9% (CI 19.6, 22.3%).

CONCLUSION: Although the consumption of added sugars in participants with MetS decreased after the 1-year AHA dietary counselling, added sugar intake from majority of participants still exceeds recommended limits. Actions of successful public health strategies that focus on reducing added sugar intake are needed.

Comparison of control fasting plasma glucose of exercise-only versus exercise-diet among a pre-diabetic population: a meta-analysis

Wed, 06/07/2017 - 12:12pm

BACKGROUND/OBJECTIVES: Exercise is considered a protective factor in the prevention of type 2 diabetes, although its role as a sole treatment for pre-diabetes remains unknown. The present meta-analysis compared the effect of exercise-only with exercise-diet interventions on plasma glucose levels among a pre-diabetic population.

SUBJECTS/METHODS: A literature search was conducted using PubMed, EMBASE and Cochrane databases. The Cochrane Collaboration tool was used to assess the quality of each trial. Two reviewers independently performed quality assessment of all included articles. A random effects model was used to calculate the pooled effect.

RESULTS: A total of 4021 participants from 12 studies were included in this meta-analysis, 2045 of them were in the intervention group and 1976 were in the control group. Compared with the exercise-only interventions, the exercise-diet interventions showed a significant effect on decreasing fasting plasma glucose (FPG) levels, with a weighted mean difference (WMD) =-0.22 mmol/l, 95% confidence interval (CI): -0.25, -0.18 (Z=12.06, P 0.05). According to the intervention periods, the pooled effect in the 2-year group was the highest, and its WMD (95% CI) was -0.24 mmol/l (-0.43,-0.05). The pooled effects were statistically significant among the elderly and those of American and European descent, with WMD (95% CI) being -0.19 mmol/l (95% CI: -0.22, -0.15), -0.17 mmol/l (-0.21,-0.12) and -0.22 mmol/l (-0.27, -0.17), respectively.

CONCLUSIONS: Evidence from published trials indicates that exercise-diet interventions showed a significant effect on decreasing FPG levels.

Spirituality and Physical Activity and Sedentary Behavior among Latino Men and Women in Massachusetts

Wed, 06/07/2017 - 12:12pm

INTRODUCTION: To examine the relationships between spirituality and physical activity and sedentary behavior in a sample of Latino adults in Massachusetts.

DESIGN: This is a cross-sectional analysis of the Lawrence Health and Well Being Study; a study that was conducted among patients at the Greater Lawrence Family Health Center (GLFHC) in Lawrence, Massachusetts.

PARTICIPANTS: 602 Latino or Hispanic adults aged 21 to 85 years completed the study.

RESULTS: There was a significant negative relationship between spirituality and sedentary behavior (beta= -.12, p = .004). Although not statistically significant, higher spirituality was associated with increased odds of engaging in physical activity. There were no significant associations between spirituality and physical activity among men or women. Men with greater spirituality were significantly less sedentary (beta = -.17, P = .005). There was no relationship between sedentary behavior and spirituality among women.

CONCLUSIONS: This study found that individuals who are more spiritual are also less sedentary, and this association was stronger in men than women. Findings provide insight for developing future interventions to promote activity in this high-risk population, which has been greatly understudied. Future research endeavors should consider investigating the impact of spirituality-based messages to reduce sedentary behavior among Latinos.

The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans

Wed, 06/07/2017 - 12:12pm

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi pathway, such as Dicer-related helicase 1 (DRH-1), to display hypersusceptibility to VSV infection as evidenced by elevated infection rates, virus replication in multiple tissue types, and earlier mortality. Strikingly, infection of oocytes and embryos could also be observed in drh-1 mutants. Our results suggest that the antiviral RNAi response not only inhibits vertical VSV transmission but also promotes transgenerational inheritance of antiviral immunity. Our study introduces a new, in vivo virus-host model system for exploring arbovirus pathogenesis and provides the first evidence for vertical pathogen transmission in C. elegans.

Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study

Wed, 06/07/2017 - 12:12pm

BACKGROUND: Although clinical evaluations and neurocognitive assessments are commonly used to evaluate the extent of and recovery from concussion, brain bioenergetics could provide a more quantitative marker. The neurometabolic response to a concussion is thought to increase neuronal energy consumption and thus the demand for nucleoside triphosphate (NTP).

OBJECTIVE: We investigated the possible disruption in high-energy metabolism within the prefrontal cortex of college athletes who had either had a concussion within the past 6 months (n=14) or had never had a concussion (n=13). We hypothesized that concussed athletes would have imbalanced brain bioenergetics resulting from increased NTP consumption, and these biochemical changes would correspond to impaired cognitive abilities.

METHODS: We used phosphorus-31 magnetic resonance spectroscopy to quantify high-energy phosphates. We performed the neuroimaging in conjunction with neurocognitive assessments targeting prefrontal cortex-mediated tasks.

RESULTS: Our results revealed significantly lower gamma-NTP levels in the athletes after concussion. Although the concussed and non-concussed participants performed similarly in neurocognitive assessments, lower levels of gamma-NTP were associated with worse scores on neurocognitive tasks.

CONCLUSIONS: Our results support the concept of increased energy demand in the prefrontal cortex of a concussed brain, and we found that while neurocognitive assessments appear normal, brain energetics may be abnormal. A longitudinal study could help establish brain NTP levels as a biomarker to aid in diagnosis and to assess recovery in concussed patients.

Drosophilosophical: Re-thinking Adaptive Immunity in the Fly

Wed, 06/07/2017 - 12:12pm

For decades, flies have been a model for innate immunity. In this issue of Cell, Tassetto et al. describe a mechanism for antiviral RNAi spreading that parallels mammalian adaptive immunity through reverse-transcribed vDNA circles and the systemic dissemination of small-RNA-containing exosomes.

Patterns of change over time and history of the inflammatory potential of diet and risk of breast cancer among postmenopausal women

Wed, 06/07/2017 - 12:12pm

We utilized the dietary inflammatory index (DII) to investigate associations between patterns of change in, and history of the inflammatory potential of diet and risk of breast cancer in the Women's Health Initiative (WHI). We included 70,998 postmenopausal women aged 50-79 years recruited from 1993 to 1998 into the WHI Observational Study and Dietary Modification trial control group and followed through August 29, 2014. We utilized data from food frequency questionnaires administered at baseline and Year 3, to calculate average DII scores, patterns of change in DII, and used these measures in multivariable-adjusted Cox regression models to estimate hazards ratios (HR) and 95 % confidence intervals (CI) for incident invasive breast cancer and its subtypes. After 1,093,947 person-years of follow-up, 3471 cases of invasive breast cancer were identified. There was no substantial association between average DII scores or patterns of change in DII and risk of overall invasive breast cancer (HR, 1.03; 95 % CI, 0.90, 1.17; P-trend = 0.79; comparing extreme average DII quintiles). However, there was a significant nonlinear association between average DII scores and the ER-, PR-, HER2+, subtype (HR, 2.37; 95 % CI, 1.08, 5.20; P-trend = 0.18; comparing extreme quintiles). For patterns of change in DII, the age-adjusted association with ER-, PR-, HER2+ subtype comparing women in the proinflammatory stable to those in the anti-inflammatory stable categories (HR, 1.82; 95 % CI, 1.06, 3.13) persisted in the multivariable-adjusted model but was less precise (HR, 1.85; 95 % CI, 0.96, 3.55; P = 0.06). Dietary inflammatory potential may differentially influence the development of specific breast cancer phenotypes.

Behavioral activation for smoking cessation and mood management following a cardiac event: results of a pilot randomized controlled trial

Wed, 06/07/2017 - 12:12pm

BACKGROUND: Smoking cessation following hospitalization for Acute Coronary Syndrome (ACS) significantly reduces subsequent mortality. Depressed mood is a major barrier to cessation post-ACS. Although existing counseling treatments address smoking and depression independently in ACS patients, no integrated treatment addresses both. We developed an integrated treatment combining gold standard cessation counseling with behavioral activation-based mood management; Behavioral Activation Treatment for Cardiac Smokers (BAT-CS). The purpose of this pilot randomized controlled trial was to test feasibility, acceptability, and preliminary efficacy of BAT-CS vs. Standard of Care (SC).

METHODS: Participants were recruited during hospitalization for ACS and were randomly assigned to BAT-CS or SC. The nicotine patch was offered in both conditions. Smoking, mood, and stress outcomes were collected at end-of-treatment and 24-week follow-up.

RESULTS: Fifty-nine participants (28 BAT-CS, 31 SC) were recruited over 42 weeks, and assessment completion was above 80% in both conditions. Treatment acceptability and fidelity were high. At 24 week follow-up adjusted odds ratios favoring BAT-CS were 1.27 (95% CI: 0.41-3.93) for 7-day point prevalence abstinence and 1.27 (95% CI: 0.42-3.82) for continuous abstinence. Time to first smoking lapse was significantly longer in BAT-CS (62.4 vs. 31.8 days, p = 0.03). At 24-weeks, effect sizes for mood and stress outcomes ranged from eta2partial of.07-.11, with significant between treatment effects for positive affect, negative affect, and stress.

CONCLUSIONS: The design of this study proved feasible and acceptable. Results provide preliminary evidence that combining behavioral activation with standard smoking cessation counseling could be efficacious for this high risk population. A larger trial with longer follow-up is warranted.

TRIAL REGISTRATION: NCT01964898. First received by clinicaltrials.gov October 15, 2013.

Informal Caregivers’ Experience During Acute Exacerbation of COPD in Older Adults: A Dissertation

Tue, 06/06/2017 - 4:32pm

Chronic obstructive pulmonary disease (COPD) has been recognized as a leading cause of mortality in older adults involving acute exacerbations as life-threatening events that lead to frequent hospitalization for care. Informal caregivers have been essential to helping older adults with COPD during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A lack of empirical knowledge exists regarding the experience of informal caregivers of older adults with AECOPD in situation awareness for recognizing, understanding, and responding to an AECOPD in an emergent situation. This qualitative descriptive study explored situation awareness and its components of perception, comprehension and projection of next steps, including the caregiver’s confidence level during the AECOPD event. Fifteen informal caregivers, ages 31-77 years (mean age 48), who provided care for older adults with COPD were interviewed from an underserved community health center. The overarching theme derived from this study was something was wrong and something needed to be done. Subthemes emerged as a heightened sense of awareness, caregiver tipping point, planning next steps, caregiver confidence, and caregiver commitment. This study utilized situation awareness theory as a relevant guiding framework in exploring the experience of lay informal caregivers caring for older adults with AECOPD events. Study findings provided a description of the complex processes involved, including confidence level, for informal caregiver’s in situation awareness to recognize and respond to an AECOPD event in the older adult. Future targeted interventions need to address strategies to enhance individualized care for older adults with AECOPD events for managing care at home.

Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration

Tue, 06/06/2017 - 2:30pm

BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process.

METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development.

RESULTS: Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland.

CONCLUSION: Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF treatment increases protein citrullination and that PAD2 inhibition blocks EGF-induced cell migration suggest that PAD2 likely functions within the EGF signaling pathway to mediate cell migration.

Waivers represent a quieter way for Republicans to change health care

Fri, 06/02/2017 - 8:15am

How the Trump administration can use waivers to alter Medicaid and the Affordable Care Act (ACA), reforming health care at the state level. Health policy analyst Rachel Gershon delves into Section 1332 and 1115 waivers, and why they may be the next step after a failed American Health Care Act, for STAT news.

Making addiction treatment work for inmates

Fri, 06/02/2017 - 8:15am

Nationwide, 65 percent of inmates meet the medical criteria for substance use disorder, but just 11 percent receive treatment while incarcerated. Warren J. Ferguson, MD, writes in CommonWealth magazine about the need to improve treatment of substance use disorder in justice-involved individuals.

A UMass Medical School correctional health collaborative will address substance use disorder by assessing current screening and treatment practices for opioid addiction, making recommendations for improvements, and implementing proven practices to create a model. The collaborative partners include the state departments of corrections in Connecticut and Rhode Island and Massachusetts sheriffs who oversee houses of correction in Middlesex and Barnstable counties.

The initiative is funded by National Institute on Drug Abuse the Agency for Health Care Research and Quality.

Identification and Characterization of Rab39a and Its Role in Crosspresentation

Thu, 06/01/2017 - 2:07pm

Crosspresentation allows antigen presenting cells to present peptides from exogenously derived antigens onto MHC Class I for presentation to CD8+ T cells. Though this pathway shares key players with the Classical Class I and Class II pathways, several questions remain. A genomewide siRNA screen was performed to look for genes that selectively affected the crosspresentation or the Class II pathways. Among the genes identified in the screen was the Rab GTPase Rab39a. Rab39a was required for efficient crosspresentation but was dispensable for the presentation of endogenously expressed antigen. Both TAP-dependent and independent antigen required Rab39a for efficient presentation. Rab39a localized to late endosomes and phagosomes, though interestingly it was not required for the Class II pathway. Analysis of phagosomes from Rab39a KO or rescued cells has shown that in the presence of Rab39a, phagosomes were enriched for the open form of MHC Class I as well as TAP1, a member of the peptide loading complex. The enriched open form of MHC-I was peptide receptive, suggesting that it could contribute to crosspresentation. Phagosomes from Rab39a positive cells had reduced degradative capability and had increased levels of Sec22b, a SNARE protein reported to deliver ER-golgi sourced cargo to phagosomes. Furthermore, inhibition of ER-golgi transport via brefeldin A abolished the phenotype conferred by Rab39a. Thus, we hypothesize that Rab39a mediates the delivery of ER-golgi derived cargo to the antigen containing phagosome. This delivery allows peptide receptive MHC-I, as well as the peptide loading complex to reach the antigen, thereby facilitating crosspresentation.

Axon Death Pathways Converge on Axed to Promote Axon Disassembly

Thu, 06/01/2017 - 1:51pm

Axons use a conserved program to actively drive their own destruction after injury. Axon degeneration is present in many neurological disorders and an axon death program could be a major pharmaceutical target to preserve neuronal function. This intrinsic signaling cascade activates pro-degenerative dSarm/Sarm1, rapidly depletes axonal stores of NAD+, and terminates in cytoskeletal breakdown. Conversely, loss of dSarm/Sarm1, maintenance of NAD+ levels or its biosynthetic enzyme Nmnat, result in long-term morphological perseveration of severed axons. Exactly how dSarm/Sarm1 and loss of NAD+ execute axon death remains poorly defined.

We sought to uncover novel regulators of axon death and maintenance by performing a deficiency screen and a forward genetic mutagenesis screen in axotomized Drosophila wing sensory neurons. We identified a BTB domain protein enriched in neurons, we named Axundead (Axed), which is specifically required for axon death. Severed axons harboring loss of function mutations in axed, similar to dSarm mutants, remain preserved for 50 days post axotomy. Spontaneous neurodegeneration induced by activated dSarm or dNmnat depletion are both suppressed in axed mutants, but not in dSarm mutant alleles. Additionally, severed axed mutant axons also expressing activated dSarm or lacking Nmnat are preserved. These results indicate that dSarm acts upstream of dNmnat loss, and both events precede essential Axed function and axon destruction. Thus, the axon death pathway converges on Axed function.

Impact of Intra-Articular Injection Use on Patient-Reported Outcomes Among Patients with Knee Osteoarthritis

Thu, 06/01/2017 - 1:51pm

Background: Knee osteoarthritis (OA) is the most common type of OA and is a major cause of pain and thus results in disability for daily activities among persons living in the community. OA currently has no cure. In addition to the conflicting recommendations from clinical guidelines, evidence about the extent to which long-term use of intra-articular injections improves patient outcomes is also lacking.

Methods: Using data from the Osteoarthritis Initiative (OAI), marginal structural models (MSMs) applying inverse probability treatment weights (IPTW) were used to examine the effectiveness of intra-articular injections and changes in symptoms over time. The specific aims of this dissertation were to: 1) evaluate longitudinal use of intra-articular injections after treatment initiation among persons with radiographic knee OA; 2) quantify the extent to which intra-articular injection relieves symptoms among persons with radiographic knee OA; and 3) evaluate the performance of missing data techniques under the setting of MSMs.

Results: Of those initiating injections, ~19% switched, ~21% continued injection type, and ~60% did not report any additional injections. For participants initiating corticosteroid (CO) injections, greater symptoms post-initial injection rather than changes in symptoms over time were associated with continued use compared to one-time use. Among participants with radiographic evidence of knee OA, initiating treatments with either CO or hyaluronic acid (HA) injections was not associated with reduced symptoms compared to non-users over two years. Compared to inverse probability weighting (IPW), missing data techniques such as multiple imputation (MI) produced less biased marginal causal effects (IPW: -2.33% to 15.74%; -1.88% to 4.24%). For most scenarios, estimates using MI had smaller mean square error (range: 0.013 to 0.024) than IPW (range: 0.027 to 0.22).

Conclusions: Among participants with radiographic evidence of knee OA living in the community, the proportion of those switching injection use and one-time users was substantial after treatment initiation. In addition, initiating injection use was not associated with reduced symptoms over time. With respect to issues of missing data, using MI may confer an advantage over IPW in MSMs applications. The results of this work highlight the importance of using comparative effectiveness research with non-experimental data to study these commonly used injections and may help to understand the usefulness of these treatments for patients with knee OA.

Lived Experience of Caregivers of Relatives with Alcohol and Opiate Dependence (A phenomenological study)

Thu, 06/01/2017 - 12:46pm

Substance abuse is a relapsing chronic illness. In 2014, an estimated 27 million persons reported using illicit drugs in the United States (SAMHSA, 2014). Substance abuse negatively impacts societies, productivity, healthcare costs and families. Families play an important role in relapse prevention and sobriety. With adequate family support, substance abuse positively responds to treatment. Many individuals (about 66 million Americans) play the role as an informal caregiver for a relative with chronic illnesses such as substance abuse but few studies exist on the caregiving experiences. What we know about the family caregiving experience is restricted to data from quantitative studies which do not explain the complexities and competing challenges that exist. Different approaches are thereby needed to deepen our understanding of the family caregiver burden of living with a relative with substance abuse problems. Such studies will enable us to understand the original experience and moment of learning of a relative’s substance abuse problems, decision making and support that follows thereafter. This moment calls for major decision making and encounter with treatment services.

The purpose of this study was to explore the lived experience of caregivers of relatives with alcohol and opiate dependence. This study utilized Max van Manen’s (2014) Phenomenology of Practice. Ten participants (N=10) were recruited for this study. Van Manen’s guided existential inquiry was used in the analysis of experiential material collected through interviews. Four main themes emerged from the data: (1) Being in the moment: the extension of the self; (2) The dawn of reality: the being of acceptance; (3) Deciding in the moment: the healthcare experience; (4) Uncertainties and struggle: a lifelong process. These themes described how the participants: experienced, accepted and processed a relative’s substance abuse problem, encountered treatment services and experienced the uncertainties and struggles involved in caring for a relative with substance abuse problems. Two main findings emerged from these themes; the impact of guilt and stigma on seeking care and the need to see addiction as a disease instead of as a moral character failure. This calls for coalitions with stakeholders to decrease stigma, enhance acceptance process and increase access to treatment.

Advances in stroke: Advances in interventional radiology 2013

Thu, 06/01/2017 - 9:45am

The simultaneous publication of 3 randomized control trials comparing intravenous thrombolysis therapy to the endovascular treatment (EVT) of acute ischemic stroke might have lead to the erroneous conclusion that EVT has no place in the management of acute ischemic stroke.However, careful analysis of these studies shows that these reports have shortcomings because of changes in imaging and device technology and to study designs.

Dynamic contrast-enhanced MRI findings of acute pancreatitis in ectopic pancreatic tissue: case report and review of the literature

Thu, 06/01/2017 - 9:45am

CONTEXT: Acute pancreatitis in ectopic pancreatic tissue is an uncommon cause of acute abdominal pain and can be difficult to diagnose on imaging. Our aim is to raise awareness and aid in the diagnosis of this entity by highlighting helpful dynamic contrast-enhanced MRI imaging findings.

CASE REPORT: We report a 51-year-old man with acute onset epigastric pain presented to ER. With the presence of elevated serum lipase, the clinical diagnosis of acute pancreatitis was made. Contrast enhanced CT demonstrated normal pancreas and a focal mass at the duodenojejunal flexure, mimicked a neoplasm. Subsequent dynamic contrast enhanced MR images demonstrated enhancement pattern of the lesion similar to the native pancreatic tissue enhancement, a finding raised the possibility of acute pancreatitis in ectopic pancreatic tissue, but tumor was not excluded. Finally, patient undergone surgical bowel resection including the suspected mass that was proved as an ectopic pancreatic tissue on microscopic examination.

CONCLUSION: We concluded that findings on dynamic contrast enhanced MR imaging can be characteristic and diagnostic of acute pancreatitis in ectopic pancreatic tissue in the appropriate clinical setting.