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Recent documents in eScholarship@UMMS
Updated: 3 hours 11 min ago

Age and different influenza viruses

Thu, 08/10/2017 - 3:02pm

Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring

Thu, 08/10/2017 - 3:02pm

OBJECTIVE: The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features.

METHOD: The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay.

RESULTS: No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features.

CONCLUSIONS: The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.

Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections

Thu, 08/10/2017 - 3:02pm

Dengue viruses (DENV) cause significantly more human disease than any other arbovirus, with hundreds of thousands of cases leading to severe disease in thousands annually. Antibodies and T cells induced by primary infection with DENV have the potential for both positive (protective) and negative (pathological) effects during subsequent DENV infections. In this review, we summarize studies that have examined T-cell responses in humans following natural infection and vaccination. We discuss studies that support a role for T cells in protection against and those that support a role for the involvement of T cells in the pathogenesis of severe disease. The mechanisms that lead to severe disease are complex, and T-cell responses are an important component that needs to be further evaluated for the development of safe and efficacious DENV vaccines.

Relationship of preexisting influenza hemagglutination inhibition, complement-dependent lytic, and antibody-dependent cellular cytotoxicity antibodies to the development of clinical illness in a prospective study of A(H1N1)pdm09 Influenza in children

Thu, 08/10/2017 - 3:02pm

The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus-specific antibodies specifically can bind to infected cells and lyse virus-infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). We evaluated preexisting HAI, CDL, and ADCC antibodies in young children enrolled in a prospective cohort study of dengue during the epidemic with influenza A(H1N1)pdm09 virus to determine associations between preexisting antibodies and the occurrence of clinical or subclinical influenza virus infection. Though both preexisting HAI and CDL antibodies were associated with protection against clinical influenza, our data suggested that CDL was not a better correlate than HAI. We found that ADCC antibodies behaved differently from HAI and CDL antibodies. Unlike HAI and CDL antibodies, preexisting ADCC antibodies did not correlate with protection against clinical influenza. In fact, ADCC antibodies were detected more frequently in the clinical influenza group than the subclinical group. In addition, in contrast to HAI and CDL antibodies, HAI and the ADCC antibodies titers did not correlate. We also found that ADCC, but not CDL or HAI antibodies, positively correlated with the ages of the children.

High Antibody-Dependent Cellular Cytotoxicity Antibody Titers to H5N1 and H7N9 Avian Influenza A Viruses in Healthy US Adults and Older Children

Thu, 08/10/2017 - 3:01pm

Human influenza is a highly contagious acute respiratory illness that is responsible for significant morbidity and excess mortality worldwide. In addition to neutralizing antibodies, there are antibodies that bind to influenza virus-infected cells and mediate lysis of the infected cells by natural killer (NK) cells (antibody-dependent cellular cytotoxicity [ADCC]) or complement (complement-dependent lysis [CDL]). We analyzed sera obtained from 16 healthy adults (18-63 years of age), 52 children (2-17 years of age), and 10 infants (0.75-1 year of age) in the United States, who were unlikely to have been exposed to the avian H7N9 subtype of influenza A virus, by ADCC and CDL assays. As expected, none of these sera had detectable levels of hemagglutination-inhibiting antibodies against the H7N9 virus, but we unexpectedly found high titers of ADCC antibodies to the H7N9 subtype virus in all sera from adults and children aged > /=8 years.

Connecting Communities to Health

Thu, 08/10/2017 - 1:16pm

Libraries have a long history of meeting public demand for consumer health information. A recent IMLS study showed that an estimated 37 percent of library computer users (28 million people) use the computers and seek assistance from librarians for health/wellness issues. How can you help connect these library users to the health information they need? Learn about the free, authoritative health information resources available from the National Library of Medicine (NLM), as well as best practices for working with all types of patrons looking for medical, health and wellness information. You will also learn more about the National Network of Libraries of Medicine (NNLM) New England Region professional development and funding opportunities.

Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development and craniofacial morphogenesis.

Thu, 08/10/2017 - 12:20pm

BACKGROUND: Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown.

RESULTS: The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch.

CONCLUSIONS: Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches via repression of cyclin-dependent kinase inhibitors. This article is protected by copyright. All rights reserved.

Role of Tim3 in Mediating T Cell Exhaustion During Chronic Mycobacterium Tuberculosis Infection

Thu, 08/10/2017 - 11:25am

Mycobacterium tuberculosis infection is one of the leading causes of mortality worldwide. One third of the population is estimated to be infected, however only 5-10% of those individuals can transmit the disease. While T cell immunity initially limits mycobacterium growth, it is unclear why T cell immunity fails to sterilize the infection and prevent subsequent recrudescence. One hypothesis is T cell exhaustion is mediating the failure of T cell immunity late during infection. Here we show the development of T cell exhaustion during chronic infection, and that the inhibitory receptor T cell-immunoglobulin and mucin domain containing 3 (TIM3) mediates the development of T cell exhaustion. TIM3 accumulates on the surface of T cells throughout the course of infection and there is a subsequent decrease in effector cytokine production, such as IL-2, TNFα, and IFNγ. Furthermore, antibody blockade of TIM3 restores T cell function and improves bacterial control. Our results show that TIM3 is mediating T cell exhaustion during chronic TB infection and leading to suboptimal bacterial control.

Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions

Wed, 08/09/2017 - 2:40pm

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.

SPECT/CT: an update on technological developments and clinical applications

Wed, 08/09/2017 - 2:40pm

Functional nuclear medicine imaging with single-photon emission CT (SPECT) in combination with anatomical CT has been commercially available since the beginning of this century. The combination of the two modalities has improved both the sensitivity and specificity of many clinical applications and CT in conjunction with SPECT that allows for spatial overlay of the SPECT data on good anatomy images. Introduction of diagnostic CT units as part of the SPECT/CT system has also potentially allowed for a more cost-efficient use of the equipment. Most of the SPECT systems available are based on the well-known Anger camera principle with NaI(Tl) as a scintillation material, parallel-hole collimators and multiple photomultiplier tubes, which, from the centroid of the scintillation light, determine the position of an event. Recently, solid-state detectors using cadmium-zinc-telluride became available and clinical SPECT cameras employing multiple pinhole collimators have been developed and introduced in the market. However, even if new systems become available with better hardware, the SPECT reconstruction will still be affected by photon attenuation and scatter and collimator response. Compensation for these effects is needed even for qualitative studies to avoid artefacts leading to false positives. This review highlights the recent progress for both new SPECT cameras systems as well as for various data-processing and compensation methods.

Direct Intracranial Injection of AAVrh8 Encoding Monkey beta-N-Acetylhexosaminidase Causes Neurotoxicity in the Primate Brain

Wed, 08/09/2017 - 2:40pm

GM2 gangliosidoses, including Tay-Sachs disease and Sandhoff disease, are lysosomal storage disorders caused by deficiencies in beta-N-acetylhexosaminidase (Hex). Patients are afflicted primarily with progressive central nervous system (CNS) dysfunction. Studies in mice, cats, and sheep have indicated safety and widespread distribution of Hex in the CNS after intracranial vector infusion of AAVrh8 vectors encoding species-specific Hex alpha- or beta-subunits at a 1:1 ratio. Here, a safety study was conducted in cynomolgus macaques (cm), modeling previous animal studies, with bilateral infusion in the thalamus as well as in left lateral ventricle of AAVrh8 vectors encoding cm Hex alpha- and beta-subunits. Three doses (3.2 x 1012 vg [n = 3]; 3.2 x 1011 vg [n = 2]; or 1.1 x 1011 vg [n = 2]) were tested, with controls infused with vehicle (n = 1) or transgene empty AAVrh8 vector at the highest dose (n = 2). Most monkeys receiving AAVrh8-cmHexalpha/beta developed dyskinesias, ataxia, and loss of dexterity, with higher dose animals eventually becoming apathetic. Time to onset of symptoms was dose dependent, with the highest-dose cohort producing symptoms within a month of infusion. One monkey in the lowest-dose cohort was behaviorally asymptomatic but had magnetic resonance imaging abnormalities in the thalami. Histopathology was similar in all monkeys injected with AAVrh8-cmHexalpha/beta, showing severe white and gray matter necrosis along the injection track, reactive vasculature, and the presence of neurons with granular eosinophilic material. Lesions were minimal to absent in both control cohorts. Despite cellular loss, a dramatic increase in Hex activity was measured in the thalamus, and none of the animals presented with antibody titers against Hex. The high overexpression of Hex protein is likely to blame for this negative outcome, and this study demonstrates the variations in safety profiles of AAVrh8-Hexalpha/beta intracranial injection among different species, despite encoding for self-proteins.

Flow diverter implantation in a rat model of sidewall aneurysm: a feasibility study

Wed, 08/09/2017 - 2:40pm

BACKGROUND: More challenging animal models are needed to elucidate the efficacy of flow diverter (FD) designs and the mechanisms behind observed complications. The purpose of this study is to demonstrate the feasibility of implanting a FD in a sidewall aneurysm rat model.

METHODS: An end-to-side anastomosis was created in the abdominal aorta of 36 rats using a decellularized donor pouch. A FD was subsequently implanted.

RESULTS: After up to 3 months of follow-up, we observed that rats displayed normal growth and behavior. Mortality within the groups was low (2 rats, 5.6%). All aneurysms thrombosed after FD implantation and showed progressive soft tissue replacement of the thrombus during follow-up. The abdominal aortas remained patent.

CONCLUSIONS: This model can be used to test the effects of FDs in future studies.

Magnetic Resonance Imaging-Directed Ultrasound Imaging of Non-Mass Enhancement in the Breast: Outcomes and Frequency of Malignancy

Wed, 08/09/2017 - 2:40pm

OBJECTIVES: This study was performed to determine the frequency, predictors, and outcomes of ultrasound (US) correlates for non-mass enhancement.

METHODS: From January 2005 to December 2011, a retrospective review of 5837 consecutive breast magnetic resonance imaging examinations at our institution identified 918 non-mass enhancing lesions for which follow-up or biopsy was recommended. Retrospective review of the images identified 879 of 918 lesions (96%) meeting criteria for non-mass enhancement. Patient demographics, pathologic results, and the presence of an adjacent landmark were recorded. Targeted US examinations were recommended for 331 of 879 cases (38%), and 284 of 331 women (86%) underwent US evaluations.

RESULTS: The US correlate rate for non-mass enhancement was 23% (64 of 284). An adjacent landmark was significantly associated with a US correlate (P < .001). Biopsy was recommended for 43 of 64 correlates (67%). Ultrasound-guided biopsy was performed on 39 of 43 (91%); 7 of 39 (18%) were malignant. No correlate was seen for 220 of 284 lesions (77%). At magnetic resonance imaging-guided biopsy, 14 of 117 (12%) were malignancies. For all biopsied non-mass enhancements, the malignancy rate was 18% (55 of 308) and was significantly more prevalent in the setting of a known index cancer (P < .001), older age (P < .001), the presence of a landmark (P = .002), and larger lesion size (P = .019).

CONCLUSIONS: Non-mass enhancement with an adjacent landmark is more likely to have a US correlate compared to non-mass enhancement without an adjacent landmark. Non-mass enhancement in the setting of a known index cancer, older age, a landmark, and larger lesion size is more likely to be malignant. However, no statistical difference was detected in the rate of malignancy between non-mass enhancement with (18%) or without (12%) a correlate. Absence of a correlate does not obviate the need to biopsy suspicious non-mass enhancement.

Tourniquet parent artery occlusion after flow diversion

Wed, 08/09/2017 - 2:40pm

BACKGROUND: The Pipeline Embolization Device (PED) is increasingly used for both on- and off-label purposes for treatment of intracranial aneurysms. The device gradually slows flow of blood into the aneurysm, but the high metal coverage of PED promotes endothelialization of the device. Occasionally, this leads to in-stent stenosis that is clinically well tolerated. We present a multi-institutional Pipeline series that includes three cases of gradual asymptomatic occlusion within the PED and parent vessel.

METHODS: Institutional databases at each participating center were searched for patients treated with the PED. Patients with at least 50% stenosis or occlusion were selected and all relevant clinical and radiographic data were reviewed.

RESULTS: A total of 326 cases performed by five neurointerventionalists across four institutions were reviewed. Among these there were three cases of complete occlusion and two cases of stenosis of more than 50%, for an occlusion rate of 0.9%. All patients were clinically asymptomatic.

CONCLUSIONS: A gradual tourniquet-like occlusion can occur following placement of the PED, leading to vessel occlusion. This has been clinically well tolerated by patients in our series due to the formation of pial collaterals as the stenosis progresses, likely due to ischemic preconditioning. Small parent vessel, pre-existing stenosis, fusiform pathology, overlapping devices, and suboptimal antiplatelet therapy seem to be predisposing factors. Further experience and follow-up will allow us to characterize the risk factors and optimize post-procedural therapy for these patients.

Development of a high resolution MRI intracranial atherosclerosis imaging phantom

Wed, 08/09/2017 - 2:40pm

BACKGROUND AND PURPOSE: Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD.

MATERIALS AND METHODS: A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR).

RESULTS: Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5-6.2, showing reproducible phantom durability.

CONCLUSIONS: A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

Use of self-expanding stents for better intracranial flow diverter wall apposition

Wed, 08/09/2017 - 2:40pm

Background Flow diverter (FD) malapposition is associated with stroke-related complications. We document the use of self-expanding nitinol stents to remove/reduce the ledge of a FD deployed for aneurysm treatment. Methods We identified five patients who were treated with the Pipeline embolization device (PED) in conjunction with a Neuroform EZ stent for inadequate wall apposition of the ends of the FD at our institution between May 2014 and July 2015. Among other parameters, angiographic results, cone-beam computed tomography assessment of wall apposition and patient clinical outcome were evaluated. Results Incomplete device end apposition was seen in three cases, and precarious positioning of the distal end of the PED over the aneurysm neck was seen in two cases. In all five cases, successful treatment with good wall apposition and proper pinning of the PED distal edge was achieved using an additional Neuroform EZ stent. Appropriate aneurysm neck coverage and flow stagnation was seen in all cases. The combination of high radial outward force and open-cell design permits the Neuroform EZ stent to jail the malappositioned edges of the FD while maintaining good vessel-wall apposition itself and prevent migration of the PED. Short-term follow-up angiography showed device patency and complete aneurysm obliteration in all cases. Conclusions Preliminary results of this small case series suggest that the Neuroform EZ stent allows for effective treatment of FD malapposition in selected patients amenable for this endovascular approach. Long-term and larger cohort studies are needed to validate these results.

4D Reconstruction with Respiratory Correction for Gated Myocardial Perfusion SPECT

Wed, 08/09/2017 - 2:40pm

Cardiac SPECT images are known to suffer from both cardiac and respiratory motion blur. In this work, we investigate a 4D reconstruction approach to suppress the effect of respiratory motion in gated cardiac SPECT imaging. In this approach, the sequence of cardiac gated images is reconstructed with respect to a reference respiratory amplitude bin in the respiratory cycle. To combat the challenge of inherent high imaging noise, we utilize the data counts acquired during the entire respiratory cycle by making use of a motion-compensated scheme, in which both cardiac motion and respiratory motion are taken into account. In our evaluation study, we first use Monte Carlo simulated imaging data wherein the ground truth is known for quantitative comparison. We then demonstrate the proposed approach on eight sets of clinical acquisitions, in which the subjects exhibit different degrees of respiratory motion blur. The quantitative evaluation results show that 4D reconstruction with respiratory correction could effectively reduce the effect of motion blur and lead to a more accurate reconstruction of the myocardium. The mean-squared-error of the myocardium is reduced by 22%, and the LV resolution is improved by 21%. Such improvement is also demonstrated with the clinical acquisitions, where the motion blur is markedly improved in the reconstructed LV wall and blood pool. The proposed approach is also noted to be effective on correcting the spill-over effect in the myocardium from nearby bowel or liver activities.

Complement-Related Regulates Autophagy in Neighboring Cells

Tue, 08/08/2017 - 12:52pm

Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a better understanding of the regulatory mechanisms within multicellular animals. My research determined Macroglobulin complement-related (Mcr), a Drosophila complement orthologue, can activate autophagy during developmental cell death. Unlike most known autophagy regulators, Mcr functions in a cell non-autonomous manner to trigger autophagy in neighboring cells. To my knowledge, this is the first identified autophagy factor that cell non-autonomously activates autophagy. Additionally, I found that Mcr, a secreted protein, instructs the autophagy machinery through the immune receptor Draper, suggesting a relationship between autophagy and the control of inflammation. Lastly, Mcr is dispensable for both nutrient deprivation-induced autophagy in the fat body and developmentally programmed autophagy in the dying midgut of Drosophila. Therefore, this study unveils a mechanism in a multicellular organism by which autophagy is systematically controlled in distinct cell contexts.

Integrated behavioral health practice facilitation in patient centered medical homes: A promising application

Tue, 08/08/2017 - 8:35am

INTRODUCTION: The purpose of this study was to assess the degree of behavioral health (BH) integration change in patient-centered medical homes (PCMHs) when using a practice facilitator (PF) specially trained in implementing integrated care and how a quasi-experimental design assists in this process.

METHOD: Twelve PCMHs, 8 Federally Qualified Health Centers and 4 private practices, with varying degrees of BH services participated in this study. The degree of BH integration was assessed with a quasi-experimental design using the Maine Health Access Foundation's Site Self Assessment (MeHAF SSA) at baseline and after implementing site-specific BH services. The sites tracked completion of unique objectively measured goals being implemented using the Goal Attainment Scale (GAS) score.

RESULTS: At the conclusion of the study, sites saw a statistically significant increase in the level of BH integration from a baseline of 2.73 (SD = 0.44) to a postintervention score of 3.49 (SD = 0.22) with improvements from mild-moderate overall integration to moderate-advanced overall integration (p < .001). In addition, 10 out of the 12 sites achieved successful implementation of unique goals with assistance from the PF.

DISCUSSION: This study provides the first quasi-experimental/pretest-posttest evidence utilizing real-world data that the practice facilitation method is an effective solution toward increasing the degree of BH integration. This paper describes the real-world efforts to evaluate the degree of BH integration change in PCMHs when using a PF with content expertise in BH integration within primary care.

Implementing an Online Health Information Platform for People With Serious Mental Illness

Mon, 08/07/2017 - 4:27pm

Introduction: Individuals with serious mental illness (SMI) die, on average, 25 years earlier than the general population. Higher rates of smoking, alcohol consumption, poor nutrition, lack of physical activity, obesity, lack of preventive healthcare, and other modifiable risk factors, as well as side effects associated with certain antipsychotic medications, place individuals with SMI at high physical health risk. They are designated a health disparity population by the US National Association of State Mental Health Program Directors and as a vulnerable group worldwide by the World Health Organization. While the Internet provides intriguing opportunities to support person-centered health care, web-based resources often convey new barriers and consequently, contribute to greater health disparities for individuals with SMI. Many individuals with disabilities or a chronic illness, report feeling frustrated, overwhelmed, and confused using the Internet. Web design accommodations for this population have been recommended, but not generally applied.

Methods: Phase one of this three-year project focused on an environmental scan of available resources and needs assessment. We conducted six IRB-approved focus groups (n=42) with individuals with SMI and with health information providers (librarians, researchers and practitioners) with the goal of embracing user experience and design accommodations required for individuals with SMI.

Conclusion: Through the results of the focus groups, we identified central themes regarding the general usage of online resources among people with SMI (e.g., types of online sources used, criteria for choosing the appropriate website, types of information searched) as well as themes identifying the specific needs and requirements that this population have in gathering information (e.g., the need for holistic information, suggestions for coping skills, content encouraging hope, and language that avoids labeling and stigma)). We can conclude that people with SMI lack literacy skills on how to appropriately select and use online health information. There is a need for online tools providing holistic information about how to manage physical and mental health.