University Of Connecticut Health Center Research Articles

TMS Targets for Multiple Sclerosis Related Depression Derived Using a Precomputed Functional Connectome (P11-3.014)

TMS Targets for Multiple Sclerosis Related Depression Derived Using a Precomputed Functional Connectome (P11-3.014)

Exploring relationships between neuroticism, depression, and the progression of cognitive decline over time

<h3>Introduction</h3> Cognitive decline is prevalent in older adults, and predicting onset of cognitive decline in patients is a significant challenge for physicians. Studies have shown a relationship between neuroticism and the onset of cognitive decline in a ten-year time span, and have identified one aspect of neuroticism (N6 – vulnerability to stress) to be specifically elevated in those who later develop cognitive impairment. However, little is known about the onset of cognitive decline in a shorter time span, or if other aspects of neuroticism might be predictors. In addition, the effects of depression in this relationship have yet to be determined. The purpose of this study is to evaluate the relationship between the various facets of neuroticism and the onset of cognitive decline in a 1 to 3 year time span in the presence and absence of depression in a cohort of elderly subjects. <h3>Methods</h3> This is a retrospective cohort study. Subjects participated in "Neurobiology of Late-life Depression" (NBOLD) study at the University of Connecticut Health Center (UCHC) and Olin Neuropsychiatry Research Center at the Institute of Living in Hartford Hospital. Participants were screened for depression using the Center for Epidemiologic Studies – Depression (CES-D) scale, with a score of 16 or greater as a cut-off for depression. The NEO PI-R was used to screen for neuroticism. CERAD neurophysiological tests were used to screen for cognitive decline, and were administered annually. Statistical analysis of the data involved linear regression and correlation analysis was done to assess the significance of the predictive value of various facets of neuroticism in future cognitive decline development. Mixed model analysis was done to examine how changes in neuroticism score can moderate the rate of cognitive decline. Analysis was done by using baseline neuroticism scores and cognition scores after one, two, and three years. <h3>Results</h3> 163 subjects were enrolled. 28.8% of subjects identified as male, and 71.2% identified as female. The mean age was 72.27 ± 7.44 years. 89.6% identified as White, 7.7% identified as Black or African American, 1.8% identified as Asian, and 0.61% identified as mixed race. 1.8% had completed 9^th grade, 14.1% had graduated high school, 22.7% had completed some college, 20.9% had a college degree, and 40.5% had completed post-graduate education124 subjects had depression at the time of baseline measurement, and 39 comparison subjects did not have depression at baseline. Two facets of neuroticism were shown to be statistically significant predictors of cognitive decline in the non-depressed patients. High baseline N6 (vulnerability of stress) was a predictor of a lower CERAD score at 1 year (p=0.08) and 3 years (p=0.09). High baseline N4 (self-consciousness) was also found to be a predictor of lower CERAD score at 1 year (p=0.01), 2 years (p=0.03), and 3 years (p=0.08). In addition, improvement in N4 over time was shown to cause a lower rate of progression of cognitive decline in non-depressed patients. The findings for depressed patients were not found to be statistically significant. <h3>Conclusions</h3> Both N6 and N4 are statistically significant predictors of cognitive decline 1 to 3 years after baseline neuroticism measurement. Improvement in N4 is associated with a lower rate of cognitive decline. These results were found in non-depressed patients but not depressed patients. These findings raise the possibility that longer periods of follow-up are needed to illustrate the association between neuroticism, cognitive decline, and depression. Investigating predictive factors of cognitive decline is key to foreseeing the development of the disease early on, allowing patients to prepare and access care that may be difficult to obtain as cognitive conditions progress. <h3>This research was funded by</h3> All subjects in the study were enrolled in NBOLD, a NIMH R01 grant entitled "Neurobiology and Adverse Outcomes of Neuroticism in Late-Life Depression".

Evaluating the Effects of the COVID-19 Pandemic on Depression and Resilience in Older Adults

IntroductionSince March 2020, the COVID-19 pandemic has affected the physical and mental health of older adults. We know how social isolation and loneliness may adversely affect one's health, mood, and cognition, specifically in adults over 65. However, when faced with adversity, studies have shown older adults to be at least, if not more, resilient than their younger counterparts. This study aimed to understand the extent of psychosocial impact the pandemic had on older adults with and without depression currently enrolled in the Neurobiology of Late-Life Depression (NBOLD) Study. In conjunction with the Brief Carroll Depression and Brief Resilience Scales, we used a novel measure of pandemic-related experiences across several life domains in older adults, the Epidemic-Pandemic Impacts Inventory-Geriatrics Adaptation (EPII-G).Based on prior knowledge of how detrimental social isolation can be on mental health and how resilient older people can be, we hypothesized that depression scores would increase during the pandemic. We also suspected that resilience scores at least remain constant or possibly improve.According to the Centers for Disease Control and Prevention, adults 65 and older account for 14.3% of cases and 80% of COVID-19 related deaths in the United States. Between “stay at home” guidelines and visitation restrictions along the continuum of aging services, there is concern over the lasting effects of social isolation. Therefore there is a need to examine and map the ways by which one's physical and social environments impact loneliness. Although loneliness is considered to be a subjective feeling related to a person's experience, it is one of three main factors leading to depression and a factor in cause of suicide.Despite this, one characteristic has shown to be protective against these stressors. Resilient individuals exhibit internal qualities like self-reliance and optimism and have external support systems in place allowing them to adapt more readily in the face of change.There is still little research available regarding outcomes and factors from COVID-19 impacting older adults’ depression and resilience, which this study aims to address, while strengthening the validity of the EPII-G.MethodsThe study population included older adults previously diagnosed with Major Depressive Disorder (MDD) and non-depressed controls, enrolled in the N-BOLD study at University of Connecticut Health Center. Inclusion criteria for participants included: age of 60 or greater, ability to read and write English, and Mini-Mental State Examination score of 25 or greater. Depressed subjects met the criteria for MDD, either episodic or recurrent. Participants provided additional informed consent for the study. Baseline data was collected prior to the COVID-19 pandemic, with second interviews taking place mid-2020, and additional follow-up summer 2021. The study utilized the EPII-G, Brief Carroll Depression Scale (BC), and Brief Resilience Scale (BRS). The surveys were verbally administered by the research staff both in-person and via phone interviews.ResultsFrom mid-2020 to summer 2021, both depressed and emotional control groups saw an increase in total BC depression score. Older adults with a history of depression showed BC scores increase from 2.47 to 3.12, and older controls experienced increases from 0.5 to 1.11.Despite an increase in depression score, both cohorts also saw an increase in BRS resilience score, with the depressed group and control group showing increases in BRS from 18.18 to 19.75 and 20.93 to 23.33 respectively.We found a negative correlation between positive home life of person in the home on EPII-G and BC scores, with a correlation coefficient of -0.3645 and p-value of 0.0616. There was also a positive correlation with positive home life of person in the home and social activities for self and BRS scores, with correlation coefficients of 0.26304 and 0.29869 and p-values of 0.0845 and 0.0489 respectively.ConclusionsIndividuals who didn't see disruption to their normal routine and had the means to communicate with loved ones had strong psycho-social supports in place, but were still vulnerable to the detrimental effects of isolation. Through their years of experience, older adults have had the time needed to develop protective factors such as self-reliance. They have also lived through poignant events such as war and economic depression, putting suffering into perspective. As many no longer work or attend school like their younger counterparts, they experienced less disruption to daily routine. This strong foundation has contributed to the resilience needed to overcome the stressors that surfaced during the pandemic.By continuing to follow these groups, we can evaluate changes in depressive symptoms, how long they persist, and if individuals return to baseline over time, as well as to continue to strengthen the EPII-G's validity.This research was funded byResearch is supported by National Institute of Mental Health grant R01 MH108578.Chart: https://apps.aagponline.org/abstracts/uploads/2022/f1peuxbywkablos.pdf

First Author Spotlight

First Author Spotlight

Convolutional neural network for automated mass segmentation in mammography

BackgroundAutomatic segmentation and localization of lesions in mammogram (MG) images are challenging even with employing advanced methods such as deep learning (DL) methods. We developed a new model based on the architecture of the semantic segmentation U-Net model to precisely segment mass lesions in MG images. The proposed end-to-end convolutional neural network (CNN) based model extracts contextual information by combining low-level and high-level features. We trained the proposed model using huge publicly available databases, (CBIS-DDSM, BCDR-01, and INbreast), and a private database from the University of Connecticut Health Center (UCHC).ResultsWe compared the performance of the proposed model with those of the state-of-the-art DL models including the fully convolutional network (FCN), SegNet, Dilated-Net, original U-Net, and Faster R-CNN models and the conventional region growing (RG) method. The proposed Vanilla U-Net model outperforms the Faster R-CNN model significantly in terms of the runtime and the Intersection over Union metric (IOU). Training with digitized film-based and fully digitized MG images, the proposed Vanilla U-Net model achieves a mean test accuracy of 92.6%. The proposed model achieves a mean Dice coefficient index (DI) of 0.951 and a mean IOU of 0.909 that show how close the output segments are to the corresponding lesions in the ground truth maps. Data augmentation has been very effective in our experiments resulting in an increase in the mean DI and the mean IOU from 0.922 to 0.951 and 0.856 to 0.909, respectively.ConclusionsThe proposed Vanilla U-Net based model can be used for precise segmentation of masses in MG images. This is because the segmentation process incorporates more multi-scale spatial context, and captures more local and global context to predict a precise pixel-wise segmentation map of an input full MG image. These detected maps can help radiologists in differentiating benign and malignant lesions depend on the lesion shapes. We show that using transfer learning, introducing augmentation, and modifying the architecture of the original model results in better performance in terms of the mean accuracy, the mean DI, and the mean IOU in detecting mass lesion compared to the other DL and the conventional models.

Differences in rates of low-dose computed tomography screening for lung cancer amongst various outpatient care centers.

245 Background: Despite low-dose computed tomography (LDCT) screening for lung cancer recommended by the United States Preventive Services Task Force (USPSTF) demonstrating a relative reduction in mortality, there remains low rates of testing nationwide. Yet studies are limited regarding specific differences in screening rates amongst various outpatient care settings. Methods: We performed retrospective chart reviews of patients followed by resident providers within an academic internal medicine residency program who met USPSTF guidelines for lung cancer screening between 2015-2020. This was conducted at three separate outpatient clinic sites including a state-funded academic institution, inner city community health center, and veteran affairs medical center. Data collection included patient demographic and smoking histories as well as rates of ordered and completed LDCT screening. Results: A total of 832 patients were identified as current or former smokers between the ages of 55 and 80 years: 320 from Hartford Hospital Community Health Center (HHCHC), 262 from University of Connecticut Health Center (UCHC), and 250 from the Veteran Affairs (VA) Medical Center. 85 (27%) of these patients from HHCHC, 84 (32%) from UCHC, and 56 (22%) from the VA met USPSTF eligibility criteria for LDCT screening. Overall compliance rates of screening were found to be 44% at HHCHC, 59.5% at UCHC, and 51.8% at the VA. Results are outlined in Table. Conclusions: Screening rates for lung cancer with LDCT remain low but have been steadily improving throughout the United States following new recommendations and increased awareness provided by multiple medical organizations. We sought to compare differences in compliance rates amongst various outpatient clinics within the same internal medicine residency program at University of Connecticut. Our findings demonstrate significant differences in LDCT screening for lung cancer between the program’s community health center versus its state and federally funded outpatient clinics. Automatic reminders to providers can potentially improve rates of lung cancer screening. Patients should also be educated about the importance of screening to improve adherence with imaging. [Table: see text]

Cone Beam Computed Tomography Report Satisfaction Among Dental Referrers

Background and Objectives: This study was to evaluate referring dentists’ satisfaction with Cone Beam Computed Tomography (CBCT) reports prepared at the Department of Oral and Maxillofacial Radiology (OMFR) at the University of Connecticut Health Center (UCHC). Material and methods: This study was an anonymous survey of 150 UCHC dental faculty and residents and was approved by our IRB. The survey consisted of 23 questions asking respondents whether they had ordered CBCT studies, and if so, their impressions of the quality and usefulness of the reports and images sent back from OMFR, and their level of trust in the radiologist expertise. Questionnaires were distributed twice through participants’ school mailboxes with a one-week interval. Results: The majority of CBCT scans referrals (62%) were for implant treatment planning. Overall, 66.7 % of respondents were satisfied with CBCT reports. 73% indicated that the reports do not need modification, but a majority indicated that standardization of reports would be helpful. Conclusion: The use of CBCT scans are useful for the dentist. Most of the participants who had used that equipment proved that it should be allowed in that facility as it will improve their service delivery to the patients.

Open Sharing During COVID-19: CRISPR-Based Detection Tools.

Open Sharing During COVID-19: CRISPR-Based Detection Tools.

Influence of age and cancer history on prevalence of autoimmunity in patients with metastatic melanoma: A large retrospective study.

e22016 Background: While immune checkpoint inhibitors (ICIs) have improved the survival rates of metastatic melanoma in recent years, immune-related adverse events (irAEs) remain a major toxicity. Studies have established that pre-existing autoimmunity increases the risk of severe irAEs following ICI therapy (1). Melanoma is common cancer in older patients, and older age is believed to be a risk factor of autoimmunity. However, there is controversy concerning the influence of age increasing the risk of irAEs between clinical trials, which exclude patients with confirmed or suspected autoimmunity, and less-selective but lower-power case reports (2). In order to understand potential irAE risk following ICI treatment, we measured the prevalence of pre-existing autoimmune disease by age and cancer type. Methods: We studied 293,938 patients aged 18-106 years old who were treated at the University of Connecticut Health Center between 2000 and 2018 using GE Centricity’s IDX database. Patients were organized into four study groups based on International Classifications of Diseases codes (ICD-9 and ICD-10), specifically primary melanoma and three comparisons groups: non-cutaneous neoplasms alone, melanoma with non-cutaneous neoplasms, and patients without cancer history. A list of 340 ICD codes corresponding to 105 autoimmune conditions were queried. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (27.0%, 29.4%, respectively) compared to the rates in patients with melanoma alone and those without cancer history (11.1%, 8.7%, respectively, p &lt; 0.05). In patients with both melanoma and non-cutaneous cancers, those with metastases had an 11.7% increase in autoimmune prevalence compared to patients without metastases (p &lt; 0.0001), the largest metastasis-associated increase observed across all cancer groups. Lastly, a logistic regression demonstrated that age is weakly correlated with autoimmunity (r = 0.01, p &lt; 0.0001). Conclusions: The findings suggest that a history of metastasis, non-cutaneous cancer, and advanced age are associated with a higher prevalence of pre-existing autoimmunity in melanoma patients. As ICIs are indicated for metastatic melanoma, our findings warrant future studies and careful risk assessment of autoimmunity in senior patients.

Siliconoma mimicking a locally invasive fungating breast malignancy.

The Breast JournalVolume 26, Issue 6 p. 1253-1254 BREAST IMAGES Siliconoma mimicking a locally invasive fungating breast malignancy Matthew J. Hadfield DO, Corresponding Author Matthew J. Hadfield DO hadfield@uchc.edu orcid.org/0000-0002-8768-0082 Department of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut Correspondence Matthew J. Hadfield, University of Connecticut Health Center, 263 Farmington Avenue, Farmington 06032, CT. Email: hadfield@uchc.eduSearch for more papers by this authorWoo Cheal Cho MD, Woo Cheal Cho MD orcid.org/0000-0001-5867-1403 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TexasSearch for more papers by this authorAgata Harabasz MS-4, Agata Harabasz MS-4 orcid.org/0000-0003-3121-846X Department of Internal Medicine, University of Connecticut Health Center, Farmington, ConnecticutSearch for more papers by this authorJacqueline Savage MD, Jacqueline Savage MD orcid.org/0000-0001-7384-4827 Department of Internal Medicine, Hartford Hospital, Hartford, ConnecticutSearch for more papers by this author Matthew J. Hadfield DO, Corresponding Author Matthew J. Hadfield DO hadfield@uchc.edu orcid.org/0000-0002-8768-0082 Department of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut Correspondence Matthew J. Hadfield, University of Connecticut Health Center, 263 Farmington Avenue, Farmington 06032, CT. Email: hadfield@uchc.eduSearch for more papers by this authorWoo Cheal Cho MD, Woo Cheal Cho MD orcid.org/0000-0001-5867-1403 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TexasSearch for more papers by this authorAgata Harabasz MS-4, Agata Harabasz MS-4 orcid.org/0000-0003-3121-846X Department of Internal Medicine, University of Connecticut Health Center, Farmington, ConnecticutSearch for more papers by this authorJacqueline Savage MD, Jacqueline Savage MD orcid.org/0000-0001-7384-4827 Department of Internal Medicine, Hartford Hospital, Hartford, ConnecticutSearch for more papers by this author First published: 20 April 2020 https://doi.org/10.1111/tbj.13833Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume26, Issue6Special Issue in Breast PathologyJune 2020Pages 1253-1254 RelatedInformation

WEAKENED ROLE OF VENTROMEDIAL AND DORSOLATERAL PREFRONTAL CORTEX IN REGULATING AMYGDALA ACTIVITY IN LATE-LIFE DEPRESSION – A DYNAMIC CAUSAL MODELLING STUDY ON RESTING STATE FMRI

Introduction Research in older adults has generally found greater emotional well-being despite physical and cognitive decline. A literature review indicates that although older adults have structural and functional degradation in the dorsolateral and ventrolateral prefrontal cortices (dlPFC, vlPFC, key brain regions related to emotion regulation in younger adults), they may adaptively and automatically use strategies that involve alternative or additional brain regions to regulate emotion as a compensatory mechanism (for example, ventromedial prefrontal cortex, vmPFC). However, few studies have confirmed this hypothesis. More importantly, it is imperative to examine emotion regulation patterns in older adults with major depression (also known as late-life depression, LLD) to clarify the neural mechanisms of emotion regulation deficits in LLD. We hypothesize that LLD may have weakened connectivity between vmPFC and dlPFC in regulating activity of brain regions related to emotional processing (such as the amygdala). Methods We have analyzed the 7-min resting-state fMRI and T1-weighted brain imaging data which was acquired from NBOLD project conducted at University of Connecticut Health Center (UCHC). The data was from 37 healthy older subjects (9 males, age(mean±SD)= 75.5±7.5 yrs) and 102 LLD patients (32 males, age(mean±SD)=71.5 ±7.4 yrs). We first examined whether in healthy subjects, smaller dlPFC volume is associated with greater vmPFC activity measured by amplitude of low-frequency fluctuation (ALFF) using DPABI program. The dlPFC volume was measured using FreeSurfer software on T1-weighted images. We then examined whether vmPFC exert greater control on amygdala activity than dlPFC using spectral dynamic causal modelling (spDCM) program of SPM12. Finally we compared differences between healthy and LLD subjects in information flow among dlPFC, vlPFC, vmPFC and amygdala using spDCM. Results As we predicted, there was significant correlation between lower left dlPFC volume and greater ALFF in the vmPFC (r=-0.42, p Conclusions Negative correlation between the vmPFC resting activity and dlPFC volume in the healthy older adults suggest a possible compensatory activity of vmPFC. The spDCM analysis confirmed our hypothesis that vmPFC may exert a key role in regulating emotion to compensate the dlPFC volume reduction in healthy older adults, whereas the compensatory effect is weaker in the LLD group compared with healthy subjects, which could explain poor emotion regulation in LLD. Future studies using emotion regulation tasks directly are warranted to confirm the compensatory role of the vmPFC in emotion regulation in older adults and its the weakened role of emotion regulation in LLD. This research was funded by: The study was supported by NIMH grant R01 MH108578 (PI, David C. Steffens).

Effect of a Multicomponent Home-Based Physical Therapy Intervention on Ambulation After Hip Fracture in Older Adults

Disability persists after hip fracture in older persons. Current rehabilitation may not be sufficient to restore ability to walk in the community. To compare a multicomponent home-based physical therapy intervention (training) with an active control on ability to walk in the community. Parallel, 2-group randomized clinical trial conducted at 3 US clinical centers (Arcadia University, University of Connecticut Health Center, and University of Maryland, Baltimore). Randomization began on September 16, 2013, and ended on June 20, 2017; follow-up ended on October 17, 2017. Patients aged 60 years and older were enrolled after nonpathologic, minimal trauma hip fracture, if they were living in the community and walking without human assistance before the fracture, were assessed within 26 weeks of hospitalization, and were not able to walk during daily activities at the time of enrollment. A total of 210 participants were randomized and reassessed 16 and 40 weeks later. The training intervention (active treatment) (n = 105) included aerobic, strength, balance, and functional training. The active control group (n = 105) received transcutaneous electrical nerve stimulation and active range-of-motion exercises. Both groups received 2 to 3 home visits from a physical therapist weekly for 16 weeks; nutritional counseling; and daily vitamin D (2000 IU), calcium (600 mg), and multivitamins. The primary outcome (community ambulation) was defined as walking 300 m or more in 6 minutes at 16 weeks after randomization. The study was designed to test a 1-sided hypothesis of superiority of training compared with active control. Among 210 randomized participants (mean age, 80.8 years; 161 women [76.7%]), 197 (93.8%) completed the trial (187 [89.0%] by completing the 6-minute walk test at 16 weeks and 10 [4.8%] by adjudication of the primary outcome). Among these, 22 of 96 training participants (22.9%) and 18 of 101 active control participants (17.8%) (difference, 5.1% [1-sided 97.5% CI, -∞ to 16.3%]; 1-sided P = .19) became community ambulators. Seventeen training participants (16.2%) and 15 control participants (14.3%) had 1 or more reportable adverse events during the intervention period. The most common reportable adverse events reported were falls (training: 6 [5.7%], control: 4 [3.8%]), femur/hip fracture (2 in each group), pneumonia (training: 2, control: 0), urinary tract infection (training: 2, control: 0), dehydration (training: 0, control: 2), and dyspnea (training: 0, control: 2). Among older adults with a hip fracture, a multicomponent home-based physical therapy intervention compared with an active control that included transcutaneous electrical nerve stimulation and active range-of-motion exercises did not result in a statistically significant improvement in the ability to walk 300 m or more in 6 minutes after 16 weeks. ClinicalTrials.gov Identifier: NCT01783704.

The people behind the papers - Li-Juan Duan and Guo-Hua Fong.

Vascular development critically involves pruning, which helps to remodel an immature network containing excess microvessels into a mature and functioning one. The mechanisms of vascular remodelling and the relationship between the endothelial cells and the other cell types with which they are closely associated are, however, currently poorly understood. A new Development paper now demonstrates a crucial role for oxygen sensing by astrocytes in vascular remodelling of the mouse retina. We caught up with the two-author team behind the paper: research associate Li-Juan Duan and her supervisor Guo-Hua Fong, Professor of Cell Biology at the University of Connecticut Health Center, to hear more about the story.

Resources for Nursing Editors, Authors, and Peer Reviewers

At the most recent International Academy of Nursing Editors (INANE) meeting in Denver, Colorado, we presented a poster summarizing resources for editors, authors, and peer reviewers. This poster generated lively discussion and there were many ideas about adding to these resources and finding a way to share the information on an ongoing basis. All comments were much appreciated and used to create this article and list of resources. Readers are invited to comment at the end of this article and add to the information we present. Although a large variety of resources exist, nursing editors may not be aware of where to find them; therefore, each person ends up doing her or his own research which is time consuming and inefficient. Here, we provide readers of Nurse Author & Editor with a collated list of useful resources, separated into topic areas, that we have found to be accurate and easy to use, and will help you improve the quality of your journal(s). The resources are meant to be shared and used with authors and reviewers who request additional information as they work on manuscripts. Committee on Publication Ethics The Committee on Publication Ethics (COPE) was established in 1997 in the United Kingdom and now has over 11,000 members worldwide from all academic fields. COPE gives advice, support, and education on all aspects of publication ethics, in particular how to handle cases of research and publication misconduct. Many nursing journals are published by companies that are COPE members. Even if a journal is not a member of COPE, the resources are free and readily available on the website (http://publicationethics.org/resources). Reviewers note that COPE has practical and timely information that is easily accessible. Flowsheets guide editors, authors, and publishers who need to make difficult decisions about potential misconduct or unethical situations. COPE discussion forums provide interactive sessions where expert advice is offered and best practices developed. Outcomes from the forum sessions are posted on the website. The EQUATOR (Enhancing the QUAIity and Transparency Of health Research) Network is an international initiative that seeks to improve the reliability and value of published health research literature by promoting transparent and accurate reporting and wider use of robust reporting guidelines. It is the first coordinated attempt to tackle the problems of inadequate reporting systematically and on a global scale; it advances the work done by individual groups over the last 15 years. All authors should have a digital identifier and ORCiD is the leading source to provide one. From the website: ORCID provides a persistent digital identifier that distinguishes you from every other researcher and, through integration in key research workflows such as manuscript and grant submission, supports automated linkages between you and your professional activities ensuring that your work is recognized. In summary, these resources are the beginning compilation of resources predominantly for editors. They can have utility for any nurse author or peer reviewer who seeks more information about the complexities of publishing ethical research and clinical information in reputable journals. We hope to grow this resource and make it readily available to all. Geraldine S. Pearson, PhD, RN, FAAN, is the Editor of the Journal of the American Psychiatric Nurses Association. She is Associate Professor, University of Connecticut School of Medicine and Director, HomeCare Program at the University of Connecticut Health Center. Contact Geri at GPEARSON@uchc.edu. Kristen Overstreet is a Senior Partner at Origin Editorial (origineditorial.com) the managing editor for the Journal for Nurses in AIDS Care (JANAC) and the Journal of the American Psychiatric Nurses Association. She is the immediate past president of the International Society of Managing and Technical Editors and was the founding editor of the society's newsletter in 2008. You can contact Kristin at kristen@origineditorial.com

Panel Handout: Collective Bargaining at Academic Medical Centers - University of Connecticut Health Center

Panel Handout: Collective Bargaining at Academic Medical Centers - University of Connecticut Health Center

A conditional estimating equation approach for recurrent event data with additional longitudinal information.

Recurrent event data are quite common in biomedical and epidemiological studies. A significant portion of these data also contain additional longitudinal information on surrogate markers. Previous studies have shown that popular methods using a Cox model with longitudinal outcomes as time-dependent covariates may lead to biased results, especially when longitudinal outcomes are measured with error. Hence, it is important to incorporate longitudinal information into the analysis properly. To achieve this, we model the correlation between longitudinal and recurrent event processes using latent random effect terms. We then propose a two-stage conditional estimating equation approach to model the rate function of recurrent event process conditioned on the observed longitudinal information. The performance of our proposed approach is evaluated through simulation. We also apply the approach to analyze cocaine addiction data collected by the University of Connecticut Health Center. The data include recurrent event information on cocaine relapse and longitudinal cocaine craving scores. Copyright © 2016 John Wiley & Sons, Ltd.

Cellulose based micro- nano structured scaffolds for bone regeneration

Event Abstract Back to Event Cellulose based micro- nano structured scaffolds for bone regeneration Aja Aravamudhan1, 2 and Sangamesh G. Kumbar1, 2, 3, 4 1 University of Connecticut Health Center, Institute for Regenerative Engineering, United States 2 University of Connecticut Health Center, Department of Orthopeadic Surgery, United States 3 University of Connecticut Health Center, Department of Materials Science and Engineering, United States 4 University of Connecticut Health Center, Department of Biomedical Engineering, United States Introduction: Several polymer based scaffold systems have been used as an alternative to traditional autografts and allografts to repair non-healing defects of the bone. These materials fail to provide required osteoconductive, osteoinductive, and osteointegrative properties in line with autografts. Natural polymers have the advantage of being similar to biological macromolecules and elicit favorable tissue healing responses, in contrast to synthetic polymers that are used conventionally in scaffolds for bone regeneration. In this study, we present the characterization of cellulose acetate based scaffolds in comparison to synthetic poly(lactic-co-glycolic acid) (PLGA) scaffolds with respect to their ability to promote hMSC’s progression into osteoblastic lineage in vitro, biocompatibility in a rat subcutaneous implantation model and bone healing capability in a mouse calvarial defect model. Materials and Methods: Cellulose acetate (CA) (Sigma-Aldrich, 30kD) and (PLGA) (P) microparticles were prepared using emulsion solvent evaporation method. Solvent sintering technique[1],[2] was employed to prepare CA scaffolds and heat sintering was used for PLGA. Composite scaffolds of CA (CAc) PLAGA (Pc) were prepared by coating 0.1 % collagen solution on the scaffolds. In-vitro studies, using hMSCs in basal media (BM) and osteogenic media (OM), were conducted by seeding 500,000 cells per tablet type scaffold. Osteoblastic differentiation was monitored by alkaline phosphate activity assay and mineralization along with change in osteogenic gene expression (RUNX2, Col1, Col3, and BSP after 21 days). Further, CA, CAc and PLGA scaffolds were implanted subcutaneously in rats to determine the biocompatibility of the materials by contrasting the immune responses between the groups using histological staining. The scaffolds seeded with bone marrow stomal cells from donor mice (Col 3.6 cyan+) were implanted in critical sized (3.5mm dia) calvarial defect in mice (Col 3.6 GFP+) and its ability to heal bone was evaluated by histological staining. Results and Discussion: Osteogenic genes such as RUNX2, collagen1 and BSP showed greater expression on the CA and CAc groups in contrast to the PLGA groups (Figure 1.a.). The CA and CAc scaffolds showed greater progression of osteogenic phenotype as seen by greater protein levels of Col1 and BSP (Figure 1.b.) and mineralization of osteoinduced hMSCs on these scaffolds (Figure 1.c.). Among the scaffolds implanted subcutaneously (Figure 2.a.), the foreign body response (FBR) reduced significantly over time on the CA groups, while the FBR response increased over time on PLGA (Figure 2.b.). These results indicate the long-term biocompatibility of CA groups over synthetic PLGA. Finally, CA scaffolds seeded with MSCs showed uniform bone formation in contrast to PLGA scaffolds that had islands of new bone formation (Figure 2.c.). The greater hydrophilic and biomimetic nature of CA may be attributed to these differences. Conclusions: The CA and CAc scaffolds induced and maintained osteoblastic differentiation of the seeded hMSCs. The biocompatibility and cellularity of CA increased over time, while that of PLGA decreased over time. The stable and more hydrophilic properties of CA could be attributed to these results. Finally the bone formation by CA scaffolds was uniformly well distributed through the scaffold than PLGA, reflecting the superior osteogenic performace of the polysaccharide-based scaffolds. Hence CA based polysaccharide platform may be a viable alternative to synthetic polymers like PLGA in bone tissue engineering. Coulter Foundation, National Science Foundation (IIP-1355327, IIP- 1311907 and EFRI-1332329); Raymond and Beverly Sackler Center

Inverse gradient matrix system for osteochondral tissue engineering

Event Abstract Back to Event Inverse gradient matrix system for osteochondral tissue engineering Deborah Dorcemus1, 2, 3, Eve George2, 4 and Syam Nukavarapu1, 2, 3, 5 1 University of Connecticut, Biomedical Enigneering, United States 2 University of Connecticut Health Center, Institute for Regenerative Engineering, United States 3 University of Connecticut Health Center, Orthopaedic Surgery, United States 4 Georgia Institute of Technology, Biomedical Enigneering, United States 5 University of Connecticut, Materials Science and Engineering, United States Introduction: Osteoarthritis (OA) is a growing issue worldwide, yet many of the clinical treatments for OA are only palliative[1]. Since osteochondral (OC) defect repair remains a significant problem in orthopedic surgery, researchers are currently working to develop matrix systems for OC repair and regeneration[2]. While some success was reached using single and bi-phasic designs, overtime, the need for more tailored systems became apparent[3]-[5]. Our group has introduced a graded structure with bone and cartilage supporting layers arranged in reverse gradients in order to achieve an integrated OC matrix system. We hypothesize that by carefully tailoring each biomaterial phase we can not only support regeneration of the bone phase, but also provide the cues necessary to promote regeneration of the cartilage phase. Here, we aim to design and investigate the hydrogel phase with varying mechanical strength to support cartilage regeneration, and explore the gel’s integration into the polymeric phase creating a new generation scaffold system for OC defect repair and regeneration. Materials and Methods: Using the Hystem kit (ESIŸ BIO), a hyaluaronan gel (HA) was mixed with a polyethylene glycol (PEG) cross-linker in ratios of 1:1 – 1:7 (PEG:HA), and characterized for storage/loss modulus using a rheometer. After a range of gels were selected based on their mechanical profiles (1:2, 1:4, and 1:7), 400-500k mesenchymal stem cells were seeded in the gels and cultured for 21 days in chondrogenic media. After 21 days the GAG content of the samples were determined through alcian blue staining as well as the DMMB assay. Additionally, immunofluorescence (IF) staining was done to observe collagen II, aggrecan, and Sox9. Finally, using thermal sintering and porogen leaching, poly(85 lactide-co-15 glyclolide) (PLGA) microspheres were fabricated into a gradient scaffold which was infiltrated with the selected gel prior to μCT analysis[6]. Results and Discussion: Based on the rheological data it was determined that modification of the PEG:HA ratio can vary the overall modulus of the gels (~10Pa -45Pa). After 21 days of culture the results show that with an increase in modulus there is also an increase in GAG expression and presence of key proteins such as collagen II and aggrecan (Figure 1). The time sensitive crosslinking of the HA gel allows it to infiltrate the available pore space of the gradient matrix prior to full gelation, acting as a chondro-inductive secondary phase/cell delivery vehicle. This said, as supported by the μCT data, when the designed gel is used to infiltrate the pore space of the matrix we find that there is in fact an inverse gradient of hydrogel to polymer (Figure 2). Conclusions: The complexity of OC tissue regeneration lies in the need to not only regenerate cartilage and bone but also the interface region. Based on the quantitative and qualitative expression data, we established a gel matrix suitable for regeneration of the cartilage phase of OC tissue by studying the effects of mechanical strength on cartilage regeneration. With the identified cartilage phase incorporated into the graded PLGA structure we have now designed an inverse gradient matrix system capable of supporting fully integrated OC tissue regeneration. AO Foundation (S-13-122N); National Science Foundation (1311907); Musculoskeletal Transplant Foundation (MTF); Connecticut Institute for Clinical and Translational Sciences (CICATS)

Acoustic radiation force to mechanically load hydrogel-encapsulated osteoblasts for regenerative engineering-based bone repair

Acoustic radiation force to mechanically load hydrogel-encapsulated osteoblasts for regenerative engineering-based bone repair

Cytoplasmic dynein associated peptide-linked nanoparticles for non-viral vector applications

Event Abstract Back to Event Cytoplasmic dynein associated peptide-linked nanoparticles for non-viral vector applications Ercia Carbone1, Komal Rajpura1, Ho Man Kan1, Tao Jiang1 and Wai Hong Lo1 1 University of Connecticut Health Center, Institute for Regenerative Engineering, United States Statement of Purpose: Poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NP) hold great promise for gene delivery applications. Non-viral polymeric nanoscale vectors offer several advantages over viral vectors[1]. However, most non-viral vectors suffer from significantly lower transfection efficiencies than viral vectors. This is because during their way to the nuclei of cells, non-viral vectors must overcome a series of diffusional and enzymatic barriers [1]. Interestingly, it has been shown that a number of viruses exploit microtubules by interacting with cytoplasmic dynein motor protein (a motor protein responsible for retrograde movement along microtubules) in order to enter the nucleus of the host cell. Cytoplasmic dynein is a large, multisubunit molecular motor that translocates various cargoes toward the nucleus. The consensus peptide sequence “K/R-X-T-Q-T” has been shown to be important for interacting with one of the dynein subunits [2]. Here, we develop dynein associated peptide-linked polymeric nanoparticles for non-viral vector applications. It is hypothesized that the novel dynein peptide-linked nanoparticles will hijack the endogenous dynein motor system intracellularly, and consequently move along microtubules toward the nucleus (-ve end of microtubule) (Fig.1). Methods: Dynein-associated peptide “LysGluThrGlnThrCys (KETQTC)” and the control peptide “LysGluThrAlaThrCys (KETATC)” were synthesized and labeled with FITC commercially at the N-terminus of the peptides (LifeTein, Inc). Note that the additional Cys residue is to facilitate the conjugation of the Asp to PLGA NPs; Maleimide-PEG-PLGA and Methoxy-PEG-PLGA were purchased from Polyscitech. This NP was fabricated using a water-in-oil-in-water (W/O/W) double emulsion technique using a mixture of 1:9 (Maleimide-PEG-PLGA : Methoxy-PEG-PLGA) [3]. The particle size distribution and zeta potential measurements of the NPs were determined by dynamic laser scattering. Conjugation of the peptides to the NP was performed as previously described [3]. Equal amounts of peptide-linked NPs or control peptide-linked NPs were mixed with purified dynein LC8 protein (1 mg) (ProSpec) for 1 hour at 4°C. The complex, i.e. peptide-linked NPs bound to LC8, was precipitated by centrifugation. The precipitated NPs were washed 3x with PBS and subsequently boiled with 2x sample buffer (Bio-rad). The proteins were resolved by SDS-PAGE (Bio-rad) and subsequently analyzed by immunoblot analysis with anti-LC8 antibody (Millipore). Human MG63 osteoblasts (ATCC) were cultured on coverslips with dynein peptide-linked NPs or control peptide-linked NPs for various time points. After removing the NPs and washing the coverslips 4x with PBS, the cells were fixed with 4% PFA (Santa Cruz). Nuclei were stained with popdium iodide (PI) nucleic acid stain. Cells were then mounted by a mounting solution, and fluorescent signals on the cells were observed via confocal microscopy (Zeiss LSM ConfoCor 3). Results: The average diameter of the NPs is 143.8 nm and the zeta potential is -26.43 mV. Biochemical binding analysis showed that purified recombinant dynein LC8 protein efficiently binds to KETQT-NPs. In contrast, LC8 protein does not bind well to the control peptide (KETAT)-NPs (Fig.2A). We further demonstrated that the KETQT-NPs can interact with endogenous dynein LC8 protein in MG63 cell lysates (Fig. 2B). To investigate the localization of the peptide-NPs in cells, we incubated the NPs with cells for various time points. Figure 2C shows that the FITC signals from KETQT-NPs (green) are colocalized with cells’ nuclei (red), whereas the FITC signals from the control NPs do not. Conclusions: Taken together, our data demonstrated that the KETQT-NPs can bind to dynein subunit (LC8) in vitro and in vivo, and these NPs can be enriched in nuclei region when they were incubated with cell culture. Future research including live-cell imaging will be used to trace the movement of the NPs in cells. Our dynein associated NPs may have a significant impact in non-viral vector development for gene therapy applications. This work was supported by funding from the State of Connecticut Stem Cell Research Foundation.