It’s Your Game (IYG)-Tech, a stand-alone 13-lesson Internet-based sexual health life-skills curriculum adapted from an existing effective sexual health curriculum—It’s Your Game… Keep it Real (IYG). IYG-Tech development adaptation steps were to: 1) Select a suitable effective program and gather the original program materials; 2) Develop “proof of concept” lessons and test usability and impact; 3) Develop the program design document describing the core content, scope, and methods and strategies; and 4) produce the new program. Lab- and school-based tests with middle school students demonstrated high ratings on usability parameters and immediate impact on selected psychosocial factors related to sexual behavior—perceptions of friends’ beliefs, reasons for not having sex, condom use self-efficacy, abstinence intentions, negotiating with others to protect personal rules, and improved knowledge about what constitutes healthy relationships . Youth rated IYG-Tech is favorably compared to other learning channels (>76.2% agreement) and rated the lessons as helpful in making healthy choices, selecting personal rules, detecting challenges to those rules, and protecting personal rules through negotiation and refusal skills (89.5% – 100%). Further efficacy testing is indicated for IYG-Tech as a potential strategy to deliver effective HIV/STI, and pregnancy prevention to middle school youth.Adolescent sexually transmitted infection (STI) and birth rates indicate a need for effective middle school HIV/STI, and pregnancy prevention curricula to delay, or mitigate consequences of, early sexual activity. Individual and organizational barriers to adoption, implementation, and maintenance, however, can hamper dissemination of evidence-based sexual health curricula, adversely impacting fidelity and reach. Internet-based approaches may help mitigate these barriers. This paper describes the development and feasibility testing of  Adolescent births and sexually transmitted infections (STIs) represent serious public health concerns in the United States. Despite recent declines, the 2012 birth rate of women 15 – 19 years of age is 29.4 births per 1000 in the United States . The preProgram barriers may include the difficulty to locate, obtain, and implement programs  or lack of sufficient training from program developers , length Policy and infrastructure initiatives are improving Internet connectivity to schools. Despite variability in reliable connectivity and bandwidth the Internet is a timely dissemination channel for sexual health interventions that promise to be educationally effective, cost-effective, and of high fidelity . EvaluatIYG-Tech, a 13-lesson Internet-based curriculum, was adapted from It’s Your Game… Keep it Real (IYG), an effective middle school sexual health curriculum that has been shown to delay sexual behavior in two randomized trials  comprised two phases: 1) Adaptation of an existing hybrid (classroom/computer) evidence-based program  into a completely Internet-based curriculum, and 2) Evaluation of the new program in a feasibility pilot test. The Adaptation phase approximated the stepped sequence described by Systematic translation frameworks informed our adaptation and development process, providing guidance on the incorporation of theoretically and empirically-based evidence . The devIYG-Tech Project the adaptation steps included to , an effective HIV, STI, and pregnancy prevention curriculum designed for middle school youth. IYG had demonstrated effectiveness in significantly delaying sexual initiation among sexually inexperienced students in two randomized controlled trials  and 4 lessons of computer-based, tailored multimedia activities  underlies all IYG activities, teaching students to select personal rules regarding risk behaviors, to detect signs or situations that might challenge these rules, and to use refusal skills to protect these rules. The IYG curriculum research and development team worked on the adaptation process for IYG Tech, following validated development protocols, informed by empirical findings from the target population, and existing computer lesson assets.Adaptation is optimized through consultation with the original developers and assets of the original intervention . The IYGd trials . Based od trials , social d trials , and thed trials , IYG comth grade . For eactivities . A life-IYG-Tech, a usability study was conducted to determine the immediate psychosocial impact of the original 8 IYG computer-based lessons in order to understand the needed scope for a broader computer-based curriculum. These lessons were redesigned as a “proof-of-concept” for an Internet-based application to determine acceptability and feasibility of adjustments in look, feel, and functionality.A proof-of-concept is the demonstration of a preliminary design and/or prototype used to test the feasibility of a program or product before it is more fully developed. While shown effective, the randomized controlled trials of IYG were unable to provide information on the relative effects of program components such as group process, individual computer lessons, and journaling activities. Prior to developing IYG curriculum had been delivered from the hard drives of dedicated laptop computers. The original IYG interface featured a 3-dimensional (3-D) virtual “mall” with first-person “shooter” navigation game dynamics. Increasing the dissemination potential of the program necessitated changes to the lesson interface, file compression, and image resolution. A “proof-of-concept” was developed to establish that original lesson content could be translated to minimize platform and bandwidth and to optimize Internet accessibility to schools. The look and feel of the original 3-D IYG mall interface and the active user control over navigation was replaced with a 2-dimensional (2-D) Flash-based interface and passive automatic user relocation within the IYG “mall” environment. Video components were compressed in size and embedded in Adobe Flash format to optimize accessibility, with some degradation of resolution, and interactive 3-D elements were replaced with 2-D Flash interactive elements.The original computer-based lessons of the IYG lessons was conducted at two local community organizations and at a large university in southeast Texas, with a convenience sample of 7th- and 8th-grade students (N = 33), 12 – 14 years of age (Mage = 13.9 ± 1.14 years), primarily female (58%), and African American (70%), recruited through local public middle schools in a large, urban school district in southeast Texas and through the university. The sample size was consistent with usability testing protocols that do not require statistical significance to determine major usability problems  in a simulated classroom setting using laptop computers with headphones. Youth completed pre-tests  and then completed each lesson individually. At the end of each lesson, each student completed usability questionnaires regarding that lesson. Students also completed usability assessments of the lessons as a whole. Upon completion of all lesson activities, students also completed psychosocial and attitudinal surveys (post-tests) that were administered via the same laptop computers. Sessions were observed by study personnel who documented any problems  and provided assistance as required. Students received a $50 gift card for their participation. Breakfast, lunch, and between-lesson breaks were provided. Compensation was also provided to external staff whose presence was needed at community organization sites.Likability was based on how much the youth liked different lesson activities and program elements entire program, pictures/colors, sounds, buttons, cartoons, videos, transitions using 5-point Likert scale ratings, ranging from “dislike a lot” to “like a lot”. Credibility was based on the perceived correctness of the content presented using a 3-point Likert scale rating of “right,” “wrong”, and “don’t know” and whether the content could be trusted . Ease of use was based on perceived difficulty of the entire program and directions within the program  and if youth needed help from the teacher or another adult to use the Internet-adapted IYG lessons . Understandability was based on whether youth could understand the words used . Acceptability was based on the pace of Internet-adapted IYG activities . Parameters of understandability of words used, motivational appeal (if youth would use these lessons again and recommend it to others), ease of use (if youth needed help from the teacher or another adult to use the adapted lessons), and perceived impact  were rated using a 3-point Likert scale .Usability parameters including likability, credibility, acceptability, understandability, ease of use, motivational appeal, and perceived impact were assessed using adapted Likert scale ratings and open-ended response formats . LikabilIYG-Tech and to establish feasibility for data collection and analysis for any impending efficacy field trial. The study sample, while sufficient for usability testing, is insufficiently powered to detect impact. However, exploratory analysis of mediators  immediately subsequent to IYG-Tech provides an indication of the need for further lesson content above those in the original computer lessons. Psychosocial measures included beliefs about abstinence until marriage, beliefs about waiting to have sex, perceived friends’ beliefs about waiting to have sex, perceived friends’ sexual behaviors, reasons for and against having sex, self-efficacy to refuse sex, condom knowledge, condom attitudes, perceived friends’ beliefs about condoms, self-efficacy to use condoms, and perceived likelihood of having sex. All these psychosocial measures have been validated among multi-ethnic, urban-dwelling public school student populations , according to distribution assumptions, using SAS software (version 9.2).Usability measures were administered via paper-pencil surveys upon completion of relevant lessons. Psychosocial and attitudinal measures were administered via an audio-computer-assisted self-interview on laptop computers to enhance privacy and confidentiality. Data were analyzed using descriptive and inferential statistics , easy to use (88%), and understandable (88%), with most students requiring no assistance (76%) (The Internet-adapted ce (76%) . Most stIYG lessons, students perceived their friends as having more positive beliefs about waiting to have sex, cited more reasons for not having sex, had greater self-efficacy to use condoms, and had greater intentions to abstain from sex until marriage (t(23 to 30) = 2.390 to 3.589, p < .05). Students also reported that learning from computers increased their confidence and was very enjoyable (t(22) = 2.121 to 2.912, p < .05), but they also reported that using computers did not make the time pass more quickly nor allow them to learn more quickly (t(22) = −2.237 to −2.206, p < .05; Immediately after completing the Internet-adapted The significant change observed in psychosocial mediators demonstrated the potential of the Internet adapted lessons. While positive, delivery of the Internet-based lessons impacted fewer psychosocial mediators than observed in the original field trial of the IYG curriculum . Additiounderstandability (88% vs. 100% for IYG) with more students requiring assistance (24% vs. 0% for IYG). Conversely, appropriateness of time on task rated lower than the original IYG computer lessons (66% vs. 85.7% – 100% for IYG). A positive “by-product” of the current usability testing was the impact on attitudes toward technology for education in the classroom, a desirable but unexpected result from youth who are already sophisticated technology end-users. Collectively, these findings suggested the potential for the adapted Internet-based lessons as a feasible channel for sexual health education but that the original 8 IYG computer lessons would require supplemental content development to at least approximate the immediate impact of the original 24 lesson curriculum.Results of usability testing suggested that the “proof-of-concept” Internet-based lessons could be developed with acceptable usability ratings and positive impact despite down-grade from a 3-D interface in favor of reduced bandwidth. Usability ratings were similar to those of the original IYG computer program for credibility (91% vs. 92.9% for IYG), perceived effect of the program in helping make healthy choices (91% vs. 93% for IYG), and ease of use (88% – 100% vs. 78% – 100% for IYG). The adapted lessons rated lower on IYG-Tech, the proposed Internet-based curriculum. The design document, developed for the original IYG curriculum, to describe the program’s functionality, look and feel, screen maps, and scripts, was reviewed and amended to provide the “blue print” for production.A design document outlines the specifications  of a software product or, in the case of Content analysis of the original IYG curriculum helped to determine the scope of IYG-Tech. In the original IYG curriculum, the core content, scope, and best practice characteristics had been delineated using an Intervention Mapping (IM) process , and behavioral mediators to current sexual health behaviors and determine whether modification or amendment would be required for the IYG-Tech version. The original matrices were found to be relevant to the new IYG-Tech program. process . These w process . Targete process . The oriIYG curriculum but required further focus in computer-based activity included skills training in refusing to have sex and avoiding unhealthy relationships , values clarification , negotiating risk reduction strategies , and health service utilization .The learning objectives from the original IYG program (n = 193) were also reviewed by the research team to determine the extent to which each learning objective was covered in the original IYG lessons  and in which types of lesson activities the learning objectives were covered (i.e. classroom and/or computer-based lessons). This analysis provided information on what content needed to be adapted to supplement the existing 8 IYG computer-based lessons. Of the 193 learning objectives listed in the original IYG planning matrices, 158 (88.9%) were covered in the 8 existing IYG computer lessons, either solely in the computer lessons , more comprehensively in the computer lessons than the classroom , or of equal comprehensiveness in the computer as in the classroom  . The claIYG-Tech lesson activities were listed in one of four categories: 1) as computer-based activities from the original IYG curriculum that were already adapted for the Internet and needed no change (n = 95), 2) computer activities from the original IYG curriculum that were already adapted for the Internet but required some minimal modification (n = 73), 3) computer activities adapted from pre-existing classroom activities in the original IYG curriculum that would be new Internet-based activities (n = 13), and 4) newly created Internet-based activities (n = 158).Specifications for IYG-Tech lessons included branched logic to tailor content based on student gender, sexual experience, and sexual intentions. For students who are not sexually experienced or have few intentions to engage in sexual activity peer videos were framed to include messages reinforcing continued abstinence. For students who are sexually experienced, peer videos were framed to reinforce initiation of abstinence, risk reduction strategies, and STI testing.Theoretical methods (e.g. modeling and guided practice to address skills and self-efficacy) and practical strategies  informed activity content. Dynamic between-activity transitions and fact sheets were developed where more expansive content focus was required . Other design document specifications included lesson number and format, flow charts, storyboards, and interface design. The Development of the design documents was an iterative process with components being presented to the teen advisory board for review and feedback on the appropriateness of activity content and language for credibility, authenticity, and appropriateness. For example, youth feedback assisted in the development of more realistic refusal skills simulations that portrayed more persistent peer pressure than originally scripted.IYG-Tech comprises 13 lessons designed to be accessible to 8th grade students. The curriculum length was guided by the need to provide adequate content, suitability of implementation in a typical school semester, and prior empirical data suggesting minimal optimal dose for behavior change to be 13 lessons , refusal skills training, the importance of testing if a person is sexually active, and skills training in condom and contraceptive use  access to the program.tive use . The curIYG-Tech was conducted to determine the feasibility of delivery in a typical school setting and its impact to inform readiness for further efficacy testing.A school-based pilot test of IYG-Tech computer lessons was conducted at a Southeast Texas middle school with a convenience sample comprised of 7th and 8th grade students (n = 22), 13 – 15 years of age (14.4 ± .46 years), female (50%), and minority (91% Hispanic and 9% African American). Participation was voluntary; written parental permission and child assent were obtained. The study was approved by the University of Texas Institutional Review Board (HSC-SPH-09-0413).A single group, pre-test post-test usability study of the IYG-Tech computer lessons over approximately a two week period (testing two lessons during a 90 minute class period each day). The students accessed the program in a classroom setting using laptop computers. Prior to accessing the program activities, students completed a demographic survey. Each student was then provided with a laptop computer containing the IYG-Tech lessons and head-phones and asked to complete each of the 35-minute Internet-based lessons individually. At the end of each lesson, each student completed a usability survey regarding that lesson. Lessons were observed by study personnel who logged problems  and provided assistance as required. Students received $50 for their participation. Students completed a demographic form, a usability survey for each lesson, and pre/post slider bar questions within the lessons.Students were recruited and participated in the usability testing during P.E or an elective class period at their school. Students tested the 13 Usability parameters were as previously described for the lab-based usability study. Motivational appeal was also assessed on whether youth compared IYG-Tech favorably against their favorite computer game, other school lessons, and other computer-based school lessons, and other health lessons . Perceived impact was assessed by asking youth if IYG-Tech would help them make healthy decisions on 29 parameters specific to the content of IYG-Tech including friendships, selecting and protecting personal rules, enabling better risk reduction communication and negotiation , increasing understanding of reproduction and the developing body, and lowering risk of pregnancy and STD’s using a 3-point Likert scale .IYG-Tech program as text questions accompanied by audio and provided immediately before and after each lesson. The response set was a 10-point Likert scale slider bar adapted from previously reported motivational enhancement methods  and for all individual activities (62.5% – 100%)  but less so when compared to favorite computer games (36.9% – 81.2%). Youth indicated they would recommend IYG-Tech lessons to their class (72.2% – 94.7%) but provided lower agreement on playing lessons again (31.3% – 70%).Usability ratings across all 13  – 100%) . ProgramPsychosocial determinants: As a result of lesson exposure students increased their perceived importance of, and confidence in, negotiating with others to protect their personal rules (p < .05) and significantly increased knowledge about what constitutes a healthy relationship (p < .05)  . Psychosp < .05) .After a program has been shown to be effective, a logical next step is its dissemination. Failure in dissemination, however, limits effective programs from reaching their full public health potential. Until recently, minimal progress had been made in the widespread dissemination of effective HIV, STI, and pregnancy prevention programs to youth, especially those targeted to middle schoolers . More reIYG-Tech is an innovative contribution to sexual health education in that it is a completely online interactive curriculum, adapted from the effective IYG program. As an online curriculum, it is designed to mitigate conventional dissemination challenges of classroom-based curricula that can occur at the program, individual, and organizational level. While an Internet-based solution does not eradicate program level barriers, it does greatly optimize a facilitator’s ability to locate and acquire the program. Implementation of computer-based lessons can also vastly simplify facilitation, provided that school computer specifications meet broadband and connectivity requirements for the program.IYG-Tech is designed to provide high fidelity through a stand-alone curriculum requiring minimal-to-no facilitation. This delivery method may eliminate the barriers of teacher training and program fidelity. An Internet-based curriculum can provide confidential lesson content to students that are tailored on their sexual experience and intentions while reducing discomfort for facilitators who are not required to directly deliver what may be perceived as sensitive material.Continued and repeated trainings and technical assistance have been the conventional method to overcome cited individual level barriers to classroom-based program implementation. These methods are designed to raise awareness, and reduce confusion about education policies , increasIYG-Tech. The adaptation of existing evidence-based programs (guided by well-established adaption frameworks) for access through interactive communication technology platforms  to consumer school districts  while allatforms  providesIYG-Tech had a number of advantages including the strength of evidence of the original blended curriculum, the availability of the IYG creators in the adaptation process, and the existence of 8 original computer-based lessons and associated assets. Despite this, there were challenges in the creation of a digital version of the IYG curriculum that included ensuring that original learning objectives were fully represented, that a new Internet-based functionality of the original computer-based lessons could be achieved, and that the newly developed “proof-of-concept” lessons and prototype curriculum were acceptable to end users, feasible for delivery in the middle school setting, and impactful of mediators of sexual behavior.The adaptation of IYG to IYG-Tech impact was necessarily restricted to assessment of immediate pre-post change in psychosocial variables, but these results on psychosocial impact are encouraging, particularly considering the concatenated exposure to IYG-Tech necessitated in this study.The significant impact demonstrated in the evaluation of the Internet-adapted lessons included increased student perceptions of their friends having more positive beliefs about waiting to have sex, greater reasons for not having sex, greater self-efficacy for using condoms, and greater intentions to abstain from sex until marriage. These findings were also among the findings reported in the previous IYG field trials . AssessmIYG-Tech learning experience include a one-to-one student-instructor (computer) ratio and a triangulation of strategies to target behavioral determinants including numerous examples of modeling of skilled behavior  and situational behaviors  that influence normative perceptions as well as skills; confidential and personalized management of sensitive and potentially embarrassing issues; and individualized (tailored) intervention messages to specific characteristics of the users such as gender and sexual experience. Research studies have reported the potential of technology to impact sexual health knowledge , attitudes (regarding communication), self-efficacy, intentions, and self-reported behavior  or the full IYG-Tech curriculum (school-based feasibility test) with immediate post-test; the single-group pre-test/post-test study design without a control group to mitigate threats to internal validity; the purposive sampling of participants; and the potential of demand characteristics to influence youth responses and feedback. Pilot feasibility studies of the type reported here are necessarily limited and designed to provide a measure of confidence that broader field trials are warranted and to highlight “red flags”  that suggest field testing is premature. Further, while most schools have internet connectivity, they vary in the number of available computers, Internet reliability, and bandwidth. The study described here cannot adequately address these challenges which may become apparent in broader efficacy trials. Of course, the digital approach to sexual health may provide an insufficient solution to organizational barriers. These barriers include the concern of school officials about negative community reactions and perceived controversy of sex education , providing empirical evidence to inform each subsequent development step. This work provides a guide for future work on adaptation of evidence-based programs onto a communication technology platform.The development and testing of


States’ decisions not to expand Medicaid under the Affordable Care Act (ACA) could potentially affect access to care and health status among their low-income residents.The 2010–2012 nationally representative Medical Expenditure Panel Survey data were analyzed in 2015 to compare 9755 low-income adults aged 18–64 years from Medicaid-expanding states with 7455 adults from nonexpanding states. Multivariate logistic regression models were fitted to evaluate the differences in access to care, receipt of preventive services, quality of care, attitudes about health and self-reported health status by Medicaid expansion status. The differences in care utilization and medical expenditures between the two groups were examined using a 2-part modeling approach.Compared to their counterparts in Medicaid expansion states, low income adults in the nonexpanding states were more likely to be black and reside in rural areas and were less likely to have a usual source of care  and recommended preventive services such as dental checkups , routine checks , flu vaccinations , and blood pressure checks . They also had less care utilization, fewer prescriptions, and less medical expenditures, but more out-of-pocket expenditures .Low-income adults in Medicaid nonexpanding states, who are disproportionately represented by blacks and rural residents, were worse off for multiple health-related outcomes compared to their counterparts in Medicaid expanding states at the baseline of ACA implementation, suggesting that low income adults residing in nonexpanding states may benefit markedly from the expansion of Medicaid. The Affordable Care Act (ACA) was designed to expand Medicaid coverage to all U.S. residents with family income at or below 138% of the federal poverty level (FPL), including non-disabled childless adults who were previously not eligible for Medicaid in most states . As of NThe study sample was based on pooled data from 3 years (2010–2012) of the Medical Expenditure Panel Survey (MEPS) Household Component, which is a nationally representative survey of the US civilian non-institutionalized population conducted by the Agency for Healthcare Research and Quality (AHRQ). The MEPS collects data on health insurance, and health care access, utilization, and expenditures through household interview, supplemented by a self-administered questionnaire (SAQ) on health and health opinions. More information about the survey design and contents can be found online . The comAdults aged 18–64 years with a family income ≤ 138% FPL (N = 17212) were identified, including 9755 from the Medicaid expanding states  and 7457 from the nonexpanding states , respectively representing 19.5 million and 22.3 million residents in the nation. The categorization reflects states’ decision on Medicaid expansion in February 2015 when we performed the analysis. The 2), normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2) or obese (≥30 kg/m2). Current smoking status was included.Demographic characteristics used in the analysis include gender, age, race/ethnicity, marital status, education, employment status, residence in a metropolitan statistical area (MSA) and health insurance. Chronic conditions were ascertained with a series of questions about whether a person was ever diagnosed with any of the following conditions: high blood pressure, stroke, heart disease, emphysema, high cholesterol, cancer, diabetes, arthritis and asthma. The number of conditions was enumerated for each person and categorized as 0, 1 and “2 or more.” Body mass index (BMI) was calculated based on reported height and weight and categorized as underweight . Expenditures were also available by payment source .Quality of care was measured with SAQ from the health plan version of CAHPS® , an AHRQ-sponsored family of survey instruments designed to measure quality of care from the consumer’s perspective. We examined the frequency of “always” to the following three questions during the past 12 months: 1) if had an illness, injury or condition needing care right away, how often received the care right away; 2) if any appointment was made with a doctor or clinic for health care, how often an appointment was made as soon as he/she thought it was needed; and 3) if visited doctor and any care, tests or treatment was believed necessary, how often it was easy to access the care.Attitudes about health was assessed in SAQ with two items for attitudes toward health insurance and another two items for attitudes that might influence decisions to purchase health insurance or to use health services: 1) do not need health insurance; 2) health insurance is not worth the money it costs; 3) more likely to take risks than the average person; and 4) can overcome illness without help from a medically trained person. For each item, one of the five options was selected: disagree strongly, disagree somewhat, uncertain, agree somewhat, and agree strongly. We dichotomized our outcomes as “disagree strongly” or not.Health status was generated via multiple questions. Perceived health status and perceived mental health status were rated as excellent, very good, good, fair or poor at the household interview. The SAQ contained three measures of health status: 1) the Short-Form 12 Version 2 (SF-12v2) [SF-12v2) , from whSF-12v2) ; 2) KessSF-12v2) , where aSF-12v2) ; and 3) SF-12v2) .The access-restricted de-identified data file was used to acquire the resident state of the participants, and the participants were assigned to one of two groups based on their states’ Medicaid expansion status (Yes or No/under discussion). Demographic characteristics were described for expansion and non-expansion groups separately, and their difference was tested using Wald Chi-square tests. The crude rate and 95% confidence interval (CI) were calculated for each health-related outcome in the expansion and non-expansion groups. Multivariate logistic models were fitted to calculate the prevalence ratio (PR) and 95% CI  for occuAnalyses were conducted in 2015. STATA statistical software  was used in the 2-part modeling analysis. SAS and SAS-Callable SUDAAN  were used in all other analyses. All estimates were weighted to account for the MEPS complex survey design and nonresponse.Compared to the expansion group, the non-expansion group was significantly more likely to be female, black (25.6% vs. 16.8%), less educated, employed, living in non-MSA area (21.7% vs. 14.6%), uninsured (42.1% vs. 30.6%), and not currently enrolled in Medicaid . No diffCompared to the individuals in the expansion group, those in the non-expansion group were less likely to have a usual source of health care  after controlling for demographic factors. They were also less likely to have dental checkups, routine physical checks, flu vaccinations and blood pressure checks as guidelines recommend . No statOn average, an individual in the non-expansion group had 1.16 (CI = 0.56–1.76) fewer office-based visits, 0.19 (CI = 0.09–0.28) fewer outpatient visits, 0.09 (CI = 0.05–0.41) fewer inpatient night stays, 0.08 (CI = 0.01–0.14) fewer dental visits, and 1.52 (CI = 0.05–2.98) fewer prescriptions annually than those in the expansion group . The aveThis study presents a systematic comparison of the low-income adult populations by Medicaid state-level expansion status across multiple health-related outcomes, including access to care, preventive care receipt, care utilization and expenditures, quality of care, and certain self-reported health status. Our results showed that there were a higher proportion of low-income people in the nonexpanding states that did not have a usual source of care, did not meet guidelines for receipt of preventive services including dental checkups, routine physical checks, flu vaccinations and blood pressure checks. We also found that annual health care utilization and medical expenditures were on average significantly lower for low-income individuals in the non-expansion group; however, the out-of-pocket cost for the same group was significantly higher. The decision not to expand Medicaid may further increase these disparities between the two sets of states, especially when non-expanding states are disproportionately represented by disadvantaged segments of the population the blacks and rural residents. Furthermore, this may lead to unintended consequences in widening the black-white and rural-urban disparities in access to care and health outcomes nationwide.The higher percentage of low income persons with a usual source of care and access to multiple preventive care services in Medicaid expanding states compared to those in the non-expanding states may in part reflect Medicaid prior expansion in certain ACA participating states. These differences between the two sets of states are likely to widen in the future in view of previous positive findings on expansion of medical care to the poor. For example, Sommers et al found that states that expanded adult Medicaid eligibility in the early 2000s experienced significantly reduced mortality as well as improved coverage, access to care and self-reported health . FurtherWe found that for most of the types of care, low-income people from nonexpanding states had a significantly lower utilization compared to those from the expanding states. The lower utilization of health care services may reflect a higher unmet need of health care among nonexpanding states’ residents. The total medical expenditure was accordingly lower in the nonexpanding states. When expenditures were examined by source of payment, the government in the nonexpanding states spent about $1300 less per person per year on their low-income residents than in the expanding states and private insurance spent similar amount, while the out-of-pocket expenditure per person per year was about $100 more for residents in nonexpanding states. Moving forward, with the expanding states continuing to increase their health care spending on low-income, uninsured residents through Medicaid expansion and the spending of nonexpanding states decreasing, the disparities in access to care, care utilization, and potential health care financial burdens that we observed in this baseline study seem likely to become wider.Notwithstanding the nationally representative sample and the best available survey data on care utilization and medical expenditure, this study was limited on its health status component given the self-report nature of these outcomes. Particularly, we had limited variables on mental health despite it is an important topic as mental illness disproportionally affects low-income populations . Future In summary, this examination of many key baseline health characteristics immediately before the implementation of the ACA found that the low-income population in Medicaid nonexpanding states had worse access to care, less preventive care utilization, less medical expenditures and more out-of-pocket costs compared to those in expanding states. Unless the non-expanding states reverse their policies, their decisions may lead to widening of the disparities in access to care and outcomes in the low income population between the two sets of states, as well as the disparities between blacks and whites and between rural and urban residents nationwide.S1 Appendix(DOCX)Click here for additional data file.


Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients. Multimodal approaches combining several imaging methods may further our understanding of the mechanisms underlying the epileptic process and aid in more accurately localizing abnormal neuronal activity, especially in patients with drug-resistant epilepsy –2. In suNoninvasive presurgical workup will usually include long-term EEG, video-EEG and neuropsychological testing, which do not always provide the localization accuracy and precision required for surgical planning. Morphological magnetic resonance imaging (MRI) scans are also routinely acquired in epileptic patients to identify structural brain lesions such as tumors, cortical dysplasia or hippocampal sclerosis, which can define the seizure onset zone and guide surgical resection . In the Imaging techniques such as positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) –15, dipoSince the 1980s, perfusion changes during epileptic processes have been investigated using SPECT in combination with technetium-99m hexamethyl-propylene amine oxime (Tc-99m HMPAO) or Tc-99m ethyl cysteinate dimer (Tc-99m ECD), especially during the ictal and postictal phases . While i18F]FDG-PET or SPECT, which are still considered the most useful neuroimaging techniques in the assessment of epileptic patients. Moreover, because it does not require the injection of radioligands, thus obviating the need to wait for tracer uptake, ASL can be usefully applied to map brain changes during the interictal, as well as the ictal and early postictal phases. To date, ASL has seldom been employed in epilepsy [18F]FDG-PET in a group of 6 patients with drug-resistant focal epilepsy [18F]FDG-PET.Recently, newer MRI methods to study local cerebral perfusion have been proposed, offering several substantial advantages over nuclear medicine techniques, including noninvasiveness, no radiation exposure, easier accessibility, and higher spatial resolution –34. Amonepilepsy –40, but epilepsy –42. In aepilepsy . In all The complexity and high variability of epilepsy  often preclude group analyses, so that the individual peculiarities of each patient need to be assessed separately. The simplest quantitative approach to patient-specific analysis is represented by a one-versus-many parametric test, where a single patient is compared to a group of age-matched controls –44. In oIn this study, we used source imaging and electrophysiological data as the reference for focus localization to further assess the feasibility of ASL in detecting perfusion changes related to the epileptic focus in patients affected by drug-resistant focal epilepsy and potential candidates for surgery. Furthermore, we aimed to quantitatively detect the brain perfusion abnormalities in each patient, defining a template-based approach combined with a heteroscedastic model for the automatic detection of statistically significant CBF changes. Finally, the findings from postsurgery MRI scans and the clinical outcomes in a subgroup of patients were used as “ground truth” to evaluate the localization accuracy of the ASL and ESI results.18F]FDG-PET, had been applied: the results from these patients are here completed with the more recent postsurgical information (when available) and ASL analyses. All new patients were classified as having either right or left temporal lobe epilepsy on the basis of clinical and electrophysiological information. In this new group, only one patient was evaluated with invasive EEG (sEEG) prior to surgery (patient no. 7).The study population was 6 consecutive patients  with drug-resistant focal epilepsy admitted for presurgical assessment according to the following criteria: (i) drug-resistant epilepsy ; (ii) noA control group underwent MRI evaluation using the same sequences as the patient group. The control group was composed of 17 healthy subjects  with no history of neurological or psychiatric disorders.In accordance with the Declaration of Helsinki, written informed consent to take part in the study was obtained from all control subjects and patients. The study protocol was approved by the Local Ethics Committee of the University Department and Hospital of Verona. The individuals in this manuscript have given written informed consent (as outlined in PLOS consent form) to publish these case details.This 46-year-old, right-handed woman reported, at the age of 20, experiencing several brief episodes characterized by abnormal hearing followed by loss of consciousness on one occasion, after which she was discharged from the hospital with a diagnosis of partial epilepsy. Since then, she has had no more auditory symptoms, later classified as auras, despite having 5–6 seizures per month that she describes as sudden moments during which she cannot speak but is aware of her environment. After an attack, however, she often finds herself on the floor, unaware that she has fallen. Witnesses recalled right-sided mouth deviation, right-hand fiddling, and dystonic posturing of the left hand, followed by generalised convulsions. Standard EEG showed runs of sharp waves and rarer slow waves over the right frontotemporal leads. The MRI scan revealed no morphological abnormalities. The sEEG, subsequent to other imaging exams (hdEEG and ASL), pointed to an epileptogenic zone located over the right temporal pole, mainly involving the superior (T1) and middle (T2) temporal gyri. The patient underwent surgical removal of these portions, and has been seizure-free ever since (7 months).This 62-year-old, right-handed woman suffered repeated episodes of febrile convulsions at the age of 23 months. She remained seizure-free until age 18 years, when she began experiencing brief, sudden episodes of loss of contact that went unnoticed at that time. At the age of 32, she presented a generalized seizure, and a diagnosis of epilepsy was made. Currently, she has 3–4 seizures per month characterized by oral automatism, right-hand fiddling, and left dystonic hand posturing. On repeated occasions, relatives reported brief episodes of incongruous activity, during which she is unresponsive. Standard EEG showed runs of fast, spiky activity over the frontotemporal right leads, sometimes with bilateral expression over the frontal areas. Repeated MRI scans were reportedly normal.This 68-year-old, right-handed woman began suffering, at the age of 20, brief, sudden episodes of flushing, sensation of something rising from the stomach to the head followed by intense asthenia. The episodes clustered during a few months every year, then disappeared at the age of 35. Around age 60, they started again, this time associated with pervasive fear: she was initially referred for psychiatric evaluation because of suspected panic attacks. Standard EEG revealed right frontotemporal spikes, and a diagnosis of epilepsy was made. Fluid attenuated inversion recovery (FLAIR) MRI images showed bilateral hippocampal hyperintensity that was more evident on the right side.This 48-year-old, right-handed man suffered febrile convulsion episodes at the age of 2 years. At the age of 18, after a secondary generalized seizure, a diagnosis of temporal epilepsy was made. With hindsight, he referred always having had brief episodes of altered sensation associated with something rising from the stomach; witnesses also reported oral automatism. Since then, he has continued to experience weekly seizures despite appropriate drug treatment. Standard EEG showed the presence of sub-continuous spiky activity over the frontotemporal left leads. The MRI scan revealed no morphological abnormalities. The patient has been seizure-free since surgical resection of the left temporal lobe (1 year ago).This 48-year-old, right-handed man reported having suffered during childhood brief and sudden episodes of nausea misinterpreted as gastric disturbances at that time. At the age of 30, during hospitalization for injuries sustained in a car accident, a diagnosis of focal epilepsy was made based on EEG data and history. A few partial seizures occurred over the following months, then remitted for 15 years while he was on carbamazepine. At the age of 45, seizures reoccurred weekly, characterized by a rising gastric sensation, tachycardia, and subsequent depersonalization. Witnessed episodes were described as the patient fiddling with his right hand, dystonic posturing of the left arm, oral automatism, and inability to speak. Standard EEG showed only rare anterior temporal spikes, with right predominance. FLAIR MRI images showed mild bilateral hippocampal hyperintensity.This 28-year-old, right-handed woman had a positive family history for generalized epilepsy . At the age of 26, she began experiencing repeated déjà vu episodes and uncomfortable feelings sometimes associated with anxiety and tachycardia. She was unaware of subsequent vocalizations, left head version and bilateral hand fiddling, and referred suffering headaches after the symptoms resolved. Antiepileptic treatment was only partially effective. Standard EEG showed left frontotemporal spikes. MRI scans revealed altered signal areas in the right lateral frontobasal lobe, left anteroinferior frontal lobe, medio-posterior portion of the left hippocampus, and at the left frontoparietal junction.HdEEG was performed using 256 channels . The net was adjusted so that Fpz, Cz, Oz, and the pre-auricular points were correctly placed according to the international 10/20 system. The net's geodesic tension structure is such that all electrodes could be evenly distributed over the scalp at approximately the same location in all patients. The data were recorded against a vertex electrode reference (Cz) at a sampling rate of 250 Hz. Patients were seated in a relaxed position; the total EEG recording time was around 40 min.1/TIs/TI2 = 700/1400/1600 ms and 90° flip angle. Sixteen axial slices in ascending order were prescribed and positioned parallel to the anterior-posterior commissure line  in order to cover the presumed focus location. The labeling slice was 10 cm thick and was separated from the proximal slice of the acquisition volume by a 20-mm gap. A calibration scan with the same parameters as the ASL sequence but longer TR (10 s) was also acquired to estimate the equilibrium magnetization of arterial blood (M0b). The overall acquisition time for ASL was approximatively 6 mins, including the additional calibration scan. A high-resolution whole brain anatomical scan was acquired for each subject using a 3D T1-weighted magnetization prepared rapid acquisition gradient echo sequence . Other high-resolution anatomical images, including T2-weighted, FLAIR and inversion recovery with 2D readout, were also acquired in order to assess for the presence of structural alterations such as hippocampal sclerosis or malformations of cortical development.The experiment was performed using a 3T MRI scanner  with a standard transmit/receive head coil. For the ASL data, a pulsed PICORE sequence  with the Q2TIPS scheme (QUIPSS II with thin-slice TI1 periodic saturation) was used . Interlehttp://sites.google.com/site/cartoolcommunity/). The T1-weighted anatomical images were used to create a realistic model of the brain for source localization. In each patient, the hdEEG and MRI data and the solution space were restricted to the gray matter. The solution space for the distributed source model contained from 3,028 to 3,088 points uniformly distributed over the gray matter of the brain and mapped onto the spherical head model with anatomical constraints (SMAC) space [3].HdEEG data were analyzed using Cartool software (C) space . The peaC) space ; in the C) space  constraiASL data were preprocessed and analyzed using FSL 5.0.1  and Matlab 7.14  with a dedicated home-made code created for this study. Motion correction was applied separately to the Control and Label volumes using the MCFLIRT tool and taking the first volume as reference. In particular, a six-parameter 3D rigid-body registration with a normalized correlation cost function was used. The ASL calibration scan was used for estimating the coregistration parameters from ASL to the individual T1-weighted image by applying a 3D rigid-body registration with a normalized mutual-information cost function and 7 degrees of freedom.ΔM is the difference signal, TI1 and TI2 are the sequence time parameters described above, n is the slice number, slicetime is the time taken to acquire each single slice (~ 50ms), T1B is the longitudinal relaxation time of blood (1664 ms at 3T), and α is the inversion efficiency (0.95 for pulsed ASL) FDG-PET, in the present study we further investigated the applicability of ASL in epilepsy by means of an automatic approach to reliably identify areas of epileptiform activity. Previous studies in ASL and epilepsy reported only on qualitative assessment of the CBF maps FDG-PET which generally showed areas of hypometabolism in regions beyond the temporal and frontal lobe in patients with temporal and frontal lobe epilepsy, respectively [Collectively, our results suggest that, differently from source imaging, perfusion alterations generally involve a series of areas. This is in agreement with previous studies with [ectively , 71–72. ectively , is the ectively , and froIn conclusion, multiple imaging modalities in the same patient allow for a more accurate and precise identification of the epileptogenic zone, providing better surgical outcomes and reduced postoperative deficits. The use of completely noninvasive techniques such as ESI and ASL could reduce the need for more expensive and risky sEEG investigations in candidates for surgery or allow for better targeting of intracranial electrode implantations if deemed necessary. The combined use of these two techniques shows good sensitivity in localizing the epileptic focus in relation to the resected zone identified on the postoperative anatomical scan and provides complementary electrical and perfusion information to better understand the underlying pathological mechanisms.


To validate the practicality of focused echocardiography with A-F mnemonic performed by non-specialists in patients with suspected acute coronary syndrome (ACS).This prospective observational study was conducted in the Emergency Room within 12 months period. Study population consisted of consecutive patients with preliminary diagnosis of an ACS.The following data were analyzed: demographics, clinical condition, medical history, ECG, transthoracic echocardiography (TTE) and levels of cardiac necrotic markers. TTE was performed within the first 15 minutes after the admission by the resident on-call. TTE images were interpreted and reported with mnemonic A-F. All studies were recorded and reviewed within 24 hours by the cardiologist.1312 consecutive patients were enrolled to the study. TTE with A-F mnemonic revealed: RWMAs in 82,87% patients with confirmed ACS, other significant cardiac pathologies were found in 2,21% in ACS and 46,52% in non-ACS groups respectively. On the basis of these findings, 20  ACS and 29  non-ACS group patients underwent target operative treatment. Survey showed that both echocardiographic image acquisition and its interpretation with A-F mnemonic, took less than 5 minutes in 95% of cases. Residents found A-F mnemonic algorithm simple and useful. No differences were found in key findings between TTE performed by resident and the cardiologist.Focused echocardiography with A-F mnemonic allows both confirmation of acute myocardial ischemia and detection of the other life-threatening cardiac conditions resulting in proper bedside decision of directed treatment. Mnemonic based TTE enables reliable examination by properly trained residents. The workup of chest pain management (including suspected ACS) includes: clinical presentation, medical history, physical examination, risk stratification, laboratory tests, and non-invasive imaging -4. AmongThe purpose of the present study was to validate the usefulness and practicality of focused transthoracic echocardiography with A-F mnemonic, performed by non-echocardiographers in patients with acute chest pain.The observational study was approved by the Local Ethical Committee of John Paul 2nd Hospital in Cracow (ref. number 792) and informed consent was obtained from all study participants.The study was conducted in the Emergency Room of the Interventional Cardiology Department of John Paul 2nd Hospital in Cracow, within 12 months period (January 2013 to January 2014).We prospectively enrolled all patients admitted to the Emergency Room with preliminary diagnosis of an acute coronary syndrome made by the pre-hospital health care providers. The diagnosis was based on typical clinical symptoms and ECG findings: new or presumed new significant ST-segment-T-wave (ST-T) changes, new left bundle branch block (LBBB) or development of pathological Q waves. Exclusion criteria were: age < 18 years and difficult acoustic window resulting in inability to obtain interpretable ultrasound images. 59 patients  were excluded from final analysis because of difficult acoustic window and un-interpretable ultrasound images.14 residents (at least after the completion of third year of training) were included in the study. All of them had basic skills in TTE and performed at least 75 examinations before participation in the study. Additionally, they underwent a minimum of 30-minutes didactic and 1,5-hour structured hands-on dedicated practice with the A-F examination scheme.In the Emergency Room, clinical condition was assessed according to both Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) classifications. Prior myocardial infarction, coronary revascularization and pre-hospital cardiac arrest, were noted. In order to confirm the diagnosis of ACS, further investigations were instituted including: ECG, transthoracic echocardiography (TTE) and blood tests for measurement of biomarkers for myocardial damage.Electrocardiogram (ECG) was performed within 5 minutes after the admission to the Emergency Room and repeated in 15-minutes intervals in symptomatic patients with an initial non-diagnostic ECG and during every recurrence of symptoms. The ECG recording included: standard 12-leads, right precordial leads  and posterior leads (V7-V9) when appropriate.According to newly introduced institutional fast-track protocol, transthoracic bedside echocardiography was performed within the first 15 minutes after patient’s presentation, by the resident on-call. Duration of the examination was recorded and usefulness of the mnemonic was assessed by the physicians. TTE images were interpreted with the simplified mnemonic A-F, introduced in our Emergency Room in order to standardize bedside cardiac examination. In A-F mnemonic, consecutive letters of an alphabet represent a particular anatomical structure or measure of cardiac function: A-aorta, B-both ventricles, C-contractility, D-dimensions, E-effusion, F-further abnormalities , cardiac isoenzyme of creatine kinase (CK-MB) and high sensitivity troponin T (hsTnT), at the time of admission and, if necessary, by repeated measurements every 3–6 hours within the first day of hospitalization. Blood tests were assayed by routine automated laboratory techniques . All biochemical analyses were performed in the central hospital laboratory, certified with cardiac and clinical chemistry program by RIQAS .Coronary angiogram was performed in the following groups of patients: with typical chest pain and typical ischemic ECG changes (as stated above), regardless of cardiac biomarkers on admission; with atypical clinical presentation  but with elevated cardiac biomarkers on admission and/or typical evolution  of biomarkers in following 3–6 hours; with atypical clinical presentation  and negative cardiac biomarkers, but with multiple risk factors  and new or presumed new regional wall motion abnormalities in TTE on admission (performed according to A-F mnemonic) Figure .Figure 1Medical data were analyzed independently by the authors and in each case a consensus was achieved. No ambiguous echocardiographic examinations were recorded, all results were clearly stated in a dichotomic manner: echocardiographic abnormality present or not.Statistical analysis was performed using STATISTICA v 8.0 software. Numerical data were expressed as mean values ± SD.1312 consecutive adult patients  were enrolled to the study. Baseline demographic and clinical data are shown in Table Chest pain was present in 98,1% of patients, with 51,68% of patients in 4 CCS class. Dyspnea was observed in 36,28% of patients, with 8,69% of patients in NYHA 4 class. ECG on admission revealed ST-depression in 56,55% and ST-elevation in 37,35% of patients , with normal wall thickness and no features of post-infarction scar, in 99,5% of patients with STEMI and 78,5% with NSTEMI, and it was considered an echocardiographic finding enhancing the probability of ACS. Coexisting cardiac pathology (apart from ACS) was revealed in 23 patients  with confirmed ACS. In 20 of them , with significant structural disease , TTE was a decisive diagnostic tool determining the choice of a treatment. After coronary angiography, all these patients underwent urgent coronary artery bypass grafting with additional target procedure: aortic valve replacement, mitral valve annuloplasty or VSD closure.In patients in whom the initial suspicion of ACS was not finally confirmed, the final diagnosis was established based on echocardiography alone or additional diagnostic tests . In 127 patients 46,52%) from this group, clinically significant echocardiographic abnormalities were found during the AF-mnemonic - based TTE exam  -5. It isAlthough some might argue that TTE has no added value in the non-shocked patient, all recent clinical guidelines for diagnosis and management of myocardial infarction, emphasize the role of TTE as the initial imaging modality in patients with acute chest pain -4,12-14.Performing TTE should not delay direct treatment of suspected ACS. In all patients with typical clinical manifestation and ST elevation on ECG, emergency coronary angiography and subsequent revascularization should be initiated as soon as possible. However, limited bedside TTE usually does not take more than five minutes and may be performed simultaneously with other procedures on admission . High prevalence of other cardiac and non-cardiac life-threatening conditions mimicking the clinical presentation of ACS, justifies the implementation of additional imaging tests in the management of patients with suspected ACS. In our study population, final ACS diagnosis was confirmed in 79,19% of enrolled patients.Correct and quick diagnosis of a suspected acute coronary syndrome at admission determines outcome of the treatment. However, unquestionable value of TTE may be limited by the lack of skill and competency in the physicians. The full echocardiographic examination seems to be too complicated, extensive and time-consuming and some important pathologies may be overlooked and omitted especially when distracting abnormalities are present. Thus echocardiographic diagnosis of ACS in an Emergency Room should concentrate on: evaluation of presence of new RWMAs; global left ventricular systolic function assessment (as a predictor of outcome); and identification of other pathologies leading to chest pain or dyspnea.In order to improve the standard of care of patients with suspected ACS in our Emergency Room, we decided to introduce a new fast-track protocol based on TTE performed by the residents on-call. Our present study confirmed the utility of early simplified TTE in ACS suspected patients. RWMAs were present in 82, 87% of patients with confirmed ACS . The study showed that new RWMAs on echocardiography strongly supported ACS diagnosis and was a deciding factor for a further coronary angiography in patients with atypical clinical symptoms and/or atypical ECG changes. TTE with A-F mnemonic revealed significant cardiac pathology in 127  non-ACS and 23  ACS patients. On the basis of these findings, 20  of ACS and 29  of non-ACS group patients underwent target invasive treatment .All echocardiographic examinations were repeated within 24 hours by a cardiology consultant with expertise in echocardiography, and all digital clips recorded and described based on A-F mnemonic by residents, were reviewed by investigators blinded to the final diagnosis. Comparison of both examinations confirmed 100% coincidence of A-F-based findings. In almost 20% of cases cardiologists reported extra findings extending beyond the A-F scheme, but none of these however had any impact on the choice of the treatment. This excellent coherence between TTE reports done by residents and cardiologists-echocardiographers is puzzling. It may result from their competency in echocardiography. All residents had basic skills in echocardiography with at least 75 exams performed till the end of 2012 (mean 86 examinations/resident).Vignon et al.  in a proDefined competence level is required to perform trustworthy examination. According to European Association of Echocardiography (EAE)  350 examIt is well documented that focused bedside echocardiography can bring important anatomical and hemodynamic information in an acute setting. It can affect the patient’s management, direct further diagnosis and modify therapeutic decision. Panaoulas et al.  proved aWe recently validated the usefulness of A-F mnemonic in patients with non-ST-segment elevation ACS . AnalysiIn summary we conclude that: 1. Limited echocardiography with A-F mnemonic is useful in patients with suspected acute coronary syndrome. It allows both confirmation of acute myocardial ischemia and detection of the other life-threatening cardiac conditions requiring definite treatment. 2. This 5 minutes exam covers a sufficient spectrum of morphological and functional abnormalities of the heart, great vessels and adjacent structures, which can alter the diagnostic and therapeutic management in suspected ACS. 3. Residents with a basic knowledge of echocardiography and short training can perform a reliable initial TTE assessment according to A-F mnemonicPatients with difficult acoustic window (4.3%) were excluded from final analysis because of un-interpretable ultrasound images.Cardiology consultants did not repeat the study, but reviewed the stored digital 10-seconds video clips, recorded by residents.Echocardiographic evidence of new regional wall motion abnormalities is one of the diagnostic criteria for an acute myocardial infarction  whereas impaired left ventricular global systolic function is a factor related with a poor prognosis. Detection of RWMAs may be challenging especially for non-echocardiographers. Although detection of post-MI scar usually does not cause difficulties , differentiation between preexisting and new hypokinesia may be difficult. Therefore it must be stressed out that echocardiography is only an imaging modality used in the diagnostic process among the others and does not replace clinical reasoning.


Mutations in the melanocortin-4 receptor (MC4R) represent the commonest genetic form of obesity and are associated with hyperphagia.The aim of this study was to investigate whether melanocortin signaling modulates anticipatory food reward by studying the brain activation response to food cues in individuals with MC4R mutations.We used functional magnetic resonance imaging to measure blood oxygen level-dependent responses to images of highly palatable, appetizing foods, bland foods, and non-food objects in eight obese individuals with MC4R mutations, 10 equally obese controls, and eight lean controls with normal MC4R genotypes. Based on previous evidence, we performed a region-of-interest analysis centered on the caudate/putamen  and ventral striatum.Compared to non-foods, appetizing foods were associated with activation in the dorsal and ventral striatum in lean controls and in MC4R-deficient individuals. Surprisingly, we observed reduced activation of the dorsal and ventral striatum in obese controls relative to MC4R-deficient patients and lean controls. There were no group differences for the contrast of disgusting foods with bland foods or non-foods, suggesting that the effects observed in response to appetizing foods were not related to arousal.We identified differences in the striatal response to food cues between two groups of obese individuals, those with and those without MC4R mutations. These findings are consistent with a role for central melanocortinergic circuits in the neural response to visual food cues. Mutations that disrupt signaling through the melanocortin 4 receptor (MC4R) represent the commonest highly penetrant genetic form of obesity, being found in 2–5% of severely obese individuals . MC4Rs aP = .624; fullness, P = .551).MC4R mutation carriers were identified by direct nucleotide sequencing . MC4R muWhile lying in the scanner, participants viewed images of appetizing , disgusting , and bland foods , plus non-food household objects (30 unique items in each category). To control for the possibility that areas engaged by appetizing foods reflect increased emotional arousal, we included a disgusting food category matched to the appetizing foods on rated arousal . Images Functional imaging data were acquired using a 3T Tim Trio (Siemens) scanner. Whole-brain T2*-weighted echo planar images (EPIs) were acquired with a repetition time of 2000 milliseconds, echo time of 30 milliseconds, flip angle of 78º, and 32 axial oblique slices with 3-mm isotropic resolution. A total of 336 volumes were acquired, for a total imaging time of 11 minutes 12 seconds. A high-resolution structural MP-RAGE scan for normalization purposes was also acquired .www.fil.ion.ucl.ac.uk/spm). The first six volumes were discarded to allow for equilibration effects. The EPIs were corrected for slice time differences and realigned to the first scan by rigid body transformations to correct for head movements. EPI and structural scans were coregistered and normalized to the T1 standard template in Montreal Neurological Institute space  and smoothed with a Gaussian kernel of 8 mm FWHM. Data were analyzed using general linear models within SPM5. At the first level, condition effects were estimated using boxcar regressors convolved with the canonical hemodynamic response function, and movement parameters were included as regressors to account for residual movement-related variance. Data were high-pass filtered (128 s) to remove low-frequency signal drift. Statistical parametric maps were then generated for each individual subject by estimating activation contrasts between conditions . To determine group differences at the second level, we set up an ANOVA at the whole-brain level for each contrast and conducted a region-of-interest (ROI) analysis. Based on strong evidence for the involvement of dorsal and ventral striatum in food-reward processing, and more specifically in obesity, our primary ROIs were 8-mm radius spheres centered on the caudate/putamen     and vent z = 12) . CorrectP < .001 uncorrected. For completeness, we also performed a whole-brain analysis for all contrasts at the uncorrected P < .001 level, with an extent threshold of 10 voxels . Significant or borderline group main effects in our ROIs were followed up with post hoc t tests between each of the groups.An additional exploratory analysis of other brain regions that have also been implicated in reward and in obesity, including amygdala, orbitofrontal cortex, and somatosensory cortex, as well as the insula/frontal operculum in disgust processing, was performed using the more lenient threshold of Images of appetizing foods shown to individuals undergoing fMRI scanning are associated with the activation of specific brain regions involved in a reward network that includes the striatum, amygdala, ventral tegmental area, and orbitofrontal and prefrontal cortex, which are the source and target of dopaminergic neurons that mediate food reward . In viewP = .04 small-volume correction (svc)] . The dorsal striatum showed a similar group effect to appetizing foods vs bland foods , reflecting a significantly reduced response in the obese group compared with the MC4R-deficient patients and lean controls . A similar pattern was also apparent in the left ventral striatum  (P = .008 svc) and a similar trend relative to the lean controls. For each of these contrasts, the MC4R group did not significantly differ from lean controls. There were no group differences in dorsal or ventral striatum for the contrast of disgusting foods with bland foods or non-foods, suggesting that the effects observed in response to appetizing foods were not related to arousal more generally.A comparison of appetizing foods compared to non-foods produced a significant difference between the groups in the left dorsal striatum (caudate-putamen)  , reflect.05 svc] A, where P < .001 uncorrected, revealed group differences in response to disgusting foods relative to non-foods in the right frontal operculum  (P < .001), but no difference from lean controls. The frontal operculum is involved in processing taste information and relating it to motivation, emotion, and visceral activity (P < .001 uncorrected) for appetizing foods vs non-foods compared to obese  and lean controls  in the inferior parietal cortex , which corresponds to the somatosensory cortex area that encodes sensation in the mouth, lips, and tongue  which has previously been associated with variability in responses to food reward (P = .57) and disgust  postscanning.Differences in brain activation were not explained by differences in reward sensitivity between the groups as assessed by the Behavioral Activation Scale-drive scale  .Several studies have reported changes in striatal activation in response to food-related stimuli in obese individuals. Some have proposed that a hyper-responsiveness of reward circuitry, when presented with food images, increases the risk for overeating , 14. OthIt has been suggested that differences in striatal activation may reflect differences in dopaminergic tone. Obese rats, relative to lean rats, show reduced D2 receptor density in the hypothalamus and in the striatum, and chronic excessive intake of high-calorie foods and attendant weight gain results in down-regulation of postsynaptic D2 receptors, increased D1 receptor binding, and decreased D2 sensitivity in animals , 18. ObeThe explanation for increased activation of oral somatosensory cortex in the MC4R-deficient group is unclear. Pharmacological studies in rodents suggest that melanocortins do not modulate taste (as measured by licking frequency for sucrose/quinine). It is plausible that increased oral somatosensory cortex activation in MC4R-deficient humans may reflect increased anticipatory orosensory activity or salivation in response to appetizing food images in this group, although this was not formally tested. Increased somatosensory cortex activation has been observed in response to food reward (but not to monetary reward) in some previous studies . Using p


To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements.The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes.Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher  than for average mGCC , and mGCIPL  but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements.Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection. The diagnosis of glaucoma in clinical practice largely depends on identification of characteristic structural changes to the optic nerve head, which are often accompanied by functional deficits on visual field testing.,2 As glaRecent advances in imaging technologies, especially the development of optical coherence tomography (OCT), provide a means for the objective evaluation of structural changes to the optic nerve head and retina in glaucoma, and offer the potential for improved detection of disease. It has been shown that circumpapillary retinal nerve fiber layer (cpRNFL) measurements from OCT have good ability to differentiate glaucomatous and healthy eyes with AUC ranging from 0.728 to 0.969.–9 10]10]Although cpRNFL thinning is a useful marker of glaucomatous damage, there is growing recognition that measurement of the glaucomatous macula may also reveal changes that could potentially aid diagnosis. The macuRecent studies have shown that OCT measurements of macular structures such as macular ganglion cell complex (mGCC) may be useful for differentiating healthy and glaucomatous eyes.–17 mGCC Conventionally, it is necessary to perform two separate scans, one for macular, and one for circumpapillary measurements. A new OCT technology, swept-source OCT (SS-OCT), which has a faster scan speed and longer wavelength than SD-OCT, allows a wide-angle scan protocol to image a larger 12 X 9 mm area of the posterior pole thereby including optic nerve head and macula in a single scan, with the capability to segment both mGCIPL and cpRNFL.The primary aim of the current study was to evaluate the ability of mGCIPL and mGCC measurements to differentiate glaucomatous from healthy eyes. mGCIPL and mGCC measurements were obtained using both SD-OCT and SS-OCT with the aim of comparing the diagnostic ability of the two devices. As the diagnostic ability of different layers may differ depending on the stage of disease, we also evaluated the performance of these devices in eyes with early glaucoma and compared performance to cpRNFL measurements by both OCT devices.clinicaltrial.gov identifier: NCT00221897, National Eye Institute) at the University of California San Diego (UCSD). DIGS is a prospective longitudinal study designed to evaluate optic nerve structure and visual function in glaucoma. Written informed consent was obtained from all participants, and UCSD Human Research Protection Program Institutional Review Board prospectively approved all methods (IRB # 140276). All study methods adhered to the tenets of the Declaration of Helsinki for research involving human subjects and the study was conducted in accordance with the regulations of the Health Insurance Portability and Accountability Act.This was a cross-sectional observational study of participants from the Diagnostic Innovations in Glaucoma Study (DIGS)  abnormal SAP test results and/or documented evidence of progressive disc damage on masked grading of stereophotographs, with or without an abnormal SAP result. Healthy subjects were recruited from the general population through advertisements or from the staff and employees at UCSD. Healthy subjects had IOP less than 22 mmHg with no history of increased IOP, normal SAP and disc appearance in both eyes.SAP was performed using the Humphrey Field Analyzer II  and the 24–2 Swedish interactive threshold algorithm . All visual fields were evaluated by the UCSD Visual Field Assessment Center (VisFACT). Visual fSimultaneous stereoscopic optic disc photography was performed for all subjects at their annual dilated examination. Digitized film and digital stereoscopic images  were reviewed with a stereoscopic viewer  by two or more experienced graders. Each grader was masked to the subject's identity and to the other test results. Details of the methodology employed to grade optic disc photographs as glaucomatous at the UCSD Optic Disc Reading Center have been provided previously.,22 GlaucmGCIPL, mGCC, and cpRNFL thicknesses were assessed from images acquired using SS-OCT , and SD-OCT  on the same day or within 5 weeks. The Deep Range Imaging OCT is a SS-OCT device that uses a wavelength-sweeping laser with a center wavelength of 1050 nm and a tuning range of approximately 100 nm. For the SS-OCT segmentation software (version 9.12) was used to identify the limits of the RNFL and IPL, and to determine the thickness of mGCIPL, mGCC, and cpRNFL, throughout the scan. mGCIPL thickness includes the ganglion cell layer and the inner plexiform layer IPL; mGCC thickness includes the GCIPL and the RNFL. Data was exported using the manufacturer’s OCT-Batch utility (version 4.3.0.118). The quality of each scan and accuracy of the segmentation algorithm was independently reviewed by masked reviewers (Z.Y. and T.L.). Eight eyes were excluded due to clipped, poorly focused images, and images with segmentation failure and motion artifacts. To measure mGCIPL and mGCC thickness, a circle of 6 mm in diameter was automatically centered on the fovea . AverageMacular and cpRNFL measures were also acquired separately two cube scans, the optic disc cube scan and macula cube scan with Cirrus HD-OCT , which ut-tests and Chi square tests were used for group comparison for normally distributed variables. Receiver operating characteristic (ROC) curves were constructed to assess the ability of each parameter to distinguish subjects with glaucoma from healthy controls. A ROC curve is a plot of the true-positive rate (TPR) versus the false-positive rate (FPR) for all possible cut-points. The area under the ROC curve (AUC) was used to summarize the diagnostic accuracy of each parameter. An AUC of 1.0 represents perfect discrimination, whereas an area of 0.5 represents chance discrimination.[n = 1000 resamples). Observations from two eyes of the same subject are likely to be correlated, which can lead to underestimation of true variance. A between-cluster variance estimator was therefore used to account for correlations between eyes of the same subject and calculate robust variance estimates. [Normality assumption was assessed by inspection of histograms and using Shapiro-Wilk tests. Student mination.,26 ROC cmination.,28 Confitimates.  All stat2) for each pairwise comparison.Bland-Altman plots were used to determine the agreement between corresponding average and sectoral measures of SS-OCT and SD-OCT. The diffDataset for this study was presented in A cohort of 147 eyes of 102 participants was included in this study, among them 106 eyes were diagnosed of having glaucoma and 41 were healthy eyes. Among 106 eyes of glaucoma patients, 66 were diagnosed by the development of at least three consecutive abnormal SAPs alone, 11 by progressive glaucomatous change on disc stereophotograph alone, and 29 eyes were positive for both criteria. The macular and circumpapillary measurements from SS-OCT and SD-OCT, including mGCIPL, mGCC and cpRNFL thickness, are shown in 2 = 0.95), however SD-OCT provided thicker values with a mean difference of 8.6 μm , however, there was fixed bias in mGCC thickness between SS-OCT and SD-OCT in all average and sectoral mGCC measurements and proportional bias in all with the exception of superonasal and inferonasal sectors  and 114.6 ± 7.2 μm versus 94.8 ± 14.7 μm respectively using SD-OCT (P<0.001) . Similar sectors , Fig 2B.Average cpRNFL in healthy versus glaucomatous eyes was 102.4 ± 15.6 μm versus 71.1 ± 18.2 μm (P < 0.001) when measured by SS-OCT wide-angle scan, and 95.3 ± 8.6 versus 72.4 ± 12.1 μm (P < 0.001) when determined by SD-OCT optic disc cube scan. In healthy eyes, cpRNFL was thickest in the inferior sector and superior sectors and thinnest in the nasal and temporal sectors for both SS-OCT and SD-OCT . ConsistAUCs showing the ability of SS-OCT and SD-OCT to distinguish eyes with and without glaucoma are presented in Among sectoral mGCIPL measurements, the sector showing highest diagnostic ability for glaucomatous damage was the inferotemporal sector (AUC = 0.81 for SS-OCT and 0.83 for SD-OCT). The worse performing mGCIPL sector was the inferonasal sector for SS-OCT (AUC = 0.65), and inferonasal and superonasal sectors for SD-OCT (AUC = 0.63). The inferotemporal sector was also the best performing mGCC sector (AUC = 0.84 for SS-OCT and 0.82 for SD-OCT) and the worse performing mGCC sector was the superonasal sector (AUC = 0.71 vs. 0.67 for SS-OCT and SD-OCT respectively). The best performing cpRNFL sector was the superior sector  and the worse performing the nasal sector (AUC = 0.59 r SS-OCT and. 0.55 for SD-OCT). There was no significant difference between SS-OCT and SD-OCT in AUCs of average and sectoral mGCIPL, mGCC and cpRNFL measurements .As diagnostic ability depends on the stage of disease, we also examined the ability of the macula and circumpapillary measurements to distinguish healthy eyes from those with early glaucoma . These findings indicate that both mGCIPL and mGCC are potentially useful measures for the identification of glaucomatous damage, even at early stages of disease. Individual measures with the highest glaucoma discrimination ability were SD-OCT measured minimum mGCC (AUC = 0.86), minimum mGCIPL (AUC = 0.86), and superior cpRNFL (AUC = 0.90).Although average and sectoral mGCIPL thicknesses were measured with two different scan protocols of two different OCT devices, the ability to detect glaucoma was similar. Among all average and sectoral mGCIPL measures (except minimum thickness in SD-OCT), the range of AUCs using both OCT devices  were remarkably similar. However, between the two OCT devices we were able to detect both fixed and proportional bias for each corresponding mGCIPL measure, which reflect systemic differences between the two imaging modalities, with the result that readings from SS-OCT and SD-OCT are not interchangeable.The macular parameter with the best overall performance for distinguishing healthy and glaucomatous eyes were SD-OCT minimum mGCIPL and mGCC thickness, which achieved an AUC of 0.86 and were also good at detecting eyes with early glaucoma . This observation is consistent with previous reports in which minimum mGCIPL and minimum mGCC thickness were among the best performing OCT parameters for glaucoma discrimination.,32 WhileInitial studies examining the role of macular thickness measurements in glaucoma found that quantification of full retinal thickness was helpful for glaucoma diagnosis.,33–38 HoTo determine whether mGCIPL may be useful in glaucoma diagnosis, Wang et al. manually segmented mGCC to isolate mGCIPL, and demonstrated that mGCIPL thickness were thinner in eyes of glaucoma patients. AutomateIn agreement with previous studies, we found mGCIPL and mGCC had largely similar glaucoma diagnostic ability to cpRNFL.–17 DespiMeasures of cpRNFL and macular GCC/GCIPL can be acquired with two separate scans, or in a single wide-field scan. Acquiring macular and optic nerve head measurements from a single scan is potentially less time consuming, and minimizes problems with alignment if comparing macular and circumpapillary data.2 in its wide-angle scan protocol, whereas macula cube scan with Cirrus HD-OCT samples 1111.1 (200 X 200 / 6 X 6) axial scans per mm2. Despite these limitations of wide-angle scanning, the current results suggest that wide-angle scan can offers a similar diagnostic value while reducing the time that patients have to spend on adjunctive imaging in the glaucoma clinic.In the present study, we evaluated whether macular measures obtained from a wide-angle scan can offer similar diagnostic performance as measures obtained from a separate macula cube scan. Our results showed that average and sectoral macular and cpRNFL measures acquired from SS-OCT wide-angle scan performed similarly well as corresponding measures obtained from separate macular and disc cube scans by SD-OCT. On the other hand, we must keep in mind the potential differences between images acquired with wide-angle scan protocol versus disc circle scan or macula scan. According to our data, cpRNFL thickness measured by SS-OCT wide-angle scan appear to be thicker than those measured by SD-OCT, whereas mGCIPL measurements are smaller comparing to the corresponding measures by SD-OCT. . BesidesThe present study has limitations. A limitation of this study does not evaluate the diagnostic performance of mGCIPL and mGCC measures in the context that closely resembles the clinical setting. Other co-morbidities such as diabetic retinopathy and retinal vascular occlusive diseases can also cause significant changes in the thickness of macular layers, and they often involve those patients of the similar age group as glaucoma. With the goal of evaluating the ability of differentiating healthy from glaucomatous eyes, we excluded eyes with co-existing pathologies that affect macular thickness. This approach will certainly limit our ability to directly generalize the glaucoma diagnostic accuracy using mGCIPL and mGCC measurements established in this study into actual glaucoma clinic populations. Secondly, this cross-sectional study did not evaluate how well the different devices, and scan patterns can identify glaucomatous progression; this remains to be determined with longitudinal study. Additionally, the correlation between the structural measurements with SS-OCT and SD-OCT was determined by Pearson correlation with inter-eye correction. However, similar inter-eye correction cannot be performed in Bland-Altman agreement analysis. Lastly, there was a significant difference in age distributions between healthy controls and glaucoma patients in this cohort. For this reason we adjusted for age in the ROC analysis. However, Bland-Altman analysis cannot be adjusted for age, and this should be taken into consideration when interpreting the results.In conclusion, our analysis demonstrated that, similar to cpRNFL, both mGCIPL and mGCC offer good ability to differentiate healthy and glaucomatous eyes, with SS-OCT wide-angle scan providing mGCIPL and mGCC measures as useful as SD-OCT macular scan. In addition we found since there are differences in the thickness values measurements of mGCIPL and mGCC obtained with SD-OCT and SS-OCT, the measurements should not be used interchangeably in patient management decisions.S1 TableThe dataset used in this study contains mGCIPL, mGCC and cpRNFL measures by SS-OCT and SD-OCT from 106 eyes of glaucoma patients and 41 eyes of healthy participants.(CSV)Click here for additional data file.


To evaluate the effectiveness of ceftriaxone treatment in attenuating relapse-like ethanol drinking behavior in male P rats following 14-weeks of continuous ethanol consumption.After 14-weeks of continuous access to free choice of 15% and 30% ethanol, male P rats were deprived of ethanol for two weeks. On the last five days of abstinence period, P rats were treated, once a day, with either saline or ceftriaxone . This was followed by re-exposure to ethanol for the next 10 days to simulate the relapse-like ethanol drinking behavior.Ceftriaxone treatment (during abstinence) reduced ethanol intake upon re-exposure to ethanol, compared to the saline treated P rats. This statistically significant reduction in ethanol consumption in P rats following treatment with ceftriaxone (200 mg/kg/day) was observed from Day 2 to Day 9. Similarly, water consumption in P rats treated with ceftriaxone was significantly higher than the saline treated group between Day 2 and Day 7. Importantly, ceftriaxone treatment at both doses did not cause any significant changes in body weight compared to saline treated group.We report here that ceftriaxone at higher dose has been found to be effective in the attenuation of relapse-like ethanol-drinking behavior in chronic ethanol intake model. This is in accordance with previous data from our lab in cocaine animal model demonstrating that only higher dose of ceftriaxone has been effective in attenuating cocaine relapse. Relapse rates for addiction were found to be similar to those of chronic illness such as hypertension, asthma, diabetes . VariousThe significance of glutamatergic system in development of alcohol dependence has been extensively studied . EthanolCeftriaxone was found effective in preventing relapse to cocaine seeking in rats ,25. FurtWhile previous work concerning efficiency of ceftriaxone treatment in relapse-like ethanol- drinking behavior proved effective following five-weeks of exposure to ethanol, our aim for the present study was to evaluate the therapeutic value of ceftriaxone treatment in relapse-like ethanol-drinking by P rats following 14-weeks of ethanol dependence. After 14-weeks of continuous access to free choice of 15% and 30% ethanol solutions, P rats were deprived from ethanol for 2 weeks. On the last 5 days of this abstinence period, P rats were treated, daily once, with either saline or ceftriaxone . This was followed by re-exposure to ethanol for the next 10 days to simulate the relapse-like ethanol-drinking behavior.Male P rats were obtained from the Indiana University School of Medicine  breeding colonies. Animals, single housed in wood-chip bedded plastic cages, were housed in a temperature (21°C) and humidity (50%) controlled vivarium maintained on a 12/12 hour light/dark cycle. Rats had ad lib access to food and water for the entire duration of this study, including abstinence period. Protocol approved by the Institutional Animal Care and Use Committee of the University of Toledo, Health Science Campus, Toledo, OH, was used for this study. The protocol was designed based on the guidelines set forth by the Institutional Animal Care and Use Committee of the National Institutes of Health and the Guide for the Care and Use of Laboratory Animals . Before the start of the treatment (i.p.), animals were divided in three groups: 1) saline group (n=5); 2) ceftriaxone 50 mg/kg treatment group (n=5); 3) ceftriaxone 200 mg/kg treatment group (n=5). Ceftriaxone was administered as a solution made in physiological saline.2 inhalation.P rats at the age of 90 days old were given continuous access to two concentrations of ethanol solution, 15% and 30%, prepared with distilled water for 14 consecutive weeks. Multiple choices of ethanol solutions (15% and 30%) is an established model of ethanol drinking that is known to enhance ethanol intake in P rats ,29. StarWe used general linear model (GLM) repeated measures for statistical analysis  of data related to ethanol consumption, water intake, and P rat body weight. Furthermore, to observe the day-wise effect of treatment, data were analyzed employing one-way ANOVA for comparing the three treated groups using post hoc dunnett’s (two-sided) test with equal variances assumption since there was homogeneity of variance for ethanol and water intakes as well as body weight. All statistical tests were based on p<0.05 level of significance.The effect of ceftriaxone treatment on relapse-like ethanol drinking behavior was monitored for 10 days following abstinence. Following treatment with ceftriaxone, P rats consumed significantly higher amounts of water when compared to saline treated animals . A signiA GLM repeated measures analysis revealed a significant main effect of Day  along with a significant Day X Treatment interaction effect  in body weights. One-way ANOVA did not reveal any significant differences in body weights between both ceftriaxone and saline treated groups . These fWe report in this study that after long term continuous ethanol consumption (14 weeks) followed by two week deprivation, a dose dependent (50 vs. 200 mg/kg/day) effect was observed upon relapse-like ethanol drinking paradigm. During the 10 days of re-exposure to free-choice ethanol, the 200 mg/kg/day dose of ceftriaxone reduced ethanol intake from Day 2 to Day 9 compared to saline treated group. However, towards the end of the present study (Day 10), animals treated with the 200 mg/kg/day dose of ceftriaxone were found to consume amounts of ethanol equivalent to the saline-treated group. The lower dose (50 mg/kg/day) of ceftriaxone, did not change the ethanol drinking pattern following re-exposure.These findings are in accordance with our previous studies that demonstrated that ceftriaxone at higher dose (200 mg/kg/day) attenuated reinstatement to cocaine-seeking behavior; however, the lower dose of ceftriaxone (50 mg/kg/day) did not induce any effect . It is iModulation of glutamatergic neurotransmission, including treatment with ceftriaxone, has been proved effective in attenuating relapse to drug addiction ,27,32,33Ceftriaxone and other compounds have been shown to modulate the glutamatergic neurotransmission primarily through the upregulation of GLT1 and xCT levels in the NAc in model of relapse to cocaine-seeking behavior ,36. InteIn the present study, although effective initially in reducing ethanol intake following re-exposure to ethanol in a 14 week relapse-like ethanol drinking paradigm, ceftriaxone (200 mg/kg/day) treatment did not maintain a statistically significant reduction in ethanol intake towards the end of the study period (Day 10). An explanation for the observed deviation of results compared to our previous study based on five-weeks of ethanol exposure can be found in the fact that changes in CNS neurotransmission are based on length of exposure . Long-teCeftriaxone treatment has been found effective in upregulating GLT1 levels in brain reward regions at 200 mg/kg, i.p. in rats ,45. ThisWe conclude here that higher dose of ceftriaxone was effective in attenuating relapse-like ethanol-drinking behavior. However, the lower dose of ceftriaxone was ineffective. These findings are in accordance with our previous studies that revealed that higher dose of ceftriaxone, a dose known to upregulate GLT1 in PFC and NAc, was effective in attenuating reinstatement to cocaine-seeking behavior. Together, these findings suggest that the dose of ceftriaxone inducing upregulation of GLT1 is effective in the attenuation of relapse-like ethanol-drinking and cocaine-seeking behaviors.