Class of 2012 Abstract / Specific Aims: To assess the number of patients referred to ASHLine during the health screenings performed by University of Arizona College of Pharmacy students; and to identify the comfort level of students who asked patients about their smoking status. Methods: An anonymous questionnaire was sent via electronic mail to evaluate students’ comfort levels in implementing a smoking cessation referral program and subject demographics. Chart reviews quantified the number of patients referred to a smoking cessation program. Main Results: A total of 1,147 patients were screened for smoking cessation, 85 of which said they still smoked. Of the 85 who smoked, only 2 (0.17%) were referred to ASHLine. There was no significant increase in the comfort level of students (based on three domains) who participated in a smoking cessation training program or students in different years of their professional education. It was found that more students were comfortable with completing the required smoking cessation paperwork if they attended three or more health fairs (P=0.014). Conclusions: The comfort level of students with smoking cessation education is independent of the number of patients referred to a local smoking cessation program.

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The premise of the Simple View of Reading is that reading comprehension is the product of two components – decoding and language comprehension. Each component is necessary but not sufficient. To support teachers in identifying end-of-second-grade students who may have difficulties in one or both of the components, parallel listening comprehension and reading comprehension screening measures were developed and investigated in two preliminary pilot studies and one large-scale administration. The first pilot study, conducted with 41 end-of-second-grade students, established administration times for the listening comprehension screening (LCS) and the reading comprehension screening (RCS) and confirmed the appropriateness of the 75 items on each of the measures. The second pilot study, conducted with 12 end-of-second- grade students with varying reading levels, demonstrated that the LCS and RCS could differentiate readers with good comprehension from readers with poor comprehension. The large-scale administration, conducted with 699 end-of-second-grade students, aided in the development of shorter final versions of the LCS and RCS and provided data to determine the score reliability and validity of the final versions of the measures, each of which had 42 items. Item response theory (IRT) was used to identify the most apposite and discriminating items for use on the final versions of the LCS and RCS. Score reliability (Cronbach’s alpha) on the final LCS was estimated to be .89 and was estimated to be .93 on the final RCS. Various sources provided content and criterion-related validity evidence. In particular, criterion-related validity evidence included strong correlations with the Gates-MacGinitie Reading Tests and strong sensitivity, specificity, and positive predictive indices. Construct validity evidence included group differentiation and a confirmatory factor analysis (CFA), all of which supported a single underlying construct on the LCS and a single underlying construct on the RCS. In a subset of 214 end-of-second-grade students from the larger study, partial correlation and structural equation modeling (SEM) analyses supported the discriminant validity of the LCS and RCS as measures of comprehension. The listening and reading comprehension screening measures will assist second-grade teachers in identifying student learning needs that cannot be identified with reading-only comprehension tests.

Whether to screen for prostate cancer in aging men is a topic that is fairly well researched, but recommendations are controversial, because the evidence supporting any recommendation is equivocal. The evidence clearly does not support routine screening of all average-risk men, but for men aged 55 to 69 years, either not routinely screening, or engaging each man in shared decision making for his individual preference on screening, is reasonable and consistent with the evidence. Many organizations, including the American Cancer Society, have not yet reassessed their guidelines, in response to the US Preventative Services Task Force revised guideline.

PROBLEM STATEMENT: An estimated 3.1 million adolescents in the United States experience depression episode each year. Adolescents experiencing depression are prone to poor academic performance, impaired social functioning, increased incidence of substance abuse, and increased risk for suicide. Primary care providers often do not conduct depression screenings during healthcare visits for various reasons. Southwest Virginia school system does not have a depression screening protocol making depression symptoms often unidentified. SUMMARY OF EVIDENCE: Depression screenings should be conducted during well child exams. Missed screenings place adolescents at risk for poor healthcare outcomes. DESCRIPTION OF PRACTICE OR PROTOCOL: The pediatric nurse practitioner health services coordinator for southwest Virginia schools conducts well-child exams for adolescents. Depression screening was an area for practice improvement. VALIDATION OF EVIDENCE: The Patient Health Questionnaire (PHQ)-2 was administered during the health service coordinators’ well child visit and aggregate data was collected on a handwritten form relaying the PHQ-2 score, PHQ 9 score, and referral to parent. RELEVANCE OF PMH NURSING: All students receiving a well child visit over 8 weeks were screened for depression (n=44). There were 16 (35.5%) of students who screened positive on the PHQ-2 and were administered the PHQ-9. There were 13 (81.3%) (n=16) students who were administered the PHQ-9 and scored greater than 4. The number of referrals to parents generated were 10 (76.9%) (n=13). FUTURE IMPLICATIONS: Southwest Virginia schools need a policy and procedure describing the administration of the PHQ-2 and PHQ-9 screening instrument.

Classic Galactosemia (CG) is an autosomal recessive disorder caused by deleterious mutations of galactose-1-phosphate uridyltransferase (E.C. 2.7.7.12) (GALT) gene, which results in the inability to metabolize galactose and the accumulation of galactose-1-phosphate (gal-1-p) in patients' cells. Newborn screening has resulted in presymptomatic diagnosis and treatment. Although a galactose-restricted diet prevents the neonatal lethality of this disorder, many well-treated patients continue to develop debilitating complications such as premature ovarian insufficiency (POI), dyspraxic speech, ataxia and other neurological defects. The causes of these unsatisfactory outcomes remain unclear, but accumulation of gal-1-p is regarded as the major factor responsible for these chronic complications. In previous studies we found that gal-1-p was a competitive inhibitor of the UTP dependent, glucose-1-phosphate pyrophosphorylase (EC 2.7.7.9) and inositol monophosphatase (EC 3.1.3.25). As a result there were deficiencies in cellular UDP-glucose and UDP-galactose as well as impaired G-protein-stimulated inositol responses of Ca++ release, respectively. In this study, we found that when we challenged GALT-deficient yeast and GALT-deficient human diploid fibroblasts with galactose, these cells exhibited environmental stress and endoplasmic reticulum (ER) stress, which was characterized by the up-regulation of the gene encoding the master regulator of ER stress, GRP78/BiP. In separate studies using GALT-deficient diploid fibroblasts and comparative expression arrays, we found that the expression level of a tumor suppressor gene called aplysia ras homolog I (ARHI) was significantly higher in patient cells under galactose challenge. This ARHI gene was lost in rodents during evolution and GALT knockout mice did not express the human phenotype for galactosemia whereas over-expression of this gene in transgenic mice resulted in phenotypes characteristic of those seen in patients with galactosemia. We therefore propose here that ARHI could be an important target of galactose toxicity in Classic Galactosemia, and also explain the absence of patient phenotypes in GALT knock-out mice. In order to prevent accumulation of gal-1-p caused by GALT-deficiency, we experimentally screened over 300,000 chemical compounds against human galactokinase (GALK) in vitro. To date, we obtained from two high-throughput screenings (HTS), 200 GALK inhibitors with IC50s ranging from 700nM to 35μM. We subsequently established selectivity and toxicity profiles of 34 selected GALK inhibitors. Based on these results, we selected four compounds for further characterization, which included kinetic studies, site-directed mutagenesis and molecular docking experiments. From these experiments, we learned how these compounds interacted with the GALK enzyme and built detailed binding models for each of them. We demonstrated that three of the in vitro inhibitors of GALK could lower intracellular gal-1-p accumulation in GALT-deficient cells. Of considerable interest to us was that one of the compounds, cluster 25-1, not only reduced gal-1-p accumulation, but also corrected the level of GRP78/BiP back to background in the galactose-challenged GALT-deficient cells. These results were the first to demonstrate a direct link between GALT-deficiency and ER stress and provided proof of concept that we could prevent both gal-1-p accumulation and ER stress with GALK inhibitors in GALT deficient human cells. Lastly, we developed a new, virtual method of identifying novel GALK inhibitors by combining software-based, high-throughput virtual screening (HTVS) and fragment-based linkage using docking software. The initial HTVS validation experiments with compounds from the "ZINC" database identified four active GALK inhibitors with IC50s ranging from 70μM to 400μM. We then used HTVS to identify chemical fragments which bind to the active site of the human GALK enzyme. Using fragment-linking software, we identified chemical fragments which could potentially result in high-affinity inhibitors when chemically joined.

Background: The prevalence of uncorrected refractive error among school-age children is on the rise with a detrimental effect on academic performance and socio-economic status of those affected. School vision screening appears to be an effective way of identifying children with uncorrected refractive error so early intervention can be made. Despite the increasing popularity of school vision screening programs in recent times, there is a lot of debate on its effectiveness in reducing the proportion of children with uncorrected refractive error in the long term especially in settings where resources are limited. Objective: To assess the effectiveness of school vision screening programs in reducing children with uncorrected refractive error in LMIC. Search Methods: To identify studies suitable for this systematic review, a comprehensive and systematic search strategy was employed. We searched various databases and the search was restricted to articles published in English. We included RCTs, cross-sectional studies, case-control studies, and cohort studies. Participants included school children who had undergone vision screening as part of school vision screening programs in the LMIC setting and found to have a refractive error. Two independent reviewers screened the result of the search output and performed a full-text review of the search result to identify papers that met the pre-defined inclusion criteria. Data extraction and risk of bias assessment for the included studies was performed by the two independent reviewers and discrepancies were resolved by consensus and through consultation. The certainty of the evidence was assessed using the GRADE approach. Main Result: We found thirty relevant studies conducted in ten different countries that answered our review questions. Our review showed that school vision screening may be effective in reducing the proportion of children with an uncorrected refractive error by 81% (95% CI: 77%; 84%, moderate certainty evidence), 24% (95% CI: 13%; 35%, moderate certainty evidence,) and 20% (95% CI: 18%; 22%, moderate certainty evidence) at two, six, and more than six months respectively after its introduction. Our review also suggest that school vision screening may be effective in achieving 54% (95% CI: 25%; 100%, moderate certainty evidence), 57% (95% CI:46%; 70%, low certainty evidence), 38% (95% CI: 29%; 51%, moderate certainty evidence) and 41% (95% CI: 24%; 68%, low certainty evidence) level of spectacle wear compliance among school children at less than three months, at three months, at six months and at more than six months respectively after its introduction. Our review further found moderate to high certainty evidence indicating that school vision screening together with the provision of spectacles may be relatively cost-effective, safe and has a positive impact on the academic performance of children. Conclusion: Result of this review shows that school vision screening together with the provision of spectacle may be a safe and cost-effective way of reducing the proportion of children with uncorrected refractive error with a long-term positive impact on academic performance of children. Most of the studies included in this review were however conducted in Asia and the applicability of this finding to countries in other regions especially those outside the LMIC circle is not clear.

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