Screen Plus Research Articles

Role of IgG food test in patients with allergic diseases

<abstract> <p>The role of immunoglobulin G (IgG) food elimination in allergic diseases is controversial. This main aim is to clarify the beneficial effects of specific immunoglobulin G (sIgG) food elimination on improving allergic diseases. International guidelines disagree about the beneficial roles of IgG food elimination on allergic diseases. However, many studies have proven the role of IgG food elimination on allergic diseases. In atopic dermatitis children, studies have shown that milk, egg, wheat, and soya are positive for sIgGs and there sIgG elimination will improve atopic dermatitis. In allergic rhinitis, the sIgG4 food test is usually positive to seafood, and IgG food elimination will improve both allergic rhinitis and asthma symptoms. In asthma, persistent IgE egg sensitizers have higher sIgG1 to egg than partial IgE egg sensitizers. Additionally, high sIgG1 to egg is a risk factor for future asthma (with sensitivity of 64% and specificity of 74%). In asthma, persistent sIgG1 egg sensitization is risk for future asthma and IgG food elimination will improve asthma (especially milk and egg). In chronic urticaria, the most common positive sIgGs to food are cola nut, yeast, wheat, red kidney bean, pea, corn, and egg white in Saudi Arabia. Women and patient aged < 40 years have higher positive sIgG rates to several foods. In food intolerance, IgG food elimination will improve the symptoms of food intolerance. Furthermore, primary prevention of food intolerance can be achieved by early IgG food elimination. In conclusion, despite those most international guidelines disagree about the beneficial role of IgG food elimination on allergic diseases; some studies support its role. This test may be used if patients' symptoms do not improve after the IgE food tests. Moreover, IgG food companies should offer cheap short lists, such as ImuPro Screen 22 foods or ImuPro Screen Plus 44 foods.</p> </abstract>

Sociodemographic Comparison of Children With High-risk Medical Conditions Referred vs Identified Through Screening Plus Outreach for COVID-19 Therapeutics

Minoritized groups are less likely to receive COVID-19 therapeutics, but few studies have identified potential methods to reduce disparities. To determine whether screening plus outreach, when compared with referral alone, increases identification of vulnerable pediatric patients at high risk for severe disease eligible for COVID-19 therapeutics from low-resourced communities. A retrospective cohort study of COVID-19 medication allocation between January 1, 2022, and February 15, 2022, at Lurie Children's Hospital, a quaternary care children's hospital, in Chicago, Illinois. The cohorts were pediatric patients referred for COVID-19 therapeutics or with a positive SARS-CoV-2 polymerase chain reaction within the hospital system followed by outreach. Screening involved daily review of positive cases of SARS-CoV-2, followed by medical record review for high-risk conditions, and communication with clinicians and/or patients and families to offer therapy. Diagnosis of COVID-19. The primary measure was difference in child opportunity index (COI) scores between the 2 cohorts. Secondary measures included presence and duration of symptoms at diagnosis, medication uptake, race and ethnicity, insurance type, qualifying medical condition, sex, primary language, and age. Of 145 total patients, the median (IQR) age was 15 (13-17) years, and most were male (87 participants [60.0%]), enrolled in public insurance (83 participants [57.2%]), and members of minoritized racial and ethnic groups (103 participants [71.0%]). The most common qualifying conditions were asthma and/or obesity (71 participants [49.0%]). From 9869 SARS-CoV-2 tests performed, 94 eligible patients were identified via screening for COVID-19 therapeutics. Fifty-one patients were identified via referral. Thirty-two patients received medication, of whom 8 (25%) were identified by screening plus outreach alone. Compared with referred patients, patients in the screening plus outreach group were more likely to have moderate, low, or very low COI composite scores (70 patients [74.5%] vs 27 patients [52.9%]); public insurance (65 patients [69.1%] vs 18 patients [35.3%]); and asthma or obesity (60 patients [63.8%] vs 11 patients [21.6%]). Patients in the referral group were more likely to be non-Hispanic White (23 patients [45.1%] vs 19 patients [20.2%]) and receive medication (24 patients [47.1%] vs 8 patients [8.5%]). Compared with referral patients, screening plus outreach patients for COVID-19 medications were more socially vulnerable, with lower COI scores, and more likely to have asthma or obesity. Future studies should investigate communication strategies to improve uptake of these medications after outreach.

Photorefraction Screening Plus Atropine Treatment for Myopia is Cost-Effective: A Proof-of-Concept Markov Analysis.

PurposeThe prevalence of myopia is increasing globally, putting individuals at risk of myopia-associated visual impairment. Low-dose atropine eye drops have been found to safely reduce the risk of progression from myopia to higher levels of myopia and pathological states. In New Zealand, school children have an eye check at age 11. In this study, we aimed to estimate the cost-effectiveness of introducing photorefractive screening for myopia at age 11 in the New Zealand context, with atropine 0.01% eye drops treatment for those screening positive.Patients and MethodsA Markov cohort simulation was used to model the impact of screening plus atropine compared to usual care across a lifetime horizon and societal perspective with a 3% discount rate. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER), with utility measured in quality-adjusted life-years (QALYs). Multivariate sensitivity analyses were carried out to investigate factors influencing cost-effectiveness.ResultsThe ICER for screening plus atropine was NZ$1590 (95% CI 1390, 1791) per QALY gained, with 7 cases of lifetime blindness prevented per 100,000 children screened.ConclusionScreening for myopia with photorefraction at age 11 and atropine 0.01% eye drop treatment of children screening positive is likely to be cost-effective. These results suggest that a real-world trial and cost-effectiveness analysis would be worth considering in New Zealand.

Clinical Performance of Two Automated Immunoassays, EliA CTD Screen and QUANTA Flash CTD Screen Plus, for Antinuclear Antibody Screening.

BackgroundRecently, two fully automated immunoassays for antinuclear antibody (ANA) screening were introduced EliA CTD Screen (Thermo Fisher Scientific, Freiburg, Germany) and QUANTA Flash CTD Screen Plus (Inova Diagnostics, San Diego, USA). We evaluated their clinical performance in comparison with the indirect immunofluorescence assay (IIFA) and analyzed samples with discrepant results.MethodsIn total, 406 serum samples (206 from patients undergoing routine checkups and 200 from rheumatology clinic patients) were assayed using EliA, QUANTA Flash, and IIFA. We evaluated assay concordance and agreement and confirmed the presence of anti-extractable nuclear antigen (ENA) antibodies in samples with discrepant automated immunoassay and IIFA results. Additionally, we compared the clinical performance of each assay in diagnosing ANA-associated rheumatic disease (AARD) and adjusted the cut-off values.ResultsIn rheumatology clinic samples, the concordance and agreement were 91.5% and strong between EliA and QUANTA Flash, 79.0% and weak between EliA and IIFA, and 80.5% and moderate between QUANTA Flash and IIFA, respectively. In automated immunoassay-positive, IIFA-negative samples (N=15), all anti-ENA antibodies detected (6/15) were anti-Sjögren’s syndrome antigen A/Ro (Ro60) antibodies. The automated immunoassays and IIFA showed high accuracy for diagnosing AARD, and adjusted cut-off values improved their sensitivities (EliA with 0.56 ratio, 82.9% sensitivity; QUANTA Flash with 9.7 chemiluminescent units, 87.8% sensitivity).ConclusionsThe two automated immunoassays showed reliable performance compared with IIFA and can be efficiently used with the IIFA in clinical immunology laboratories. Clinical cut-off values can be adjusted according to the workflow in each laboratory.

Abstract 9176: Quarterly versus Annual ECG Screening for Atrial Fibrillation in Older Chinese (AF-CATCH): A Prospective, Randomised, Controlled Trial

Introduction: Screening for atrial fibrillation before symptoms manifested and subsequent initiation of oral anticoagulants (OACs), could prevent stroke and death. The most cost-effective strategy to screen atrial fibrillation in high-risk population aged 65 and over remains unknown. Methods: We performed a randomised controlled trial that compares different screening frequencies of 30-second single-lead ECG (AliveCor® Heart Monitor) in the detection of atrial fibrillation in Chinese residents (≥65 years old) in 5 community health centres in Shanghai. Only participants without atrial fibrillation history and atrial fibrillation rhythm at baseline were eligible for inclusion in the trial. Participants were randomised in a 1:1 ratio into annual (G1) and quarterly screening (G2) groups: the quarterly screening group was further randomised in a 3:1 ratio into subgroups of quarterly screening (G2-1) and quarterly screening PLUS (G2-2, ECG weekly for 1-month then quarterly). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was performed for all randomised patients who had at least one ECG recording during follow-up. This trial was registered at ClinicalTrials.gov, number NCT02990741. Results: Between April 17, 2017, and June 26, 2018, a total of 8240 participants were randomised into G1 (n=4120), G2-1 (n=3090) and G2-2 (n=1030), with a mean of 1.6, 3.5 and 5.2 ECG records respectively during a median of 2.1 years follow-up (13,284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in G1 (4.1/1000 person-years) and 47 in G2 (6.7/1000 person-years; hazard ratio with G1, 1.71; 95% confidence interval [CI] 1.06-2.76; P =0.03). 40 incident cases were detected in G2-1 (7.2/1000 person-years; hazard ratio with G1, 1.83; 95% CI 1.12-3.00; P =0.02) and 7 in G2-2 (4.8/1000 person-years; hazard ratio with G1, 1.24; 95% CI 0.54-2.86; P =0.61). No significant difference was noted between G2-1 and G2-2 (hazard ratio with G2-1, 0.68; 95% CI 0.30-1.52; P =0.35). Conclusions: Quarterly 30-second single-lead ECG screening significantly increased the detection rate of incident atrial fibrillation, additional weekly screening in the first month did not yield added predictive value.

Quarterly versus annual ECG screening for atrial fibrillation in older Chinese (AF-CATCH): a prospective, randomised, controlled trial

Abstract Background Screening for atrial fibrillation before symptoms manifested and subsequent initiation of oral anticoagulants (OACs), could prevent stroke and death. The most cost-effective strategy to screen atrial fibrillation in high-risk population aged 65 and over remains unknown. Methods We performed a randomised controlled trial that compares different screening frequencies of 30-second single-lead electrocardiography (ECG) in the detection of atrial fibrillation in Chinese residents (≥65 years old) in 5 community health centres in Shanghai. Participants without atrial fibrillation were randomised in a 1:1 ratio into annual (G1) and quarterly screening (G2) groups: the quarterly screening group was further randomised in a 3:1 ratio into subgroups of quarterly screening (G2–1) and quarterly screening PLUS (G2–2, ECG weekly for 1-month then quarterly). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was performed for all randomised patients who had at least one ECG recording during follow-up. Results Between April 17, 2017, and June 26, 2018, a total of 8240 participants were randomised into G1 (n=4120), G2–1 (n=3090) and G2–2 (n=1030), with a mean of 1.6, 3.5 and 5.2 ECG records respectively during a median of 2.1 years follow-up (13,284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in G1 (4.1/1000 person-years) and 47 in G2 (6.7/1000 person-years; hazard ratio with G1, 1.71; 95% confidence interval [CI] 1.06–2.76; P=0.03). 40 incident cases were detected in G2–1 (7.2/1000 person-years; hazard ratio with G1, 1.83; 95% CI 1.12–3.00; P=0.02) and 7 in G2–2 (4.8/1000 person-years; hazard ratio with G1, 1.24; 95% CI 0.54–2.86; P=0.61). No significant difference was noted between G2–1 and G2–2 (hazard ratio with G2–1, 0.68; 95% CI 0.30–1.52; P=0.35). Conclusion Quarterly 30-second single-lead ECG screening significantly increased the detection rate of incident atrial fibrillation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Healthcare Company

Examining the benefits and harms of Alzheimer\u2019s disease screening for family members of older adults: study protocol for a randomized controlled trial

BackgroundMultiple national expert panels have identified early detection of Alzheimer’s disease and related dementias (ADRD) as a national priority. However, the United States Preventive Services Task Force (USPSTF) does not currently support screening for ADRD in primary care given that the risks and benefits are unknown. The USPSTF stresses the need for research examining the impact of ADRD screening on family caregiver outcomes.MethodsThe Caregiver Outcomes of Alzheimer’s Disease Screening (COADS) is a randomized controlled trial that will examine the potential benefits or harms of ADRD screening on family caregivers. It will also compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening. COADS will enroll 1800 dyads who will be randomized into three groups (n = 600/group): the ‘Screening Only’ group will receive ADRD screening at baseline and disclosure of the screening results, with positive-screen participants receiving a list of local resources for diagnostic follow-up; the ‘Screening Plus’ group will receive ADRD screening at baseline coupled with disclosure of the screening results, with positive-screen participants referred to a dementia collaborative care program for diagnostic evaluation and potential care; and the control group will receive no screening. The COADS trial will measure the quality of life of the family member (the primary outcome) and family member mood, anxiety, preparedness and self-efficacy (the secondary outcomes) at baseline and at 6, 12, 18 and 24 months. Additionally, the trial will examine the congruence of depressive and anxiety symptoms between older adults and family members at 6, 12, 18 and 24 months and compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening between the two groups randomized to screening (Screening Only versus Screening Plus).DiscussionWe hypothesize that caregivers in the screening arms will express higher levels of health-related quality of life, lower depressive and anxiety symptoms, and better preparation for caregiving with higher self-efficacy at 24 months. Results from this study will directly inform the National Plan to Address Alzheimer’s Disease, the USPSTF and other organizations regarding ADRD screening and early detection policies.Trial registrationClinicalTrials.gov, NCT03300180. Registered on 3 October.

(Invited) Screening Plus Testing of Cathode Materials for Ca and Mg Batteries

While the current state-of-the-art in rechargeable batteries is the Li-ion technology, research efforts are intensified towards the development of alternative technologies to satisfy the ever-increasing demand for enhanced energy density. The development of rechargeable batteries based on the intercalation reaction of multivalent cations (Ca2+, Mg2+, Al3+) is a current challenge for electrochemical energy storage. Designing such batteries demands the identification of competitive electrode materials and electrolytes for each particular active ion. In the last years, we have combined computational and experimental techniques in the search of potential cathode materials that could reversibly insert Mg/Ca ions [1-4]. First principles calculations are used to predict three fundamental electrochemical properties of materials: average intercalation voltage, specific capacity and ionic mobility. Benchmarking the computational results with experimental evidences is a necessary step to accelerate reliable materials design based on DFT calculations. Therefore, our experimental investigations comprise the synthesis, characterization and electrochemical testing of materials. In this work, we confront computational and experimental results for selected oxides, nitrides, sulphides and silicate materials. We will show that the combined computational/experimental approaches lead to proof of concept and rationalization for the reversible electrochemical intercalation and deintercalation of calcium in TiS2 [4]. Acknowledgments: Authors are grateful for financial support from Ministerio de Ciencia e Innovación (grant MAT2014-53500-R), the European Union H2020-FETOPEN funded project CARBAT-766617 and Toyota Motor Europe.

Evaluation of mericon E. coli O157 Screen Plus and mericon E. coli STEC O-Type Pathogen Detection Assays in Select Foods: Collaborative Study, First Action 2017.05.

QIAGEN mericon Escherichia coli O157 Screen Plus and mericon E. coli Shiga toxin-producing E. coli (STEC) O-Type Pathogen Detection Assays use Real-Time PCR technology for the rapid, accurate detection of E. coli O157 and the "big six" (O26, O45, O103, O111, O121, O145) (non-O157 STEC) in select food types. Using a paired study design, the assays were compared with the U.S. Department of Agriculture, Food Safety Inspection Service Microbiology Laboratory Guidebook Chapter 5.09 reference method for the detection of E. coli O157:H7 in raw ground beef. Both mericon assays were evaluated using the manual and an automated DNA extraction method. Thirteen technicians from five laboratories located within the continental United States participated in the collaborative study. Three levels of contamination were evaluated. Statistical analysis was conducted according to the probability of detection (POD) statistical model. Results obtained for the low-inoculum level test portions produced a difference between laboratories POD (dLPOD) value with a 95% confidence interval of 0.00 (-0.12, 0.12) for the mericon E. coli O157 Screen Plus with manual and automated extraction and mericon E. coli STEC O-Type with manual extraction and -0.01 (-0.13, 0.10) for the mericon E. coli STEC O-Type with automated extraction. The dLPOD results indicate equivalence between the candidate methods and the reference method.

Solid phase assays versus automated indirect immunofluorescence for detection of antinuclear antibodies.

Solid phase assays (SPAs) and automated microscope systems are increasingly used to screen for antinuclear antibodies (ANAs). The goal of this study was to evaluate the performance of three automated ANA screening assays; NOVA Lite HEp-2 using NOVA View® (NV, Inova Diagnostics), an automated indirect immunofluorescence method, EliA™ CTD Screen (Fluorescence Enzyme Immunoassay, FEIA; Thermo Fisher) and QUANTA Flash® CTD Screen Plus (Chemiluminescence immunoassay, CIA; Inova Diagnostics). The assays were performed on 480 diagnostic samples from patients with an ANA-associated rheumatic disease (AARD; systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, inflammatory myopathy, mixed connective tissue disease) and on 767 samples from diseased and healthy controls. Using cut-offs proposed by the manufacturers, the sensitivity was 95%, 80.5% and 86% for NV, FEIA and CIA, respectively. The corresponding specificity was 61% (NV), 97.5% (FEIA) and 88% (CIA). The sensitivity associated with a specificity of ~95% was 79%, 82% and 78% for NV, FEIA, and CIA, respectively. Receiver operating characteristics (ROC) curve analysis revealed no differences in area under the curve (AUC) between the 3 assays when all diseases were grouped. For Sjögren's syndrome, the AUC was higher for SPAs than for NV, whereas for systemic sclerosis, the AUC was higher for NV than for CIA. For all assays, the likelihood ratio for AARD increased with increasing antibody levels and for double positivity of NV with SPA. In conclusion, the performance of automated SPA and IIF was assay- and disease-dependent. Taking into account antibody levels and combining IIF with SPA adds value.

RAZOR: A Phase II Open Randomized Trial of Screening Plus Goserelin and Raloxifene Versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer

Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention.Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density.Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period.Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed.Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58-66. ©2017 AACR.

Analytical and clinical comparison of two fully automated immunoassay systems for the detection of autoantibodies to extractable nuclear antigens

BackgroundDetection of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IIFA) is increasingly substituted by fully automated solid phase immunoassays. This study evaluated the performance of an automated chemiluminescence immunoassay (CIA) and fluorescence enzyme immunoassay (FEIA) and compared their performance to that of IIFA. MethodsThe study included an unselected prospective study population suspected of systemic autoimmune rheumatic disease. ANA were measured by IIFA, while in parallel sera were tested by CIA QUANTA Flash CTD Screen Plus on the BIO-FLASH® and FEIA EliA CTD Screen on the Phadia® 250 system. As validation, retrospective cohorts of patients with ANA-associated rheumatic disease (AARD) and healthy controls were tested. ResultsProspectively, sensitivity of IIFA, CIA and FEIA was 90%, 99% and 92%, respectively. Specificity was 76%, 76% and 84%, respectively. Total percent agreements between the three methods were 75.2% (IIFA vs. CIA), 79.2% (IIFA vs. FEIA) and 85.4% (FEIA vs. CIA). The AUC values were 0.95 for CIA and 0.93 for FEIA and did not significantly differ. Retrospectively in individual AARD cohorts, similar results were obtained comparing both CTD screens. ConclusionsBoth FEIA and CIA CTD screen significantly outperformed IIFA, with a higher specificity for FEIA and higher sensitivity for CIA. Based on ROC analysis, major contributor to the difference between the two solid phase immunoassays was the cut-off.

Clinical performance evaluation of a novel, automated chemiluminescent immunoassay, QUANTA Flash CTD Screen Plus.

The QUANTA Flash(®) CTD Screen Plus is a chemiluminescent immunoassay (CIA) for the detection of the major antinuclear antibodies (ANA) on the BIO-FLASH(®) platform. NOVA View(®) is an automated fluorescence microscope that acquires digital images of indirect immunofluorescent assay (IFA) slides. Our goal was to evaluate the clinical performance of the two automated systems and compare their performance to that of traditional IFA. Sera from patients with systemic autoimmune rheumatic diseases (SARD, n = 178), along with disease and healthy controls (n = 204), were tested with the CTD CIA and with NOVA Lite(®) HEp-2 ANA, using both the manual method of reading the IFA slides and the NOVA View instrument. The CTD CIA showed 78.1% sensitivity for SARD, coupled with 94.1% specificity. Manual IFA and NOVA View showed somewhat higher sensitivity (81.5 and 84.8% in SARD, respectively), but significantly lower specificity (79.4 and 64.7%, respectively). Both automated systems displayed somewhat different performance, due to the different principals of ANA detection: IFA with NOVA View digital image interpretation had higher sensitivity, while the CTD CIA showed higher specificity. With the added benefits of full automation, the new CTD CIA is an attractive alternative to traditional ANA screening.

Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia functionremain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an invivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a flagellar matrix protein that accumulates specifically when cilia motility is impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential component of the nexin-dynein regulatory complex. Analysis of 295 individuals with PCD identified recessive truncating mutations of C21orf59 in four families and CCDC65 in two families. Similar to findings in zebrafish and planaria, mutations in C21orf59 caused loss of both outer and inner dynein arm components. Our results characterize two genes associated with PCD-causing mutations and elucidate two distinct mechanisms critical for motile cilia function: dynein arm assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for CCDC65.

Screening and brief intervention for drug use in primary care: the Assessing Screening Plus brief Intervention’s Resulting Efficacy to stop drug use (ASPIRE) randomized trial

Methods In this randomized trial (the Assessing Screening Plus brief Intervention’s Resulting Efficacy to stop drug use (ASPIRE) study) we tested the efficacy of a brief negotiated interview (BNI), and an adaptation of motivational interviewing (AMI), compared to no BI. Primary care patient participants had Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) drug specific scores of ≥4. Primary outcome at 6 months was number of days use of the drug of most concern (DOMC) in the past 30 days.

Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

The GISS Trial: a Phase II Prevention Trial of Screening Plus Goserelin, Ibandronate, versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer

Genetic testing for inherited mutations in breast cancer genes provides valuable information for disease prevention. Today, premenopausal women with increased risk for breast cancer have only limited nonsurgical options to reduce their risk. The GISS trial, a randomized, multicenter, open-label phase II trial, assessed the feasibility of a preventive treatment with goserelin and ibandronate for premenopausal women at increased risk for breast cancer. The primary endpoints were refusal to undergo randomization and discontinuation of treatment. Safety and quality of life were also evaluated. Between the years 2001 and 2003, 31 of 322 eligible women participated in the trial; 15 received goserelin/ibandronate plus screening, 15 screening only, and 1 withdrew her consent after randomization. The treatment duration was 24 months. Here, mainly the results from the first 12 months were evaluated because of the low compliance thereafter. Hot flushes, headache, and vaginal dryness/discharge occurred more often in the goserelin arm. No difference was observed between the two arms in the agreement to randomization, compliance, or any other endpoints. Acceptance of chemoprevention with goserelin and ibandronate was low. Premenopausal women at increased risk for breast cancer should be better informed about chemoprevention through physician counseling and a more feasible study design (e.g., oral medication) should be provided. This is the first chemoprevention trial in premenopausal women at increased risk for breast cancer.

Novel Thioredoxin-related Transmembrane Protein TMX4 Has Reductase Activity

In the endoplasmic reticulum (ER), a number of thioredoxin (Trx) superfamily proteins are present to enable correct disulfide bond formation of secretory and membrane proteins via Trx-like domains. Here, we identified a novel transmembrane Trx-like protein 4 (TMX4), in the ER of mammalian cells. TMX4, a type I transmembrane protein, was localized to the ER and possessed a Trx-like domain that faced the ER lumen. A maleimide alkylation assay showed that a catalytic CXXC motif in the TMX4 Trx-like domain underwent changes in its redox state depending on cellular redox conditions, and, in the normal state, most of the endogenous TMX4 existed in the oxidized form. Using a purified recombinant protein containing the Trx-like domain of TMX4 (TMX4-Trx), we confirmed that this domain had reductase activity in vitro. The redox potential of this domain (-171.5 mV; 30 degrees C at pH 7.0) indicated that TMX4 could work as a reductase in the environment of the ER. TMX4 had no effect on the acceleration of ER-associated degradation. Because TMX4 interacted with calnexin and ERp57 by co-immunoprecipitation assay, the role of TMX4 may be to enable protein folding in cooperation with these proteins consisting of folding complex in the ER.

Verbal cued recall as a predictor of conversion to Alzheimer's disease in Mild Cognitive Impairment

This study was set up to investigate whether neuropsychological tests are able to predict conversion to AD among Mild Cognitive Impairment (MCI) patients. At baseline the cognitive part of the Cambridge Examination for Mental Disorders of the Elderly (CAMCOG), the Mini Mental Status Examination (MMSE), the Geriatric Depression Scale (GDS), a Dutch variation of Rey's Auditory Verbal Learning Test, the Memory Impairment Screen plus (MISplus) and the Visual Association Test (VAT) were administered to 40 patients diagnosed with MCI. After 18 months, MCI-patients were reassessed and a follow-up diagnosis was established. Of those who were seen for follow-up (n = 31), seven fulfilled (NINCDS-ADRDA) criteria of probable AD, while 24 did not convert. A binary logistic regression analysis showed that the MISplus contributed most to the prediction of conversion (OR = 0.28, 95% CI 0.099-0.790). With a cut-off of 2 out of 6, a positive predictive value of 71.5%, a negative predictive value of 91.5% and an overall diagnostic accuracy of 87.0% were achieved. This prospective, longitudinal study shows that a score of 0 or 1 out of 6 on the MISplus may be a good indicator of future (within 18 months) progression to AD among MCI-patients.

The Influence of Atopic Status and Potential Risk Factors for Sensitization on Histamine Skin Reactivity in Unselected Belgian Children

The histamine skin response is widely used as a standardized positive control in the performance of skin prick testing. As a part of the Aalst Allergy Study, we investigated whether histamine skin reactivity, using histamine 10 mg/mL, was influenced by age, gender, ethnic origin, environmental exposure, specific sensitization patterns, or other factors. The parents of 2021 nonselected children aged 3.4-14.8 years completed a baseline questionnaire and gave written informed consent for skin prick testing with seven common aeroallergens on their child. Sensitized children had significantly larger histamine wheal sizes than nonsensitized children (mean 4.3 vs 4.0 mm, p < 0.05). A significant difference was found in histamine wheal size between nonsensitized versus multiply sensitized children (p < 0.001), but not between mono-sensitized versus multiply sensitized children (p = 0.105). The only other factors associated with significantly larger histamine wheal sizes were a history of eczema and a history suggestive for asthma on the Brief Pediatric Asthma Screen Plus. The histamine wheal was absent in 8.9% of children. In conclusion, sensitization and some other clinical indicators of atopy were associated with a larger histamine skin wheal. Other conditions including gender and environmental exposure did not have an influence on histamine skin reactivity, which strengthens the use of histamine as a reference in skin prick testing in this age group.